Datasets:

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kenhktsui

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code-natural-language-classification-dataset

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Q: Bar Button item not showing in SWIFT I created a simple Bar button item in my project but it is not showing when I run it. This is how I declare it @IBOutlet weak var songSelectionBar: UIBarButtonItem! Here is a screen shot of my project. I am fairly new to swift so I know I am doing something that should be simple (or maybe not). Here is some more code from the project. This function returns the contents of the directory. My understanding is that I should use a tableview to display the output of this function. Can anyone point me to an example or show me how to do this? Thanks func getMusicFilesInDirectory() -> [String] { //var wavFiles:[String] // We need just to get the documents folder url let documentsUrl = NSFileManager.defaultManager().URLsForDirectory(.DocumentDirectory, inDomains: .UserDomainMask).first! // now lets get the directory contents (including folders) do { let directoryContents = try NSFileManager.defaultManager().contentsOfDirectoryAtURL(documentsUrl, includingPropertiesForKeys: nil, options: NSDirectoryEnumerationOptions()) print(directoryContents) } catch let error as NSError { print(error.localizedDescription) } // now filter the directory to extract only Wav Files do { let directoryUrls = try NSFileManager.defaultManager().contentsOfDirectoryAtURL(documentsUrl, includingPropertiesForKeys: nil, options: NSDirectoryEnumerationOptions()) print(directoryUrls) let wavFilesDir = directoryUrls.filter(){ $0.pathExtension! == "wav" }.map{ $0.lastPathComponent! } wavFiles = ["Wav Music Files:\n" + wavFilesDir.description] } catch let error as NSError { print(error.localizedDescription) } return wavFiles } A: If you just declare the IBOutlet,not drag it out from IB,you should get rid of the "weak". The IB has a strong reference to it's IBOutlet,so you must use it's IBOutlets with weak. By contrast,if you manually declare an IBOutlet,you must keep a strong reference to it.

minipile

NaturalLanguage

mit

--- abstract: 'This paper focuses on the optimal sensor placement problem for the identification of pipe failure locations in large-scale urban water systems. The problem involves selecting the minimum number of sensors such that every pipe failure can be uniquely localized. This problem can be viewed as a minimum test cover (MTC) problem, which is NP-hard. We consider two approaches to obtain approximate solutions to this problem. In the first approach, we transform the MTC problem to a minimum set cover (MSC) problem and use the greedy algorithm that exploits the submodularity property of the MSC problem to compute the solution to the MTC problem. In the second approach, we develop a new *augmented greedy* algorithm for solving the MTC problem. This approach does not require the transformation of the MTC to MSC. Our augmented greedy algorithm provides in a significant computational improvement while guaranteeing the same approximation ratio as the first approach. We propose several metrics to evaluate the performance of the sensor placement designs. Finally, we present detailed computational experiments for a number of real water distribution networks.' address: - Massachusetts Institute of Technology - Vanderbilt University - Massachusetts Institute of Technology - Vanderbilt University author: - Lina Sela Perelman - Waseem Abbas - Xenofon Koutsoukos - Saurabh Amin - Lina Sela Perelman - Waseem Abbas - Xenofon Koutsoukos - Saurabh Amin bibliography: - 'fdi.bib' title: - 'Sensor placement for fault location identification in water networks: a minimum test cover approach' - 'Sensor placement for fault location identification in water networks: a minimum test cover approach' --- , , , Fault identification; Minimum test cover; Water networks. Introduction ============ Infrastructure deterioration, demand-supply uncertainty, and risk of disruptions pose new challenges in maintaining modern infrastructures. Resilient urban infrastructures including water distribution systems, transportation networks, and electric grids are crucial for societal well-being. *Smart* infrastructure operation driven by sensing and actuation technologies have been identified as one of the primary solutions towards resilient urban systems [@urbaninfra:edit; @6855316]. Through a network of sensors, an individual fault or correlated failures in a system component can be detected and localized, and restorative actions can be executed in response to these faults. Whereas network observability for a given sensing capability has been widely studied in the context of fault detection, sensor placement for fault isolability, i.e. the ability to distinguish between faults, has not been a commonly studied problem, especially in the context of pipe bursts in water distribution networks. The goal of this work is to *design a sensor placement configuration for identification of pipe failure locations by using the minimum number of sensors.* The underlying idea behind our approach is to ensure that the sensor placement results in a collective output that is *unique* for each failure event. Specifically, our main contributions are as follows, we: - Define the *localization* of pipe bursts as the design objective of a sensor network configuration, and using ideas from combinatorial optimization, we formulate the fault location identification problem as a *minimum test cover* (MTC) problem; - Develop a computationally efficient *augmented greedy* algorithm to solve the minimum test cover problem (resp. identification problem), which is significantly faster in comparison to the previous approaches and therefore, scalable to large-scale networks; and - Test and evaluate our sensor placement approach on a batch of real-networks of various sizes and parameters using practically relevant performance measures. Our paper is motivated by the need to consider localization of pipe bursts in the deployment phase of new sensing technologies, since this consideration can significantly reduce the response time and overall costs of fault localization to the distribution utilities. We base our work on the use of low-cost, high-rate online sensors measuring water pressure for remote detection of pipe burst using data mining techniques. Real-world examples are the PIPENET in Boston, MA, US [@Stoianov:2007:PWS:1236360.1236396] and the WaterWise in Singapore [@allen:smart]. The sensor placement problem is not unique to the water sector and can be found in many engineering applications for system operation. We discuss some of the related work in Section \[sec:review\]. In Section \[sec:problem\], we present the network and the sensing models and formulate the detection and identification problems as the minimum set cover (MSC) and minimum test cover (MTC) problems, respectively. A key aspect of the MTC problem formulation is the choice of the objective function, which is to select the minimum number of *tests* from a collection of tests such that every event can be uniquely classified in one of the given *categories* based on selected tests’ outcomes [@Moret1]. In our setup, the set of outcomes of tests comprise of the output vector from sensors, events are pipe failures, and classification categories are the possible locations of the failed pipes. In Section \[sec:oldsol\], we present a solution approach as in [@Halldorsson:2001:AMT:647911.740635; @svard2013realizability], in which the MTC is first transformed to the MSC and then solved using the greedy approximation [@Minoux1]. In Section \[sec:New\_Algo\] we present an *augmented greedy* algorithm for solving the MTC that does not require the complete transformation of the MTC to the equivalent MSC, and directly computes the objective function in a greedy fashion. This algorithm is much faster than the standard greedy approach and considerably improves the scalability of our approach. In Sections \[sec:applications\] and \[sec:app2\], we demonstrate our approach using a benchmark and a batch of twelve real water distribution networks of various sizes and specifications. We suggest four metrics to evaluate the performance of the design including detection, identification, and localization scores. Although we demonstrate our results in the context of water networks, our algorithm provides an improved solution to the generic test cover problem. Section \[sec:conclusions\] summarizes our work and proposes future extensions. Problem formulation {#sec:problem} =================== Consider the problem of placing online sensors measuring hydraulic pressures with high frequency such that the identification of pipe failure locations is maximized. Based on the number of pipes where link failures (i.e., pipe bursts) can happen, we consider $n$ link failures as a set of failure events, denoted by $\mathcal{L} = ~ \{ \ell_1, \dots, \ell_n \}$. For the ease of presentation and without the loss of generality, let $\ell_j$ denote the failure event at the $j^{th}$ pipe. Moreover, we define a set of sensors that can be placed at $m$ nodes of the network as $\mathcal{S}= \{ S_1, \dots, S_m \}$. Here, $S_i$ denotes the location of the $i^{th}$ sensor. The outputs from sensors, which are based on the change in pressure induced by the failure event, are denoted by $\mathbf{y}_{{\mathcal{S}}}$. Network dynamics and sensing model ---------------------------------- A water distribution network can be represented by a graph comprising nodes (supply and demand) connected by links (pipes, valves, and pumps). Physical failures of the infrastructure, such as pipe bursts, cause a disturbance in the flow, which moves through the system as a pressure wave known as *water hammer*, or *surge* with very high velocity, varying typically in the range of $600 - 1500 [\frac{m}{s}]$ [@Dalius]. This implies that the steady state analysis employed by traditional methods such as supervisory control and data acquisition (SCADA) systems are inadequate and that the transient system dynamics between the initial and the final steady state conditions need to be considered. The transient system state can be typically described by mass and momentum partial differential equations [@wylie1993fluid]. The method of characteristics (MOC) is a numerical technique typically used to approximate the solution of the hydraulic transients. The MOC transforms the partial differential equations into ordinary differential equations that evolve along specific characteristic lines of the numerical grid, which are solved explicitly to compute the head and flow, $h_{i,t+1},q_{i,t+1}$, at new point in time and space. Here, $t$ and $i$ indicate the discrete points of the numerical grid. For a given pipe, the two characteristic equations describing the hydraulic transients are formulated as [@Dalius]: $$\begin{aligned} h_{i,t+1} &= \frac{1}{2} \big[ h_{i-1,t} + h_{i+1,t} + b \left( q_{i-1,t} - q_{i+1,t} \right) \nonumber \\ &\qquad {} + r \left( q_{i+1,t} |q_{i+1,t}| - q_{i-1,t} |q_{i-1,t}| \right) \big] \label{eq:3a}\\ q_{i,t+1} &= \frac{1}{b} \big[ h_{i,t+1} -h_{i+1,t} + q_{i+1,t} - r |q_{i+1,t}| \big], \label{eq:3b}\end{aligned}$$ where $r$ is the resistance coefficient associated with the steady state, and $b$ is the impedance coefficient associated with the transient state. For $b = 0$ the set of equations , is reduced to the steady state, where the head loss along a pipe occurs only due to friction [@todini]. Additional information describing transient dynamics can be found in the supporting information (SI) [@perelman2015]. The effect of a pipe burst at location $i$ can be translated into boundary conditions using the orifice head-flow relation [@wylie1993fluid]. Before the burst occurs, the cross-section area of the orifice is equal to zero and it increases during a burst, hence we can expect a sudden change in the hydraulic head. The relationship between the head and the pressure, measured by the sensors at location $i$, is related to the elevation of the sensor location. If $z_i$ is the elevation, and $p_{i,t}$ is the pressure at location $i$ at any given time $t$, then $p_{i,t} = \left( h_{i,t} - z_i \right)\rho g$, where $g$ is the gravitational acceleration $[\frac{m}{sec^2}]$ and $\rho$ is water density $[\frac{kg}{m^3}]$. Hence, the disturbance caused by a pipe burst that reaches the sensor location can be detected by sensing the hydraulic pressure. Similar approaches have been suggested in [@6901220]. The disturbance caused by the pipe burst quickly dissipates with the distance between the burst event $\ell_j$ and the location of the sensor $S_i$. For the purpose of sensor placement, we are interested in obtaining the sensor’s output as a result of some event $\ell_j$. Let $y_{S_i}(t,\ell_j) \in \{0,1\} $ be a discrete state (output) of the sensor $S_i$ at time $t$, where 1 represents a possible detected event and 0 represents otherwise. Let $\xi$ be a function characterizing the distance between the expected pressure (i.e., when there is no pipe burst), denoted by $\hat{p}_{i,t}$, and the measured pressure, denoted by $p_{i,t}$. The sensor output can then be formulated as: $$\label{eq:3} y_{S_i}(t,\ell_j) = \left\{ \begin{array}{lcl} 1 & \;\;\;\text{if}\;\; \xi \left( p_{i,t} - \hat{p}_{i,t}\right) \geq \varepsilon \\ 0 & \;\;\;\text{otherwise}\\ \end{array} \right.$$ where $\varepsilon$ is a threshold value. A simple detection model would be where the sensor $S_i$ indicates an event if the change in the pressure is above some threshold value $\varepsilon $. We note here that when the failure event $\ell_j$ occurs during a given time period, then the output of $S_i$ will be $1$ (or $0$) independent of the time of the event $\ell_j$. Hence, we can neglect the time dependency of the sensor output to detect the event and can restate the output of the sensor as: $$\mathbf{y}_{S_i}(\ell_j) = \left\{ \begin{array}{lcl} 1 & \;\;\;\text{if}\;\;y_{S_i}(t,\ell_j) = 1,\;\;\text{for any }t>0 \\ 0 & \;\;\;\text{otherwise}\\ \end{array} \right.$$ Let $\mathbf{y}_{\mathcal{S}}(\ell_j) = \left[ \mathbf{y}_{S_1}(\ell_j), \cdots, \mathbf{y}_{S_m}(\ell_j) \right]$ be the fault signature [@1335513] of the failure event $\ell_j$ represented by a boolean vector of the outputs of sensors in the set $\mathcal{S}$. Consequently, for a sensor set $\mathcal{S}$ and the set of events $\mathcal{L}$, we can instantiate a boolean matrix of dimensions $\lvert \mathcal{L} \rvert\times \lvert {\mathcal{S}} \rvert$ called the *influence matrix* and denoted by $\mathcal{M}$. The $j^{th}$ row of $\mathcal{M}$ consists of sensors’ outputs in response to the event $\ell_j$, i.e., $\mathbf{y}_\mathcal{S}(\ell_j)$. Similarly, $\mathcal{M}_{ij}=1$ indicates that a sensor $S_i$ detected the failure at link $\ell_j$, and $\mathcal{M}_{ij}=0$ means otherwise. Each row of the influence matrix $\mathcal{M}$ is analogous to the notion of fault signature in the model-based fault diagnosis systems literature [@1335513]. $$\label{eq:sensing_model} \mathcal{M}\left(\mathcal{L},{\mathcal{S}}\right) = \left[ \begin{array}{c} \mathbf{y}_{{\mathcal{S}}}(\ell_1)\\ \mathbf{y}_{\mathcal{S}}(\ell_2)\\ \vdots\\ \mathbf{y}_{\mathcal{S}}(\ell_n)\\ \end{array} \right]$$ Furthermore, for the set of link failures $\mathcal{L}$, and the set of all possible sensor locations $\mathcal{S}$, let $C_i\subseteq \mathcal{L}$ be the set of link failure events detected by the sensor $S_i$, i.e., $C_i=\{\ell_j\in\mathcal{L}| \; \mathbf{y}_{S_i}(\ell_j)=1\}$. If $\mathcal{C}$ is a collection of all such $C_i$’s, i.e., $\mathcal{C}=\{C_i:\;\forall i\}$, then for a given subset of sensors $S\subseteq\mathcal{S}$, we define $\mathcal{C}_S\subseteq \mathcal{C}$ as a set of subsets of failure events, where a subset corresponds to a sensor in $S$ that detects the failure events in that subset, i.e., $\mathcal{C}_S=\{C_i:\; S_i\in S\}$. \[ex:1\] To illustrate the network dynamics, consider a small network having $8$ nodes connected by $10$ links as shown the Figure \[fig:3\]. A pipe burst event is simulated in the middle of pipe $\ell_1$ and system response at network nodes is recorded. For the ease of notations, we designate the failure events as pipes’ ids, $\ell_j$. The transient simulations were computed using the HAMMER software [@Bentley]. Figure \[fig:4\] shows simulated pressure heads and boolean outputs $\mathbf{y}_{S}$, for sensors located at nodes 2 and 4. Thus for $S = \{S_2,S_4\}$ the sensors’ state is $\mathbf{y}_{S} (\ell_1) = [1,0]$. If sensors are placed at all nodes of the network, then the sensors’ state in the case of failure at $\ell_1$ is $\mathbf{y}_{\mathcal{S}} (\ell_1) = [1,1,1,0,1,0,0,0]$, $\mathbf{y}_{\mathcal{S}} (\ell_2) = [1,1,1,1,0,1,0,0]$, and so on. The corresponding influence matrix is $$\mathcal{M}( \mathcal{L},\mathcal{S}) = \bordermatrix{ & S_1& S_2& S_3& S_4& S_5& S_6& S_7& S_8\cr \ell_1&1 & 1 & 1 & 0 & 1 & 0 & 0 & 0 \cr \ell_2&1 & 1 & 1 & 1 & 0 & 1 & 0 & 0 \cr \ell_3&1 & 1 & 0 & 1 & 1 & 0 & 0 & 1 \cr \ell_4&1 & 0 & 1 & 1 & 1 & 1 & 1 & 0 \cr \ell_5&1 & 0 & 1 & 1 & 0 & 1 & 1 & 0 \cr \ell_6&0 & 1 & 1 & 1 & 1 & 0 & 1 & 1 \cr \ell_7&0 & 0 & 1 & 1 & 1 & 1 & 1 & 1 \cr \ell_8&0 & 1 & 0 & 1 & 1 & 0 & 1 & 1 \cr \ell_9&0 & 0 & 1 & 1 & 0 & 1 & 1 & 1 \cr \ell_{10}& 0 & 0 & 0 & 1 & 1 & 1 & 1 & 1}.$$ Next, we formulate the detection and identification problems as the minimum set and test cover problems, respectively. Detection as MSC {#sec:dmsc} ---------------- For the set of events $\mathcal{L}$ and the set of sensors $\mathcal{S}$, we define a *detectable event* as the one for which there exists at least one sensor in $\mathcal{S}$ that detects the event. The *detection problem* is to select the minimum number of sensors $S\subseteq\mathcal{S}$, such that when a detectable event occurs, at least one sensor in $S$ detects the event. For a given subset of sensors $S$, we define the *detection function*, denoted by $f_D$, as follows: $$\label{eq:6} f_D(\mathcal{C}_S) = \left\lvert \bigcup\limits_{C_i\in\mathcal{C}_S}C_i\right\rvert.$$ The detection function in gives the number of link failures in $\mathcal{L}$ that can be detected by the sensors in $S$. The detection problem is to select a subset of sensors $S\subseteq\mathcal{S}$ with the minimum cardinality such that all detectable events are detected, i.e. $f_D(\mathcal{C}_S) = f_D(\mathcal{C}_\mathcal{S})$. The detection performance of a subset of sensors $S$ is defined as the *normalized detection score*, $I_D(S)$ and is computed as $f_D(\mathcal{C}_S)/|\mathcal{L}|$. The detection problem is equivalent to the *minimum set cover* problem, which could be defined as: (Minimum set cover (MSC)) \[def:set\_cover\] Let $\mathcal{L}$ be a finite set of elements, and $\mathcal{C}=\{C_i:\;C_i\subseteq\mathcal{L}\}$ be the collection of given subsets of $\mathcal{L}$. The minimum set cover is to find $\mathcal{C}_s\subseteq\mathcal{C}$ with the minimum cardinality such that $\bigcup\limits_{C_i\in\mathcal{C}}C_i= \bigcup\limits_{C_j\in\mathcal{C}_s}C_j$. In the above definition, if $\mathcal{L}$ is the set of link failures and $\mathcal{C}$ is the collection of $C_i$’s corresponding to all the available sensors, then a set cover of minimum size $\mathcal{C}_s$, gives the minimum number and locations of sensors that solve the detection problem. Thus, we get the following: The problem of detection of link failures in a network is equivalent to the minimum set cover problem, and a solution to MSC is therefore, a solution to the detection problem. The MSC problem is closely related to the *maximum coverage* problem [@vazirani2013approximation], which emerges when the number of sensors that could be used is limited, i.e., $|S|\le B$. The objective of the maximum coverage problem is to select the sensors such that the number of detectable events is maximized and the constraint $|S|\le B$ is satisfied. In Section \[sec:ds\] we discuss the *greedy* solution approach, which is very much similar for the MSC and the maximum coverage problems. Identification as MTC --------------------- \[sec:Ident\_as\_MTC\] For the identification of link failures, the goal is to *uniquely* detect the events in $\mathcal{L}$, i.e. to distinguish between events using the outputs of sensors. We note that event $\ell_i\in\mathcal{L}$ can be distinguished from event $\ell_j\in\mathcal{L}$, if there exists a sensor in $\mathcal{S}$ that gives different outputs for $\ell_i$ and $\ell_j$. In such a case, we say that the *pair-wise event* $\ell_i,\ell_j$ is *detectable* if $\exists S_p\in\mathcal{S}:\;\mathbf{y}_{S_p}(\ell_i)\ne\mathbf{y}_{S_p}(\ell_j)$. In terms of the influence matrix of the network, if a pair-wise event $\ell_i,\ell_j$ is detectable, then there exists a column with different $i$ and $j$ row entries. It follows that an event $\ell_i$ can be uniquely detected if all pair-wise events $\ell_i,\ell_j, \;\forall j\ne i$ are detectable. The *identification problem* is now defined as follows: *for a given $\mathcal{L}$ and $\mathcal{S}$, the identification problem is to select a subset of sensors $S\subseteq\mathcal{S}$ with the minimum cardinality, such that every detectable pair-wise event can be detected by at least one sensor in $S$.* The *identification function* of $S$, $f_I(\mathcal{C}_S)$, is the number of pair-wise events that are detected by a subset of sensors $S\subseteq \mathcal{S}$, and will be further discussed in Section \[sec:t2s\]. The identification problem is equivalent to the *minimum test cover* problem, which is defined as follows [@Bontriddr1]: (Minimum test cover (MTC)) \[def:test\_cover\] Consider a finite set $\mathcal{L}$ and a collection of subsets $\mathcal{C}=\{C_i: \;C_i\subseteq\mathcal{L}\}$. The minimum test cover is to find $\mathcal{C}_t\subseteq\mathcal{C}$ with the minimum cardinality such that if for a pair of elements $\{\ell_u,\ell_v\} \in\mathcal{L}$, there exists ${C}_i\in\mathcal{C}$ that contains either $\ell_u$ or $\ell_v$ but not both, then there exists some ${C}_j\in\mathcal{C}_t$ that also contains either $\ell_u$ or $\ell_v$, but not both. The identification problem is to find a subset $\mathcal{C}_t\subseteq\mathcal{C}$ of minimum cardinality, or equivalently the corresponding subset of sensors $S\subseteq\mathcal{S}$, such that if $\mathbf{y}_\mathcal{S}(\ell_j)$ is unique with respect to the set of all sensors $\mathcal{S}$, then $\mathbf{y}_S(\ell_j)$ is also unique with respect to a subset of sensors $S$, which is the MTC problem defined above. Thus, we can state: The problem of identification of link failures in networks is equivalent to the minimum test cover problem, and therefore, a solution to MTC is also a solution to the identification problem. \[Detection vs. Identification\]\[exmp:2\] Follow-ing example \[ex:1\], consider two sensors placed at nodes 2 and 4, $S = \{S_2,S_4\}$. For the detection problem, we note that $C_2\cup C_4 = \mathcal{L}$. That is, at least one of the sensors in $S$ has an output $1$ whenever a link fails. Thus, sensors $S_2$ and $S_4$ *cover* (detect) all link failures and solve the detection problem. For the identification problem, sensors $2$ and $4$ are not sufficient as they generate only three unique states associated with the 10 events, which makes it impossible to distinguish between all link failures. For example, the state $\{1,0\}$ is uniquely associated with a failure in link $\ell_1$, whereas, the state $\{1,1\}$ can be associated with a failure in any of the links $\ell_2,\ell_3, \ell_6, \text{or } \ell_8$. However, for the set of sensors $S^* = \{S_1,S_2,S_3,S_5 \}$, which solves the MTC problem for example \[ex:1\], the output is unique for each link failure, i.e. ten distinct indicator vectors, each corresponding to a unique failure event, are obtained. Greedy MTC solution {#sec:oldsol} =================== It is well known that both MSC and MTC are NP-hard problems [@Garey1; @vazirani2013approximation]. In this section, we first introduce an approximate solution to the MSC, which will be utilized in Section \[sec:New\_Algo\] for constructing a computationally efficient solution of the MTC problem. Detection solution {#sec:ds} ------------------ MSC has been studied extensively owing to its wide variety of applications in theoretical as well as practical domains. A straight-forward way to solve the MSC is by the *greedy approach*. The greedy approach is to select, in each iteration, a sensor that detects the maximum number of undetected link failures, until all link failures are detected, or no further link failure can be detected by any sensor. In the maximum coverage problem, iterations continue until a given number of sensors are selected. If $n$ is the total number of link failures, $m$ is the total number of sensors, then *greedy* algorithm for the MSC gives the best approximation ratio of $\mathcal{O}(\ln n)$ [@Garey1; @Lund1]. In fact, if $k$ is the maximum number of link failures that can be detected by any sensor, then the greedy algorithm has an approximation ratio of $\mathcal{O}(\ln k)$, which is the best possible (unless P=NP) [@vazirani2013approximation]. In our context, $k$ depends on the network topology and the sensing model as in (\[eq:sensing\_model\]). Similarly, for the maximum coverage problem, the greedy algorithm gives the approximation ratio of $(1-1/e)$, which is again the best possible. Although the greedy approach gives the best known approximation ratio, its straightforward implementation requires a large number of function (as in (\[eq:6\])) evaluations. The running time of greedy approach is a function of the number of sensors and events, $\mathcal{O}(mn)$. For large scale systems, in which $n$ and $m$ are very large, this simple greedy approach becomes computationally intractable owing to a large number of function evaluations, even if computing a function is not expensive. However, greedy algorithm can be made faster by reducing the number of function evaluations if the *submodularity* property is satisfied [@Minoux1]. Submodular functions can be defined as follows: (Submodularity) \[def:submodular\] Let $\mathcal{C}$ be a finite set and $f$ be a set function, $f:2^\mathcal{C}\longrightarrow \mathbb{R}$. Moreover, $\mathcal{C}_s\subseteq \mathcal{C}_r\subseteq\mathcal{C}$, and $C_i\in\mathcal{C}\setminus \mathcal{C}_r$, then $f$ is submodular whenever $$\label{eq:submodular} f\left(\mathcal{C}_s\cup\{C_i\}\right) - f(\mathcal{C}_s) \ge f\left(\mathcal{C}_r\cup\{C_i\}\right) - f(\mathcal{C}_r)$$ For the detection problem, this means that as the number of link failures detected by the selected sensors increases, the marginal value of adding a sensor to the cover decreases. It can be shown that the function in is submodular (see [@perelman2015]), and the submodularity of $f_D$ can be exploited to obtain the *lazy greedy* algorithm as in [@Minoux1]. The basic idea behind the lazy greedy approach is to eliminate the redundant computations in each iteration. This can be further explained as follows: For the $\kappa^{th}$ iteration, let $F_\kappa(C_i)$ denotes the utility of adding a sensor $i$ to the cover, i.e. $f_D(\mathcal{C}_s\cup\{C_i\} - f_D(\mathcal{C}_s)$, then by the submodularity of $f_D$, we know that $F_{\kappa+1}(C_i)\le F_\kappa(C_i)$. Moreover, without the loss of generality, we assume that $F_\kappa(C_1)\ge F_\kappa(C_2)\ge\dots$, then $C_1$ is the greedy choice in the $\kappa^{th}$ iteration. However, in the next iteration, if $F_{\kappa+1}(C_2)\ge F_\kappa(C_3)$, then $F_{\kappa+1}(C_2)\ge F_{\kappa+1}(C_j),$ $\forall j\ge 3$, which means that there is no need to compute $F_{\kappa+1}(C_j),\;\forall j\ge 3$. This saves a large number of potential computations and improves scalability of the solution approach to large scale systems. Identification solution {#sec:3.2} ----------------------- One approach to solve the MTC problem is to first transform it to an equivalent MSC problem [@Bontriddr1], and then to solve the MSC problem using lazy greedy algorithm, as explained earlier. The greedy approach to solve the MTC yields a $(2\ln n + 1)$ approximation ratio algorithm, which is the best possible [@Moret1]. A solution of the equivalent MSC is a solution to the original MTC problem. Thus, a straight-forward way to solve the identification problem for link failures is to first obtain an equivalent detection problem, in which each event represents a *pair-wise* link failure, and then utilize the greedy approach to solve the corresponding detection problem. We call this the *transformed lazy greedy (TLG)* and will use it in Section \[sec:app\] to demonstrate the simulation results. Next, we summarize the transformation of the MTC to the MSC problem as outlined in [@Bontriddr1]. ### Transformation of MTC to MSC {#sec:t2s} Given an instance of the MTC, i.e., $\mathcal{L}$ and $\mathcal{C}=\{C_i\}$, where $C_i\subseteq\mathcal{L}$, we transform the MTC to the MSC by taking the following two steps: - *Create a new set of events*: $\mathcal{L}^t= \{\ell^t_{12}, \cdots,\ell^t_{(n-1)n}\}$. For each unordered pair $\{\ell_i,\ell_j\}$, define a new element $\ell_{ij}^t$; $\mathcal{L}^t$ consists of all such $\ell_{ij}^t$’s. - *Create a new sets of sensors’ outputs*: $\mathcal{C}^t =\{C_1^t,\cdots,C_m^t\}$, where $C_v^t = \{\ell_{ij}^t:\lvert\{\ell_i,\ell_j\}\cap C_v\rvert = 1\}, \;\forall k\in\{1,\cdots,m\}$. In other words, $\ell_{ij}^t\in C_v^t$ if and only if exactly one of $\ell_i$ or $\ell_j$ is in $C_v$. Moreover, for a subset of sensors $S\subseteq\mathcal{S}$, we define $\mathcal{C}^t_S = \{C^t_v: S_v\in S\}$. Hence, we obtain a new identification matrix $\mathcal{M}^t(\mathcal{L}^t,\mathcal{S})$ of dimensions $\dbinom{n}{2}\times m$, in which each row corresponds to a *pair-wise link failure* and each column represents sensor’s output. If a specific row in $\mathcal{M}^t$ represents a pair $\ell_i,\ell_j$, then the $v^{th}$ column entry of the corresponding row in $\mathcal{M}^t$ is an *exclusive OR* of the $(i,v)^{th}$ and $(j,v)^{th}$ entries of the influence matrix $\mathcal{M}$. The above point illustrates the fact that to localize an event $\ell_i$, there always exists a sensor that distinguishes $\ell_i$ from $\ell_j$ by producing different outputs for $\ell_i$ and $\ell_j$ respectively, i.e., if a sensor output is $1$ (resp. $0$) in case of $\ell_i$, then its output for $\ell_j$ is $0$ (resp. $1$), for all $j\ne i$. Note that for a given subset of sensors $S$, the identification function, which is the number of pair-wise link failures detected by $S$, is essentially same as the detection function of $S$ in the corresponding MSC instance i.e., $$\label{eq:objidnt} f_I(\mathcal{C}_S) =f_D(\mathcal{C}_S^t),$$ where $f_D$ is defined as in . The *normalized identification score*, denoted by $I_I(S)$, is computed by dividing $f_I$ by the total number of pair-wise events, $|\mathcal{L}^t|$. ### Greedy approach based solution Once the MTC problem has been transformed to the MSC problem, a straightforward way to obtain a solution is to employ the greedy algorithm, as outlined in Algorithm \[alg:1\]. **Input:** $\mathcal{C} = \{C_1,\cdots,C_m\},\;C_i\subseteq\mathcal{L}$ **Output:** MTC: $\mathcal{C}^{{\ast}}\subseteq\mathcal{C}$ **Initialize:** $\mathcal{C}^{{\ast}}\gets \emptyset$ **Transform:** the test cover instance to the set cover instance, i.e., from a given $\mathcal{L}$ and $\mathcal{C}$, obtain a corresponding $\mathcal{L}^t$ and $\mathcal{C}^t$ (Section \[sec:t2s\]). **Solve:** using greedy algorithm\[algo:greedy\] (a) Select $C_{i^\ast}^t\in\mathcal{C}^t$ (i.e., the sensor $i^\ast$) covering the most uncovered elements in $\mathcal{L}^t$. (b) Add to current set $\mathcal{C}^{{\ast}}\gets \mathcal{C}^{\ast} \cup \{C_{i^\ast}\}$. (c) Repeat until all elements in $\mathcal{L}^t$ are covered, or no new element in $\mathcal{L}^t$ can be covered by any $C_i^t\in\mathcal{C}^t$. As in the case of the MSC problem, the lazy greedy approach, which exploits the submodularity property of the set cover problem, can be utilized. However, if there are $n$ link failures that need to be localized, then the corresponding set cover instance contains $\dbinom{n}{2}$ events, and the time complexity of the greedy approach in Algorithm \[alg:1\] is $\mathcal{O}\left(m\dbinom{n}{2}\right)$, where $m$ is the total number of sensors. Even for small-sized networks with a limited number of possible link failures, this approach becomes quite inefficient owing to a large number of computations required. Moreover, employing lazy greedy also achieves desired computational efficiency for realistic size of failure event set. In the next section, we focus on improving the computational time of the solution of the MTC problem. Augmented greedy MTC solution {#sec:New_Algo} ============================= The main idea behind the augmented greedy approach is to achieve a computationally efficient approximation algorithm. We do so by avoiding the complete transformation of the MTC to the MSC and directly evaluating the function , thus eliminating the need to *pre*-compute the identification matrix $\mathcal{M}^t(\mathcal{L}^t,\mathcal{S})$. For example, for a network with $m = 2000; n = 2000;$ we would require $\sim 4 \text{ } GB$ computer memory to store the transformed MSC. In each iteration of the greedy algorithm for the MTC solution, a sensor that covers (detects) the most pair-wise link failures from a total of $\dbinom{n}{2}$ pair-wise failures, is selected. Thus $\mathcal{O}\left(\dbinom{n}{2}\right)$ comparisons are made in a single iteration for each potential sensor. In the augmented greedy approach, we avoid this by significantly reducing the number of comparisons made in each step. In fact, for each sensor, the number of comparisons made in a single iteration are always bounded by $\mathcal{O}\left(K\dbinom{k}{2}\right)$, where $k$ is the maximum number of link failures that are detected by any sensor, and $K$ is the number of sensors that are included in the test cover until that iteration. Since $k$ is typically much smaller than $n$, a large number of computations are thus avoided in each iteration. To explain our approach, we first observe that a sensor $i$ that detects $k$ events (i.e., $\lvert C_i \rvert = k$) can distinguish between $k$ detected events and $(n-k)$ undetected events. Thus, such a sensor detects $k(n-k)$ *pair-wise* events (i.e., $\lvert C^t_i \rvert = k(n-k)$). Unlike the detection problem, in which a sensor with a large $k$ is desirable for the detection purposes, a sensor that detects a large number of failures is not always useful for the identification. Figure \[fig:knk\] shows the number of pair-wise events detected by a sensor as a function of the number of (single) events detected by the sensor. The maximum number of pair-wise events, which are link failures in our case, are detected when $k=n/2$. Moreover, if a sensor $i$ included in a test cover and $\ell_u,\ell_v \in C_i$, then a distinction between the occurrence of $\ell_u$ and $\ell_v$ is not possible through the sensor $i$. Thus, a set of sensors that can distinguish between events $\ell_u,\ell_v\in C_i$, or equivalently that can detect pair-wise events corresponding to the events in $C_i$, also need to be included in the test cover. Based on this observation, we suggest an augmented greedy approach to compute the test cover without computing the $\dbinom{n}{2}$ events priori. Let $C^{\ast}\subseteq\mathcal{C}$ be the test cover until the current iteration, and $\mathcal{C}_{cov}$ be the set of link failures detected by the sensors that are included in the test cover, i.e., $\mathcal{C}_{cov} = \bigcup\limits_{C_u\in C^\ast}C_u$. Thus, the utility of adding $C_i$ to $C^\ast$ (i.e., adding sensor $S_i$ to the test cover) in each iteration is based on the following two factors: (i) How many pair-wise link failures corresponding to the links which are **not included** in $\mathcal{C}_{cov}$ can be detected by $C_i$? We define this value as $x_i$. (ii) How many pair-wise link failures corresponding to the links already **included** in $\mathcal{C}_{cov}$ can be detected by $C_i$? We define this value as $y_i$. The overall utility of adding sensor $S_i$ to the test cover, denoted by $w_i$, is the sum of $x_i$ and $y_i$. A sensor $S_{i^\ast}$ that maximizes this overall utility, let $w_{i^\ast}$ denote the maximum utility, will then be included in the test cover, and $\mathcal{C}_{cov}$ will be updated to $\mathcal{C}_{cov}\gets \mathcal{C}_{cov}\cup C_{i^\ast}$. Now, we state how to compute $x_i$ and $y_i$ in the $j^{th}$ iteration. (i) *Computing $x_i$* – If $n_j$ is the number of link failures that are not yet included in $\mathcal{C}_{cov}$, (i.e., $n_j = n- \lvert\mathcal{C}_{cov}\rvert$), and $C_i$ contains $k_{i,j}$ of such link failures, then $x_i =~k_{i,j}(n_j-~k_{i,j})$. Note that computing $x_i$ is very straight forward and does not require computing pair-wise link failures from a given set of link failures. (ii) *Computing $y_i$* – If a sensor $u$ is already included in the test cover, then the pair-wise link failures corresponding to the links in $C_u$ remain undetected. Thus, $y_i$ computes how many of such pair-wise link failures can be detected by the inclusion of sensor $i$ in the test cover. To make it precise, we proceed as follows: If $X$ and $Y$ are two sets, then we define: $$\beta(X) = \text{set of all 2-element subsets of}\; X,$$ and $$\label{eq:beta} \alpha(Y,\beta(X)) = \{a\in\beta(X):\;\lvert Y \cap a \rvert = 1\}.$$ Here, $\alpha(Y,\beta(X))$ is a set consisting of such $2$-element subsets of $X$ that have exactly one common element with $Y$. For instance, if $X=\{1,2,3\}$ and $Y=\{1,3\}$, then $\beta(X)=\{\{1,2\},\{1,3\},\{2,3\}\}$, and $\alpha(Y,\beta(X))=\{\{1,2\},\{2,3\}\}$. To compute $y_i$, first we compute the set of link failures common to $C_i$ and $\mathcal{C}_{cov}$ and call it as $Y_i=C_i\cap\mathcal{C}_{cov}$. Now, if sensor $u$ is already included in the test cover, and $G_u\subseteq\beta(X_u)$ is the set of undetected pair-wise link failures corresponding to the links in $X_u\subseteq C_u$, then $$y_i = \sum\limits_{C_u\in C^{\ast}}\left\vert \alpha(Y_i, G_{u})\right\vert \vspace{-0.35cm}$$ The complete algorithm is stated in Algorithm \[euclid\]. \[algo:fast\] **Input:** $\mathcal{C} = \{C_1,\cdots,C_m\},\;C_i\subseteq\mathcal{L}$ **Output:** MTC: $\mathcal{C}^{{\ast}}\subseteq\mathcal{C}$ **Initialization:** $\mathcal{C}_{cov} = \emptyset$; $\mathcal{C}^{{\ast}}=\emptyset $; $G_0=\emptyset$; $j=1$; $n = |\mathcal{L}|$; $w_{i^\ast}=1$; $n_j \gets n-\left\vert \mathcal{C}_{cov}\right\vert$ $X_i \gets \left(C_i \setminus \mathcal{C}_{cov}\right); k_{i,j}\gets \left\vert X_i\right\vert$ $x_i\gets k_{i,j}(n_j-k_{i,j})$ $Y_i\gets C_i\cap \mathcal{C}_{cov}$ $y_i \gets \sum\limits_{t=0}^{j-1}\left\vert \alpha(Y_i, G_{t})\right\vert$ $w_i = x_i + y_i$ **end for** $w_{i^{\ast}}\gets \max w_i$ .5 ------------------------------------------------------------------------ height .2pt .5 $\mathcal{C}^{{\ast}}\gets \mathcal{C}^{{\ast}} \cup \{C_{i^{\ast}}\}$ $\mathcal{C}_{cov} \gets \mathcal{C}_{cov} \cup C_{i^{\ast}}$ $G_j \gets \beta(X_{i^{\ast}})$ $G_t \gets G_t \setminus \alpha(Y_{i^{\ast}},G_t)$ **end for** $j\gets j+1$ **end if** **end while** Consider the network shown in Figure \[fig:3\]. Let $k_i$ be the number of failure events detected by the sensor $i$, i.e., $|C_i| = k_i$, where $C_i\subseteq\mathcal{S}$. In the first iteration ($j=1$) of the while loop, size of the event space is $n=10$, and $k_{i,j}=k_i$, $\forall i$. Then, the number of new pair-wise link failures detected by the sensor $i$ is given by $x_i = k_{i,j}(n - k_{i,j})$. Since there are no sensors in the test cover in the first iteration, $y_i=0$ for all the sensors. The maximum value of $w_{i}$ is attained for the sensors $1$ and $2$ with $w_1=w_2=x_1=x_2=5(10-5)=25$. We include sensor $1$ in the test cover, thus $\mathcal{C}^\ast = C_1$ after the first iteration of the while loop. The set of all undetected pair-wise events for sensor $1$, $G_1 = \left\{\{1,2\},\{1,3\},\cdots,\{4,5\} \right\}$, are then updated. Finally, we update the number of covered events as $\mathcal{C}_{cov}= \{1,2,3,4,5\}$. For the second iteration, i.e., $j=2$, size of the event space is updated as $n_2 = 5$. A complete account of the states of variables of the algorithm for the example is provided in the [@perelman2015]. The algorithm returns the test cover consisting of sensors $\{1,2,3,5\}$ that uniquely identify all link failures. The augmented greedy approach in Algorithm \[euclid\] produces the same solution as the greedy approach in Algorithm \[alg:1\]. Thus, Algorithm \[euclid\] has the same approximation ratio as the standard greedy algorithm, which has been proven to be the best possible. Since a large number of computations are avoided in the execution of Algorithm \[euclid\], it is more efficient than the simple greedy. In contrast to the $\mathcal{O}\left(\dbinom{n}{2}\right)$ comparisons performed in each iteration for a sensor in Algorithm \[alg:1\], $\mathcal{O}\left(\sum\limits_i^{m_j} \dbinom{k_i}{2}\right)$ comparisons are done in each iteration of the Algorithm \[euclid\]. Here, $n$ is the total number of link failures, $k_i$ is the number of link failures detected by the sensor $i$ (i.e., $k_i=|C_i|$), and $m_j$ is the number of sensors included in the test cover until that iteration. Thus, if $k=\max({k_i})$, then Algorithm \[euclid\] is at least $n/k$ times faster than the simple greedy approach as shown below. Moreover, typically $k<<n$ in the case of link failure detection in water distribution networks, thus, $n/k$ factor turns out to be a significant improvement. \[prop:compare\] Let $\sum\limits_i k_i= n$, and $k=\max (k_i)$, then $$\label{eq:one} \sum\limits_{i}{\dbinom{k_i}{2}}\le \frac{k}{n}\dbinom{n}{2}$$ *Proof –* $$\begin{split} \sum\limits_{i}{\dbinom{k_i}{2}} & = \frac{1}{2}\left(\sum\limits_i k_i^2 - \sum\limits_i k_i\right) \le \frac{1}{2}\left(k\sum\limits_i k_i -n\right) \\ & = \frac{1}{2}\left(kn - n\right)\le \frac{1}{2}\left(kn-k\right) =\frac{k}{n}\dbinom{n}{2}.\qed \end{split}$$ We note that Algorithm \[euclid\] is somewhat similar to the two-step greedy algorithm presented in [@Bontriddr1]. However, in our approach, both $x_i$ and $y_i$ are computed in the same iteration resulting in a more efficient implementation. Application to a benchmark network {#sec:applications} ================================== We first test our approach on a medium-size water network. *Net1* is a benchmark system that has been extensively studied in the context of sensor placement for water quality [@ostfeld]. The system consists of 126 nodes, 168 pipes, one reservoir, one pump, and two storage tanks and its layout is shown in Figure \[fig:net1\]. The system supplies a daily demand of $5.15\times10^3 [m^3/day]$ and has a total pipe length of $37.5\times10^3[m]$. For all our simulations, we consider a single failure event occurring at the center of each pipe and enumerate all possible failure events. For the detection problem, when fully calibrated transient model of the network is not available, we approximate the disturbance propagation using a simple distance based model emulating the dissipation of the pressure wave with the distance from the origin. As in [@fd:deshpande], our influence model is based on the shortest distance threshold model, assuming that the disturbance in pressure can be sensed within a specified distance from the location of the burst, i.e., $\mathbf{y}_{S_i}(\ell_j)= \{ 1 \hspace{0.5em} | \hspace{0.5em} d (S_i,\ell_j) \leq \varepsilon \}$, where $d$ is the length of the shortest path between two locations $S_i$ and $\ell_j$, and $\varepsilon$ is some threshold. Figure \[fig:net1\] shows an example of the influence range (in red) of a burst in LINK-126 of the network for a threshold distance of $\varepsilon = 1000 [m]$, i.e., a sensor located in the red region can detect the pipe failure. Assuming that a sensor can be placed at any of the 126 network nodes and any of the 168 network pipes can fail, we solve the MTC problem, as described previously in sections \[sec:Ident\_as\_MTC\], \[sec:3.2\], and \[sec:New\_Algo\]. Figure \[fig:net1\_1\] shows the normalized identification score, $I_I$, defined in Section \[sec:t2s\], as a function of the number of sensors using the greedy approach. As noted in Section \[sec:ds\], we observe that the identification score function exhibits a diminishing return property. The maximum identification score of 0.99 is attained with 48 sensors. Observing that the identification score of the network is not sufficient to evaluate the quality of the design, since it does not indicate about the number of events that are uniquely identified and, respectively, the number of events that are not uniquely identified. For this reason, we suggest two complementary metrics for evaluating the performance of the sensor network design: *Localization score* – Let $L\subseteq\mathcal{L}$ be a subset of all such link failures for which the outputs of sensors in $S$ is same, i.e., $ \mathbf{y}_S(\ell_i) = \mathbf{y}_S(\ell_j)$, $\forall \ell_i=\ell_j \in L$. We call such a subset of link failures $L$ as a *localization set*. A localization can be associated with every unique vector of sensors’ outputs. Localization score is the total umber of localization sets obtained under the sensor configuration $S$. We note that it is not possible to distinguish between the failure events in a localization set by merely observing the outputs of sensors. We define the normalized localization score, $I_L(S)$, as the ratio of the total number of localization sets formed under the sensor configuration $S$ to the total number of event failures. Ideally, the normalized localization score should be equal to 1, indicating that each fault can be uniquely identified. [0.23]{}   [0.23]{} *Localization size* – is the number of faults associated with a unique output of sensors, or the number of elements in a localization set $L$. A localization size of higher value means that it would be difficult to identify the location of the fault, and additional local inspection methods might be needed. We define the worst set size, $I_W(S)$ as the largest localization set. For complete localization it is required that, $I_W(S)=1$, indicating that all faults could be distinguished from each other, and therefore could be uniquely detected. Continuing Example \[exmp:2\] for the two-sensor design $ S= \{S_2,S_4 \}$, three localization sets are formed, i.e. $L_1 =\{ \ell_1 \}, L_2 = \{ \ell_4,\ell_5,\ell_7, \ell_9,\ell_{10}\}, L_3 = \{ \ell_2,\ell_3, \ell_6,\ell_8 \}$. The corresponding localization sizes are $|L_1| = 1, |L_2| = 5, |L_3| = 4$. The normalized localization score is thus $I_L = 3/10$ and the worst localization size is $I_W = 5$. It means that if an event is detected, its distinction between three distinct groups is possible, but further distinction within the groups is not possible, with the largest indistinctive group of 5 links. With the four-sensor design, $ S^*= \{S_1,S_2,S_3,S_5 \}$, the optimal normalized localization score and the maximum localization size of 1 are achieved, and we observe ten unique outputs of sensors, each associated with a unique failure event. Figure \[fig:net1\_2\] shows the normalized localization score as a function of the number of sensors. The highest localization score of 0.65 is achieved when 48 sensors are installed. This result indicates that 110 unique vectors of sensors output are associated with the 168 failure events. Figure \[fig:net1\_3\] shows the worst, median, and minimum localization set sizes as a function of the number of sensors for Net1. We observe that initially sizes of localization sets decrease rapidly with the number of sensors, until the worst localization-set-size reaches a plateau at 20 sensors, and does not improve further. This implies that deploying more sensors might improve local performance, but will not improve the overall network localization performance, making further deployment of sensor unattractive for the water utility from the cost viewpoint. Application to real networks {#sec:app2} ============================ We tested our approach on a batch of real water networks. Principal information is listed in Table \[tab:1\] and the complete data can be obtained from [@doi:10.1061/(ASCE)WR.1943-5452.0000352] for Nets 2-10 and from [@exeter] for Nets 1,11,12. In all our simulations we again assume, that a single failure can occur at each of the network links and that sensors can be placed at each of the network nodes, and set the distance threshold to $\varepsilon = 1000 [m]$. =0.11cm ----------- ------------ ----------------- ------------ ------------ **Length** **Demand** **No. of** **No. of** **$[km]$** $10^3[m^3/day]$ **pipes** **nodes** **Net1** 37.56 5.15 168 126 **Net2** 91.29 7.59 366 269 **Net3** 96.58 8.58 496 420 **Net4** 137.05 5.78 603 481 **Net5** 123.20 6.20 644 543 **Net6** 166.60 5.66 907 791 **Net7** 153.30 8.93 940 778 **Net8** 152.25 7.91 1124 811 **Net9** 260.24 5.67 1156 959 **Net10** 247.34 9.33 1614 1325 **Net11** 760.89 71.88 3032 1891 **Net12** 1844.04 108.8 14822 12523 ----------- ------------ ----------------- ------------ ------------ : Network data \[tab:1\] MSC vs. MTC ----------- First, we compare the sensor placement design for the identification problem obtained from our approach with the design for the detection problem, i.e. *MTC vs. MSC* (Sections \[sec:dmsc\], \[sec:Ident\_as\_MTC\]). We demonstrate our results using *Net9*, from the Kentucky dataset. Although the system supplies similar daily demand as Net1, it is spatially more distributed with approximately 260 $[km]$ of pipes. Network layout and main features are shown in Figure \[fig:net2\] and Table \[tab:1\]. Figure \[fig:net2\] schematically illustrates the difference between the MTC and MSC problem formulations in the context of Net9. Consider three sensors installed in the network, Figure \[fig:net2\] demonstrates the seven localization sets corresponding to seven unique sensor states, $[0,0,1],\cdots, [1,1,1]$ and the detection set, being the union of the localization sets. Whereas the detection problem tries to maximize the detection set, the identification problem aims to identify distinct subsets. Figure \[fig:net2\_2\] provides a comparison between the detection and localization scores for the MTC (blue circles) and MSC (red squares) designs. For the detection problem, 25 sensors are sufficient to cover the entire system, hence, we also select the first 25 sensors for the identification problem and compare their performance. From Figure \[fig:net2\_2a\] it can be seen that the two designs overlap for the first 7 sensors and the MSC design only slightly outperforms the MTC design when comparing the detection scores for a higher number of sensors. At the same time, the MTC design significantly outperforms the MSC design when comparing the localization scores as shown in Figure \[fig:net2\_2b\]. Similar results were attained for the other networks. [0.23]{} ![MTC versus MSC performance for Net9[]{data-label="fig:net2_2"}](fig9_paper_Fig4ky4_aug_2_solutions_R2000.pdf "fig:")   [0.23]{} ![MTC versus MSC performance for Net9[]{data-label="fig:net2_2"}](fig10_paper_Fig5ky4_aug_2_solutions_R2000.pdf "fig:") Augmented greedy vs. transformed lazy greedy -------------------------------------------- \[sec:app\] Next, we compare the solution approach based on the augmented greedy (AG) (Section \[sec:New\_Algo\]) and the transformed lazy greedy (TLG) (Section \[sec:3.2\]). Table \[tab:2\] lists the running times (Intel Core i7, 2.9 GHz, 16 GB of RAM) for the augmented greedy and the transformed lazy greedy approaches. For Nets 1-10, the new algorithm is $3$ to $8$ times faster than the transformed lazy greedy approach, depending on the maximum number of events detected by any sensor (see Proposition \[prop:compare\]). The solutions obtained using the two approaches were identical. [For Nets 11-12, we were not able to apply the TLG due to the memory requirements and applied only the AG, which further emphasizes the advantage of the AG approach.]{} Finally, Table \[tab:2\] lists the maximum number of sensors and the corresponding four performance scores: normalized detection $I_D$, identification $I_I$, and localization $I_L$ scores, and worst localization set size $I_W$. For all networks, the layouts and the simulation plots illustrating these metrics as a function of the number of sensors are available in [@perelman2015]. These results demonstrate that: (1) The number of sensors required solely for detection purpose is significantly lower than the number of sensors required for localization. (2) Between the two localization measures, $I_L$ and $I_W$, the localization score is more conservative than the worst set size, requiring a larger number of sensors. For example, consider the design for Net9, then to detect 95% of the events, i.e., $I_D = 0.95$, 18 sensors are sufficient, whereas to achieve $I_L = 0.5$ we require 79 sensors, and 38 to achieve $I_W = 20$. This is observed for all tested networks. =0.13cm --------------- ------------- ------ ------ ------ ---- ------------- ------------- **No. of** **TLG** **AG** **sensors** **$[min]$** **$[min]$** **Net1** 48 0.99 0.99 0.65 12 0.23 0.08 **Net2** 98 0.99 1.00 0.86 12 2.39 0.58 **Net3** 134 0.99 1.00 0.86 7 6.93 1.65 **Net4** 138 0.99 1.00 0.91 8 11.98 4.93 **Net5** 164 0.99 1.00 0.86 6 15.58 3.85 **Net6** 258 1.00 1.00 0.86 8 45.46 6.31 **Net7** 139 1.00 1.00 0.83 8 49.12 9.31 **Net8** 195 1.00 1.00 0.70 8 80.55 28.07 **Net9** 359 1.00 1.00 0.87 6 91.57 11.06 **Net10** 408 1.00 1.00 0.89 14 257.41 39.48 [**Net11**]{} 717 1.00 1.00 0.69 9 – 50.53 [**Net12**]{} $1000^*$ 1.00 1.00 0.38 17 – 1800 --------------- ------------- ------ ------ ------ ---- ------------- ------------- : Simulation results TLG - transformed lazy greedy; AG - augmented greedy;\ $^*$terminated after 1000 iterations \[tab:2\] Related work {#sec:review} ============ *Event detection in water networks.* In the urban water sector, majority of previous works focused on the sensor placement for detecting hypothetical contamination events assuming perfect sensors capable of detecting all types of contaminants [@berry; @5350461]. In a related work [@Krause08efficientsensor], to detect the presence of contaminants in large water distribution systems, the notion of penalty reduction function was introduced to realize various objective functions such as reduction of detection time and the expected population affected. Submodularity of the penalty reduction function was then used to solve sensor placement problems efficiently and with provable guarantees. Moreover, various data and model-driven techniques also exist that are applied for system’s state estimation and event detection and isolation [@eliades2014contamination; @rosich2012fault]. The basic premise in these methods is that once the sensors are in place, data is collected and transmitted in real-time. The difference between measurements, such as pressure [@perez2014leak] and flow [@ragot2006fault], and their estimated values obtained using the network hydraulic model, is then computed. Model based leakage detection techniques are employed primarily on the operational side with the objective to efficiently utilize available measurements along with the available system model to determine the system faults. Our approach is somewhat related to [@fd:deshpande; @fdi:sarrate], which consider pipe bursts as failure events. In [@fd:deshpande], detection of events in networks is studied using distance decaying sensing function. The problem is formulated as a continuous $p$-median facility location problem and solved using a gradient descent algorithm. However, in contrast to [@fd:deshpande], in which only the detection problem is considered, we consider detection as well as location identification of link failures. In [@fdi:sarrate] both the detection and location identification of failure events are considered in the problem formulation. In this work, we consider the placement of online high-rate pressure sensors. Additional surface and inline detection techniques include acoustic, umbilical, and autonomous robots. These tools are principally used to verify and pinpoint the location of the burst, their operation is typically time consuming and expensive, and they are not suitable for continuous operation [@6901220]. Ideally, flow meters can also be used for detecting and localizing leaks in water networks. However, these are more expensive and can be typically installed on main pipelines only at the inlets of sub-networks [@Narayanan:2014:OMF:2602339.2602346]. Furthermore most flow meters do not react instantaneously to changes in flow, hence are more suitable for persistent leaks [@doi:10.1080/15730621003610878]. *Approximation algorithms.* The sensor placement problem is not unique to the water sector and can be found in many engineering applications. Sensor placement is in essence a combinatorial optimization problem, in which a minimum number of sensors are deployed to minimize the uncertainty about the events of interest. The dominant approach is to cast the sensor placement problem as the classical *minimum set cover* (MSC) problem, in which given a set of $n$ elements and a collection of $m$ subsets, the goal is to select as few subsets as possible such that their union covers all elements. The MSC problem is known to be NP-hard [@Moret1]. The *greedy algorithm* guarantees the best possible approximation ratio of $(\ln n + 1)$. A key feature in the efficient and practically feasible greedy algorithm is exploiting the submodular property, i.e. decreasing marginal utility of the objective function. Extensive literature exists on the greedy approximation for submodular functions. In [@Krause:2008:NSP:1390681.1390689], a mutual information criterion was proposed to select the most informative sensors to monitor a spatial phenomenon modeled by a Gaussian process. The submodularity property of the criterion, as shown in [@nemhauser1978analysis], was then exploited to obtain a polynomial time algorithm guaranteeing a constant factor approximation of the optimal sensor set. *Model-based diagnosis.* Fault detection and identification (FDI) and consistency based diagnosis (DX) are two distinct approaches which rely on computing sets of events in a faulty system based on the discrepancies between the observed and predicted system behavior [@1335513]. In the FDI community fault diagnosis is captured by localizing faults based on residuals that capture these faults. The problem is then to select a set of residual generators that are sensitive to the set of faults [@krysander2008sensor; @Raghuraj; @svard2013realizability]. In the DX community, the diagnosis is derived by computing a set of conflicts that capture the faulty components that explain the observed failures [@abreu2009low; @de2011hitting; @feldman2008computing]. To compute the minimum set of residual generators or the minimum set of conflicts, the problem often relies on the MSC or the minimum hitting set (MHS) formulation. The MSC problem is equivalent to the MHS, in which given the same input as in the MSC, the goal is to find the smallest subset of elements that *hits* (i.e. has a non empty intersection) every subset [@1335513]. [In previous works [@krysander2008sensor; @Raghuraj; @svard2013realizability] the isolation solution is obtained by first computing the set of all *pair-wise* faults from a given set of faults, and then using greedy heuristics to solve the MSC or the MHS problems. This is similar to the TLG approach described in Section \[sec:3.2\]. Computing all pair-wise events is the main computational bottleneck, especially when applied to large scale networks. The AG presented in Section \[sec:New\_Algo\] is a faster implementation of the greedy approach for the solution of the MTC. Its main feature is avoiding the transformation of the MTC to the MSC/MHS, which makes it more suitable for large-scale distributed systems, as demonstrated for Nets 11-12 in Table \[tab:2\].]{} Conclusions and future work {#sec:conclusions} =========================== In this work, we focused on the sensor placement for fault location identification in water networks. We cast the problem as the minimum test cover problem and suggested a fast solution approach. Additionally, we tested and analyzed the solutions using multiple performance criteria for a suite of real water networks. The outcomes of our approach could provide a better diagnosis of failure events in terms of improved localization and response to failure events in operational mode, and could significantly reduce potential physical losses and service disruptions in water networks. In this work we assumed perfect sensing information, future extension will include sensor placement robust to erroneous and corrupt data. This work was supported in part by FORCES (Foundations Of Resilient CybEr-Physical Systems), which receives support from the National Science Foundation (NSF award numbers CNS-1238959, CNS-1238962, CNS-1239054, CNS-1239166), the AFRL LABLET - Science of Secure and Resilient Cyber-Physical Systems (Contract ID: FA8750-14-2-0180, SUB 2784-018400), and the NSF CAREER award \#1453126. **Supporting Information** Transient modeling {#app:T} ================== Unsteady state flow in a closed conduit can be described by mass and momentum equations formulated as [@wylie1993]: $$\frac{\partial h}{\partial t} + \frac{a^2}{gA}\frac{\partial q}{\partial x} = 0$$ $$\frac{1}{gA}\frac{\partial q}{\partial t} + \frac{\partial h}{\partial x} + \frac{cq|q|}{2gDA^2} = 0$$ where $h$ is the hydraulic head $[m]$, $q$ is the volumetric flow rate $[\frac{m^3}{sec}]$, $g$ is the gravitational acceleration $[\frac{m}{sec^2}]$, $x$ is distance along the pipe $[m]$, $t$ is the time $[sec]$, $a$ is the wave speed in the conduit $[\frac{m}{sec}]$, $c$ is a friction factor, $D$ is the pipe diameter $[m]$, and $A$ is the pipe cross sectional area $[m^2]$. The method of characteristics (MOC) is one of the most common numerical techniques used to approximate the solution of the hydraulic transient. Additional techniques used are finite differences and node characteristic method. A detailed derivation of the governing equations and the solution scheme can be found in [@Dal; @wylie1993]. The MOC transforms partial differential equations into ordinary differential equations that apply along specific lines (characteristics), $C^+$ and $C^-$, in the *space-time*, $x\text{-}t$, plane. Two characteristic equations are solved explicitly to compute the head and flow, $h_*, q_*$, at new point in time and space, $(\cdot)_*$, given that the conditions at a previous time step along the characteristic grid are known, i.e., $h_+, q_+$ and $h_-, q_-$. For a given pipe, the two comparability equations are formulated as: \[eq:a3\] $$\begin{aligned} C^+: \frac{a}{gA}\left ( q_* - q_+\right) + \left ( h_* - h_+ \right ) + \frac{c\Delta x} {2gDA^2}q_+|q_+| = 0 \label{eq:a3a} \\ C^-: \frac{a}{gA}\left ( q_* - q_-\right) - \left ( h_* - h_- \right ) + \frac{c\Delta x} {2gDA^2}q_-|q_-| = 0 \label{eq:a3b}\end{aligned}$$ Rearranging equations and we get: \[eq:a4\] $$\begin{aligned} C^+: h_* = C_P - bq_* \label{eq:a4a} \\ C^-: h_* = C_M + bq_* \label{eq:a4b}\end{aligned}$$ where $$\begin{aligned} C^+: & \hspace{0.5em} C_P = h_+ + q_+ \left ( b - r |q_+| \right ) \\ C^-: &\hspace{0.5em} C_M = h_- - q_- \left ( b - r |q_-| \right ) \end{aligned}$$ and $$b = \frac{a}{gA}$$ $$r = \frac{c \Delta x}{2gDA^2}$$ $b$ is a function of the physical characteristics of the pipe and the wave speed of the fluid in the conduit. The parameter $b$ can be viewed as the characteristic impedance, which is associated with the transient state. $r$ is a function of the physical characteristics of the pipe, that can be viewed as pipe’s resistance coefficient, and is associated with the steady state. If $b=0$ the set of equations is reduced to the steady state equations, where the head losses along the pipe occur only due to friction. We designate the points $(\cdot)_+,(\cdot)_-,(\cdot)_*$ over a *space-time* grid of characteristics. If $i$ and $t$ are indices for space and time, respectively, then: $(\cdot)_* \rightarrow (h_{i,t+1},q_{i,t+1}),(\cdot)_+ \rightarrow (h_{i-1,t},q_{i-1,t}),(\cdot)_- \rightarrow (h_{i+1,t},q_{i+1,t})$. Then solving first for $h_{i,t+1}$, by eliminating $q_*$ in , for a single node in the numerical grid, we get: $$\begin{aligned} h_{i,t+1} &= \frac{1}{2} \big[ h_{i-1,t} + h_{i+1,t} + b \left( q_{i-1,t} - q_{i+1,t} \right) \nonumber \\ &\qquad {} + r \left( q_{i+1,t} |q_{i+1,t}| - q_{i-1,t} |q_{i-1,t}| \right) \big] \label{eq:3a}\\ q_{i,t+1} &= \frac{1}{b} \big[ h_{i,t+1} -h_{i+1,t} + q_{i+1,t} - r |q_{i+1,t}| \big] \label{eq:3b}\end{aligned}$$ where $r$ is the resistance coefficient, which is associated with the steady state, and $b$ is the impedance coefficient, which is associated with the transient state. If $b = 0$ the set of equations , is reduced to the steady state, where the head loss along a pipe occurs only due to friction [@todi]. At the boundaries specific conditions need to be defined describing the head-flow relation. Common boundary conditions, such as cross-connections and control valves, can be found in [@wylie1993]. We give an example for boundary condition for pipe burst at location $i$ using the orifice head-flow equation: $$\label{eq:5a} h_{i,t+1} + \frac{b}{2}C_dA_{d,t+1} \sqrt{2gh_{i,t+1}} - \frac{C_M +C_P }{2} = 0$$ where $C_d$ is the orifice discharge coefficient, $A_{d}$ is the cross-section area of the orifice, $C_P = h_{i-1,t} + q_{i-1,t} \left ( b - r |q_{i-1,t}| \right ) $, $ C_M = h_{i+1,t} - q_{i+1,t} \left ( b - r |q_{i+1,t}| \right )$. Before the burst occurs the coefficient $A_d$ is equal to zero and Equation reduces to Equation . During a burst $A_d$ is positive, hence we can expect a change in the hydraulic head. The relationship between the head and the pressure measured by sensors at location $i$ is relative to the elevation of location $i$, denoted by $z_i$, i.e., at any given time, $p_{i,t} = \left( h_{i,t} - z_i \right)\rho g$. Hence, we can expect to detect the pipe burst by observing the differences between the expected and the measured pressures at a given time and location in the network. Similar approaches have been previously suggested in [@69012]. Figure \[fig:2\] shows a raw pressure signal recorded by Visenti [@visent] online sensor during a pipe burst event with $250 [Hz]$ sampling frequency. Figure \[fig:2\] shows the dynamic nature of pressure, a sharp drop in the pressure during a pipe burst event, and a rapid return to normal operating range. The duration of drop in pressures is just under a few seconds, hence cannot be detected using a more traditional methods such as supervisory control and data acquisition (SCADA) systems, which typically operate on minutes scales. ![Pressure signal during a burst event recorded from online sensor installed in a water system[]{data-label="fig:2"}](transient4.pdf) Submodularity {#app:A} ============= \[lem:submodular\] The detection function $f_D$ (as defined in the Equation (6) of the main paper) is submodular. *Proof –* Let $\mathcal{C}_s\subseteq \mathcal{C}_r\subseteq \mathcal{C}$, and $C_i\in\mathcal{C}\setminus \mathcal{C}_r$, then we need to show $$f_D\left(\mathcal{C}_s\cup\{C_i\}\right) - f_D(\mathcal{C}_s) \ge f_D\left(\mathcal{C}_r\cup\{C_i\}\right) - f_D(\mathcal{C}_r)$$ Assume that $C_i'=C_i\setminus\bigcup\limits_{C_j\in \mathcal{C}_s}C_j$, then $$\label{eq:p1} f_D(\mathcal{C}_s\cup\{C_i\}) = f_D(\mathcal{C}_s\cup\{C_i'\}) = f_D(\mathcal{C}_s) + f_D(\{C_i'\})$$ Moreover, let $\lambda = \left(\bigcup\limits_{C_k\in \mathcal{C}_r}C_k\right)\setminus \left(\bigcup\limits_{C_j\in \mathcal{C}_s}C_j \cup C_i'\right)$, and $\mu = \bigcup\limits_{C_k\in \mathcal{C}_r}C_k\cap C_i'$, then $$\label{eq:p2} f_D(\mathcal{C}_r \cup\{C_i\}) = f_D(\mathcal{C}_r\cup\{C_i'\}) = f_D(\mathcal{C}_s\cup\{C_i'\}) + f_D(\{\lambda\}),$$ and $$\label{eq:p3} f_D(\mathcal{C}_r) = f_D(\mathcal{C}_s) + f_D(\{\lambda\}) +f_D(\{\mu\}).$$ Substituting into gives, $$f_D(\mathcal{C}_s\cup\{C_i\}) - f_D(\mathcal{C}_s) -f_D(\{\mu\}) = f_D(\mathcal{C}_r \cup\{C_i\}) - f_D(\mathcal{C}_r)$$ The required result follows directly. Augmented greedy – Example 3 (cont.) ==================================== In each iteration, for every sensor $i$ not in the test cover, $C_i$ is decomposed into two sets namely, $X_i=C_i\setminus\mathcal{C}_{cov}$ and $Y_i=C_i\cap\mathcal{C}_{cov}$. The utility of including a sensor in the test cover is calculated in terms of $x_i$ and $y_i$. $x_i$ computes the number of pair-wise link failures detected by $C_i$ corresponding to the links not in $\mathcal{C}_{cov}$, whereas $y_i$ computes the undetected pair-wise link failures corresponding to the links in $\mathcal{C}_{cov}$ that can be detected by $C_i$. Then, a sensor that maximizes the utility is selected and $\mathcal{C}_{cov}$, which is the set of covered (detected) events, and $G_u$, which is the set of undetected pair-wise events corresponding to the events detected by the sensor $u$ already included in the test cover, are updated. We give detailed steps of the algorithm using the illustrative example in the paper (Figure \[fig:3\]). Recall the influence matrix: $$\mathcal{M}( \mathcal{L},\mathcal{S}) = \bordermatrix{ & S_1& S_2& S_3& S_4& S_5& S_6& S_7& S_8\cr \ell_1&1 & 1 & 1 & 0 & 1 & 0 & 0 & 0 \cr \ell_2&1 & 1 & 1 & 1 & 0 & 1 & 0 & 0 \cr \ell_3&1 & 1 & 0 & 1 & 1 & 0 & 0 & 1 \cr \ell_4&1 & 0 & 1 & 1 & 1 & 1 & 1 & 0 \cr \ell_5&1 & 0 & 1 & 1 & 0 & 1 & 1 & 0 \cr \ell_6&0 & 1 & 1 & 1 & 1 & 0 & 1 & 1 \cr \ell_7&0 & 0 & 1 & 1 & 1 & 1 & 1 & 1 \cr \ell_8&0 & 1 & 0 & 1 & 1 & 0 & 1 & 1 \cr \ell_9&0 & 0 & 1 & 1 & 0 & 1 & 1 & 1 \cr \ell_{10}& 0 & 0 & 0 & 1 & 1 & 1 & 1 & 1}$$ =0.11cm --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------   $j=1$ $j=2$ $j=3$ $j=4$ $j=5$ --------------------- -------------------------------------- ---------------------------------------------- ---------------------------------- ----------------------------------- --------------------------------- $\mathcal{C}_{cov}$ $\emptyset$ $\{1,2,3,4,5\}$ $\{1,2,3,4,5,6,8\}$ $\{1,2,\cdots,9\}$ $\{1,2,\cdots,10\}$ $n_j$ $10$ $5$ $3$ $1$ $0$ $X_1,Y_1$ $\mathbf{\{1,2,3,4,5\}},\;\emptyset$ – – – – $X_2,Y_2$ $\{1,2,3,6,8\},\;\emptyset$ $\mathbf{\{6,8\},\{1,2,3\}}$ – – – $X_3,Y_3$ $\{1,2,4,5,6,7,9\},\;\emptyset$ $\{6,7,9\},\{1,2,4,5\}$ $\mathbf{\{7,9\},\{1,2,4,5,6\}}$ – – $X_4,Y4$ $\{2,3,\cdots,10\},\;\emptyset$ $\{6,\cdots,10\},\{2,3,4,5\}$ $\{7,9,10\},\{2,\cdots,6,8\}$ $\{10\},\{2,3,\cdots,9\}$ $\emptyset,\;\{2,3,\cdots,10\}$ $X_5,Y_5$ $\{1,3,4,6,7,8,10\},\;\emptyset$ $\{6,7,8,10\},\{1,3,4\}$ $\{7,10\},\{1,3,4,6,8\}$ $\mathbf{\{10\},\{1,3,4,6,7,8\}}$ – $X_6,Y_6$ $\{2,4,5,7,9,10\},\;\emptyset$ $\{7,9,10\},\{2,4,5\}$ $\{7,9,10\},\{2,4,5\}$ $\{10\},\{2,4,5,7,9\}$ $\emptyset,\;\{2,4,5,7,9,10\}$ $X_7,Y_7$ $\{4,5,\cdots,10\},\;\emptyset$ $\{6,\cdots,10\},\{4,5\}$ $\{7,9,10\},\{4,5,6,8\}$ $\{10\},\{4,5,\cdots,9\}$ $\emptyset,\;\{4,5,\cdots,10\}$ $X_8,Y_8$ $\{3,6,\cdots,10\},\;\emptyset$ $\{6,\cdots,10\},\{3\}$ $\{7,9,10\},\{3,6,8\}$ $\{10\},\{3,6,7,8,9\}$ $\emptyset,\;\{3,6,\cdots,10\}$ $x_1,\;y_1$ $\mathbf{25,0}^\ast$ – – – – $x_2,\;y_2$ $25,0$ $\mathbf{6,6}^\ast$ – – – $x_3,\;y_3$ $21,0$ $6,4$ $\mathbf{2,3}^\ast$ – – $x_4,\;y_4$ $9,0$ $0,4$ $0,2$ $0,1$ $0,0$ $x_5,\;y_5$ $21,0$ $4,6$ $2,3$ $\mathbf{0,3}^\ast$ – $x_6,\;y_6$ $24,0$ $6,6$ $0,2$ $0,1$ $0,0$ $x_7,\;y_7$ $21,0$ $0,6$ $0,0$ $0,0$ $0,0$ $x_8,\;y_8$ $24,0$ $0,4$ $0,2$ $0,0$ $0,0$ $G_0$ $\emptyset$ $\emptyset$ $\emptyset$ $\emptyset$ $\emptyset$ $G_1$ $\left\{ $\left\{ $\{\{1,2\},\{4,5\}\}$ $\emptyset$ $\emptyset$ \begin{array}{lll} \begin{array}{lll}\{1,2\},\{1,3\},\{2,3\},\\ \{1,2\},\{1,3\},\{1,4\},\\ \{4,5\}\\ \{1,5\},\{2,3\},\{2,4\},\\ \end{array}\right\}$ \{2,5\},\{3,4\},\{3,5\},\\ \{4,5\}\\ \end{array} \right\}$ $G_2$ – $\{\{6,8\}\}$ $\emptyset$ $\emptyset$ $\emptyset$ $G_3$ – – $\{\{7,9\}\}$ $\emptyset$ $\emptyset$ $G_4$ – – – $\{10\}\rightarrow\emptyset$ $\emptyset$ -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- \ $^\ast$ is the selected sensor with the maximum utility, i.e. $w_{i^{\ast}}\gets \max w_i$. Initialization : $\mathcal{C}_{cov} = \emptyset$; $\mathcal{C}^{{\ast}}=\emptyset $; $G_0=\emptyset$; $n = 10$; First iteration of the while loop, $j=1$. : We denote the total number of events detected by sensor $i$ as $k_i$, i,.e., $k_i = |C_i|$. Similarly, $k_{i,j}$ denotes the number of undetected events that are detected by the sensor $i$ in the $j^{th}$ iteration, i.e., $k_{i,j} = |C_i\setminus \mathcal{C}_{cov}|$. In the first iteration $k_{i,j} = k_i$, $\forall i$. In this example, the set of all $k_{i,1}$’s is $\{5,5,7,9,7,6,7,6\}$. Then, for each sensor $i$, we compute the number of new pair-wise events detected, $x_i = k_{i,1}(n - k_{i,1})$. For instance, for sensor $1$, $x_1=5(10-5)=25$. Next, we need to compute $y_i$ for all $i$. Since there is no sensor in the test cover in the first iteration, $y_i=0$ for all $i$. The total utility of selecting a sensor is equal to $w_i = x_i + y_i$. The maximum $w_{i^\ast}$ is attained for sensors $1$ and $2$. We select sensor $1$ to be included in the test cover, and update $\mathcal{C}^{{\ast}}\gets \{C_{1^{\ast}}\}$, and $G_1$, which is the set of all undetected pair-wise events corresponding to the events in $X_1 = C_1\setminus \mathcal{C}_{cov}$. Here, $G_1 = \left\{\{1,2\},\{1,3\},\cdots,\{4,5\} \right\}$. Finally, we update the set of covered (detected) events $\mathcal{C}_{cov}~\gets~\mathcal{C}_{cov}\cup C_1 = C_1=\{1,2,3,4,5\}$. Second iteration of the while loop, $j=2$. : At the beginning of second iteration, the event space has been reduced from 10 to 5, i.e., $n_2 = 5$. For each sensor $i$, we first compute $X_i$, which is the set of undetected events (events that are not in $\mathcal{C}_{cov}$) that are detected by the sensor $i$, i.e., $X_i \gets \left(C_i \setminus \mathcal{C}_{cov}\right)$. Then, we compute $x_i = k_{i,2}(n_2 - k_{i,2})$, where $k_{i,2}$ is $| X_i|$. For instance, for sensor $2$, $C_2 = \{1,2,3,6,8 \}$, then $X_2 \gets \left(C_2 \setminus \mathcal{C}_{cov}\right) = \{6,8\}$ and $k_{2,2} = 2$. Then $x_2 = 2(5-2) = 6$. Next, for each sensor $i$, we compute $y_i$, which is the number of pair-wise events in $G_1$ that are detected by the sensor $i$. For instance, in the case of sensor $2$, six of the pair-wise events in $G_1$, given by $\{\{1,4\},\{1,5\},\{2,4\},\{2,5\},\{3,4\},\{3,5\}\}$, are detected by the sensor $2$. Thus, we get $y_2 = 6$. The values of $y_i$ for all $i$ are given in Table 1. After this, the utility of each sensor is computed as $w_i = x_i + y_i$. For sensor $2$, the value of $w_2$ is $12$, which turns out to be the maximum among all the sensors in the second iteration. Thus, sensor $2$ is included in the test cover. We update $\mathcal{C}^{{\ast}}\gets \mathcal{C}^{{\ast}} \cup \{C_{2^{\ast}}\}$, $\mathcal{C}_{cov}= \{1,2,3,4,5,6,8\}$, and $$\begin{split} G_1 &\gets G_1 \setminus \left\{\{1,4\},\{1,5\},\{2,4\},\{2,5\},\{3,4\},\{3,5\} \right\}\\ &= \{\{1,2\},\{1,3\},\{2,3\},\{4,5\}\}. \end{split}$$ At the same time, a new set $G_2$ is created, which contains the set of pair-wise events in $X_2$. Since $X_2 = \{6,8\}$, we get $G_2 = \{\{6,8\}\}$. Next iteration. : We continue with the same steps until no improvement can be made, i.e. $w_i = 0$ for each sensor. At the end of the algorithm, sensors in the set $\{1,2,3,5\}$ are included in the test cover. For this example, a complete account of the values of variables in each iteration of the algorithm is given in Table 1. Evaluation on real networks (cont.) =================================== For all networks [@datab; @doi:10.1061/(ASCE)WR.1943-5452], the layouts and the simulation plots illustrating the four performance metrics are shown in Table \[tab:10\]. For the ease of presentation, the worst localization set size, $I_W$, is normalized by dividing it by the number of pipes. -- -- -- -- \[tab:10\] -- -- -- -- \[tab:gt\] -- -- -- -- \[tab:gt\] [1]{} Centre of Water Systems University of EXETER. http://emps.exeter.ac.uk/engineering/research/cws/ downloads/benchmarks/. Accessed: 2015-04-14. Visenti. http://www.visenti.com/. M. D. Jolly, A. D. Lothes, and L. Ormsbee. Research database of water distribution system models. *Journal of Water Resources Planning and Management*, 140(4):410–416, 2014. D. Misiunas. *Failure monitoring and asset condition assessment in water supply systems.* PhD thesis, LUND University, Sweden, 2005. E. Todini and L. Rossman. Unified framework for deriving simultaneous equation algorithms for water distribution networks. *Journal of Hydraulic Engineering*, 139(5):511–526, 2013. E. B. Wylie, V. L. Streeter, and L. Suo, *Fluid transients in systems.* Prentice Hall, 1993. T. T. Zan, H. B. Lim, K. Wong, A. J. Whittle, and B. Lee. Event detection and localization in urban water distribution network. *IEEE Sensors Journal*, 14(12):4134–4142, 2014.

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648 S.E.2d 471 (2007) BARLOWE v. The STATE. No. A07A0769. Court of Appeals of Georgia. June 25, 2007. *472 Jason S. Monroe, Atlanta, for appellant. Jewel C. Scott, District Attorney, Jonathan O. Oden, Assistant District Attorney, for appellee. PHIPPS, Judge. Mark Whitney Barlowe appeals from the denial of his plea in bar, claiming that the denial violated the prohibition against successive prosecutions under OCGA § 16-1-7(b). Finding no error, we affirm. In determining whether a trial court properly denied a plea in bar "[w]here the evidence is uncontroverted and no question regarding the credibility of witnesses is presented, we review de novo the trial court's application of the law to undisputed facts."[1] The undisputed evidence shows that on October 15, 2005, Barlowe, who was under the age of 21, was cited for possession of alcohol by a minor. Barlowe had gone to a movie theater that day with his sister and two other girls, all of whom were minors. An officer with the Clayton County Police Department, who was providing security at the theater, noticed that Barlowe smelled of alcohol, and a beer can was found under Barlowe's theater seat. Barlowe was charged on accusation for underage possession of alcohol in the State Court of Clayton County on November 14, 2005. After leaving the movie theater on October 15, one of the girls who had accompanied Barlowe stated that Barlowe had touched her inappropriately during the movie. The girl's parents contacted the police, and the matter was investigated by an officer with the City of Morrow Police Department who was not involved with Barlowe's possession of alcohol citation. Barlowe was charged with child molestation and sexual battery. On December 1, 2005, a Clayton County assistant district attorney received a file on the Barlowe case that included a police report on the molestation and sexual battery charges. This police report indicated that Barlowe had also been cited with possession of alcohol. Barlowe's counsel asked the assistant district attorney in December to charge Barlowe with possession of alcohol along with molestation and sexual battery in the superior court, but the assistant district attorney did not take any action to move the possession of alcohol charge from state court to superior court so that all of the charges could be prosecuted together. On January 27, 2006, Barlowe pled guilty in state court to the misdemeanor possession of alcohol charge. On April 12, 2006, he was indicted in superior court on the felony molestation and sexual battery charges. Barlowe then sought to bar his prosecution in the superior court on these charges, asserting that they should have been prosecuted *473 with the possession of alcohol charge. The superior court denied Barlowe's plea in bar. "[A] successive prosecution is barred when the conduct of an accused establishes more than one crime and they are not prosecuted in accordance with OCGA § 16-1-7(b)."[2] Section 16-1-7(b) provides, in pertinent part, that: If the several crimes arising from the same conduct are known to the proper prosecuting officer at the time of commencing the prosecution and are within the jurisdiction of a single court, they must be prosecuted in a single prosecution. For OCGA § 16-1-7(b) to apply, the prosecutor handling the proceedings must actually know of the crimes.[3] "The burden is on the defendant to show such knowledge on the part of the prosecuting officer."[4] The prosecuting officer in the state court is the person whose knowledge matters in this case, because Barlowe's plea in state court is the proceeding that he claims bars his superior court prosecution. Where a criminal defendant first pleads guilty to a misdemeanor in state court and is later prosecuted in superior court for felony charges allegedly arising out of the same conduct, we look to the knowledge of the state court solicitor to determine if the state court proceedings bar the subsequent superior court proceedings.[5] Here, a showing was made as to the knowledge of the assistant district attorney who prosecuted the sexual battery and molestation charges in superior court, but there is no evidence in the record concerning the knowledge of the officer who handled the first prosecution in state court. The trial court, therefore, properly denied the plea in bar.[6] Judgment affirmed. JOHNSON, P.J., and MIKELL, J., concur. NOTES [1] Summers v. State, 263 Ga.App. 338, 338, 587 S.E.2d 768 (2003) (citation omitted). [2] State v. McCrary, 253 Ga. 747, 748, 325 S.E.2d 151 (1985). [3] Turner v. State, 238 Ga.App. 438, 438-439, 518 S.E.2d 923 (1999). [4] Mack v. State, 249 Ga.App. 424, 425, 547 S.E.2d 697 (2001) (footnote omitted). [5] See Powe v. State, 257 Ga. 563, 564, 361 S.E.2d 811 (1987) (finding "proper prosecuting officer" was assistant state court solicitor who handled taking of guilty plea); Baker v. State, 257 Ga. 567, 569, 361 S.E.2d 808 (1987) (finding guilty plea to misdemeanor charge in state court did not bar later prosecution of felony charge arising from same conduct, where defendant did not establish that state court solicitor had actual knowledge of felony charge); Turner, supra at 440, 518 S.E.2d 923 (same). [6] Because Barlowe failed to demonstrate the prosecuting officer's actual knowledge, we do not reach the issue of whether the crimes charged against Barlowe arose from the same conduct.

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NOTE: This disposition is nonprecedential. United States Court of Appeals for the Federal Circuit ______________________ EVIDEO OWNERS, MAURO DIDOMENICO, INDIVIDUALLY AND ON BEHALF OF ALL THOSE SIMILARLY SITUATED, DOUGLAS BUERGER, CRAIG LINDEN, REALVIRT LLC, PAUL BAROUS, Plaintiffs-Appellants v. UNITED STATES, Defendant-Appellee ______________________ 2016-2149 ______________________ Appeal from the United States Court of Federal Claims in No. 1:15-cv-00413-LKG, Judge Lydia Kay Griggsby. ______________________ Decided: March 13, 2017 ______________________ PATRICK RICHARD DELANEY, Ditthavong & Steiner, P.C., Alexandria, VA, argued for plaintiffs-appellants. NICOLAS RILEY, Appellate Staff, Civil Division, United States Department of Justice, Washington, DC, argued for defendant-appellee. Also represented by MARK R. FREEMAN, BENJAMIN C. MIZER; NATHAN KELLEY, Office of 2 EVIDEO OWNERS v. US the Solicitor, United States Patent and Trademark Office, Alexandria, VA. ______________________ Before MOORE, O’MALLEY, and HUGHES, Circuit Judges. PER CURIAM. For the reasons articulated in the decision by the United States Court of Federal Claims, we affirm. We order Appellants to show cause within fifteen days why sanctions should not be imposed for a frivolous appeal pursuant to Federal Rule of Appellate Procedure 38. AFFIRMED COSTS Costs to Appellee. 

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Chavez uses decree for disaster fund in Venezuela CARACAS, Venezuela - CARACAS, Venezuela (AP) - Venezuelan President Hugo Chavez on Sunday said he was signing his first decree under new powers granted to him by congress to create a fund for housing reconstruction after devastating floods and landslides. The National Assembly earlier this month granted Chavez broad powers to enact laws by decree for a year and a half. Opponents have condemned that and a package of other laws approved by Chavez's congressional allies, saying the measures are a power grab by the president and will enable him to crack down on dissent. "Here it is, the first of the laws... that I'm going to sign," Chavez said Sunday during a televised speech. He said it's one of multiple decrees in the works "to tend to the emergency" and that the government fund will initially have 10 billion bolivars ($2.3 billion) to pay for rebuilding areas devastated by torrential rains. Chavez said more than 130,000 Venezuelans have gone to government shelters due to the disaster. "That's what the enabling law is especially for. Where do some insane people get that it's for installing a dictatorship in Venezuela?" Chavez said at the event in western Zulia state, accompanied by Bolivian President Evo Morales. Since Dec. 17, Chavez has used an outgoing National Assembly packed with loyalists to gain new abilities to crack down on some types of messages on the Internet, increase government control of universities that are bastions of dissent, and block foreign funding to human rights groups, among other changes. Opposition politicians have denounced the maneuvers as a virtual "coup" before a new legislature takes office Jan. 5 with enough opposition lawmakers to prevent passage of some types of major laws. "They say I'm carrying out a coup. It's the excuse for the one they'd like to carry out," Chavez said. "There will be no coup here, neither by Chavez nor against Chavez. There will be democracy, democracy and more democracy here. Only that it's the new democracy." Chavez, who was first elected in 1998, has long thrived on confrontation with his adversaries while vowing to lead the country toward a socialist system. Opponents have denounced the latest laws as the "Cuban package," referring to Chavez's close relationship with Fidel Castro. Among the controversial laws pushed through this month by his allies in the National Assembly are one that allows suspension of any lawmakers who leave a party mid-term and another that is expected to speed up the process if Chavez decides to nationalize more banks. Lawmakers barred foreign funding for any nongovernment organizations that defend "political rights," a change that critics say will hobble some human rights groups. The National Assembly also passed a law making it easier for the government to revoke TV or radio licenses, and another extending broadcast-type regulations to the Internet - barring messages that "disrespect public authorities," ''incite or promote hatred" or crimes, or that could create "anxiety in the citizenry or alter public order." While lawmakers have held late-night sessions, Chavez's government has also seized a list of ranches in western Venezuela as part of a nationwide effort to take over large swaths of farmland - drawing strong criticism from business leaders who say the ranches are highly productive. Noel Alvarez, president of the country's largest business chamber Fedecamaras, last week objected to the new laws and farm seizures, urging Venezuelans to "defend the constitution and democracy." Alvarez also publicly urged the military to exercise "freedom of conscience" and stand by the constitution. That remark led prosecutors to announce an investigation against him, saying Alvarez had urged the armed forces to "disobey orders."

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1. Field of the Invention The present invention relates to high density memory devices based on phase change based memory materials, including chalcongenide based materials and other materials, and to methods for manufacturing such devices. 2. Description of Related Art Phase change based memory materials are widely used in read-write optical disks. These materials have at least two solid phases, including for example a generally amorphous solid phase and a generally crystalline solid phase. Laser pulses are used in read-write optical disks to switch between phases and to read the optical properties of the material after the phase change. Phase change based memory materials,like chalcogenide based materials and similar materials, also can be caused to change phase by application of electrical current at levels suitable for implementation in integrated circuits. The generally amorphous state is characterized by higher resistivity than the generally crystalline state, which can be readily sensed to indicate data. These properties have generated interest in using programmable resistive material to form nonvolatile memory circuits, which can be read and written with random access. The change from the amorphous to the crystalline state is generally a lower current operation. The change from crystalline to amorphous, referred to as reset herein, is generally a higher current operation, which includes a short high current density pulse to melt or breakdown the crystalline structure, after which the phase change material cools quickly, quenching the phase change process allowing at least a portion of the phase change structure to stabilize in the amorphous state. It is desirable to minimize the magnitude of the reset current used to cause transition of phase change material from crystalline state to amorphous state. The magnitude of the reset current needed for reset can be reduced by reducing the size of the phase change material element in the cell and of the contact area between electrodes and the phase change material, so that higher current densities are achieved with small absolute current values through the phase change material element. One direction of development has been toward forming small pores in an integrated circuit structure, and using small quantities of programmable resistive material to fill the small pores. Patents illustrating development toward small pores include: Ovshinsky, “Multibit Single Cell Memory Element Having Tapered Contact,” U.S. Pat. No. 5,687,112, issued Nov. 11, 1997; Zahorik et al., “Method of Making Chalogenide [sic] Memory Device,” U.S. Pat. No. 5,789,277, issued Aug. 4, 1998; Doan et al., “Controllable Ovonic Phase-Change Semiconductor Memory Device and Methods of Fabricating the Same,” U.S. Pat. No. 6,150,253, issued Nov. 21, 2000. Problems have arisen in manufacturing such devices with very small dimensions, and with variations in process that meets tight specifications needed for large-scale memory devices. It is desirable therefore to provide a memory cell structure having small dimensions and low reset currents, and a method for manufacturing such structure that meets tight process variation specifications needed for large-scale memory devices. It is further desirable to provide a manufacturing process and a structure, which are compatible with manufacturing of peripheral circuits on the same integrated circuit.

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AHSCT is a gruelling process for any patient. Credit:MS Research Australia Amid the emotional turbulence, she has pinned her hopes on an emerging therapy called autologous haematopoietic stem cell transplantation (AHSCT), which aims to "reboot" the body's immune system without the presence of the cells that attack it. An Australian trial - run by St Vincent's Hospital in Sydney involving 35 patients with relapsing-remitting MS (RRMS), which Ms Berini has, and secondary progressive MS - found 60 per cent showed no evidence of disease activity after three years and more than half of the remainder showed an improvement in their disability scores. Led by Dr John Moore, the trial confirmed "the important role of AHSCT as a therapeutic option for patients with RRMS". The observational study, published in the BMJ’s latest Journal of Neurology, Neurosurgery and Psychiatry, concluded the results "provide further evidence that AHSCT … is a highly efficacious therapy for patients with MS even after failing multiple therapies such as natalizumab". AHSCT involves extracting stem cells from blood or bone marrow, undergoing heavy chemotherapy to destroy the MS-affected autoimmune system, leaving the patient incredibly vulnerable, before reintroducing the stem cells to restore the body's defences. It's not easy, nor fun - the process can feel like dying and a lot of patients have – and Dr Moore cautions "HSCT is still reserved for patients that have failed other therapies and is not a first-line therapy for MS". MS Research Australia chief executive Matthew Miles said the study indicated HSCT was heading in the right direction as medical professionals became more experienced, but there was still a long way to go. "It's [a long way off], but [these results are] greatly encouraging and it's progressing in the right way - this is exciting, this is exciting in a number of ways," Dr Miles said. "At one stage [in the treatment's history] some of the results showed about 5 to 7 per cent of people dying because of the treatment. That seems to have really changed now and I think we can see that with [the latest] results." Ashley Berini is in and out of hospital as she experiences relapses. Dr Miles said that, despite all of the positivity, HSCT was not a cure in the traditional sense and stressed it would not help long-term sufferers reverse the damage MS had already done. "There's a small portion of MS sufferers that may really benefit from this treatment - that's a great thing, that's another string to our bow," he said. Ms Berini has been dreaming of undergoing AHSCT since a friend underwent the procedure for MS in a trial four years ago. She said that seeing her friend’s symptoms was "kind of like looking at myself", but doctors warn against comparing symptoms with others and drawing conclusions.

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The adventures of a writer and native Pennsylvanian transplanted to Silicon Valley. Notes on California landscape, history, and culture; plus discussions of writing, reading, music, God, food, and whatever else seems like a good idea at the time. Questions? Comments? Smart remarks? Monday, September 30, 2002 Thus the NY Times begins an article on the Monster in the House, AKA your friendly local writer, as presented by a panel of authors at the New Yorker Festival. The issue is central: What kinds of loyalty does the writer owe friends and family? What sorts of consideration can a friend or relative reasonably expect when the writer turns shared experiences into prose? How much, if any, neglect, grouchiness, and bad behavior is justified by a writer’s genius and the demands of art? What does the family do when a writer’s work can be interpreted to reflect poorly on the family? But turn it around for a minute. What does a writer’s family owe the writer? How much do they have a right to demand of time, attention, care, and energy when the writer is struggling to find enough time to create? When does respect for privacy become censorship? There are plenty of stories of artists and writers who are total bastards, but there are also a lot of us who aren’t nasty enough to make space enough to write in. These days, I’m trying to write while balancing a job, a family, and the very few community obligations I will accept. (And those are important to me: church, the women’s bookstore.) It’s damned hard, even if I hadn’t been spoiled by having once had all day to write. I’ve come up with a few solutions — writing in the early morning before work, for example, which lets me devote my freshest energy to the writing and warms me up for the very different kind of writing I do on the job. I’ve also given up almost anything that could be a distraction. I don’t spend time in online forums, which used to be a central source of friendship and support. I don’t watch many movies any more. My cross-stitch and cooking are sorely neglected. I would give up sleep if I could. I know I haven’t tackled any of these issues in depth, and I need to. I also want to explore the serious question of how to talk after divorce, but that will all have to wait. In the meantime, I’m doing my best to behave with respect toward both the family and the work. Thursday, September 26, 2002 If you want to see the kind of country that's burning, here are some photos of the Uvas Canyon Park, which is adjacent to the burning areas. It's not on fire, but it's now closed anyway, as a precaution, or because the air is too smoky. As a rule, Californians put on a coat when the temperature drops below 72. However, they continue wearing shorts and sandals even when the thermometer is in the 50s. Don't they have nerves in their knees? Even from forty-odd miles away, we could see the column of smoke rising and spreading as we drove home Monday night. A 200-acre fire. Last night the smoke was a deep bruise across the southern sky. By this morning, the wildfire had spread to 2100 acres. It’s well south of where I live, but I woke this morning with a scratchy throat from the traces of smoke in the air. It’s the fire season; in this hot weather, and as dry as September always is, fires are an annual threat. In 1991 the great Oakland/Berkeley Hills fire destroyed 1500 acres and killed 25 people. That was more than a fire; given the unusual heat, a 65-mph wind, and the steep, narrow canyons where it started, a single ember from a smaller fire rapidly became a firestorm. Everybody knows LA is a desert city. But as an Easterner, I never thought of Northern California as particularly dry. Its image is so much greener and softer than the prickly landscapes I think of as desert. I thought of San Francisco as a rainy, cool, foggy city. It is cool and foggy; it is also a semi-arid city that gets only 19.9 inches of rainfall in an average year, most of it concentrated in the winter months of November through February. The moisture from the fogs adds an effective five to ten inches of rainfall to that number, making it as lushly green as many Eastern landscapes. San Jose gets about the same amount of rainfall as LA: 14.6 inches average in a year. (For the sake of comparison: that’s less than a third of Jackson’s annual 48 inches; sunny Philadelphia averages 40 inches more or less.) Lacking San Francisco’s nourishing fog, San Jose, like LA, is a semi-arid climate, teetering on the verge of desert. You can tell when it’s winter here, because the hills turn green — a profoundly disorienting experience for a lifelong Easterner. And fires are a natural part of the ecology here. As beautiful as California is, as densely populated as some parts of it, it’s still untamed. We can kill off the grizzly bears and mountain lions, grind the redwoods into toothpicks, but we’re not masters here. The fires and earthquakes and debris flows are California’s reminders that what people build is temporary. The biggest threat to our security in the new world isn't Saddam's potential to build a nuclear weapon in the next six or seven years. It's some fanatic slipping into this country in the next six or seven minutes, while we're all waving flags and singing hymns. If you were a terrorist who wanted to strike in the U.S., wouldn't you prefer that we were distracted in Iraq? It's not a stretch to imagine an American future with dirty bombs blowing up our harbors. It's not beyond the pale to imagine suicide bombers at sporting events and nerve gas attacks in subway stations. And yet there has been precious little discussion about whether an attack on Iraq lowers or raises those risks. . . . . If we're going to war to prevent a nuclear holocaust, shouldn't we at least all know how to pronounce it? It ain't nukular, George. Trust me on this. Steve Lopez, in case you don’t know, is one of the best journalists in the USA. He’s shrewd, funny, and filled with moral outrage. From 1985 on to the late 1990s, he was an award-winning columnist for the Philadelphia Inquirer. As a Bay Area native, he chronicled the shenanigans of Philadelphia politicians, citizens, and the Parking Authority with zeal, passion, and an outrageous sense of humor. His columns are collected in Land of Giants, which is worth buying, if only for the nostalgic look at Philadelphia in the days when City Council had a quorum in jail. Then there are the stories about the second MOVE crisis — the one in which the city burned down an entire block of Osage Avenue, which led to the deaths of eleven people, including all but one of the children the city was claiming to protect. Steve Lopez, as I recall, had just started writing for the Inquirer a few days earlier. A hell of an introduction to the City of Brotherly Love. Nevertheless, he developed an affection for the city and even its old-style corrupt ward heelers. This is apparent in his second novel, The Sunday Macaroni Club. He also wrote Third and Indiana, an impassioned novel about the destruction of young lives and old neighborhoods by streetcorner drug culture. Reading it broke my heart. These days he writes for the LA Times. He’s a good journalist because he’s a stubborn, tough reporter who writes incisively. He’s a great one because after all these years he still cares. Saturday, September 21, 2002 That's a Spicy Meatball! Tony came over this afternoon, bearing a chili joke he found online. Being the virtuous person I am, I websearched until I found the original. Bruce Cameron is a professional writer, and I refuse to circulate his work unattributed — even if he didn't originate the line about Sno-Cones that I especially liked. Friday, September 20, 2002 I finished reading “The Snarkout Boys and the Avocado of Death” to Maddy last night, and tonight Maddy volunteered to read to me instead. We lay on the bed and she read me “Second Grade Gorilla” by Daniel Pinkwater. Which was rather wonderful, until sleep caught up with me, and she stopped reading and tiptoed away. The image of a loving father who reads to his daughter every night — yes, that’s moving, and it’s one of the things I like about Neil Gaiman: he really seems to be a caring, devoted, observant parent. Since I first came to care about his writing through his blog, I don’t have the graphic-novel image of Gaiman as a dangerous Goth god or leather-jacketed fallen angel. What I saw was someone who wrote horror, who explored the dark, without having to pretend he was a warped reflection of Lovecraft. (Weird but true: Lovecraft patterned his persona on Poe, who was imitating Lord Byron, who was playing the role of a dramatic villain bred of Milton’s Satan and the Mad Monk of Gothic fiction, but was also considerably different in person than on the page, by all accounts. So a modern-day imitation Lovecraft would be a fourth-string copy.) But that isn’t what gave me a pang in this. It’s the idea of a daughter feeling safe with her father in her room — even on her bed, next to her. A daughter who feels safe reading to her father. I can’t even imagine it, not for myself. The word father conjures up such horror, loathing, fear, and sorrow in me that I can scarcely summon words for it. Yet I looked all those years for substitute fathers, ideal images combining what was best in my own father and the qualities I wished for in a parent. There’s a reason Abraham Lincoln became my hero. In some ways the homicidal clarity of my relationship with my father made things easier for me. I could readily separate Men as a group from Daddy — something that can be much more difficult with an ambivalent relationship. And I found good male role models in books and history. But something this tender, this kind of gentle affection and unthinking trust — that reminds me of how very different things were for me, and that’s bound to hurt. Thursday, September 19, 2002 Profiling charged on 'nightmare' flight A doctor on Delta Flight 442 was detained by U.S. marshals. By Thomas Ginsberg Inquirer Staff Writer The incident on Delta Flight 442 was scary enough last month: U.S. marshals seized an unruly passenger, then one aimed a pistol at other passengers for a half hour and shouted at them to stay seated. The event, however, didn't end there. Unknown to most passengers on the Atlanta-to-Philadelphia flight, the marshals upon landing also seized an Indian passenger from first class and silently whisked him away in handcuffs. Far from being a terror suspect, the second detainee turned out to be a former U.S. Army major and military doctor from Lake Worth, Fla., where he has had a family practice for two decades. Both detainees later were released without charge, and the physician's angry account of his ordeal offers a glimpse at the dark side of America's war on terrorism. Yesterday, suggesting that the line between security and civil-rights violations is blurring, the physician, Bob Rajcoomar, filed notice in U.S. District Court that he may sue the U.S. government for illegal detention and emotional distress. His wife had been left to wander the Philadelphia airport for three hours during his detention, never told of his whereabouts. "This is blatant racial profiling," Rajcoomar, a naturalized citizen since 1985, said by telephone from Florida. "They think they can pick up anybody, willy-nilly... . It's not in keeping with traditions of the United States." David Steigman, a spokesmen for the newly created U.S. Transportation Safety Administration, which oversees the air marshals, gave few details about the detentions or the marshals' actions and declined to discuss the potential lawsuit. Atlanta-based Delta did not comment on the legal action. Rajcoomar, "to the best of our knowledge, had been observing too closely. When the aircraft landed, the airline declined to press charges" against either man, Steigman said. Stefan Presser, legal director of the American Civil Liberties Union of Pennsylvania, which filed the lawsuit notice, called the detention a civil-rights violation that should "send a wake-up call to Americans before it's too late... . In our haste to protect ourselves, we are literally turning on each other." The dramatic hours on Aug. 31 aboard Delta Flight 442 started when a passenger from Philadelphia - described as waiflike and disturbed - caused alarm when he began looking at other passengers' luggage. Two U.S. air marshals rushed back from their first-class seats to investigate. The marshals were later identified by police as Shawn B. McCullers and Samuel Mumma, assigned to the regional Transportation Safety Administration office in Atlantic City, which declined to discuss the case. "Air marshals issued a series of warnings to passengers to stay in their seats. The unruly gentleman didn't stay in his seat, so they took action to restrain him," Steigman said. Rajcoomar, sitting in window seat 1-D, reading a book and sipping a beer, said he knew nothing until the marshals showed up and began pushing the unruly man into seat 1-C, adjacent to his. Alarmed, Rajcoomar said he stood up and asked to be moved. A flight attendant told him to take one of the first-class seats vacated by the marshals. "One [marshal] sat on the guy in the first seat; he was groaning, and the more he groaned, the more they twisted the handcuffs," Rajcoomar said. Then, in coach class, a woman rose to switch seats with her child, who was sitting in an aisle seat, according to Rajcoomar's wife, Dorothy, who was sitting in coach class because the couple could not get seats together. "That's when they started hollering," Dorothy Rajcoomar said of the marshals. One of them rushed to the divider between the first-class and coach sections and leveled his pistol at the coach-class passengers. "He took control as if he was a terrorist himself," said Bob Rajcoomar, who was then sitting in a first-class aisle seat directly in front of the marshal. "He says, 'Nobody move, nobody look down the aisle, nobody take pictures or you will go to jail, nobody do anything.' He basically hijacked everybody." One passenger, Philadelphia Common Pleas Court Judge James Lineberger, said marshals "were yelling at passengers to keep their heads and hands out of the aisle... . I couldn't believe they would do such a thing." Bob Rajcoomar said he, like every other passenger, was watching the marshal but never spoke to him. About 30 minutes later, the plane landed and Philadelphia police officers came aboard to help take away the unruly man. Thinking the incident was over, passengers began standing up, Rajcoomar said. "Then out of nowhere, hell broke loose," Rajcoomar said. "One of these marshals came down to me and said, 'Head down, hands over your head!' They pushed my head down, told me to bend down... . I just couldn't believe it. I was speechless, in shock." Unseen by his wife 30 rows back, Rajcoomar was whisked off the plane, taken to an airport police station, and locked in a cell he called so filthy "I wouldn't even put my dog in it." During detention, Rajcoomar said, he was never asked anything except his name, address and Social Security number. He asked why he was being held. "One of the marshals said something like, 'We didn't like the way you looked,' " Rajcoomar recalled. "They also said something like, 'We didn't like the way you looked at us.' " Finally, after about three hours, Rajcoomar was released without explanation. "It was like a nightmare," Rajcoomar said. "The marshals were completely out of control... . If they had pulled the trigger, we'd all be dead. I don't feel safe knowing they're there, not with this kind of behavior." Wednesday, September 18, 2002 Want to understand the peaceful security of being involved with a writer? Take a look at this relationship quiz. It's designed for writers and their vic— I mean, their significant others. This is from Eric Maisel's website . He's a writer and psychologist who specializes in creativity issues. I recently read his book Deep Writing, which is one of the few writing books that seems both insightful and realistic. And it's well-written, which not all writing books are. Obviously, not all the quiz questions apply to any writer, and the answers certainly don't. I considered posting my answers, including write-in votes, but decided that it was getting too gamy and defensive. The writing was a major issue between Billy and me, so it can be difficult to discuss the difficulties of my writing career without also bringing in the death throes of the marriage. Just one observation: For years I've said, "I'm a professional. I can write anything, take editorial changes, and do what's needed rather than recording my artistic vision." At work I still have to think that way. But I think it's time to start being an artist again at home. Last week I dreamed that I was up on a ladder in a vast room like a library, trying to clean a whitewashed ceiling. Underneath (really, above) was a beautiful fresco of gods and angels, dimly seen through the masking pallor. Tuesday, September 17, 2002 September 17, 1862 It was the bloodiest day in American history: about 23,100 young men killed, wounded, or missing, as well as four generals. A quarter of the Confederates were killed or wounded. Many of the Union soldiers died fighting on a bridge over a stream that they could easily have forded, if only General Burnsides (or anyone else) had thought to check. By the time the Battle of Antietam ended, a thirty-acre cornfield was a stubblefield so covered with dead and dying soldiers that you could walk from end to end without ever touching the ground. The best book on the battle is titled The Landscape Turned Red—a straightforward description of what happens when that many men die on such a small patch of ground. And the center of the battlefield was a Dunker church whose members were pacifists. Despite all that bloodshed, the battle was a draw, but it counted as a tactical victory for the North. Lincoln had been waiting for the right moment. A week after Antietam, he issued the Emancipation Proclamation. It freed only those slaves who were in the Confederacy, but it changed the focus of the war. It signaled the intent to deliver four million human beings from a captivity so bleak and dangerous it can scarcely be imagined. In considering the meaning of the Emancipation Proclamation, let’s not forget the human cost of battle: what it meant to those men to march into beautiful farmland, kill and die, lie out all night suffering with wounds. What it cost their families and friends, their nation that would miss a generation of leaders, thinkers, workers, human beings. I can’t weigh or judge their actions. I can only grieve for the lost, try to live mindfully, and work to relieve suffering wherever it may come. It’s not enough. It’s never enough. Photographs of the battlefield, now and immediately after the battle, can be found online. There is also an extraordinary series of paintings by a professional painter who fought there that day. · Mexico's total population · annual new cases of chlamydia in the US · abortions worldwide every two years · extra people added each year to the world population · US and Canadian citizens over 16 who surf the Internet (as of 1999) · amount in pounds that Internet abuse cost UK business (as of 1999) · drinkers in the US in 1993 who were not heavy drinkers · Americans who are functionally illiterate · Pakistanis who are illiterate · passengers a year who fly via the 3 NYC airports · decline in global forest cover, in hectares, that has been estimated to be lost between 1990 and 2100 · people whose lives and homes would be threatened by a 50cm sea level rise · number of pounds of cheddar cheese annually consumed at Taco Bells around the world · population of Nigeria · age in years of the oldest fossil ant known · acres in the US protected by 511 National Wildlife Refuges · acres around the world protected by the Nature Conservancy · new cases filed in state courts in the US in 2000 · mobile workers in the US · cases of lymphatic filiariasis, a severely disfiguring disease, to be treated by 40 countries this year · acres of longleaf pine forests that formerly spread from Virginia to Texas (currently only 3 million acres) · acres of U.S. land that is developed · acres of grassy rangeland in Texas · amount in pounds that the charity Oxfam collects per year · people in Latin America who are without safe drinking water · tax rebate checks sent to US citizens in 2001 · paper checks written in Singapore, 1999 · estimated damage in dollars of the 1992 Landers earthquake · record albums by Bon Jovi music sold around the world · record albums by Garth Brooks sold in the US · population of pigs in the US · working women in the European Economic Community · questions answered by Ask Jeeves in the second quarter of 1999 · gallons of particles of hydrocarbons and other air pollutants from cars and factories washed into the ocean every year · Americans who live in areas with chronic smog problems · pounds of material Boeing recycled in 1998 · combined usage of today’s top ten paper users, in tons, ten years ago (current figure is 208 million tons, an increase of 126%) · days in bed caused by morbid obesity in 1995 · egg production of South Carolina chickens during June 2002 · pages of documents declassified in 1998 by the National Archives · cell phone users in the US in 2000 (rising at a rate of 1 million per month) · Christmas cards sent by Australians for Christmas 2000 · American adults who planned to take family vacations in 1995 · in 1993, number of US households that visited casinos · unsolicited spam e-mails advertising pornographic web sites sent to AOL subscribers by LCGM, using forged headers In case you're wondering, I needed to jazz up the number 92 million for work this afternoon, so I did a Google search on 92 million. These are a few of the more interesting factoids I found. And no, I do not write spam for a living. Everything I write is opt-in, which means people ask for it. I certainly do not ask for the appalling spam I get on AOL. I delete 95% of it unread, but even the subject lines give me a gloomy view of humanity, not to mention a certain pity for sheep. This is a great year for seeing the aurora borealis. I haven't seen any — I'm mostly in at night, and I live fairly far south for them — but I bet my friends and family in upstate Pennsylvania and New York can see them. There are even forecasts available online that predict when the solar storms will produce the most brilliant light shows. Do check out the links. (They show up in a different text color.) These sites have gorgeous pictures of the northern lights, so if you can't get out to see them, or you're living too far south, you can still have an idea of the glory of these displays. Monday, September 16, 2002 Yes, Dammit, I Know the Anniversary Is Over But the grief goes on. The survivors can't confine their sorrow to one day a year. And so, when I ran across this while looking for something else, I decided I'd better post the link to this heartwrenching article about Gettysburg and Shanksville, PA: On Hallowed Ground. Sunday, September 15, 2002 Aromas, California Driving down to the writers’ conference Friday, I passed a sign for a town called Aromas. That must be the ideal California address. California — woodsy, pungent, spicy — is quite as beautiful to smell as it is to see. I hear some reader jesting about smog, and God knows it's true in some areas. I can't spend more than a day at a time in the LA basin (such an appropriate name for it), because the air is consistently bad. For some reason, Northern California isn't nearly as smoggy. San Francisco itself has good air, fresh off the Pacific. But the scents. . . . even in southern California, the very first time I visited there, I loved the way California smelled. Billy and I were in the Angeles National Forest just before it rained, when all the pines and chamise and sagebrush exhaled in the suddenly humid air. Months later, I opened a little bag of postcards and the scent came rushing out, so strong and unexpected I sneezed. Friday and today, driving along 101, I smelled dozens of separate fragrances, most delightful. Of course, you can smell Gilroy from several miles away: that pungent combination of garlic and fertilizer is unmistakable. In the spring, there is the delicately sweet scent of blooming cherry and peach orchards. The sod farms and hay farms and the hills smell of grass hot in the sun. Sometimes trucks carrying enormous mesh hoppers of onions, garlic, or tomatoes passed me; if you had some bread, you could make a wonderful pizza. The shrubs in the hills all have their own scents: sage, rosemary, dozens of plants whose names I don't know. The herbal, almost medicinal smells of their intense volatile oils are released in the heat, or the rain, or when the leaves are bruised by the wind. Rosemary is grown here as casually as easterners plant crown vetch or barberries, and there are times when the roadsides are blue with rosemary flowers. At intervals along the road, there are stands of eucalyptus; even on a dry day, they exude the tingling, vigorous scent that's so much more complex and satisfying than the boiled-down smell of Vicks VapoRub. After a rain, the air in those groves is like a spa. When I lived up in the hills beyond La Honda, I had to drive home through thick belts of eucalyptus, and their fragrance always raised my spirits, energized me. Once I drove through with my window open to the rain. The next morning, a cloud of fragrance rolled out when I opened the truck door. The scent of the redwoods is my favorite of all: woodsy, deeper and more subtle than cedar, it's an aroma of peace and simplicity and pleasure. When we lived in the hills, Gabriel used to come in with her fur scented with redwood needles. The writers’ conference is over, and I’ve paused on my way home to eat breakfast and log on to the Internet. I have a couple of days’ worth of e-mail to deal with, and I really wanted to post here. Yes, I did bring my laptop on this trip. But I forgot the power cord—a classically Freudian self-destructive move that shows just how scared I’ve been of writing. I’m not letting that stop me, though. There’s always another way. I also didn’t bring printouts of any work, but that was a deliberate decision. I didn’t attend the writers’ conference to get a contract, find a new agent, or validate myself through praise and recognition. In some ways I was traveling incognito—not talking about my work or reading it aloud, not showing off my knowledge or trying to gain acknowledgment as a colleague from the presenters. Yes, I did that, deplorable as it is, last time I went to a writers’ conference as an attendee—that was the 1993 RWA convention in beautiful subaqueous St. Louis, where the Gateway Arch was up to its knees in Mississippi, and I bought a small sandbag as a souvenir. I’m waffling. I could go off here into the tragicomic story of how I always encounter natural disasters when I travel. It’s amusing, and it’s well off the topic. But not today—I want to face this, dammit. I went to the writers’ conference to remember who I am. To be among people who value what matters to me: the art and craft of writing. (Which sounds redundant, but isn’t.) And to start caring enough again to overcome the fear that’s kept me frozen these long years. I have a stable home now. I have a computer to write on. I have a supportive partner. I don’t have time, but I can make that—I have to make it somehow. Even an hour a day would make a difference. I just need to build the momentum to carry me into writing every single day. For years I had what every writer dreams of: hours alone every day, hours of unspoiled time in which to devote myself to the work. Afterwards I could do errands, cook, read, sleep, handle Billy. Writing was my fulltime job. Of course, I paid a price for it, and when the price got too high, I left that marriage and that life. I’ve posted about that already, though, and there’s no point in rehashing the devil’s bargain. I chose my life above my writing, which sounds idiotic; unless I’m alive, I can’t possibly write. And of course it was more complicated than that. But the point is. The point is. I haven’t written a book in five years—well, five years come November. And I haven’t finished a book of my own in far longer. I‘ve worked on other people’s projects. I’ve been writing ad copy, marketing e-mails, persuasive junk mail. It pays the rent. It gives me a sense of achievement, and at least I’ve been able to write copy for products I believe in. But I miss my own work. And every tiny chance element of the Cuesta College Writers’ Conference seemed designed to remind me that life is short, and I’d better write today, because tomorrow I might not be breathing. In his welcome speech, David Congalton, the conference co-director, apologized to returning participants for the lack of guitar music, which had been a tradition. The guitar player dropped dead in March. Heart attack. He was 49. There was an empty chair with his picture propped against the back as a memorial. And there was more. I don’t have time now to record every detail, but the most touching moment of the conference for me came when Susan Vreeland mentioned the circumstances of her finishing the manuscript of Girl in Hyacinth Blue. She was in the hospital with lymphoma; she’d had a bone-marrow transplant, and it wasn’t clear if she would survive. But she finished the book. She wanted to make sure her writers’ group knew that she had been happy in those last months of her life. The Lump has been a distraction for me. Not anymore. Now it’s a spur. I am 43. I could have another 60 years, or I could die on the way home. I don’t want to waste the time I have left. I don’t have unbroken days to write any longer. But I can find an hour, two hours. I can do this. I have to. Friday, September 13, 2002 You Look Like You Could Use a Laugh I've been meaning to post this link to The Best of Craigslist for a while, but tonight I just had to. It's not just because it's hilarious, though it is. It's because it can make me laugh and think and feel like a human being even when I'm infernally weary (I didn't get home from work until 11PM). Craigslist.org is a San Francisco original (now available in a number of other areas around the country). It is a bulletin board with ads for jobs, apartments, ridesharing, romance, furniture, useless junk, performance art, cars, and many other things, as well as online conversations about everything else in life. I found my elderly Mac, a gorgeous antique dining-room table and chairs, my truck, and several other wonderful things on Craigslist. And the Best Of Craigslist winnows out all the ordinary ads for traveling companions or 72-piece Tupperware sets and presents us only with the Ultimate — such as the guy who is looking for a traveling companion back into the past, or the guy who's looking for work (his major qualification is his skill at playing FreeCell on company time). They're all good, but these are some of the best to start with: Wisdom on marriage and kids: RE: Almost 35, Unmarried, Depressed Wickedly funny classification of personal ads: Warm it up Craig Microsoft error messages in haiku: For Those Who Fear the Window Really unusual classified ads: horny futon mattress desperate for some hot action - $100; Lil' Unicorn is getting pissed off! (photo) - $1 Ten exciting reasons: It's great to be a cat.Good sexual advice/personal ad: Foreplay - A Reader's GuideThe Creme de la Creme of that day's personal ads: Ladies, May I Present The MenA warped and very funny personal ad: 'Modern Executive' seeks conspirator for accounting fraud and dinner.Wise advice for those who dream of Someplace Else: We all have problems. Minnesota is NOT the solution. I promise I'll post something I actually wrote at some point in the near future. Plus the Lumpdate. But right now, I'm exhausted. It's been a long, hard week, and I need to get to bed. Wednesday, September 11, 2002 WARSAW (Reuters) - Poland's Nobel Prize-winning poet Wislawa Szymborska has written a moving tribute to the victims of the Sept. 11 attacks in the United States. A photograph from Sept. 11 They jumped from the burning stories, down -- one, two, a few more higher, lower. A photograph captured them while they were alive and now preserves them above ground, toward the ground. Each still whole with their own face and blood well hidden. There is still time, for their hair to be tossed, and for keys and small change to fall from their pockets. They are still in the realm of the air, within the places which have just opened. There are only two things I can do for them -- to describe this flight and not to add a final word. I was reading Winnicott this morning on art. "Much of the pleasure of the experience of art in one form or another arises from the nearness to unintegration to which the artist's creation may safely lead the audience or viewer. . . . The appreciation of art thus keeps people on a knife-edge, because achievement is so close to painful failure." Carrying the audience right to the edge of disintegration and bringing them back again — that to me expresses art's significance spiritually, intellectually, emotionally. It explains why I could mourn for Diane through and with Mozart's Requiem, because that music carries the listener right to the edge of destruction but, in its sublime order and meaning, also consoles for the terror and loss it expresses. (I'm saying this very badly, and I said it badly the other day, discussing the Rolling Requiem.) So here are some ways to consider 9/11. Some artists' eyes to take us right to the edge and bring us back again. Tuesday, September 10, 2002 One Year Ago Just over a year ago I flew back East to pack up the rest of my belongings, ship my books west via Media Mail, and get ready for the temporary technical editor job awaiting me (due to start September 19). I came to California with a cat, a laptop, and a suitcase, but I still had hundreds of boxes of books, clothes, kitchen junk, financial records, and so much else left in somewhat leaky storage. Now I had to deal with it all. At first I gave myself a week. I would fly out September 4 and return on the 11th. And since my brother-in-law had been bumped from a flight and was giving me his free pass, I had to fly United. "Hey, I could fly through Boston! They have a flight that leaves just after 8AM." No, it went through LA, and I didn't want to change planes again to get home. But I did make one set of reservations to fly home September 11; a week or so later I changed them to Friday, September 14. Lisa knew I would need a few extra days to finish packing. She was right. I didn't know I would spend September 11 in utter shock, packing, listening to the towers collapse on the radio. I didn't know that I wouldn't be able to ship my many boxes of books Media Mail because the post offices all closed down. I didn't know I would spend those few extra days in the east desperately worried about my friends in New York — those who worked at Ground Zero or lived near enough to be vulnerable — and my friends at the Pentagon. Dreaming of rescuing one friend, a high-level financial fund manager, from her burning office at Ground Zero. Trying to find my husband, who had just left the job he'd had in Massachusetts and moved to the DC area. I didn't know I would have to wake Michele up on that Tuesday, calling from the east: We're under attack. They've flown two airplanes into the World Trade Center. I love you, but I don't know when I'll get home. Or how. Every possible way to get back to California was blocked. The airlines shut down. Amtrak shut down. Greyhound shut down. I was trapped at my sister's house in upstate New York, not quite home, 3,000 miles from home. I was able to leave on the first flight out from Ithaca. On the way to the airport I stopped and bought myself a used paperback: The Little Drummer Girl by John LeCarre. That book — a brilliant, multifaceted, profoundly humane look at the Arab/Israeli conflict, the techniques and motives of terrorists, and the use and construction of bombs — was my gesture of defiance and challenge. I read it most of the way home, in a plane so jammed I could barely breathe. I had read and reread the book before, but if there was ever a time to be willing to face it all, the humanity and desperation and fear of both sides, all sides, in that conflict, then that crowded Friday was the day. I had my cross-stitch in my carryon bag, along with the book and a lot of other miscellaneous things. When I unpacked the cross-stitch bag, I found I was carrying an eight-inch pair of scissors. Monday, September 09, 2002 A Sacred Duty I still read the Philadelphia Inquirer online to stay in touch with events back east. Also, frankly, the Inky is one of the great newspapers. Today’s edition included this story. I can't say anything that would illuminate it or make it more significant. These actions — and the words of this new liturgy — speak for themselves. NEW YORK - In a way, Episcopal priest Charles T.A. Flood has had two parishes for the last year - one at St. Stephen's on 10th Street in Center City Philadelphia, and the other at a cluster of refrigerated truck trailers near Manhattan's East River. The 58-year-old rector of St. Stephen's has been one of two primary chaplains working at New York's Office of the Chief Medical Examiner, which is the way station for all the human remains recovered from the World Trade Center site across town. The thousands of bits of remains are given identification numbers and stored in the trucks, parked in an off-limits space outside the Medical Examiner's Office on First Avenue, awaiting DNA tests and eventual burial. Ministering first to the huge team of specialists that received and analyzed the remains, and then to the family members who regularly visit the site, Mr. Flood said the experience had deepened his faith and spirituality, despite the fact that the guidelines for the interfaith chaplaincy require that the symbols and language of his Christian background be kept out of this work. "We're here as a symbol of the presence of God in the worst of circumstances," Mr. Flood said. "We are not here acting as Episcopalians." On Wednesday, the anniversary of the attacks, Mr. Flood will preside over services at St. Stephen's at noon, then head to New York and the Medical Examiner's Office for the rest of the day. Being a chaplain under almost any circumstance is a very different kind of ministry from being a parish priest or imam of a local mosque, said Jo Schrader, executive director of the 3,800-member Association of Professional Chaplains, based in Illinois. Most chaplains work in hospitals or other institutions where people face crises but may share no religious understanding. The chaplain must be able to deliver a message broad enough to include everybody, but still be meaningful to those with well-formed beliefs. "They have to have the ability to minister to anyone of any faith, or of no faith," Schrader said. "It puts a lot on their plates. There's a difference in skills. There's a difference in knowledge" compared with clergy who deal primarily with those of their own traditions. Mr. Flood, who also briefly worked directly atop the rubble pile of the World Trade Center shortly after Sept. 11, admitted that at first he found it a little unsettling to be representing not a specific church or even faith, but God. "You're stepping out as a religious shaman almost - as a stranger outside the tribe," he said. The chaplaincy at the Medical Examiner's Office was begun in mid-September by another Episcopal priest, Betsee Parker. Mr. Flood joined her in late October, and they have had volunteers come and go throughout the year. They were funded by the American Red Cross through April, and operated from a trailer office parked near the refrigerated trucks. Their "parish" consisted of the hundreds of specialists working daily at the site, and Mr. Flood said people of all faiths, and those with no real beliefs, were there. "It's hard work" to find the words to speak to such a diverse group, he said. "It's really an attempt to find common religious iconography and identity. It is not an attempt to bring everything down to mooshy pap. It's an attempt to make things so simple that everybody understands." Mr. Flood wrote the litany that is now used at the services held outside the trailers every Friday. "We give thanks," the litany says in part, "for those in our own time who have inspired us, for Mother Teresa, for Martin Luther King Jr., for Gandhi who showed us the path of peace." After a moment of silence, the litany continues: "We bless with our tears the ground which has been made holy by the blood of the innocent. The hill of Calvary where Jesus was crucified. The gas chambers where the innocent of God's chosen people were slain. The killing fields of Cambodia. The City of Oklahoma - ground consecrated by the blood of children." In the litany's concluding prayer, the leader says that "God asks us to leave this place and take up the cause of our own lives." "If an artist was lost, then some of us must find a creative spirit within ourselves and fill the void. If a person of faith was lost, then some of us must become deeper people of faith." It ends with a call for God to "hold those who died in your arms... . May these souls and the souls of all the departed rest in peace." Mr. Flood said some families who now attend the services, which are closed to outsiders and the press, want to light candles or leave flowers. Others want no religious observance at all, he said. Since April, when Red Cross funding ran out, Ms. Parker and Mr. Flood have essentially operated out of their own pockets. Though they are officially attached to the medical examiner's staff, they are not paid. Mr. Flood has been buying his train tickets to New York. He said he and Ms. Parker were prepared to keep the chaplaincy running for as long as three years, which medical examiner Charles S. Hirsch said might be the duration of the operation. Even if families should stop coming, Mr. Flood said, he felt he should be here to represent the presence of God with the dead whose remains rest in the trailers. Saturday, September 07, 2002 Lumps in the News Spent far too much time Friday at Kaiser, getting the Lump looked at. The result was (after all these days of frustration, waiting, and unreasonable delays) that the doctor looked at it, felt it, listened to the history. . . . and offered me a prescription for my eczema while I wait for the next month or so for a dermatology appointment to open up. Oh, and sometime in the next two weeks I can expect a call from a surgeon, who will grope the Lump; transfix it with needles; order various blood tests (gotta stock up on orange juice); scrutinize it magnetically, radiographically, and sonically; and then slice open my thigh and yank it out. No question, it must be removed; given its size, the trouble I’m already having with that leg, and the slight but interesting possibility of liposarcoma, they need to take it out. I can expect surgery probably around the end of September, maybe mid-October, and a pathology report within a month of the surgery. It was clear to my doctor (as it has been to me these ten days) that this is not an infected cyst. So the ten days of antibiotics (with consequent faint nausea, the omnipresent taste and smell of mold, and the disagreeable gastrointestinal symptoms) were a waste. I never had the feeling that I had an infection — and I’m sorry, but that does matter. I know my own flesh. One of the hardest things for me to convey to people is that I’m not worried about the outcome — the possibility of cancer isn’t what bothers me. In fact, the possibility is low. Lipomas run in my family, so I’ve seen them and I don’t fear them. Anyway, they’re the most common kind of soft-tissue tumor, and they’re benign by definition. I’m pushing for medical treatment on this one, though, because I had that liposarcoma scare nine years ago, and I’d rather get it out and make sure it isn’t a problem. All this I face with calm. What distresses me about this is the medical process itself. I’m not worried about the lump. I am suffering from it, and telling me it will turn out all right is no consolation for the present misery: being stripped and handled; telling the same story over and over again to indifferent ears; being pierced, sliced, dissected; being weak and in pain. I feel like a woodchuck being dissected. That was one of my father’s hobbies when I was very small, four years old or less. He approached the task with an unholy glee, and he made me watch as he cut it open and then touch the insides. I always knew that next time it could be me he was opening. My skin ripping under the scalpel, my ridged trachea sliced into silence, the gush of slime and blood as he cut into my guts (such vivid and beautiful colors), my secret internal stench of viscera. I would never eat a chocolate rabbit, fearing what I would see and taste when I bit the head off. So no wonder I loathe being subject to medical procedures. I know they are necessary. I'm willing to do the work to endure and understand my own reactions. But this is, to me, a worse nightmare than cancer. Cancer in that context is a code word for death, and death at least offers surcease. One of the irrational reactions I've had about this lump has been that I'm going to have to go through a lot of wretchedness and I won't even get to be dead at the end. When I tried to explain this today, Paul said, "Death isn't a consolation prize." It is, though, sometimes. If you're being tortured. And it's a measure of how much better my life is these days that I am not willing to die. I would rather live, even if I have to endure a lot of horrors. There are four sorts of cats: * Friendly cats, that want to achieve maximum transfer of fur to your clothing. * Scaredy cats, that have a zone of tolerance and as soon as you enter, they run away. * Indifferent cats, that have seen it all before and are not interested in you right now. * Hungry cats, tend to want your attention a whole lot more than normal. Note: this is a temporary state. There are many more kinds of cats than this. Actually, one of the things that always amazes me is how similar each of us is to our individual cats. Michele's Little Bit wants nothing more than to be in someone's lap, being petted, and happy in the knowledge that a pinned-down human cannot possibly go anywhere or do anything. She wants her people *right there* and *paying attention* to her. Though Michele herself doesn't wander around the house meowing when she isn't getting her share of attention, she is fundamentally happiest when she has her family snuggled around her. Sonja's Ivan is easily the most beautiful of all the cats, sleek and elegant and always soooo well-dressed. Though he's taking a little time to relax and get comfy with everyone, he is at heart very affectionate. Especially at night. I have never understood why he gets jumpy in the daytime but is perfectly happy to be petted after dark. Sonja is basically a warm and playful person, though she can withdraw when she's startled. And she has the best sense of style of us all. Gabriel, Spawn of Satan, AKA Fuzzbucket, is considerably more elegant than I am, but we're both essentially wild animals who come in sometimes for food and petting. Not that she permits much petting of herself; she'd much rather lick and groom the person she has chosen to sit down on. When she's done, she lets you know with a brief valedictory bite. We both need a *lot* of space, but we can be cozy, too. At least I don't stroll around on the tops of eight-foot bookshelves, though I've always loved high places best. Paul's late cats — Simon and Sinbad — were both very like him in different ways. Simon was cool, calm, and massive — one of the least excitable animals I have ever seen. Sinbad was clearly a scientist, constantly doing experiments in gravity, the breakability of glass, and the spill patterns of liquids. The results had to be reproducible, too. He used to get up on top of the fridge and carefully nudge things off with his paw to see if they would really fall this time. What better cat for a chemist? Wednesday, September 04, 2002 Arrest Those Men — They're Fiscal Terrorists! NEW YORK (Reuters) - The economic cost New York City suffers as the result of the Sept. 11 attacks will range from $83 billion to $95 billion, partly depending upon how many jobs are shifted out of the city, a new report said on Wednesday. City Comptroller William Thompson also estimated in his new report that it will cost $21.8 billion to replace the buildings, infrastructure and what he called "tenant assets" lost as a result of the attacks that toppled the World Trade Center. Think about that. Those guys stole more than three times what it would cost to replace the World Trade Center, including desks, computers, carpeting, and Muzak. They stole nearly as much as NYC lost in the aftermath of that disaster. I'll have to look up the numbers for the amount stolen in the S&L scandals of Bush Mach I. Heyyyyyyyy, these guys are pikers! According to this summary, the S&L scandal will ultimately cost the taxpayers $1.3 trillion — which might have been only $20 billion if the government had started to face facts before the 1988 election. These numbers are from a book called Inside Job. I don't know how reliable that book is, so I checked with another capitalist bastion: Forbes.In a recent article, they mentioned that just the Lincoln S&L collapse cost "billions" in investor money. (That's the one that Charles Keating was involved in.) They also mentioned the insider-trading scandals of the early 1980s and the Wedtech scandal. It's easier and more fun and a hell of a lot more dramatic to blame outside agitators for attacking America. And there's no question that September 11 was a terrible tragedy. Words can't begin to do justice to the heartbreak of ordinary people dying at their desks, or the courage of those firefighters toiling up the stairs, trying with their last breath to save lives. But I think we need to look at the less easily televised tragedies of small investors, people who have worked all their lives, whose pension funds and retirement savings have been plundered by clean-cut American citizens who already have more money than they can possibly spend. Tuesday, September 03, 2002 And Now, For Something Completely Contemptible. . . The not-so-secret dirty secret of the crash is that even as investors were losing 70%, 90%, even in some cases all of their holdings, top officials of many of the companies that have crashed the hardest were getting immensely, extraordinarily, obscenely wealthy. They got rich because they were able to take advantage of the bubble to cash in hundreds of millions of dollars' worth of stock--stock that was usually handed to them via risk-free options--at vastly inflated prices. When the bubble burst, their shareholders were left holding the bag. But, hey, they had theirs. How much did they take in? We'll get to that in a second, but first we need to explain the criteria for the list that accompanies this story. First, we looked at companies that had hit a market cap of at least $400 million--and fallen by at least 75% from the highs they reached during the bubble years. Second, we counted insider stock sales from 1999 onward. (That's why Gary Winnick's tally comes to "only" $508 million on our list; he had sold a ton of Global Crossing stock before 1999.) And third, we included only stock sold by top executives and board members; the quick profits made by the venture capital firms that funded the dot-com boom were excluded. (Also excluded in all but a very few cases--largely because it's impossible to track--was stock sold by company officers after they left their jobs. For the same reason, we did not include the cost of acquiring the shares; in most cases option prices were so low that including that cost would hardly affect the totals.) What we cared about, ultimately, was a simple, straightforward thing: How much cash did the top executives at America's Losingest Companies reap by selling their shares to the investing public? Even with these fairly narrow parameters, the numbers are astounding. Executives and directors of the 1,035 corporations that met our criteria took out, by our estimate, roughly $66 billion. Of that amount, a total haul of $23 billion went to 466 insiders at the 25 corporations where the executives cashed out the most. Those are the companies that make up this list. The top 25 include some big and obvious names: Cisco (CEO John Chambers: $239 million), for instance, and AOL Time Warner, parent of FORTUNE's publisher (chairman Steve Case: $475 million). But they also include companies you would be surprised to find on a top-25 list of any kind. Executives and directors at a software maker called Ariba raked in $1.24 billion even as its stock was falling from $150 to around $3. Yahoo executives reaped $901 million in stock sales while the company's shares fell from $250 to about $11.

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1. Field of the Invention The present invention relates to a withdrawable device of a vacuum circuit breaker for inserting and withdrawing a vacuum circuit breaker in order to connect and disconnect power terminals. 2. Description of the Related Art In general, a vacuum circuit breaker is an electric device for switching a normal current and blocking a fault current as occurred by a signal such as a relay. The vacuum circuit breaker extinguishes an arc generated when the vacuum circuit breaker breaks, in a vacuum container to quickly separate a circuit, thus protecting the circuit and device. The vacuum circuit breaker is generally installed in a circuit breaker chamber of a distributing board. Usually, in the vacuum circuit breaker, electricity flows from a main line (i.e., to which electric is incoming) to a load side (i.e., from which electricity is outgoing), and when the vacuum circuit breaker or the distributing board is inspected or when the vacuum circuit breaker or the distributing board needs repairing, contact points of the vacuum circuit breaker are separated, the vacuum circuit breaker is withdrawn to a location at which it is sufficiently insulated from a power source of the main line, and then the circuit breaker is inspected or repaired. A withdrawable device of the related art vacuum circuit breaker will now be described with reference to the accompanying drawings. FIG. 1 is a perspective view showing the configuration of the related art vacuum circuit breaker. FIGS. 2 and 3 are perspective views of the withdrawable device of the related art vacuum circuit breaker. FIG. 4 is a sectional view showing the configuration of the withdrawable device of the related art vacuum circuit breaker. FIG. 5 illustrates a braking unit in a safe state according to the related art. FIG. 6 illustrates the braking unit in an operational state according to the related art. First, with reference to FIG. 1, a withdrawable device 500 of the related art vacuum circuit breaker includes a carriage 100, on which a circuit breaker main body 140 having a main circuit 141 which is coupled to or separated from a mounting frame 130 installed at a rear side of a cradle 120 is loaded such that it can be transferred (or conveyed), a carriage moving unit 200 for moving the carriage 100 in a forward/backward direction, a braking unit for limiting a transfer distance of the carriage 100 being transferred by the carriage moving unit 200, and a girder assembly 300 supporting the carriage moving unit 200. The carriage 100 includes a box body 101 having an upper portion opened and including a wall body 101a formed with a certain height on an outer circumferential surface, and two pairs of wheels 102 form on both sides of the box body 101 such that the are inserted or withdrawn along a guide rail (not shown) installed at an inner side of both side walls of the cradle 120. With reference to FIGS. 2 and 4, the carriage moving unit 200 includes a lead screw 201 inserted in a forward/backward direction of a through hole 101b formed on the front wall body 101a of the box body 101, a transfer nut 202 installed at an inner side of the front wall body 101a of the box body in a state of being threaded with the lead screw 201, a channel-shaped bracket 203 for fixing the transfer nut 202 to the box body 101, and a handle 213 detachably installed at a front end portion of the lead screw 201 in order to rotate the lead screw 201 forward and backward. The transfer nut 202 includes a female screw unit threaded with an outer circumferential surface of the lead screw 201. Two guide recesses 202b having both end portions whose depths are different are formed on front and rear surfaces of the transfer nut 202. A guide groove 202c is formed on an outer circumferential surface of the transfer nut 202. A girder 209 fixed to a rear end portion of the lead screw 201 may be movable in a forward and backward direction without wobbling on a pair of travel rails 212 and 212′ installed in a lengthwise direction on an inner side of the box body 101 of the carriage 100. The girder assembly 300 includes a support structure 303 having a space part formed at an inner side thereof and having a bearing 214 supporting to transfer rotary power to the front end portion of the lead screw 201 that passes through a fixing hole formed at the center thereof, left and right sliding plates (not shown) installed to be movable in a left and right direction at both inner sides of the support structure 303, left and right handles 305 and 305′ fixed to the left and right sliding plates and installed to be protruded outwardly from the support structure 303, and a spring (not shown) for moving the left and right sliding plates to insert an end portion 304a into the both side walls of the cradle 120. A braking unit 204 is installed near the transfer nut 202 and selectively constraining a rotation of the transfer nut 202 by interworking with guide recesses 202b and 202c formed on the transfer nut 202. The position of the circuit breaker main body 140 loaded on the carriage 100 is fixed by means of the braking unit 204. The operation of fixing the position of the circuit breaker main body 140 by means of the braking unit 204 will now be described with reference to FIGS. 5 and 6. As shown in FIGS. 5 and 6, as for the braking unit 204, forward and backward rotation preventing pins 205 and 205′ are installed in a diagonal direction of the bracket 203 such that they can be inserted into the guide recesses 202b formed on the front and rear surfaces of the transfer nut 202. The forward and backward rotation preventing pins 205 and 205′ are connected with left and right driving pins 207 and 207′ by means of connection plates 206 and 206′. The left and right driving pins 207 and 207′ are elastically supported by springs 208 and 208′. The left and right driving pins 207 and 207′ are pressed by the girder 209 and the girder assembly 300 installed at the end portions of the lead screw 2201 when the carriage 100 moves forward and backward. A pair of support plates 211 and 211′ are installed at a certain interval in a vertical direction of the bracket 203 so that a guide pin 210 for positioning the transfer nut 202 can be inserted into the guide recess 202c of the transfer nut 202 when the forward rotation preventing pin 205 or the backward rotation preventing pin 205′ is released from the guide recess 202b of the transfer nut 202 by the left and right driving pins 207 and 207′. The rotation of the transfer nut 202 moving in the forward and backward direction of the lead screw 201 is restrained by the braking unit 204. In this case, when the carriage 100 has moved forward completely (so as to be at a testing position), the transfer nut 202 completely moves backward along the lead screw 201, so the right driving pin 207′ is brought into contact with one side of the girder assembly 300, the backward rotation preventing pin 205′ is released from the guide recess 202b of the transfer nut 202, and the transfer nut 202 is idly rotated, thus preventing the carriage 100 from moving any further. When the carriage 100 has completely moved backward (so as to be at an operation position), the transfer nut 202 moves completely to the rear side along the lead screw 201, the left driving pin 207 is brought into contact with the side of the girder 209 installed at the rear end portion of the lead screw 201, the forward rotation preventing pin 205 is released from the guide recess 202b of the transfer nut 202, and the transfer nut 202 is idly rotated, thus preventing the carriage 100 from moving any further. However, the withdrawable device of the vacuum circuit breaker has the following problem. That is, when the carriage 100 is at the testing position, the carriage 100 is simply prevented from moving forward by means of the braking unit 204 and the backward rotation preventing pin 205′ interworking with the braking unit 204, while the carriage 100 cannot be prevented from changing in its position to the front side when an external force (vibration, an impact, etc.) is applied to the lead screw 201. Based on the same principle, when the carriage 100 is at the operation position, the carriage 100 is simply prevented from moving backward by means of the braking unit 204 and the forward rotation preventing pin 205 interworking with the braking unit 204, while the carriage 100 cannot be prevented from changing in its position to the rear side when an external force (vibration, an impact, etc.) is applied to the lead screw 201. In case of the operation position, the change in the position of the carriage 100 is likely to cause a short-circuit incident, and in the occurrence of the short-circuit incident, it makes the contact state of an electrical contact portion unstable to possibly bring about an additional incident. Also, in case of the testing position, the contact point of the vacuum circuit breaker cannot be separated up to a position at which the vacuum circuit breaker is sufficiently insulated from the power surface of the main line, having a dangerousness of causing a safety accident.

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Q: Path of "New Item + Edit" class The class of New Item is "ms-list-addnew-imgSpan20" but can't find the location of the css file. I looked into the corev3.css but it wasn't there. Does anyone know where it is? A: If it is part of any external CSS file it'll be in corev15.css. But it could also be that the CSS is pushed inline as on many occasions with SharePoint 2013 (sadly).

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654 P.2d 1345 (1982) STANDARD OIL COMPANY OF CALIFORNIA, a Delaware Corporation, Plaintiff-Appellee, Cross-Appellant, v. HAWAIIAN INSURANCE & GUARANTY COMPANY, LTD., a Hawaii corporation, Defendant-Appellant, Cross-Appellee. and AIR SERVICE CORPORATION, Universal Enterprises dba Associated Aviation Activities and Southern Marine & Aviation Underwriters, Inc., Plaintiffs-Appellees, v. HAWAIIAN INSURANCE & GUARANTY COMPANY, LTD., a Hawaii corporation, Defendant-Appellant. No. 7111. Supreme Court of Hawaii. December 8, 1982. Berton T. Kato, Honolulu (Kobayashi, Watanabe, Sugita & Kawashima, Honolulu, of counsel), for defendant-appellant, cross-appellee. Warren J. Senda, Honolulu (Case, Kay & Lynch, Honolulu, of counsel), for plaintiff-appellee, cross-appellant. James F. Ventura, Honolulu (Libkuman, Ventura, Moon & Ayabe, Honolulu, of counsel), for plaintiffs-appellees. Before RICHARDSON, C.J., LUM and NAKAMURA, JJ., and OGATA and MENOR, *1346 Retired Justices, assigned temporarily. PER CURIAM. The plaintiffs-appellees, brought suit against defendant-appellant Hawaiian Insurance & Guaranty Company, Ltd. (hereinafter also "HIG"), to recover damages they allegedly sustained when HIG failed and refused to defend actions brought against them by the heirs and executors of the pilot and the passengers of a plane which crashed on May 20, 1973. In the circuit court, HIG raised as one of its principal defenses the failure to give notice as required by the insurance contract. The trial court disposed of this contention by ruling that HIG had waived notice. On appeal, the intermediate court of appeals held that it was unnecessary for it to reach the question of waiver, inasmuch as it was satisfied from the record that HIG had been given notice as required by the insurance agreement. 2 Haw. App. 451, 634 P.2d 123 (1981). We granted certiorari for the purpose of determining whether the appeals court erred in holding as a matter of law that HIG had been properly and seasonably notified. I The airplane crash claimed the lives of the pilot, Dr. Robert C.H. Chung, and his passengers, George Chappel, Myrtle Chappel, Duane Archer, Tamarah Sue Archer, and Marcia Lynn Archer. The failure of the left engine to function had caused the aircraft to plummet to the ground. Investigation revealed that contaminants in the fuel strainer of the left engine may have been a cause of the engine failure. The tanks feeding the engine had been fueled from an aviation refueler truck covered by a liability insurance policy issued by HIG for the benefit of plaintiffs-appellees, Standard Oil Company of California (hereinafter "SOCAL"), Air Service Corporation (hereinafter "ASC"), and Universal Enterprises dba Associated Aviation Activities (hereinafter "AAA"). On December 3, 1973, the heirs and executors of the Chappels and the Archers filed suit in circuit court (Civil Nos. 40848 and 40849, respectively) against Dr. Chung's estate and unnamed Doe defendants. The complaints alleged various theories of negligence and products liability. On February 22, 1974, ASC was brought in by the Chung estate as a third-party defendant in said Civil Nos. 40848 and 40849. After being served with process, ASC forwarded the same to HIG. In its letter of transmittal ASC wrote HIG: "We trust that you will take the necessary steps for our legal representation." Because of HIG's lack of action, however, defaults were entered against ASC. These defaults were later set aside as a result of a stipulation between the Chung and HIG attorneys. Thereafter, HIG transmitted the legal documents to Southern Marine and Aviation Underwriters, Inc. (hereinafter "Southern Marine"), whose attorneys subsequently defended against the suits on behalf of ASC and AAA. This was apparently done pursuant to an aviation liability insurance policy which had been issued to ASC and AAA by Southern Marine. On September 13, 1974, ASC was identified as a Doe defendant by the plaintiffs in Civil Nos. 40848 and 40849. AAA and SOCAL were respectively identified as Doe defendants by said plaintiffs on February 20, 1975, and on June 30, 1975. On February 27, 1975, the Chung Estate filed its own suit (Civil No. 44402). ASC and AAA were made party defendants in this action and were served with process on March 7, 1975. ASC and AAA forwarded the complaints and summonses to HIG which in turn forwarded them to Southern Marine whose attorneys also took over the defense of that action. In her letter of transmittal, ASC's executive secretary wrote to HIG: "We submit these to you for proper action." Civil Nos. 40848, 40849, and 44402 were later consolidated. On June 27, 1975, pursuant to stipulation, SOCAL was brought in as a third-party defendant in all three cases *1347 by ASC and AAA. In their third-party complaint, ASC and AAA alleged: Furthermore Standard Oil rented to Air Service and/or Associated Aviation Activities an aviation refueler truck in which to store the gasoline or fuel provided and by which to dispense said gasoline or fuel. In connection therewith Standard Oil assumed certain obligations and duties in connection with the maintenance and upkeep of the truck and its components. 4. If plaintiffs in said Civil Numbers have sustained injuries and damages as alleged, said injuries and damages were caused by the negligence, breach of contract, breach of warranty, breach of strict tort liability, or other fault of Standard Oil and Air Service and/or Associated Aviation Activities were in no way at fault. This was the first time the refueler truck was specifically linked to the cause of the accident. SOCAL was served with the third-party complaint and summons on June 30, 1975, but did not immediately forward them to HIG. Only on January 13, 1976, did SOCAL, through its attorneys, tender the defense of the actions to HIG as SOCAL's insurer. On January 28, 1976, HIG replied in writing, taking the position that the case was strictly a products liability case. In its letter, HIG advised SOCAL's attorneys: "Based on the pleadings, our policy, which covers only Comprehensive Automobile liability, does not apply and therefore, we decline your tender to undertake the defense of Standard Oil under our policy."[1] With HIG's refusal to defend the actions, Southern Marine undertook the defense. After the trial had commenced, SOCAL, ASC, and AAA settled with the Chungs, Chappels, and Archers. On May 21, 1976, SOCAL filed suit against HIG in circuit court (Civil No. 48381) for damages it sustained as a result of HIG's refusal to defend. A similar suit was filed by ASC, AAA, and Southern Marine on December 2, 1976 (Civil No. 50084). These two cases were later consolidated. On March 28, 1977, SOCAL moved for partial summary judgment. ASC, AAA and Southern Marine filed their motion for summary judgment on May 31, 1977. Plaintiffs-appellees urged the circuit court to find as a matter of law that HIG had a duty to defend under the insurance policy, leaving open the issue of damages. HIG contended in its memorandum opposing the motions, as it did in its answer to the complaints, that it received late notice of the actions. The circuit court granted the motions and found: "That having refused to defend ASC and SOCAL on the grounds of noncoverage, HIG has waived and cannot now assert as a defense that SOCAL and/or ASC failed to give HIG timely notice of the wrongful death claims." The circuit court later granted summary judgment to the plaintiffs-appellees on the issue of damages.[2] HIG appealed on the issues of liability and damages. SOCAL cross-appealed on the issue of apportionment of damages. The appeals were consolidated and assigned to the intermediate court of appeals. *1348 II The policy in question provided, as a condition of coverage, that "[i]f claim is made or suit is brought against the insured, the insured shall immediately forward to the company every demand, notice, summons or other process received by him or his representative." HIG argued before the appellate court that it had not received, within a reasonable time, notice that it was the conduct of its insureds in the maintenance of the truck that was being claimed as the cause of the accident. In response, the intermediate appellate court said: We cannot agree. The first of the insureds to be joined was ASC. It promptly forwarded the pleadings served upon it to HIG. Under those pleadings, there was a potential liability for the covered risk (negligence in the maintenance of the truck, including loading and unloading) and HIG was on notice of that fact from that point on. Had it defended that risk and participated in the proceedings, it would have had notice of the fact that the truck was being specifically pointed to just as soon as that fact turned up. The insured is required by the policy to give notice and forward the pleadings to the insurer. ASC and AAA did so. We do not think the result is changed by the fact that an additional insured [SOCAL] was brought into the case by a later pleading and no additional notice was sent to HIG. HIG was already on notice of the potentiality with respect to the risk insured against and the joinder of an additional insured in the proceedings did not increase or change HIG's potential liability at all. [2 Haw. App. at 460-61, 634 P.2d at 129][3] We have carefully examined the records in this case and have reached the conclusion that the intermediate appellate court did not err in holding that HIG was sufficiently and seasonably notified. In our view, HIG received the required notice in March, 1975, when it received the Chung complaints against ASC and AAA.[4] Among the allegations against them was: [That] [D]efendants Air Service and DOES IV through VI, their agents, servants and employees, in inspecting, servicing, maintaining and repairing the subject *1349 aircraft, and in failing to detect and remove blockages and obstruction to the flow of fuel into the engines, and said defendants Air Service and DOES IV through VI were otherwise negligent and careless[.] [Emphasis added] The foregoing should have alerted HIG to the possibility that the refueler truck which was covered by its policy might have been involved. The vehicle was clearly listed in the insurance contract as a gas tank truck used by ASC in its aviation-connected activities which, of course, included the refueling of aircrafts. Contrary to HIG's contentions, the pleadings did not have to specifically mention the refueler truck or establish that the refueler truck was the cause of the accident. An insurer's duty to defend arises whenever there is a potential for indemnification liability of insurer to insured under the terms of the policy. Gray v. Zurich Insurance Company, 65 Cal.2d 263, 54 Cal. Rptr. 104, 419 P.2d 168 (1966). HIG being both their insurance agent and insurer, we think it was perfectly reasonable for ASC and AAA to rely upon HIG to exercise its good judgment in their behalf. They had the right to expect that their insurance company would make a determined effort to ascertain not only from the pleadings but also from the insurer's own independent investigation whether the insured were entitled to defense representation under the policy. For as the court in Spruill Motors, Inc. v. Universal Under. Ins. Co., 212 Kan. 681, 686, 512 P.2d 403, 407 (1973), has so aptly pointed out: [A]n insurer must look beyond the effect of the pleadings and must consider any facts brought to its attention or any facts which it could reasonably discover in determining whether it has a duty to defend... . [T]he duty to defend rests primarily on the possibility that coverage exists. This possibility may be remote, but if it exists the company owes the insured a defense. The possibility of coverage must be determined by a good-faith analysis of all information known to the insured or all information reasonably ascertainable by inquiry and investigation. The Chung complaint against its insured was submitted to HIG by letter, dated March 12, 1975. The allegations should have alerted HIG to the possibility of coverage under its policy. Trial of the consolidated cases was originally scheduled for February 16, 1976. It actually apparently commenced early in March, 1976. In these and the foregoing circumstances, we conclude that HIG was adequately and seasonably notified. Affirmed. NOTES [1] Further correspondence followed from the attorneys for SOCAL, ASC and AAA but no further written response was received from HIG. However, the affidavit of HIG's former senior claims supervisor, filed in support of HIG's motion for summary judgment, alleged: During the processing of the Plaintiffs' claims, your affiant on numerous occasions during the months of January through March, 1976 orally advised Plaintiffs' counsel that the claims and tenders of defense were made too late and that one of the principal bases for HIG's refusal to accept Plaintiffs' tenders of defense was the untimeliness of the tenders and the prejudice to HIG due to the late tenders. But as we earlier noted, the question before this court is whether the intermediate appellate court erred in concluding that notice had been given to HIG according to the terms of the insurance contract between the parties. [2] Subsequently, HIG unsuccessfully moved for summary judgment and reconsideration of plaintiffs-appellees' motions for summary judgment. [3] Actually, the pleadings to which the intermediate appellate court refers as evidencing potential liability were not the third-party complaints against ASC in Civil Nos. 40848 and 40849. Rather, it was the Chung complaint against ASC and AAA in Civil No. 44402 which should have alerted HIG to the potential coverage under its policy. [4] The fact that SOCAL was not brought in as a third-party defendant in the consolidated cases until some three months later does not affect the conclusion we have reached with respect to notice. For as the intermediate appellate court pointed out: "HIG was already on notice of the potentiality [of liability] with respect to the risk insured against and the joinder of an additional insured in the proceedings did not increase or change HIG's potential liability at all." 2 Haw. App. at 460-61, 634 P.2d at 129. See also Carter v. Aetna Casualty & Surety Co., 473 F.2d 1071 (8th Cir.1973) (discussing Arkansas law); Allstate Insurance Co. v. Moon, 89 A.D.2d 804, 453 N.Y.S.2d 467 (1982); 8 J. Appleman, Insurance Law & Practice, § 4738 (1981); 2 R. Long, The Law of Liability Insurance § 13.06 (1981). Moreover, this court has consistently construed insurance contracts in favor of the insured and against the insurer. See State Farm Mutual Auto Insurance Co. v. Bailey, 58 Haw. 284, 568 P.2d 1185 (1977); Masaki v. Columbia Casualty Co., 48 Haw. 136, 395 P.2d 927 (1964). See also St. Paul Fire & Marine Insurance Co. v. Hawaiian Insurance & Guaranty Co., 2 Haw. App. 595, 637 P.2d 1146 (1981). And as the court in Miller v. Marcantel, 221 So.2d 557, 559 (La. App. 1969) has pointed out: The function of the notice requirements is simply to prevent the insurer from being prejudiced, not to provide a technical escape-hatch by which to deny coverage in the absence of prejudice nor to evade the fundamental protective purpose of the insurance contract to assure the insured and the general public that liability claims will be paid up to the policy limits for which premiums were collected. Upon reviewing the record, we find that HIG suffered no prejudice by SOCAL's delay in forwarding the papers to HIG.

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Taking an Inside Look at the Lives of BodyBuilders February 6, 2018 9mo ago The sport of bodybuilding has changed dramatically from the days of Arnold Schwartznager. Generation Iron has been taking fans and viewers through the experience and giving viewers and consumers a first-hand look. Now, the franchise is working on a third installment, "Generation Iron 3." Edwin Mejia Jr. is the producer and Vlad Yudin director of "Generation Iron 3". The pair joins Cheddar to explain how this film will be different. "Generation Iron 3" takes the fans internationally to see the sport around the world including in China and India. The pair answer the question of what it takes to be a bodybuilder today. Mejia says it is more than just being able to pick up heavy things. He says that the successful bodybuilders are smart, humorous, and have charisma. It is also a lot about what you eat and when you eat.

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Predictably patchy portmanteau pic "7 Days in Havana" sutures together seven flimsy-to-outright bad shorts set across a week in Havana, to forgettable effect. Predictably patchy portmanteau pic “7 Days in Havana” sutures together seven flimsy-to-outright bad shorts set across a week in Havana, to forgettable effect. Given that part of the production coin came from rum-maker Havana Club and advertising outfit M&C Saatchi, it’s no surprise the pic plays like a product-placement exercise more suited to a corporate website than to the cinema. Events eager to snag guests are likely to bite, but despite its name helmers, the pic will stay embargoed within the fest circuit. Benicio del Toro’s daft opener finds Josh Hutcherson’s dim tourist hooking up with a transvestite. Pablo Trapero’s whatever segment has Emir Kusturica, as himself, befriending chauffeur/musician Alexander Abreu. Julio Medem’s embarrassing telenovela-like mini-meller features a Daniel Bruehl/Melvis Estevez/Leo Benitez love triangle. Elia Suleiman’s episode, in some ways the best, shows the helmer himself feeling lost in translation. Gaspar Noe’s take on a voodoo exorcism at least has style, while Juan Carlos Tabio’s comedy drama is visually flat. Laurent Cantet’s community comedy is cute but inconsequential. Vague coherence is created by all segs being similarly luridly colored and technically cheap-looking; even the music, an expected strong suit, underwhelms.

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Q: userInteractionEnabled disable all elements in cell I want to disable cell interaction. In my function: - (UITableViewCell *) tableView:(UITableView *)tableView cellForRowAtIndexPath:(NSIndexPath *)indexPath; I added Cell.userInteractionEnabled = NO; And cell interaction is disabled, but I want to leave active button (ButtonLabel). Cell.userInteractionEnabled = NO; Cell.ButtonLabel.userInteractionEnabled = YES; The above code does not work. It is strange, because inversly is ok: Cell.userInteractionEnabled = YES; Cell.ButtonLabel.userInteractionEnabled = NO; Button is disabled but cell no. How to make my button active while cell is disabled ? A: When you set userInteractionEnabled to NO on any instance of UIView (or its subclasses), it automatically disables user interaction on all its subviews. This is exactly the behaviour that you described. I think what you want to do is to disable selection on a UITableViewCell. There are several ways to do it: If you want to prevent selection on all cells altogether, you can just set tableView.allowsSelection to NO. If you want to prevent selection on certain cells only, do Cell.selectionStyle = UITableViewCellSelectionStyleNone; And you can also override - (NSIndexPath *)tableView:(UITableView *)tableView willSelectRowAtIndexPath:(NSIndexPath *)indexPath; and return nil for cells that shouldn't trigger selection action (but this alone won't prevent the selection highlight from appearing.) A: According to your comment, you want do disable push connection for specific cell. What you can do is check in shoudlPerformSegueWithIdentifier if that cell should perform. You need to save which was the cell touched, and then: -(BOOL)shouldPerformSegueWithIdentifier:(NSString *)identifier sender:(id)sender { if (/*check if the selected cell should perform the segue*/) { return YES; } return NO; }

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Dasyphyllum diacanthoides Dasyphyllum diacanthoides. Common names in Mapudungun: Trevo and Tayu and in Spanish Palo Santo ('holy tree') and Palo Blanco ('white tree') is a species of tree belonging to the family Asteraceae and endemic to Chile and Argentina. It occurs from Curico to Chiloe (35 to 42°S) between 200 and 800 m above sea level. It grows in both moist and shaded sites and more open and arid areas. Description D. diacanthoides is an evergreen tree or shrub reaching up to 15 m (50 ft) in height with a trunk which can reach a diameter of over 2 m (80 in). The genus Dasyphyllum, to which the species belongs, is unusual in being one of the few genera of Asteraceae to include species which are trees, rather than herbs or shrubs. The soft, thin, brown bark is deeply fissured with longitudinal cracks. The glossy, leathery, yellowish-green leaves, borne alternately, are elliptical in shape with entire margins, and acute apices bearing a single, terminal spine. They are 2–6 cm in length and 1-2.5 cm wide, glabrous on both surfaces and pubescent on the margins, the petioles are 1–4 mm in length. Provided with two thorns (modified stipules), deciduous at the base of the leaves, the flowers are clustered in inflorescences (terminal Flower heads) resembling the hard, scaly flower heads of the familiar, European wildflowers the knapweeds (also members of the Asteraceae). The flowers are white and hermaphrodite, 5 stamens with the anthers attached. The fruit is a cylindrical achene about 3-3.5 mm long and 1 mm wide, pubescent, reddish pappi 5 mm long. Etymology The genus name Dasyphyllum is a compound of the Greek elements δασύς ( dasus ) 'hairy' and φύλλον ( phyllon ) 'leaf', while the specific name diacanthoides means 'resembling (Greek suffix -ό-εἶδος (o-eidos) ) plants of the genus Diacantha ', the name of which is a compound of the Greek elements δύο ( duo ) 'two' and ἄκανθα ( acantha ) 'thorn' / 'spine'. The scientific name in its entirety thus means 'the hairy-leaved plant resembling the plant bearing spines in pairs'. [Note: Diacantha is a synonym of the genus Barnadesia - to which the genus Dasyphyllum is closely related.] Medicinal use and danger of confusion with Latua The bark of Dasyphyllum diacanthoides is highly esteemed in its native Chile as a folk remedy ( both topical and oral ) for blunt trauma. When not in flower, however, the plant is easily confused with the highly toxic Solanaceous species Latua pubiflora and this ease of confusion has been responsible for many cases of anticholinergic, tropane alkaloid poisoning by Latua in the Los Lagos Region of southern Chile to which both plants are native. One of his [ Philippi's informant Señor Juan Renous's ] woodcutters had suffered a strong blow with the blunt end of his axe and went into the forest to get some bark of tayu for it. He took instead latúe [ Latua ] and drank a concoction of this poison. He became insane almost immediately and wandered into the mountains. He was found three days later in an unconscious state. Several days were required for his recovery, although he suffered severe headaches for several months. Chemistry The unusual Asteraceae subfamily Barnadesioideae, to which the genus Dasyphyllum belongs, has yielded phenolic compounds, flavonoids and triterpenoids. References Category:Dasyphyllum Category:Chilean Matorral Category:Endemic flora of Chile Category:Trees of Chile Category:Trees of Mediterranean climate Category:Drought-tolerant trees Category:Trees of mild maritime climate Category:Medicinal plants

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MCP: A multi-component learning machine to predict protein secondary structure. The Gene or DNA sequence in every cell does not control genetic properties on its own; Rather, this is done through the translation of DNA into protein and subsequent formation of a certain 3D structure. The biological function of a protein is tightly connected to its specific 3D structure. Prediction of the protein secondary structure is a crucial intermediate step towards elucidating its 3D structure and function. Traditional experimental methods for prediction of protein structure are expensive and time-consuming. Nevertheless, the average accuracy of the suggested solutions has hardly reached beyond 80%. The possible underlying reasons are the ambiguous sequence-structure relation, noise in input protein data, class imbalance, and the high dimensionality of the encoding schemes. Furthermore, we utilize a compound string dissimilarity measure to directly interpret protein sequence content and avoid information loss. In order to improve accuracy, we employ two different classifiers including support vector machine and fuzzy nearest neighbor and collectively aggregate the classification outcomes to infer the final protein structures. We conduct comprehensive experiments to compare our model with the current state-of-the-art approaches. The experimental results demonstrate that given a set of input sequences, our multi-component framework can accurately predict the protein structure. Nevertheless, the effectiveness of our unified model can be further enhanced through framework configuration.

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Atari has renamed its upcoming Ataribox console as the Atari VCS, which is a retro-inspired entertainment platform based on PC technology. The iconic video game brand is showing off the latest version of the box at the Game Developers Conference in San Francisco, where 25,000 developers are gathering this week. Atari said the machine, which an exclusive GamesBeat story originally described last year, takes inspiration from 40 years of video game history. The company is showing off the Atari VCS, Classic Joystick, and Modern Controller prototypes to the press this week at GDC. And it is working with game developers, content creators, and other partners to finalize details. In April, Atari will announce a preorder date for the Atari VCS. Earlier, Atari canceled a crowdfunding campaign on Indiegogo because its development hit a snag. Image Credit: Atari Inspired by the memorable silhouette of the original Atari 2600 Video Computer System, the new Atari VCS design had previously generated excitement within the gaming community. “Every person at Atari and every partner involved with the new platform is just as fanatical about the brand and its heritage as our biggest fans are,” said Atari Connected Devices chief operating officer Michael Arzt in a statement. “With the Atari VCS name, we know how important it is to get everything completely right, and that’s why we briefly paused an imminent launch late last year. It was a difficult decision with the countdown underway, but we weren’t willing to go forward with even one thing out of alignment. We hope that despite the delay, Atari’s fans appreciate our extreme attention to detail and are as excited about the Atari VCS as we are.” Image Credit: Atari The latest design has a blend of modern lines and classic details, which the designers hope evoke positive reactions from Atari fans. The VCS will serve up lots of classic content, but it is so much more than a “retro-box.” It is a new connected device designed for today’s living room, the company said. The new Atari VCS logo, like the hardware itself, combines past and present, drawing inspiration from Atari’s rich history of progressive graphic design from the 1970s and 1980s. The company said it paid careful attention to the industrial design and graphics for the box. Atari didn’t offer more details on the pricing, components, or other details. It did, however, say earlier that the box would sell for $250 to $300 and include an Intel-based processor running Linux. Image Credit: Atari Atari has licensed other consoles to use its name, but the last time it shipped its own console was the Atari Jaguar in 1993.

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Q: Render a full UIImageView to a bitmap image I know how to render a normal UIView to a bitmap image: UIGraphicsBeginImageContextWithOptions(view.bounds.size, NO, 0.0); [view.layer renderInContext:UIGraphicsGetCurrentContext()]; UIImage *bitmapImage = UIGraphicsGetImageFromCurrentImageContext(); UIGraphicsEndImageContext(); The problem is that if view is a UIImageView with a stretched resizable image returned from resizableImageWithCapInsets:, bitmapImage gotten this way is the original image — the un-stretched one — instead of the really displayed stretched image. I can easily tell that by the size difference between bitmapImage and view. So my question is how to render the full content displayed by a UIImageView whose image is a stretched resizable image? A: I'm an idiot! The code is perfectly working. I just messed up something somewhere else. The stupid thing is that I put the code in a method of my UIView category but I named the method image. It works perfectly for general UIViews, but as UIImageView has its own image method and UIImageView is a subclass of UIView, UIImageView's image method is called when I tried to get my bitmap image.

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Protection of platelets during long-term extracorporeal membrane oxygenation in sheep with a single dose of a disintegrin. Both short- and long-term extracorporeal membrane oxygenation (ECMO) causes platelet loss and dysfunction. Bitistatin is a reversible inhibitor of the platelet glycoprotein IIb/IIIa receptor. This study tests the hypothesis that inhibition of platelets by bitistatin during initial contact with the perfusion circuit preserves platelet number and function during long-term ECMO in sheep. Bitistatin, purified from crude snake venom, was tested for its effect on platelet count, responsiveness to ADP, release of platelet factor 4, and prevention of surface-adsorbed glycoprotein IIIa in vitro and during 24 hours of ECMO in nine splenectomized sheep. During simulated extracorporeal circulation, 0.5-1.0 microgram/ml bitistatin significantly prevented platelet adhesion, attenuated release of sheep platelet factor 4, and preserved platelet responsiveness to ADP. During ECMO at 1.8 l/min for 24 hours, a single dose of bitistatin (200 micrograms/kg) (n = 4) produced higher platelet counts (p = 0.0002) and suppressed release of platelet factor 4 (p = 0.035) for 16 hours compared with five control animals. This dose of bitistatin caused an immediate inhibition of platelet aggregation; however, between 4 and 24 hours of perfusion, platelets of bitistatin-treated animals were more responsive to ADP (p < 0.0001) compared with platelets in control animals. The amount of glycoprotein IIIa antigen extracted by Triton X-100 from the perfusion circuits was reduced in bitistatin-treated sheep. A single dose of bitistatin given before blood contact with the ECMO circuit briefly inhibits platelet adhesion and aggregation but thereafter preserves platelet numbers and function and suppresses alpha-granule release for 12-16 hours of ECMO.

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Sunday, February 10, 2013 Back from Israel Drew got home safe and sound from Israel on Thursday afternoon. He has hardly been awake since. Just kidding. He has been tired but he had a great time. As for the beginning of the week without him, Mimo had gone home for the weekend and so I got the kids up and to school Monday morning. Mimo headed back Monday morning and picked them up from my office and took them to lunch. Then I met her at PT and grabbed Lindy and we headed inside. Lynn and Will went to Old Salem and brought home some yummy treats from the bakery. They had wanted to walk around but it was too cold and windy to be outside long. Lindy did really well in PT. She worked pretty hard and did well. She got to roller skate for the first time ever. But just with one roller skate on. We put it on her better foot and it supposedly made her other, weaker foot work harder. She just thought it was cool! Tuesday Lynn picked the kids up from school and took them to gymnastics. She said they got to use these ribbons that were attached to rings. She said Lindy did what she was supposed to, after she made a fashion accessory out of the ring and ribbon. Apparently she had her arm through the ring and the ribbon wrapped around herself. Wednesday Lynn picked the kids up and brought them home for lunch and then took them to Sci Works. The kids had a blast. I hear Lindy had fun drilling in the dentist/teeth area and they both had fun on the racers. She bought us a pass for four more trips so we are all looking forward to more time at Sci Works! Thanks, Lynn! Thursday was Drew’s coming home day! Lynn picked the kids up and made welcome home signs for Drew. Drew got home around 3pm. I got home around 5pm to see him. He got the best souvenirs ever! Pretty scarves and necklaces and lotion from the Dead Sea. It was like Christmas in February! We ate dinner with Lynn and then I took the kids to choir practice and Lynn headed home. Apparently Drew headed for the couch and fell asleep. He was asleep when we got home an hour later and he never work up the rest of the night! The 7 hour time difference has been hard for him to adjust to. The only thing we did this weekend was go to our first Wake Forest basketball game of the season. Katie had a couple extra free tickets and we picked up two cheap tickets outside the doors. It was a great game to see as the Deacs played really well. Poor Lindy can’t see much so she got to play on my phone. Will paid attention for a long time but then he and Micah started playing Kris’ phone and that was more interesting to him. It was a fun afternoon. Today we had church and I had a UMW meeting and then the kids and I made their Valentines for the party this week at school. It took us most of the afternoon but we got them finished. Will has finally stopped talking about smoke detectors so much. He did mention it tonight and was asking if we had them in the bathrooms. He has gone to bed fine all week but he has been waking up super early in the mornings. He wants his Valentine’s lights on. He does go back to sleep but he hasn’t slept past 7am until this morning when he finally slept until 7:30am. Hopefully we are on the right track to sleeping longer again in the mornings. I do want to give a huge shout out to Lynn for staying with us the last 8 days. I couldn’t have handled Drew being gone for 10 days by myself. She was a huge help and the kids had a blast with her. I’m not sure they actually missed Drew because they were very excited to have Mimo around so much. I’m very thankful she could come stay with us! Thanks, Lynn! As for pictures, I just realized I didn’t get a picture of Mimo this week either. How is that possible? Here 8 days and no picture? Most of these pictures are from her cell phone as I haven’t been taking many pictures lately. I think my girl looked adorable last Monday. Love this outfit!He looked good, too!Trying to get a picture together usually ends up like this.Roller skating!I could do a whole post of Lindy sleeping pictures. I always find her in crazy positions.On the way to school one day she looked so bored!He was happy though!The Valentine decoration I made. Mimo treated the kids to yogurt after gymnastics twice while she was here. Hope they don’t expect that from us!More sleeping pictures!Playing at Sci Works!At the Wake game yesterday! Go Deacs!My Valentine girl today!My Valentine boy today.Working hard on their class Valentines!

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A cluster-based approach for semantic similarity in the biomedical domain. We propose a new cluster-based semantic similarity/distance measure for the biomedical domain within the framework of UMLS. The proposed measure is based mainly on the cross-modified path length feature between the concept nodes, and two new features: (1) the common specificity of two concept nodes, and (2) the local granularity of the clusters. We also applied, for comparison purpose, five existing general English ontology-based similarity measures into the biomedical domain within UMLS. The proposed measure was evaluated relative to human experts' ratings, and compared with the existing techniques using two ontologies (MeSH and SNOMED-CT) in UMLS. The experimental results confirmed the efficiency of the proposed method, and showed that our similarity measure gives the best overall results of correlation with human ratings. We show, further, that using MeSH ontology produces better semantic correlations with human experts' scores than SNOMED-CT in all of the tested measures.

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Background {#Sec1} ========== Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract. Although the etiology of IBD remains poorly understood, IBD pathogenesis is reportedly associated with dysfunction of the intestinal epithelial barrier and alteration of intestinal microbiota \[[@CR1]\]. Impaired epithelial barrier results in increased intestinal permeability to harmful bacteria and other antigens, leading to chronic immune response. Indeed, increased intestinal permeability is reported in IBD patients \[[@CR2]\]. This indicates that dysfunction of epithelial barrier is likely an initial event before onset or recurrence of IBD. Intestinal epithelial permeability is regulated by tight junction complex \[[@CR3]\]. Several studies have observed structural abnormalities in tight junction complexes, including down-regulation of ZO-1, Occludin and Claudin-1, in IBD patients as a cause of altered intestinal permeability \[[@CR4]\]. Therefore, modulation of intestinal permeability is a highly regarded target for novel therapeutic treatment against IBD. In addition to alterations in tight junction complex integrity, gut microbiota is critical players in intestinal permeability. An imbalance between beneficial and pathogenic bacteria is involved in IBD pathogenesis \[[@CR1]\]. Soybeans (*Glycine max*) are good sources of isoflavonoids (genistein and daidzein), which are bioactive components that have beneficial activity on health. They are known for anti-inflammatory, anti-cardiovascular, and anti-obesity activities \[[@CR5]\]. Barley (*Hordeum vulgare*) is a major part of the diet as cereal. B-glucan, an active constituent of barley, has been reported to show anti-inflammatory and anti-cancer effects \[[@CR6]\]. In our previous study, we developed a fermented barley and soybean mixture (BS) that increased production of β-glucan and isoflavonoids (genistein and daidzein). We showed that BS components produced significant protective effects against UVB-induced photoaging. Until now, it has been no report about the protective activity of BS on intestinal barrier function. In this study, we investigated whether BS protects the epithelial barrier and, if so, whether changes in tight junction protein expression and composition of microflora contribute to this effect. To answer these questions, mice with DSS-induced colitis were treated with BS, and epithelial permeability, tight junction protein expression, and fecal bacteria alteration were assessed. Methods {#Sec2} ======= Reagents {#Sec3} -------- DSS (MW 36--50 kDa) was purchased from MP Biomedicals LLC (Santa Ana, CA, USA). DMEM, fetal bovine serum (FBS), penicillin (100 unit/mL) and streptomycin (100 μg/mL) were obtained from Welgene, Inc. (Daegu, Korea). The following antibodies were used in these studies: anti-ZO-1, anti-Occludin, anti-Claudin-1, IL-6 (Thermo Scientific, Grand Island, NY, USA), and GAPDH (Santa Cruz, CA, USA). Fermented barley and soybean (BS) were obtained from Sempio Fermentation Research Center (Osong, Korea). Barley (Hordeum vulgare) was cultivated by the agricultural Technology Center of Yeonggwang-gun, Jeollanam-do, and Republic of Korea. Soybean (Glycine max (L.) MERR) was supplied by Sempio Foods Company (Seoul, Korea). Voucher specimens were deposited in the herbarium at the R&D Center of Sempio Foods Company. Briefly, fermentation was performed using enzymatically hydrolyzed barley (40 g/L) and soybean (40 g/L) mediums. The medium was autoclaved and pH was adjusted to 7.0 with 2 M ammonia solution. The pre-cultured yeast, P. jadinii (KFCC 11487P), was inoculated into the enzymatically hydrolyzed barley and soybean. Fermentation was respectively conducted at 30 °C with shaking at 20 × g for 48 h in a 5 L bioreactor, and samples were dried and stored at −18 °C \[[@CR7]\]. BS powder was dissolved in phosphate buffered saline (PBS) and then was stored at −20 °C. In vitro DSS treatment {#Sec4} ---------------------- Human colon carcinoma cell line (Caco-2) was obtained from the Korea Cell Line Bank (Seoul, Korea). Cells were grown at 37 °C in DMEM supplemented with 10% FBS, penicillin and streptomycin in a humidified atmosphere of 5% CO~2~. To test the effect of BS on DSS-treated Caco-2 cells, cells were seeded onto 12-well plates (SPL Life Science, Pocheon, Korea). After reaching 90--100% confluency, the Caco-2 cell monolayers were allowed to differentiate for an additional 14 days. Fully differentiated cell monolayers were incubated with or without 2% DSS in the absence or presence of 100, 200, and 400 μg/mL BS for 48 h. DSS was dissolved in culture media and filter-sterilized using a 0.45-μm filter \[[@CR8]--[@CR10]\]. Immunofluorescence assay {#Sec5} ------------------------ Cells grown on glass coverslips and frozen tissues were fixed and permeabilized in methanol or acetone at −20 °C. Cells or tissues were incubated with primary antibodies overnight at 4 °C, followed by incubation with FITC-labeled secondary antibody for 1 h at room temperature. Sections were then mounted with mounting medium containing 4, 6-diamidino-2-phenylindole (DAPI) for nuclear counterstaining. Images were observed by fluorescence microscopy. FITC and DAPI images were taken from the same area. Western blot analysis {#Sec6} --------------------- Whole cell and detergent-insoluble fractions were prepared as described previously \[[@CR11]\]. Briefly, whole cell protein lysates and detergent-insoluble fractions were prepared in a modified RIPA buffer containing proteinase inhibitors and phosphatase inhibitors as described elsewhere \[[@CR12]\]. Homogenates were spin down at 12,000 rpm at 4 °C for 20 min. Supernatants were collected for whole cell lysates and the pellets used as detergent-insoluble fractions. The pellets were dissolved in 0.1% SDS. Protein concentration of each samples was determined using BCA reagents (Thermo Scientific). Equivalent amounts of protein (20--80 μg) were loaded in 10% or 12% sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS--PAGE) gels and transferred by blotting to polyvinylidene fluoride membranes. The blot was incubated with primary antibodies against human ZO-1, Occludin, Claudin-1, or GAPDH. After washing, the blot was incubated with HRP-conjugated secondary antibodies. The protein--antibody complexes were detected by Absignal (Abclone, Seoul, Korea) according to the manufacturer's recommended protocol. Animal study {#Sec7} ------------ Six-week-old female C57BL/6 mice (weighing 20 ± 2 g) were received from the Orient Co. (a branch of Charles River Laboratories, Seoul, Korea). The mice were housed in a specific pathogen free (SPF) animal facility and acclimated under the conditions of 22 ± 2 °C, 40--60% relative humidity, and 12 h light/dark cycle for 7 days. Mice were divided into 4 groups of 5 mice each. The first group was vehicle-treated control and the second group was given drinking water with DSS only. The third and fourth groups of mice were treated with BS (100 and 200 mg/kg/day) through oral gavage for 3 days, then exposed to 5% DSS in their drinking water for 7 days to induce colitis. After DSS treatment, BS treatment groups were additionally administered BS for 4 days according to the experimental design. The study used the animal model to study the effects of fermented barley and soybean mixture during inflammation. In vivo permeability assay {#Sec8} -------------------------- In vivo permeability assay was performed to assess barrier function using fluorescein isothiocyanate dextran (FITC-D). For each experiment, mice were divided into 4 groups of 5 mice each. The first group was vehicle-treated control and the second group was given drinking water with DSS only. The third and fourth groups of mice were treated with BS (100 and 200 mg/kg/day) through oral gavage for 3 days, then exposed to 5% DSS in their drinking water for 7 days to induce colitis. Briefly, food and water were withdrawn for 4 h, and mice were inoculated with FITC-D by oral gavage (20 mg/kg). After 4 h, mice serum was collected and fluorescence intensity was measured (excitation, 492 nm; emission, 525 nm). Detection of viable bacteria in mesenteric lymph nodes (MLNs) represented bacterial translocation from the lumen to the MLNs. The MLNs of left colonic regions were removed aseptically and were put into eppendorf tubes with 0.1-mL sterilized PBS and tissues were homogenized by micro grinder (RPI, Mount Prospect, IL, USA). The homogenates were plated on blood agar (Thermo Fisher Scientific, Lenexa, KS, USA) and incubated for 48 h at 37 °C. The number of colonie was counted and the ratio of bacterial translocation was presented for percentages. Semi-quantitative RT-PCR and quantitative PCR (qPCR) with 16S rRNA for specific species {#Sec9} --------------------------------------------------------------------------------------- For semi-quantitative RT-PCR, 1 μg of RNA was used as a template for reverse-transcription using the Prime Script 1'st strand cDNA Synthesis kit (Takara; Kyoto, Japan). PCR was carried out with 20 ng of cDNA using a PCR pre-mixture (Takara). RT-PCR was performed to amplify genes using a cDNA template corresponding to gene-specific primer sets. The primer sequences used are as follows. Primer sequences are listed in the Additional file [1](#MOESM1){ref-type="media"}: Table S1. Fecal samples were collected before necropsy and immediately frozen in liquid nitrogen. Bacterial genomic DNA was extracted from fecal samples using a Wizard genomic DNA purification kit (Promega, Madison, WI, USA) according to the manufacturer's instructions. The abundance of specific intestinal bacterial groups was measured by qPCR. Genus- or species-specific 16S rRNA gene primers were used as described previously \[[@CR13]\]. Primer sequences are listed in the Additional file [1](#MOESM1){ref-type="media"}: Table S2. 16S rRNA of Eubacteria was used as a housekeeping gene. Statistical analysis {#Sec10} -------------------- The results are analyzed by one-way analysis of variance (ANOVA) and differences were considered statistically significant at level of *p*-values \< 0.05. Results {#Sec11} ======= The effect of BS on the structure of tight junction complexes in vitro {#Sec12} ---------------------------------------------------------------------- Since Caco-2 is an intestinal epithelial cell line and forms a monolayer when cultured to 100% confluence, it is broadly used as a model of the intestinal barrier \[[@CR14]\]. To study the protective efficacy of BS in the epithelial barrier, the Caco-2 cell line was used. When the cells were incubated with DSS, the expression of tight junction proteins such as ZO-1, and caludin-1 was decreased. BS treatment dose-dependently recovered the loss of tight junction proteins in DSS-treated Caco-2 monolayer (Fig. [1a and b](#Fig1){ref-type="fig"}). Consistent with this, immunostaining with anti-ZO-1, Occludin and Claudin-1 showed that tight junction in DSS-induced monolayer was markedly disrupted, but treatment with BS protected tight junction complex from DSS-induced damage (Fig. [1c](#Fig1){ref-type="fig"}). These data suggest that BS might contribute maintenance of epithelial barrier integrity by preserving tight junction proteins. However, BS single treatment doesn't enhanced expression of tight junction proteins (Additional file [2](#MOESM2){ref-type="media"}: Figure S2).Fig. 1The effect of BS on the structure of tight junction complexes in vitro. (**a** and **b**) Immunoblot analysis of tight junction proteins in the detergent-insoluble fractions. **c** Immunofluorescence of ZO-1, Occludin, and Claudin-1 in Caco-2 cell monolayers incubated with 2% DSS in the absence or presence of indicated concentrations of BS for 48 h. Images were collected by confocal microscopy. Magnification x600 BS prevents symptoms of DSS-induced colitis in mice {#Sec13} --------------------------------------------------- To evaluate the therapeutic effect of BS on DSS-induced colitis, we investigated the ability of BS to ameliorate DSS-induced colitis by assessing body weight, disease activity index (DAI), and colon length and by performing histological analysis. We found that BS (200 mg/kg) treatment relieved the loss of body weight from day 12 to day 15, compared to the group treated with DSS only (Fig. [2a](#Fig2){ref-type="fig"}). Following induction of colitis, the BS treatment reduced DAI scores compared with only DSS treatment (Fig. [2b](#Fig2){ref-type="fig"}). In addition, while colon length was decreased in the DSS group compared with vehicle group, BS mitigated this shortening of colon length (Fig. [2c](#Fig2){ref-type="fig"}). Colon tissues were histologically analyzed to evaluate DSS-induced inflammation and epithelial damage. We found that DSS-treated mice exhibited acute colitis with severe inflammation and crypt damage. These changes were reduced by treatment with BS (Fig. [2d](#Fig2){ref-type="fig"}). In addition to macroscopic changes, production of pro-inflammatory cytokines is also important in the development of IBD \[[@CR15]\]. Therefore, we investigated the effect of BS on pro-inflammatory cytokine production in the DSS-induced colitis model by using RT-PCR. We found that BS (200 mg/kg) significantly reduced DSS-induced mRNA levels of TNF-α, IL-1β, IL-6, and IL-12p40 in colonic tissues (Fig. [2e](#Fig2){ref-type="fig"}). At the same time, BS treated mouse showed a lower level of expression of the IL-6 in the inflamed colon (Additional file [2](#MOESM2){ref-type="media"}: Figure S4). These results indicate that the BS treatment diminished the severity of DSS-induced colitis. Moreover, nutrient supplementation leads to beneficial effects in a DSS-induced colitis model. We included LPS-induced colitis models to confirmed therapeutic activity of BS. We included Additional file [2](#MOESM2){ref-type="media"}: Figures S1 to demonstrate that activity of BS on LPS-induced colitis models. We found that BS (200 mg/kg) treatment relieved DAI scores compared with LPS treatment (Additional file [1](#MOESM1){ref-type="media"}: Figure S1A) and reduced LPS-mediated tissues damage (Additional file [1](#MOESM1){ref-type="media"}: Figure S1B).Fig. 2BS attenuated the progression of DSS-induced colitis. **a** Mice body weight was measured every other day for evaluation of BS efficacy on DSS-induced colitis, and was shown as percentage of weight change. **b** DAI and (**c**) colon length were evaluated. **d** Representative H&E stained histology from vehicle, 5% DSS, and BS-treated groups. Magnification: ×100 (*upper*), ×200 (*lower*) (**e**) Expression of pro-inflammatory cytokines in colon was assessed by semi-quantitative RT-PCR. Statistically differences were analyzed with one-way ANOVA. The data are presented as mean ± SD of triplicate experiments. \**p* \< 0.05 and \*\**p* \< 0.01 vs 5% DSS-treated group BS prevented DSS-induced disruption of tight junction complexes and loss of tight junction proteins {#Sec14} --------------------------------------------------------------------------------------------------- To investigate the protective effect of BS against DSS-induced disruption of tight junction, we examined the expression and organization of tight junction proteins including ZO-1, Occludin and Claudin-1 using immunofluorescence assay and Western blotting. Immunofluorescence assays demonstrated considerable loss of ZO-1, Occludin, and Claudin-1 in tight junction complexes of the DSS-treated group and structural discontinuities in their architecture, in the inner lining of the colonic epithelium. Interestingly, BS treatment significantly prevented the loss of tight junction proteins, ZO-1, Occludin, and Claudin-1 in tight junction complexes of colonic epithelial cells (Fig. [3a](#Fig3){ref-type="fig"}).Fig. 3Effect of BS on colonic epithelial tight junctions proteins. **a** Expression of ZO-1, Occludin and Claudin-1 was examined by immunostaining using anti-zo-1 (*green*), anti-Occludin (*green*), and anti-Claudin-1 (*green*) antibodies in vehicle, DSS, and BS-treated groups. Magnification: ×600. **b** Expression of TJ proteins in the colon was assessed by Western blot To extend our observations of dramatic changes in tight junction proteins, we conducted Western blotting using colon tissues. Compared with the control group, there were significant reductions in the expression of Occludin and Claudin-1 in the DSS-treated group. In contrast, total protein level of ZO-1 remained unchanged. This indicates that the loss of Occludin and Claudin-1 at colonic epithelial tight junctions of DSS-treated mice was paralleled by quantitatively reduced protein expression (Fig. [3b](#Fig3){ref-type="fig"}). This might indicate a redistribution of existing proteins to the basolateral membrane. On the other hand, expression of tight junction proteins in BS-treated groups was significantly higher than in the DSS-treated group (Fig. [3b](#Fig3){ref-type="fig"}), suggesting that BS may play an important role in maintaining the integrity of tight junction complexes. BS prevented increased colonic epithelial permeability in DSS-induced colitis {#Sec15} ----------------------------------------------------------------------------- To determine the effect of BS on epithelial permeability, we analyzed intestinal permeability in DSS-induced colitis model. To that end, the level of bacterial translocation was measured (Fig. [4a](#Fig4){ref-type="fig"}). Compared with control group, a significant increase of bacterial translocation into the MLNs was observed in the DSS-treated group. Interestingly, the bacterial translocation was completely prevented by administration of BS. We also measured FITC-D permeability in order to determine if BS treatment prevented disruption of epithelial barrier function induced by DSS treatment (Fig. [4b](#Fig4){ref-type="fig"}). Mice in DSS-treated group had elevated levels of FITC-D in serum, compared with those in the control group. Administration of BS reduced FITC-D serum levels compared with that in the DSS-treated group. These results show that BS decreased epithelial permeability, suggesting that BS treatment prevented gut leakiness to a greater extent.Fig. 4BS suppressed epithelial permeability and increased microbiota quantity in DSS-induced colitis model. **a** colony number of viable bacteria in MLNs, (**b**) Relative level of serum FITC-D, (**c**-**e**) fecal microbiota composition were shown in vehicle, DSS, and BS-treated groups; (**c**) *Lactobacilli*, (**d**) *Faecalibacterium prausnitzii*, and (**e**) *Bacteroides*. Statistically differences were analyzed with one-way ANOVA. The data are presented as mean ± SD of triplicate experiments. \**p* \< 0.05 and \*\*\**p* \< 0.01 vs 5% DSS treated group BS regulated composition of fecal microflora in DSS-induced colitis mouse model {#Sec16} ------------------------------------------------------------------------------- Gut microbiota are increasingly recognized as important players in intestinal permeability. The balance between beneficial and pathogenic bacteria plays a central role in the mucosal immune response in IBD. We investigated whether BS treatment changes the composition of microflora through analysis of feces (Fig. [4c-e](#Fig4){ref-type="fig"}). In this study, we observed that the quantity of bacteria associated with anti-inflammatory responses, such as *Bacteroides spp*., *Faecalibacterium prausnitzii*, and *Lactobacillus spp*., was diminished in fecal samples from the DSS-treated group compared with control group. Although contents of *Bacteroides* and *Faecalibacterium prausnitzii spp.* did not change, BS treatment prevented the decrease of *Lactobacillus spp*., suggesting that BS might contribute to the improvement of gut immune and barrier function by altering intestinal microbiota, which play a significant role in anti-inflammation. Discussion {#Sec17} ========== Although some medicines such as 5-aminosalicylic acid have been developed to treat IBD, they are not effective enough to cure it. Moreover, most of the drugs currently used to treat IBD have untoward effects. Therefore, there is a growing need to develop efficient and safe treatments for IBD. Consequently, traditional medicinal plants, herb, vegetables and their secondary metabolites are considered to be alternative treatment strategies for IBD \[[@CR16]\]. Many studies have reported that various food supplements provide many beneficial effects in the gut. β-glucan, produced by barley and oat, is known to have anti-inflammatory properties \[[@CR17]\]. Dietary β-glucan is also effective to treat IBD \[[@CR18], [@CR19]\]. Genistein and daidzein, the active isoflavonoids mainly found in soybean, are also known to have anti-inflammatory effects in a colitis-induced mouse model \[[@CR20], [@CR21]\]. In addition, genistein has protective effects on intestinal barrier function by regulating tight junction \[[@CR22]\]. Although these natural products contain many beneficial bioactive substances, there are some limits in terms of efficacy. Several studies have demonstrated that fermentation of the natural products improved biological activities \[[@CR23]\]. Therefore, in order to enhance the beneficial effects of soybean and barley, we increased the activity of β-glucans, daidzein and genistein in barley and soybean by yeast fermentation. Recently, experimental and clinical studies suggest that disruption and reassembly of tight junction is an important determinant of IBD \[[@CR24], [@CR25]\]. Our data show that BS treatment prevents DSS-induced redistribution or loss of tight junction proteins like ZO-1, Occludin, and Claudin-1 in Caco-2 monolayer. To elucidate the anti-colitis potency of BS in IBD, we used a DSS-induced colitis model. Our findings show that BS suppresses symptoms of DSS-induced colitis such as body weight loss, colon length shortening, bloody feces and stool consistency. BS treatment also reduced the DSS-induced expression of anti-inflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-12p40. The reduction in pro-inflammatory cytokines by BS may either be due to its direct suppressive effect on the expression of these pro-inflammatory cytokines or the indirect effect on epithelial barrier function. Once the epithelial barrier is damaged, foreign luminal antigenic products are able to cross the epithelial barrier and activate the immune system. Therefore, in addition to anti-inflammatory effects, we investigated the effect of BS on epithelial barrier function in DSS-induced colitis. Consistent with the in vitro experiment, we showed that BS administration recovered expression or distribution of tight junction proteins, ZO-1, Occludin, and Claudin-1, in DSS-induced colitis. Furthermore, BS reduced epithelial barrier permeability in DSS-induced colitis, as demonstrated by suppression of FITC-D uptake and bacterial translocation into MLN. Our data showed that BS might have a protective effect on barrier integrity by maintaining the expression of tight junction proteins, thereby reducing the severity of colitis. Accumulating evidence indicates that commensal bacteria are responsible for various physiological functions and are associated with immune-enhancing effects in the gut \[[@CR26]\]. Several studies have suggested a critical role of microbial imbalances in the pathogenesis of IBD \[[@CR27]\]. In IBD patients, the quantity of commensal bacteria in the intestine is reduced, and the diversity of the microbiota is also altered \[[@CR1]\]. It was reported that *Bacterioidetes*, *Lactobacillus spp*. and *Faecalibacterium prausnitzii* are reduced in IBD patients \[[@CR28]\]. Therefore, we analyzed the change of intestinal bacteria composition by using fecal DNA. We observed that *Lactobacillus spp*. was reduced in DSS-treated group, but BS administration prevented alteration of the bacterial composition. Conclusions {#Sec18} =========== In summary, our data suggest that BS is effective for the amelioration of DSS-induced acute colitis, recovering epithelial barrier function and regulating the gut microbiota community. Additional files {#Sec19} ================ Additional file 1: Table S1.Primer sets used for semi-quantitative PCR of cytokines. **Table S2.** Primer sets used for quantitative PCR of 16S rRNAof specific species or genus. (PDF 105 kb) Additional file 2: Figure S1.BS promotes recovery from LPS-induced colitis and inflammation in mice. (A) DAI of LPS (LPS, 5 mg/kg of mouse by Intra-peritoneal injection) treated mice were scored. (B) Representative H&E stained histology from Control and BS-treated groups and statistical results. Mean value was significantly different from that of the LPS treated control group (\**P* \< 0.05). BS, Fermented barley and soybean, DAI, disease activity index. LPS, Lipopolysaccharide. **Figure S2.** Basal intestinal barrier function in BS treatment. (A) Immunofluorescence of ZO-1 in Caco-2 cell monolayers incubated with BS for 48 h and images were collected by confocal microscopy. (B) RNA levels of ZO-1, Claudin1, and Occludinin BS treated Caco-2 cells measured by semi-quantitative RT-PCR. (C) BS treated mouse colon tissues were used to determine ZO-1, Claudin1 and Occludindistribution by immune fluorescence staining and images were collected by confocal microscopy. BS, Fermented barley and soybean. **Figure S3.** Effect of BS on the suppression of NF-κBactivity. (A) Western blot analysis of p65 nuclear trans-localization levels in the protein fractions of RAW 264.7 lysates. (B) The effects of BS on a NF-κBreporter assay in HEK 293 cells that were activated by the addition of LPS. The luciferase activity was measured as relative light intensity, using a plate reader in the luminescence mode. BS, Fermented barley and soybean, LPS, Lipopolysaccharide. **Figure S4.** Immunohistochemicalstaining of IL-6 in sections from BS treated mouse colon. BS, Fermented barley and soybean. (PDF 563 kb) BS : Fermented barley and soybean CD : Crohn's disease DSS : Dextran sulfate sodium FITC-D : Fluorescein isothiocyanate dextran IBD : Inflammatory bowel disease MLN : Mesenteric lymph nodes This research was supported by the Sempio fermentation research center-2013, High Value-added Food Technology Development Program 114006-04, Ministry of Agriculture, Food and Rural Affairs, and the National Institute of Biological Resources (NIBR), funded by the Ministry of Environment (MOE) of the Republic of Korea (NIBR201627201). We sincerely thank Myeong A Seong for her help with the animal studies. Availability of data and materials {#FPar1} ================================== The datasets supporting the conclusions of this article are included within the article. Authors' contributions {#FPar2} ====================== JKW and SHO developed the study aim and experimental design, performed data acquisition and analysis drafted the manuscript. SHC and JHK performed in vivo data acquisition. DEK, BSH and JEJ provided fermented barley and soybean and assisted with data analysis. SYK performed data acquisition and assisted with data analysis. SHO supervised the entire study and manuscript preparation. All authors read and approved the final manuscript. Competing interests {#FPar3} =================== The authors declare that they have competing interests. Consent for publication {#FPar4} ======================= Not applicable. Ethics approval {#FPar5} =============== All animal procedures were performed according to the approved protocol \[LCDI-2013-0045\] and institution recommendations for the proper use and care of laboratory animal, CACU (Center of Animal Care and Use), College of Pharmacy, Gachon University.

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-Kanrabat- wrote: The only reason to buy this TLK Optimus is to not already own the normal release. Because appart the weapons, the differences are negligible. Negligible?There are many, many more paint apps on the exclusive, especially in the arms and legs. Plus he has chest flames and a slightly better (but still too blue) looking head. Overall it's far and a way a better looking figure.I'm thinking of getting it, but I also feel like a better version could come as a Platinum edition later, but would require me to buy other figures I don't want.Emerje

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Religion Does Make a Difference, FairMormon Speaker Says Contributed By R. Scott Lloyd, Church News staff writer Article Highlights Far from being an illness, religious faith is a cure for many of society’s problems. Religion can be a powerful force for good in the world, in society at large, and in the lives of individuals. “Churches are almost the only element in society to have offered considerate, caring, long-lasting, and self-sacrificing support to the mentally ill.” —Andrew Sims, professor of psychiatry, University of Leeds Related Links FairMormon Speaker Says History Skills Can Strengthen Study of Book of Mormon Witnesses Many years ago, Daniel C. Peterson corresponded with a young returned LDS missionary who denounced the Church for allegedly lying about its history and Peterson for his alleged role in defending the lies. “I tried to persuade him that he was wrong,” Peterson said in his August 4 address at the FairMormon Conference. “He remained hostile, and it was easy to see that he was deeply troubled.” At length, the man’s messages stopped abruptly and, upon investigation, Peterson learned to his horror that the correspondent had killed himself with a shotgun. “Now, I don’t know exactly what went into this young man’s decision to end his life and do it in such a horrible way,” Peterson said. “There may have been—there probably were—many factors involved. But I’m reasonably confident that his loss of faith and his bitter alienation from the Church contributed.” A return to faith Peterson, a professor of Arabic and Islamic studies at Brigham Young University, is a popular and prolific—though often reviled—defender of Mormonism in speeches and writings. Customarily, he is the concluding speaker at the annual two-day conference of FairMormon, an organization not affiliated with the Church but dedicated to defending it against public criticism. Recognizing the value of professional counseling in helping people deal with emotional and psychological turmoil caused by disillusionment and loss of faith, he said there is an even more fundamental cure: “a return to faith and trust.” Not an illness but a cure Peterson’s presentation, titled “What Difference Does It Make?” was replete with statistics and quotations from scholars rebutting contentions that religious people are by definition sick or mentally ill and that atheism is healthier than faith. For example, he said that Tyler VanderWeele, professor of epidemiology at Harvard University, recently published research linking regular attendance at religious service to “a roughly 30 percent reduction in mortality over 16 years of follow-up; a five-fold reduction in the likelihood of suicide; and a 30 percent reduction in the incidence of depression.” Moreover, VanderWeele and colleagues found that regular worship is apparently associated with “greater likelihood of healthy social relationships and stable marriages; an increased sense of meaning in life; higher life satisfaction; an expansion of one’s social network; and more charitable giving, volunteering, and civic engagement,” Peterson reported. And it’s not just the social support associated with religious worship that makes the difference; that accounted for only about 20–30 percent of the measured results, Peterson noted. “Of course, none of this proves religious claims are true,” he acknowledged. “But it does strongly suggest that faith isn’t an illness.” A well-kept secret Citing a 2009 book by Andrew Sims, professor of psychiatry at the University of Leeds in England, Peterson argued that religious belief contributes substantially to overall well-being. He quoted Sims as writing that its effect on mental and physical health is “one of the best-kept secrets in psychiatry, and medicine generally. If the findings of the huge volume of research on this topic had gone in the opposite direction and it had been found that religion damages your mental health, it would have been front-page news in every newspaper in the land!” Peterson further quoted Sims as contending that “churches are almost the only element in society to have offered considerate, caring, long-lasting, and self-sacrificing support to the mentally ill,” resulting in a better outcome from a range of physical and mental illnesses. Peterson remarked, “An advocate of greater secularism might concede that religious fantasies provide a helpful crutch for stupid, ignorant, and/or irrational people, whereas better educated and more honest unbelievers face reality without such comfort.” However, a 2004 study showed that religious adults were a third less likely than secular adults to lack a high school diploma and a third more likely to have at least one college degree, Peterson said. “Secularizing writers often like to imagine how much better the world would be without religion,” he said. “They should pray that they don’t get their wish.” It makes a difference Noting that Western society has grown much more secular in recent decades, Peterson warned that this is likely to have consequences. “It makes a difference.” Though nonreligious people have long assured him that they are devoted to making life in the world better for everyone, Peterson wonders what evidence there is to demonstrate that. He cited a 2006 book by Arthur Brooks, who found in his studies that religious people are more likely to donate money and in larger amounts to charities, to donate blood, to give to homeless shelters, to return money from a cashier’s mistake, and to express empathy for the less fortunate. Peterson quoted an atheist who wrote to him, “If you live in this very moment, you’ll find happiness.” Yet, Peterson said, “life ‘in this moment’ can be hellish” for many people. Another issue, he said, is that “human potential is never fully realized in mortality. Too often, in fact, it is scarcely realized at all.” “Perhaps a skeptic might say there’s no purpose to the cosmos. … We live briefly, we die meaninglessly, and then our little candle is extinguished—as all light and life ultimately will be extinguished in the vast heat-death of the universe. “But it should certainly cause us to hope for a future in which wounds are healed, deep yearnings satisfied, and human potential fully realized. Fortunately, in the Resurrection of Christ and the Restoration of the gospel there’s a firm foundation for that hope.”

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Q: Ruby on Rails: (Beginner) How can I make my style sheet (in public/stylesheet folder) be used by my layouts? I'm learning Ruby on Rails (sorry for the newb question, I couldn't find an answer on stackoverflow), and I am having an issue with my app using the stylesheet that was assigned to the application. I put a simple css style (A colored body tag) into my public/stylesheets directory called "application.css" in my "app" I have the stylesheet called via: "<%= stylesheet_link_tag "application" %>" When I reload my page (which has no body css style specified in it, only pure simple html), I see no change. What am I doing wrong? I've tried to reset the server, I've inspected the code of the rendered page and see nothing glaring... What am I missing? The only ruby on rails warning that I get when the page opens is "Warn: could not determine content-length of the response or set Response#chunked = true", which seems to be ignorable --> What does "WARN Could not determine content-length of response body." mean and how to I get rid of it? thanks A: Put it in app/assets/stylesheets You should really do a tutorial or two on Rails before you jump in. It is a very opinionated framework and it does a lot for you automatically. If you don't know what it's doing for you automatically and where things go, you'll encounter a ton of problems like this. I'd highly, highly recommend Michael Hartl's free tutorial: http://ruby.railstutorial.org/ruby-on-rails-tutorial-book

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It is proposed to complete the currently undergoing studies on the amino acid sequence of the 'sigma' and 'beta' subunits of human pituitary FSH. The amino acid and carbohydrate sequence of biologically active fragments of FSH and LH isolated by controlled enzymatic degradation will also be undertaken. Similar studies will be performed on FSH being isolated from horse pituitary glands. Products of enzymatic and chemical degradation of proteins and carbohydrate moieties are isolated by gel filtration, chromatography and high-voltage electrophoresis. The amino acid sequences of the peptides are established by stepwise degradation by the Edman's procedure, carboxypeptidase A and B digestion. The identification of amino acid is performed by amino acid analysis or by gas liquid chromatography. The elucidation of the primary structure of FSH will aid in the eventual chemical synthesis of the hormone. Receptor for FSH, LH and HCG and prolactin will be indentified and characterized in the ovaries of rat, cow and human at various stages of the reproductive cycle. Using detergents, gel-filtration and affinity chromatography, we propose to isolate gonadotropin receptor from the ovaries. The purified receptor will be characterized in terms of hormone binding, and antigenicity as well as lipid, carbohydrate and amino acid compositions. Hormone-specific antibodies against FSH, LH, TSH and HCG and their subunits will be raised in rabbits and guinea pigs and isolated by rivanol precipitation, immunoabsorption and affinity chromatography. The pure hormones, receptors and radioimmuno and radioreceptor assays will be used in developing in vitro models to study biochemical mechanism of hormone action. BIBLIOGRAPHIC REFERENCES: Rathnam, P., and Saxena, B.B.: "Primary Amino Acid Sequence of Follicle-stimulating Hormone from Human Pituitary Glands.", The Journal of Biological Chemistry, 250, pp6735-6746, 1975. Saito, T. and Saxena, B.B.: "A sensitive, rapid, and economic radioimmunoassay of human growth hormone using ethanol-ammonium acetate", The Journal of Laboratory and Clinical Medicine, 85, pp. 497-504, 1975.

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1. Field of the Invention This invention relates to methods for generating retrieval information to execute a retrieval for specifying a stored location of a method called according to a method call when an object oriented program is executed (hereinafter called “method retrieval”), and arithmetic processing apparatuses for executing the called method by executing the method retrieval employing the retrieval information generated by the methods. 2. Description of the Related Art In conventional information processing systems with object oriented programming, properties and methods included in the classes at higher order (super classes) are automatically succeeded by the classes at lower order (subclasses), and the methods are overwritten (“override” is usually used in Java language instead of “overwrite”) in the subclasses if necessary. Program of each method is stored in a predetermined area within a memory, and a predetermined method is called in a class in execution, thereby retrieving the stored location for the method. For example, in C++ programming, link information by a virtual function is buried into a method call program on compilation, thereby specifying a stored location of the method upon a method call. In Java programming, retrieval employing a hash table hereinafter called (“hashing”) has been proposed (Japanese Laid-open Patent Publications Hei 5-120022 and 8-278894). In the conventional method for setting link information on compilation, the compilation has to be repeated by resetting the link when the design is changed by changing the class ovewriting the method, thereby extremely deteriorating development efficiency of the system. According to the hashing, a character string providing method name and message for method call is converted into a hash value, and a hash table is generated associating the hash value and the storage location of the method. Thereby, when setting of overwriting methods is changed, compilation only for the class to be changed is necessary to be repeated and setting the hash table of the class has only to be changed, so that design change of programs may be easily resolved. The hashing, however, requires ensuring a memory area corresponding to a predetermined number of hash values, but a memory area for unused hash values is ensured, resulting in waste of the memory source. Moreover, the hashing has the risk of collision where the same hash value is assigned to different methods. In order to avoid such collision, according to a separation chain method or open address hashing, unique retrieval keys are respectively set to the hash values in connection, resulting in complication of the data construction and increase of the memory capacity. When retrieval is executed, a character string before conversion to the hash value is compared with an entry content of the hash table to confirm whether or not a correct retrieval key corresponding to the character string is chosen, thereby inviting the problem that the retrieval takes time and the processing capability of the apparatus is extremely deteriorated.

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Q: mysql statement works on my desktop but fails on my web host I use XAMPP on my desktop (Apache/2.2.17 (Win32) mod_ssl/2.2.17 OpenSSL/0.9.8o PHP/5.3.4 mod_perl/2.0.4 Perl/v5.10.1 MySQL client version: mysqlnd 5.0.7-dev - 091210 - $Revision: 304625 $) I have a MYSQL SELECT statement that works fine in my desktop application, even ran it in phpMyadmin and works correctly. When I move my application up to my web host the statement fails. My web host runs Apache with MySQL client version: 5.0.92 When I used phpMyadmin on my web host it gives me the error: FUNCTION nwilin5_eib_jtest.FIELD does not exist Here is the statement: SELECT a.*, p.name as parent, p.id as parentid, c.name as cat , c.id as catid,u.username as user, f.itemid as featured , f.payment_date as FeaturedPayDate, f.limit_date as FeaturedExpDate FROM jos_classifiedsredux_ads as a LEFT JOIN jos_users as u ON a.userid = u.id LEFT JOIN jos_classifiedsredux_pay4featuredad as f ON a.id = f.itemid INNER JOIN jos_classifiedsredux_categories as c ON a.category = c.id LEFT JOIN jos_classifiedsredux_categories as p ON c.parent = p.id WHERE a.published = 1 ORDER BY FIELD (a.id, 137, 226, 134, 135, 220, 240, 233, 219, 146, 138, 136, 133) A: You need to remove the space between FIELD and ( in your ORDER BY... Change: ORDER BY FIELD (a.id, 137, 226, 134, 135, 220... To: ORDER BY FIELD(a.id, 137, 226, 134, 135, 220... Why does this matter? Your test server and your production server likely have a different setting for the IGNORE_SPACE mode... which permits a space between the function call (FIELD), and the parameter list when enabled. Permit spaces between a function name and the “(” character. This causes built-in function names to be treated as reserved words. As a result, identifiers that are the same as function names must be quoted as described in Section 8.2, “Schema Object Names”. For example, because there is a COUNT() function, the use of count as a table name in the following statement causes an error: mysql> CREATE TABLE count (i INT); ERROR 1064 (42000): You have an error in your SQL syntax The table name should be quoted: mysql> CREATE TABLE `count` (i INT); Query OK, 0 rows affected (0.00 sec) The IGNORE_SPACE SQL mode applies to built-in functions, not to user-defined functions or stored functions. It is always permissible to have spaces after a UDF or stored function name, regardless of whether IGNORE_SPACE is enabled.

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The field of epigenetics describes information transmission through cell division of heritable changes in a phenotype that does not involve DNA sequence changes. CpG island hypermethylation, histone modification, and transmitted chromatin structure are the underlying mechanisms for epigenetic transmission, and CpG island hypermethylation is a key component for altered gene expression associated with human cancers. CpG islands are DNA segments that are at least 0.5 kb in size, rich in G:C and CpG content, and found in approximately 70% of human gene promoters.[@B1] Promoter CpG islands are usually unmethylated in normal cells, with the exception of those on an inactive X chromosome or associated with imprinted genes. Although the cause is unclear, promoter CpG island hypermethylation can occur in association with cancer development and aging. Promoter CpG island hypermethylation is found in virtually all human cancer tissue types and acts as an important mechanism for the inactivation of tumor suppressor genes and tumor-related genes.[@B2],[@B3] Gastric cancer is one of the human cancers in which promoter CpG island hypermethylation is frequently found.[@B2],[@B4] In our preliminary study, which analyzed 41 candidate genes in major types of human cancers and cancer-associated normal tissues, gastric cancer demonstrated a significantly higher number of methylated genes than those of other human cancer tissue types ([Fig. 1](#F1){ref-type="fig"}). In addition, gastric cancer-associated normal mucosa also exhibited the highest number of methylated genes when compared to normal tissue from other organs, including the lung, breast, colon, and liver ([Fig. 1](#F1){ref-type="fig"}). These facts suggest the possibility that aberrant CpG island hypermethylation is more involved in the carcinogenesis of gastric cancer than in that of other human cancer tissue types. GASTRIC CANCER METHYLATION CHANGE ================================= How many genes are known to be methylated in gastric cancer? ------------------------------------------------------------ In 1996, Lee et al.[@B5] reported for the first time that p16 was inactivated in gastric cancer by promoter CpG island hypermethylation rather than by genetic mutation. Since then, many researchers have demonstrated cancer-specific hypermethylation and inactivation of candidate genes in gastric cancer tissues and have correlated this hypermethylation with clinicopathologic features. However, the number of genes demonstrated to be inactivated by promoter CpG island hypermethylation was limited until the application of array-based genome-scale DNA methylation analysis for gastric cancers. With the application of 5-aza-2\'-deoxycytidine (DAC) treatment and oligonucleotide microarrays, Yamashita et al.[@B6] estimated that approximately 421 genes are silenced by promoter CpG island hypermethylation in a gastric cancer cell line (AGS). Considering the fact that promoter CpG island hypermethylation is exaggerated in a cancer cell line compared with primary cancer tissue and that the AGS cell line has an increased rate of *de novo* methylation because of over-expression of DNMT3b, the actual number of genes silenced by promoter CpG island hypermethylation can be estimated to be less than 421 in primary gastric cancers. Our team also performed bead array-based expression analysis of gastric cancer cell lines before and after DAC treatment with subsequent confirmation of CpG island hypermethylation of the candidate genes by methylation-specific PCR. We found 140 novel genes that are silenced by promoter CpG island hypermethylation in primary gastric cancer tissue (Jung et al. in preparation). The timing of hypermethylation in multistep gastric carcinogenesis ------------------------------------------------------------------ Promoter CpG island hypermethylation is now recognized to be an important mechanism responsible for the inactivation of tumor suppressor genes or tumor-related genes. If promoter CpG island hypermethylation of some genes plays an important role in the malignant transformation of gastric epithelial cells, this pattern of hypermethylation should be found in premalignant lesions of the stomach, including gastric adenomas and intestinal metaplasia. In order to determine the frequency and timing of hypermethylation during multistep gastric carcinogenesis, Kang et al. analyzed multistep lesions of the stomach, in regards to their methylation status, in five genes[@B7] or 12 genes[@B8] using methylation-specific PCR or in 25 genes using MethyLight analysis;[@B9] they demonstrated that promoter CpG island hypermethylation occurs early in multistep gastric carcinogenesis and accumulates during progression of the gastric lesion along the multistep carcinogenesis pathway. During multistep gastric carcinogenesis, there is a steep rise in the number of methylated genes when progressing from chronic gastritis to intestinal metaplasia, which was a consistent finding in a series of studies.[@B7]-[@B9] Regardless of the status of *Helicobacter pylori* infection, the number of methylated genes in intestinal metaplasia was significantly higher than that found in chronic gastritis without intestinal metaplasia.[@B9] This suggests that intestinal metaplasia is an epigenetically altered lesion. However, even in chronic gastritis without intestinal metaplasia, promoter CpG island hypermethylation occurs in association with *H. pylori* infection[@B10] and aging.[@B11],[@B12] *Helicobacter pylori* infection-associated DNA hypermethylation --------------------------------------------------------------- *H. pylori* has been designated as a human class I carcinogen for gastric malignancy by the International Agency for Research on Cancer. Although the exact mechanism of *H. pylori*-associated gastric carcinogenesis is unknown, long-standing bacterial infection, perpetuated chronic inflammation, and sustained mucosal epithelial cell proliferation are thought to produce a carcinogenic environment. Chan et al.[@B10] were the first to demonstrate *H. pylori*-associated hypermethylation in the gastric epithelia, which was supported by subsequent studies demonstrating that the eradication of *H. pylori* infection results in a reversal of the methylation status of multiple CpG island loci.[@B13]-[@B15] Thus, it is plausible that aberrant methylation induced by *H. pylori* infection may contribute to *H. pylori* infection-associated gastric carcinogenesis. It has been reported that interleukin 1 beta can modulate CpG island methylation through the activation of DNA methyltransferase.[@B16] In an *in vitro* study, interleukin 1 beta siRNA blocked *H. pylori*-induced methylation of the *CDH1* promoter CpG island locus in a gastric cancer cell line.[@B17] In an animal model experiment by the Ushijima team, *H. pylori* infection resulted in the induction of CpG island hypermethylation of candidate genes, and the eradication led to marked decreases in methylation levels in the candidate genes. However, the suppression of inflammation by treatment with the immunosuppressive drug cyclosporine blocked the induction of DNA methylation in the candidate genes. These findings suggest that the infection-associated inflammatory response, rather than *H. pylori* itself, was responsible for the induction of altered DNA methylation.[@B18] In a subsequent gerbil study, neutrophilic inflammation caused by treatment with ethanol or NaCl did not induce DNA methylation in candidate genes, whereas chronic inflammation caused by *H. pylori* or *H. felis* infection led to altered methylation in candidate genes. This finding suggests that it is not the inflammation itself, but rather specific types of inflammation, that are necessary for methylation induction.[@B19] Aging-related hypermethylation vs inflammation-related hypermethylation ----------------------------------------------------------------------- Challenging traditional thought regarding the lack of CpG island methylation in normal tissues, a recent study indicated that 4-8% of CpG island loci are methylated in the genomic DNA of human blood, brain, muscle, and spleen tissue.[@B20],[@B21] Additionally, normal cells have been shown to acquire hypermethylation in an aging-related manner: aging-related methylation was first demonstrated for the oestrogen receptor (ER) gene by Issa et al.[@B22] and has subsequently been demonstrated in multiple genes by Ahuja et al.[@B23] In the stomach, Waki et al.[@B11] reported aging-related methylation of *CDH1*, *MLH1*, and *p16* in non-neoplastic gastric epithelia. However, because CpG island hypermethylation can be induced by chronic inflammation in the stomach and because the prevalence of *H. pylori* infection increases with age,[@B24] the interplay between aging and chronic inflammation is complicated by *H. pylori* infection. Chan et al.[@B25] found that *CDH1* methylation was associated with age in the stomach, the presence of chronic gastritis, and *H. pylori* infection using a univariate analysis, but *H. pylori* infection was the only independent factor associated with CDH1 methylation in the multivariate analysis. Furthermore, Maekita et al.[@B26] reported that there was no aging-related hypermethylation in healthy gastric mucosa. However, a current study by our team supports the presence of aging-related hypermethylation in the gastric mucosa because the number of methylated genes was significantly higher in *H. pylori*-negative adult stomach samples than in *H. pylori*-negative pediatric samples.[@B27] In WI-38 human embryonic lung fibroblasts, *p16* was found to undergo spontaneous promoter CpG island hypermethylation during passage of these cells in culture,[@B28] which supports the presence of age-related hypermethylation. Thus, we cannot exclude the possibility that aging-related methylation occurs in non-neoplastic gastric epithelia without *H. pylori* infection. Field cancerization ------------------- Many studies have shown that methylation levels or frequencies of multiple genes are higher in gastric mucosa from gastric cancer patients than in mucosa from non-cancer subjects.[@B11],[@B26],[@B29] In a stomach with enhanced CpG island hypermethylation, the affected cells may have a growth-selective advantage imparted by the expressional loss of the methylated genes, which may predispose the cells to acquiring further genetic or epigenetic defects that lead to neoplasia. Synchronous multiple gastric cancers, constituting 4-9% of gastric cancers, occur at an older age and are more commonly associated with an extensive distribution of intestinal metaplasia in the background mucosa compared with single gastric cancer.[@B30],[@B31] In a recent study, non-neoplastic gastric mucosa from synchronous gastric cancer patients was found to have more hypermethylated genes than non-neoplastic gastric mucosa from patients with a single gastric cancer, which suggests that enhanced hypermethylation in the background gastric mucosa might contribute to the development of multiple gastric cancers.[@B32] Multiple gastric cancers are not only a genetic model but also an epigenetic model for field cancerization. Based on the findings that methylation levels in gastric mucosa are significantly increased in cases with a single gastric cancer and even more so in cases with multiple gastric cancers, it has been suggested that quantitative information regarding methylation levels of specific genes may serve as a biomarker for predicting an individual\'s risk for developing gastric cancer.[@B32],[@B33] However, it should be noted that increased methylation levels or frequencies in gastric mucosa from gastric cancer patients may reflect a higher prevalence of *H. pylori* infection and intestinal metaplasia (compared with gastric mucosa from non-cancer subjects).[@B34],[@B35] Because both *H. pylori* infection and intestinal metaplasia are closely linked with increased CpG island hypermethylation, further clarification is needed regarding whether non-neoplastic gastric mucosa without intestinal metaplasia from *H. pylori*-negative gastric cancer patients harbors more hypermethylated genes than non-neoplastic gastric mucosa from *H. pylori*-negative non-cancer subjects. In Park et al.\'s study,[@B9] no significant differences were observed in the number of methylated genes or methylation levels of 25 individual genes in chronic gastritis tissue from cancer and non-cancer patients after normalization of the confounding factors of *H. pylori* and intestinal metaplasia. Because synchronous multiple gastric cancers tend to be associated with widespread intestinal metaplasia when compared with single gastric cancers, cancer-associated gastric mucosa might show higher methylation frequencies or higher methylation levels of multiple CpG island loci in multiple synchronous gastric cancer patients than in single gastric cancer patients. Prognostic implications of individual gene methylation ------------------------------------------------------ Promoter CpG island hypermethylation can be utilized as a tumor biomarker for the detection of tumor cells in gastric juice or serum or for the prediction of clinical outcomes. A dozen DNA methylation markers have been reported to be closely associated with worse or better clinical outcomes in gastric cancer patients; *MAL* or *COX2* methylation was correlated with better clinical outcomes in gastric cancer patients,[@B36],[@B37] whereas *DAPK*, *TMS1*, *IQGAP2*, *SOX2*, *CACNA2D3*, *DKK-3*, *TFPI2*, and Cystatin methylation has been correlated with worse clinical outcomes in gastric cancer patients.[@B38]-[@B44] However, most of the studies that have evaluated these DNA methylation markers for their prognostic implication used methylation-specific polymerase chain reaction (MSP). Although MSP is a highly sensitive method for detecting one methylated allele in 10,000 unmethylated alleles,[@B45] it is unreliable for detecting low levels of methylation. Another issue related to these DNA methylation markers is that a validation study was not performed to prove their utility as a prognostic marker. The final issue concerns concordance among individual gene hypermethylation: hypermethylation of one specific gene tends to be concordant with that of another individual gene; thus, better or worse survival observed in gastric cancers with hypermethylation of an individual gene may not be attributed to hypermethylation of that particular gene. Rather, survival may be related to concordant hypermethylation of multiple CpG island loci, namely CpG island methylator phenotype (CIMP). CIMP-positive gastric cancer ---------------------------- CIMP refers to a subset of malignancies that is characterized by widespread hypermethylation of multiple promoter CpG island loci. Since the CIMP concept was first introduced for the molecular pathways of colorectal cancers (CRCs) by Dr. Issa\'s group,[@B46] many investigators have attempted to characterize the clinicopathological and molecular features of CIMP-positive CRCs and have found a close association with proximal colon location, older age at onset, poor differentiation, microsatellite instability (MSI), and *BRAF* mutations.[@B47]-[@B49] Similarly, the presence of CIMP-positive gastric cancers has been reported by the same group,[@B50] which did not find distinct clinicopathologic features of CIMP-positive gastric cancers, with the exception of a close association with MSI. Since then, several researchers have attempted to characterize the clinicopathological features of CIMP-positive gastric cancers using variable methodologies for DNA methylation analysis and their own CIMP marker panels; this has led to controversial results.[@B51]-[@B56] Despite variable findings, relatively common findings include close associations of CIMP-positive gastric cancers with diffuse type-histology and better clinical outcomes. Recently, with the exclusion of MSI-positive gastric cancers and Epstein-Barr virus (EBV)-positive gastric cancers from the analysis, Park et al.[@B57] found characteristic clinicopathologic features of CIMP-positive gastric cancers that were defined as tumors with methylation of 13 or more markers during the analysis of the 16 cancer-specific DNA methylation markers; these defined CIMP-positive gastric cancers tended to show distinct clinicopathologic features, including a proclivity toward diffuse or mixed-type histology, poor differentiation, infiltrative gross types, and higher cancer stages. EBV-associated gastric cancer ----------------------------- In addition to *H. pylori*, EBV has also been recognized as a gastric cancer-causing infectious agent.[@B58],[@B59] EBV-associated gastric cancer, comprising nearly 10% of gastric cancers, are characterized by a younger age at onset, male predominance, proximal location, frequent association of lymphoid stroma, and a better prognosis.[@B60] EBV-associated gastric cancer is a prototype of the CIMP-positive types of gastric cancer and exhibits consistently higher frequencies and levels of methylation in examined cancer-related methylation markers,[@B53],[@B57],[@B61] which is independent of whether the EBV-associated gastric cancer is histologically lymphoepithelioma-like or ordinary.[@B60] Because the number of methylated cancer-specific methylation markers is far higher in EBV-associated gastric cancers than in EBV-negative gastric cancers, EBV-associated aberrant hypermethylation is a global event. However, *MLH1* methylation and resultant MSI are, if ever, rarely observed in EBV-associated gastric cancers. Although it can be speculated that the methylation machinery of EBV-associated gastric cancer is capable of recognizing its own methylation targets, it may be hypothesized that the presence of both CIMP and MSI could cause a growth disadvantage and subsequently lead to the negative selection of gastric cancer cells containing both CIMP and MSI. Tumor cells from EBV-associated gastric cancers display *DNA methyltransferase I* over-expression,[@B62] which is closely associated with *interleukin-1-beta* (*IL1B*) over-expression[@B60] or *latent membrane protein 2A*-associated phosphorylation of *signal transducer and activator of transcription 3* (*STAT3*) in EBV-associated gastric cancers.[@B63] *IL1B* is capable of increasing the expression of *DNMT1* via the production of nitric oxide, and phosphorylated *STAT3* binds to the *DNMT1* promoter and induces transcription. MSI-positive gastric cancer --------------------------- The frequency of MSI-positive gastric cancer varies from 8% to 37%. In gastric cancer, MSI is mainly caused by promoter CpG island hypermethylation of the *MLH1* gene. Somatic mutations of mismatch repair genes are very rare in sporadic gastric cancers. Thus, known clinicopathological features of MSI-positive gastric cancer, including female sex, older age of onset, antral location, ulcerofungating gross type by Borrmann\'s classification, intestinal type by Lauren classification, expanding type by Ming classification, and better survival[@B64] represent features of sporadic MSI-positive gastric cancer. Since gastric cancer is an extracolonic lesion in Lynch syndrome, we have encountered MSI-positive gastric cancer without *MLH1* methylation. Recently, our team has compared clinicopathological features between MSI-positive gastric cancers with and without *MLH1* methylation (Kim et al. in preparation). Of the known clinicopathological features for MSI-positive gastric cancer, female preponderance, older age of onset and antral location do not correspond with Lynch syndrome-associated MSI-positive gastric cancer.[@B65] Several studies have shown that *MLH1* methylation occurs in premalignant stages, including intestinal metaplasia and gastric adenoma. Thus, *MLH1* methylation has been considered an early event during multistep gastric carcinogenesis.[@B7],[@B9],[@B66],[@B67] However, a recent study of Ling et al.[@B68] has shown that MSI can develop from MSI-low or the absence of MSI due to time-dependent accumulation of DNA methylation during progression of early stage-gastric cancer, which indicates that silencing of *MLH1* due to promoter hypermethylation may appear as a later event during multistep gastric carcinogenesis. Unfortunately, the study did not investigate whether later acquisition of *MLH1* methylation occurs as a phenomenon of CIMP. *MLH1* methylation is unlikely to occur as an isolated sporadic event without concurrent hypermethylation of multiple gene promoter CpG island loci. Epigenetic regulation of microRNA --------------------------------- A new class of small non-coding RNAs known as microRNAs (miRNA) have recently been discovered. Mature miRNAs, 21 to 30 nucleotide-sized, are cleaved from 70- to 100-nucleotide hairpin miRNA precursors in the cytoplasm by the RNase III enzyme Dicer. Base-pairing between the miRNA strand and the 3\' untranslated regions of its target mRNAs (potentially hundreds of genes) directs RNA-induced silencing complex to either cause mRNA degradation or translational repression. Through these molecular mechanisms, miRNAs serve as key regulators of gene expression involved in crucial cellular processes, including development, proliferation, cellular differentiation, and apoptosis. Although the generation of miRNAs and their mode of action in regulating gene function have been intensively studied, the regulation of miRNA expression remains largely unclear. The means by which miRNA is regulated is somewhat complicated. Recently, Saito et al. demonstrated for the first time that *miR-127* is regulated by DNA hypermethylation[@B69] and since then, a dramatically increased number of studies have documented the epigenetic regulation of miRNAs.[@B70] However, in gastric cancer, approximately 113 miRNAs have been demonstrated to be dysregulated compared with normal gastric mucosal tissues but a dozen miRNA genes have been shown to be downregulated by aberrant hypermethylation, including *miR-512-5p*,[@B71] *miR-375*,[@B72] *miR-212*,[@B73] *miR-181c*,[@B73] *miR-196b*,[@B74] *miR-137*,[@B75] *miR-129-2*,[@B76] *miR-124a-1*, *miR-124a-2*, *miR-124a-3*,[@B77] *miR-34b*, and *miR-34c*.[@B78] In particular, Ando et al.[@B77] demonstrated that *miR-124a-1*, *-2*, and *-3* are frequently methylated in primary gastric cancer and in normal gastric mucosal tissues from healthy individuals with *H. pylori* infections. Among *H. pylori*-negative individuals, methylation levels are significantly higher in non-cancerous gastric mucosal tissues from gastric cancer patients than gastric mucosal tissues from healthy individuals, which suggest that methylation of miRNA genes comprises a field defect contributing to the pathogenesis of gastric cancer.[@B77] Suzuki et al.[@B78] also reported that *miR-34b/c* methylation is significantly associated with *H. pylori* infection among healthy individuals. Future perspective ------------------ Although it is well known that EBV-positive gastric cancer is featured with extensive hypermethylation of multiple genes, the mechanism leading to genome-wide hypermethylation is still unknown. Because EBV-positive gastric dysplasia or adenoma has never been reported, it seems likely that EBV-infected epithelial cells transform directly into malignant cells. DNMT1 elevation in association with EBV infection does not provide a satisfactory explanation for genome-wide extensive hypermethylation because *in vitro* transfection of *DNMT1* in cell lines or DNMT1 elevation in association with *H. pylori* infection also does not lead to such extensive hypermethylation as seen in EBV-positive gastric cancer. If we can elucidate the mechanism of EBV-associated extensive hypermethylation, we will have a better understanding of how promoter CpG island hypermethylation occurs. Although gastric cancer has shown a higher number of genes methylated compared with colorectal cancer, clinicopathological features of CIMP-positive gastric cancer are still obscure and marker panels diagnosing CIMP-positive gastric cancer are not established yet, which is in contrast to the situation in colorectal cancer. It is imperative to develop CIMP panel markers enabling the diagnosis of CIMP-positive gastric cancer and then to characterize clinicopathological features of CIMP-positive gastric cancer. In case these are accomplished, we expect to identify the precursor lesions of CIMP-positive gastric cancer and to delineate multistep morphological progression of CIMP-positive tumors. CONCLUSION ========== Although molecular pathways and morphological pathways are not well established for gastric cancers when compared with colorectal cancers, rapid development of methylation analysis technology will enable us to take a glimpse at the landscape of epigenetic alterations occurring at each step of multistep gastric carcinogenesis, which will provide molecular insights on morphological progression pathways. In addition, epigenetic studies may offer great potential for the identification of tumor biomarkers that can be utilized to detect and diagnose gastric cancer at its earliest stages, to accurately assess an individual\'s risk for gastric cancer, or to predict the response to chemotherapy or clinical outcomes. Supported by grant M10750030001-08N5003-00110 from the Korea Science and Engineering Foundation, funded by the Ministry of Education, Science and Technology (MEST); by grant 2010-0007579 from the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the MEST; and by grant 2009-0093820 from a Priority Research Centers Program through the NRF. Nam-Yun Cho contributed to this work through experiments. No potential conflict of interest relevant to this article was reported. {#F1}

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Q: 3 Colorability reduction to SAT I'd like to reduce 3 colorability to SAT. I've stuffed up somewhere because I've shown it's equivalent to 2 SAT. Given some graph $G = (V,E)$ and three colors, red, blue, green. For every vertex $i$, let the boolean variable $i_r$ tell you whether the $i$-th vertex is red (or more precisely, that the $i$-th vertex is red when $i_r = 1$). Similarly, define $i_b$ and $i_g$. Suppose two vertices $i$ and $j$ were connected by an edge $e$. Consider the clause \begin{align} (\bar i_r \vee \bar j_r) \end{align} If we demand the clause is true, it means that the vertices cannot both be red at the same time. Now consider the bigger clause $\phi_e$ \begin{align} (\bar i_r \vee \bar j_r)\wedge(\bar i_b \vee \bar j_b)\wedge(\bar i_g \vee \bar j_g) \end{align} which, if true, demands that the vertices $i$ and $j$ aren't both the same color. By itself, this clause is in 2-SAT. For every edge $e \in E$, I now make a clause $\phi_e$ of the above form and put them all together using $\wedge$'s \begin{align} \phi = \wedge_{e \in E} \phi_e \end{align} Thus, for the entire graph, I've come up with a 2SAT formula which is equivalent to 3 coloring. This is obviously wrong, but I can't tell where I've screwed up. A: With your modeling, setting $i$, $i_r$, $i_g$ and $i_b$ to false for all vertices yields a solution of the SAT problem and this is not a solution of the graph coloring problem. You need to add clauses to say that each vertex is blue or green or red, namely $(i_r\vee i_g\vee i_b)$. Then it becomes a 3-SAT problem. Note that if a vertex is assigned to more then one color, then we can take any of its colors and obtain a 3-coloring.

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Q: django haystack search form cannot find is_vald method I am using haystack to perform a simple search query against my Person model for all the selected filter attributes. I have decide to try out the Faceted Search Form and created a generic TemplateView SearchView. class SearchView(TemplateView): template_name = "index.html" results = EmptySearchQuerySet() form_class = FacetedSearchForm form = None query = '' selected_people = None def get(self, request, **kwargs): self.request = request self.query = self.get_query() if self.form.is_valid(): self.results = self.get_results() context = self.get_context_data(request, **kwargs) if request.is_ajax() or request.GET.get('ajax'): self.template_name = 'search/Taleebo/search_results.html' return self.render_to_response(context) def get_query(self): return self.request.GET.get('q') def get_results(self): return self.form.search() All the routing is working fine but when my get method is called it fails at the line self.form.is_valid() with an error that says NoneType' object has no attribute 'is_valid' I am using the default form_class so shouldn't that attribute be defined? EDIT: I am trying to now use the provided SearchView by haystack and the is_valid is no longer an issue but i am not getting any records back from 'results'. I changed my urls.py to look like this url(r'^search/person/', search_view_factory( view_class=SearchView, template='index.html', form_class=ModelSearchForm ), name='haystack_search'), A: Using any class would result in the same error, when you don't have an instance to access: class SearchView(TemplateView): (...) form = None //<= Here you set the form to None So you're calling is_valid() on None, instead of on an actual form.

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Impact of preimplantation genetic diagnosis on IVF outcome in implantation failure patients. Implantation failure (IF) is defined as three or more failed IVF attempts, and preimplantation genetic diagnosis (PGD) is being used in these patients to improve IVF outcome. PGD was performed in 49 implantation failure patients with a mean number of 4.2 +/- 1.6 previous IVF failures, and in nine fertile controls. Fluorescence in-situ hybridization (FISH) on blastomeres from biopsied day 3 embryos was performed for chromosomes 13, 16, 18, 21, 22, X and Y. There was a significantly higher rate of chromosomal abnormalities (67.4%) compared with controls (36.3%). In 57 cycles, a pregnancy rate of 34.0% and an implantation rate of 19.8% was observed in implantation failure patients compared with controls (33.3 and 24.1% respectively), with all the pregnancies in the implantation failure group coming from the transfer of at least one chromosomally normal blastocyst on day 5. It is concluded that in IVF patients, use of PGD along with blastocyst transfer improves IVF outcome.

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RAS and PKA pathways in cancer: new insight from transcriptional analysis. Through its ability to regulate the activity of a large number of transcription factors, the Ras pathway is able to control several transcriptional programs leading to proliferation, differentiation, metabolism, cytoskeletal reorganization and immune response. Cyclic AMP (cAMP) is a ubiquitous intracellular second messenger whose major intracellular target in eukaryotes is protein kinase A (PKA). Wide evidence for cross talk between the Ras and cAMP-PKA pathways is available. After reviewing some features of Ras and PKA signalling that are relevant for cancer biology, we re-analyze available genome-wide expression data for genes encoding proteins of the downstream branch of the PKA pathway in human tumor cell lines as a function of the mutational state of the Ras pathway. The observed Ras-dependent pattern of regulation of the analyzed genes may contribute to explain how the cAMP-PKA axis is involved in oncogenic processes induced by Ras.

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'Welcome To The Riley's' Opens the New Orleans Film Festival on October 14th New Orleans Film Festival will open with 'Welcome To The Riley's' on October 14th. The 21st Annual New Orleans Film Festival revealed that two Sundance favorites, Jake Scott’s “Welcome to the Rileys” and Derek Cianfrance’s “Blue Valentine,” will bookend this year’s festival. Additionally, Danny Boyle’s “127 Hours” and Darren Aronofsky’s “Black Swan” are also on tap to screen as part the 2010 NOFF lineup. The festival will run from October 14-21, with screenings across the city. “Welcome to the Rileys,” the fest’s opener follows a childless couple (James Gandolfini and Melissa Leo) who adopt a young woman (Kristen Stewart) down on her luck after Gandolfini’s character meets her on a business trip to New Orleans. The fest will close with Cianfrance’s film, which screened at Sundance and in the Un Certain Regard section of this year’s Cannes. “Blue Valentine” tells the story of a young couple (Ryan Gosling and Michelle Williams) as they try to resuscitate their disintegrating marriage. Commenting on the lineup announced so far, New Orleans Film Society president Larry Blake noted, ““We are thrilled to bring these renowned independent films to the New Orleans community as they set a strong tone for this year’s New Orleans Film Festival. Each year the festival strives to expose the latest in independent film and movie culture to the New Orleans metropolitan area.” The New Orleans Film Society produces the annual event.

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Effects of individual performance feedback on nurses' adherence to pain management clinical guidelines. The purpose of this study was to examine the effects of an individual performance feedback intervention on nurses' adherence to pain management practice guidelines. Thirty orthopedic staff nurses received individual performance feedback on their past performance of three recommended pain management practices. Nurses' performance of the three recommended practices significantly improved over the 15 weeks after the feedback intervention. Missed 4-hour pain assessments declined (t = 8.77, df = 239, P < 0.0001), reassessments after analgesics increased (t = -5.71, df = 239, P < 0.0001), and follow-up taken for unacceptable pain increased (t = -3.08, df = 178, P < 0.01). Results suggest that individual performance feedback may be an effective approach to improving nurses' pain management intervention activities.

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447 F.Supp. 1384 (1978) SIGNATORY NEGOTIATING COMMITTEE, Plaintiff, v. LOCAL 9, INTERNATIONAL UNION OF OPERATING ENGINEERS, AFL-CIO, Defendant. Civ. A. No. 76 M 827. United States District Court, D. Colorado. April 5, 1978. *1385 David R. Gorsuch, Gorsuch, Kirgis, Campbell, Walker & Grover, Denver, Colo., for plaintiff. Walter C. Brauer III, Denver, Colo., for defendant. MEMORANDUM OPINION AND ORDER FOR JUDGMENT MATSCH, District Judge. Invoking the jurisdiction granted by 29 U.S.C. § 185 and 28 U.S.C. § 1337, the parties have, upon stipulated facts, respectively moved for a summary judgment declaring the validity or invalidity of a subcontracting provision of a collective bargaining agreement under federal antitrust laws. Plaintiff, Signatory Negotiating Committee (Committee), is the collective bargaining agent for those employers in the building, heavy engineering and utility construction industry in Colorado who have assigned their rights to negotiate collective bargaining agreements with a number of labor organizations, including the defendant, Local 9, International Union of Operating Engineers, AFL-CIO, (Union). Committee does not represent any trade association; it negotiates with Union only for individual contractors who perform work calling for the skills of operating engineers. Each such contractor is an employer engaged in commerce and in an industry affecting commerce, within the meaning of 29 U.S.C. § 152(2), (6) and (7) and 15 U.S.C. § 7. The representative role of the plaintiff makes it also an employer within the scope of those statutory provisions. Many of the individual contractors have an annual gross business volume exceeding $1,000,000.00 and they make purchases of equipment, materials and supplies from outside of Colorado, for use in Colorado, of the value of more than $1,000,000.00 annually. *1386 Union is a labor organization of more than 5,000 members whose craft is almost unique in its relationship with virtually all other crafts involved in the construction industry. Thus, while the primary task of operating engineers is the movement of earth for constructing and maintaining roads and highways, dams, waterways, and cross-country utility construction, they also service the other crafts by moving machinery, equipment, material and supplies for millwrights, electricians, masons, glaziers, carpenters, iron workers, plumbers, laborers and others. Cooperation and harmony among all of the crafts at the job site are vitally important to achieve the coordination necessary for completion of a construction project, often involving multiple employers, including subcontractors. A majority of contractors who employ operating engineers work both as general contractors on some jobs and as subcontractors on other jobs. General contractors often make decisions during bid preparations about subcontracting the work of operating engineers and the same contractor may make different decisions about the use of subcontractors on various jobs. At times, the decision to use subcontractors may be made while the project is in progress. For example, a general contractor may employ engineers to operate and maintain fork lifts and cranes. If more cranes are needed, or if there is a requirement for a crane with special capabilities, a subcontract may be used. Then, the operating engineers employed by the subcontractor will be working directly with the employees of the general contractor. Subcontracts are also used for unit work. On-site preparation, foundation and caisson work, material handling and exterior land finishing could all be subcontracted at the site of a building project. Bridges, curbing and culvert installation can be subcontracted on a highway construction job. Operating engineers work with a wide variety of equipment. Most contractors tend to specialize and do not do all kinds of construction work at any one time. Accordingly, no signatory contractor owns or leases all types of equipment at any given time. When the work requires the use of equipment which the contractor does not have he may buy or lease it for operation by his own employees, or he may subcontract that part of the work to a contractor with such equipment. For more than thirty years, the plaintiff and defendant have had a collective bargaining relationship covering work to be done at the site of the construction, alteration, painting or repair of a building, structure, or other work. They have periodically negotiated a Master Agreement. The current agreement, which will expire on April 30, 1978, contains the following provisions as Article XVI: Application to Subcontractors (A) On-Site Work. 1. With respect to on-site work covered by this Agreement, that is, work done or to be done at the site of the construction, alteration, painting or repair of a building, structure or other work: a) The terms and conditions of this Agreement insofar as it affects the Contractor shall apply equally to any Subcontractor under the control of, or working under contract with such Contractor on any on-site work covered by this Agreement, and said Subcontractor with respect to such on-site work shall be considered the same as a Contractor covered hereby. b) If a Contractor shall subcontract on-site work as herein defined and covered by this Agreement, provision shall be made in such subcontract for the observance by said Subcontractor of the terms of this Agreement as to such work. 2. It is distinctly understood and agreed that this Agreement does not cover any other jobs or projects of the Subcontractor and terminates contemporaneously with the termination of such subcontract with Contractor. 3. The foregoing shall not apply to the Local Production of Material by any *1387 commercial supplier of such materials who has been and is engaged in the business of supplying such materials to the public generally from any designated site or sites other than on the project or projects of the Contractor. (B) Definition of Subcontractor. A Sub-contractor is defined as any person other than an Employee covered by this Agreement, firm or corporation who or which agrees orally or in writing to perform, or who or which in fact performs for or on behalf of a Contractor, any part or portion of the work covered by this Agreement. (C) This Article, APPLICATION TO SUBCONTRACTORS, shall not apply to the following miscellaneous types of work: striping, seeding, mulching, and planting of trees, shrubs and flowers. (D) It is distinctly understood and agreed between the Contractor and the Union that this Article has no application to any person or entity on any job or project or in the performance of any work by the person or entity when the person or entity is not a Sub-contractor as defined in (B) above, and that no Sub-contractor as defined in (B) above may be requested or required by the Union while acting and working as a subcontractor as defined in (B) above to execute any agreement with the Union except a job agreement applicable only to such subcontracted work covered by this Agreement. The parties have agreed that neither of them intended to restrict access to bidding or performing subcontract work through this article. The Union has by this means sought to insure payment of the same wages and fringe benefits by all employers of operating engineers on the same site and to minimize friction between union and non-union workers at that site. There has not been a refusal to subcontract with non-union employers as a result of this article and union contractors who have not assigned their bargaining rights to the plaintiff or otherwise agreed to become bound by the Master Agreement have not been systematically excluded from subcontracts as a result of this agreement. In addition to the Master Agreement, the Union enters into contracts with individual employers with a Short Form Agreement which does not involve the plaintiff. The Short Form Agreement incorporates many of the provisions of the Master Agreement by reference, excepting, among others, the arbitration provisions. The Short Form Agreement has been used as a project agreement, applicable only to one identified work project. It has also been used for non-union contractors who successfully bid on some portion of the work on a project being constructed by substantially all union contractors. The use of the Short Form Agreement as a project agreement has been one method of enforcing the subcontract requirements of Article XVI. The other method is to require the general contractor to include appropriate terms in the subcontract and a failure to enforce those provisions will then become a violation of the general contractor's obligations under the Master Agreement. The union security provisions of the Master Agreement become applicable to subcontractors when they have been working on the project for 31 days. The employees of the subcontractor must then become union members. The hiring hall provisions of the Master Agreement are enforced if additional workers are needed by the subcontractor at the project site. None of the provisions of the Master Agreement is enforced against the non-consenting contractors for any locations other than the site at which the covered subcontract work is being performed. Article XVI serves to protect negotiated wages from erosion through the use of cheaper labor. It also minimizes the use of subcontracting, thereby preserving work which the union workers have traditionally performed. Additionally, it reduces the *1388 possibility of disruption of the close community of interests on the construction project site, and it tends to prevent friction by decreasing the likelihood of mixing union and nonunion employees on the same project. Shortly after the Sherman Act was enacted, the Supreme Court applied its proscriptions to combinations by labor organizations. Loewe v. Lawlor, 208 U.S. 274, 28 S.Ct. 301, 52 L.Ed. 488 (1908). Six years later, Congress passed the Clayton Act, two sections of which created labor's first exemption from the antitrust laws. Section 6, 15 U.S.C. § 17, provides: The labor of a human being is not a commodity or article of commerce. Nothing contained in the antitrust laws shall be construed to forbid the existence and operation of labor . . . organizations, instituted for the purposes of mutual help . . . or to forbid or restrain individual members of such organizations from lawfully carrying out the legitimate objectives thereof; . . . Section 20, 29 U.S.C. § 52, limited the power of federal courts to issue injunctions in cases "involving, or growing out of, a dispute concerning terms or conditions of employment." The section also provided that certain enumerated union actions were not to be found violative of "any law of the United States." In 1921, the Supreme Court held in Duplex Printing Press Co. v. Deering, 254 U.S. 443, 469 [41 S.Ct. 172, 177, 65 L.Ed. 349] (1921), that neither Sections 6 nor 20 permitted secondary boycotts, and observed: . . . [T]here is nothing in [§ 6] to exempt such an organization or its members from accountability where it or they depart from its normal and legitimate objects and engage in an actual combination or conspiracy in restraint of trade. Congress responded in 1932 with the Norris-La Guardia Act, 29 U.S.C. §§ 104, 105 & 113, further restricting the courts' ability to intervene in labor disputes and again limiting the applicability of the Sherman Act as a restriction on labor union activities. The Supreme Court recognized that intent of Congress in Apex Hosiery Co. v. Leader, 310 U.S. 469, 503-04, [60 S.Ct. 982, 997, 84 L.Ed. 1311] (1940), and, in holding that a sitdown strike accompanied by violence was exempt from the antitrust laws, said . . . [A]n elimination of price competition based on differences in labor standards is the objective of any national labor organization. But this effect on competition has not been considered to be the kind of curtailment of price competition prohibited by the Sherman Act. In United States v. Hutcheson, 312 U.S. 219 [61 S.Ct. 463, 85 L.Ed. 788] (1941), the Supreme Court attempted to harmonize the Sherman Act, the Clayton Act and the Norris-La Guardia Act in these words: So long as a union acts in its self-interest and does not combine with non-labor groups, the licit and the illicit under § 20 are not to be distinguished by any judgment regarding the wisdom or unwisdom, the rightness or wrongness, the selfishness or unselfishness of the end of which the particular union activities are the means. Id. at 232, 61 S.Ct. at 466. Four years later, in Allen Bradley Co. v. Local Union No. 3, International Brotherhood of Electrical Workers, 325 U.S. 797, [65 S.Ct. 1533, 89 L.Ed. 1939] (1945), the Court reaffirmed Hutcheson but held the union subject to antitrust liability because its agreement with industry was "looking not merely to terms and conditions of employment but also to price and market control." Id. at 799-800, 65 S.Ct. at 1535. The Labor Management Relations Act of 1947, 29 U.S.C. § 141 et seq., and the Labor Management Reporting and Disclosure Act of 1959, 29 U.S.C. § 401 et seq., were major enactments establishing national policy in matters of organized labor. These statutes were fully debated in the Congress and there were those who urged the restriction of union activities by application of antitrust *1389 principles. That approach was rejected and on both occasions the lawmakers clearly expressed an intention to address apparent abuses of economic and political power of labor organizations through substantive and procedural provisions specifically designed for that purpose. See discussions of legislative history in Amalgamated Meat Cutters v. Jewel Tea Co., 381 U.S. 676, 707, 85 S.Ct. 1596, 14 L.Ed.2d 640 (1965) (separate opinion of Goldberg, J.); Bodine Produce, Inc. v. United Farm Workers Organizing Committee, 494 F.2d 541, 555-56 (9th Cir. 1974). These labor laws reflect a social policy involving humanistic values far different from the economic model of free market competition protected by the antitrust statutes. The mutual exclusivity of these systems regulating business competition and organized labor is more apparent as an abstraction than it is in the actual interplay of forces in any given factual context. When labor organizations and business enterprises combine for purposes which are destructive of competition, without any corresponding benefits for unions or the collective bargaining process, the Supreme Court has intervened with applications of antitrust principles. So, in United Mine Workers v. Pennington, 381 U.S. 657, [85 S.Ct. 1585, 14 L.Ed.2d 626] (1965) the Court determined that the union was exposed to liability for the anticompetitive effects of an agreement with large coal producers to establish an industry-wide, all-purpose wage scale with a predatory intent to drive small producers out of the market. Yet, on the same day, the Court decided Amalgamated Meat Cutters v. Jewel Tea Co., 381 U.S. 676, [85 S.Ct. 1596, 14 L.Ed.2d 640] (1965), holding that a union's imposition of restrictions on marketing hours was exempt from antitrust liability because it was "intimately related to wages, hours and working conditions" and resulted from "bona fide, arm's-length bargaining in pursuit of their own labor policies, and not at the behest of or in combination with nonlabor groups . . .." Id. at 689-90, 85 S.Ct. at 1602. The concerns of the parties in this action result, primarily, from the majority opinion in Connell Construction Co. v. Plumbers & Steamfitters Local Union No. 100, 421 U.S. 616, [95 S.Ct. 1830, 44 L.Ed.2d 418] (1975). There, Connell, a contractor in the construction industry, sought judicial invalidation of a subcontracting agreement, forced upon it by union picketing, as a restraint of trade. The coerced contract required Connell to contract or subcontract work within the union's jurisdiction only to firms who were parties to a bargaining agreement with that union. The union was a party to a multiemployer bargaining agreement with an association of contractors, which contract contained a "most favored nation" clause which provided that in the event the union granted more favorable terms to any other employer, those same terms must then be extended to all members of the association. A union security clause was also included in the association agreement. Before the union picketing, Connell did not itself employ any workers in the union's trade and it had no previous collective bargaining relationship with the union. The majority of the Court found that the coerced agreement was a direct restraint on the "business market" through the indiscriminate exclusion of non-union subcontractors. The perceived effect of the "most favored nation" clause in the multiemployer contract was the elimination of competition between association members and other subcontractors because the union would not make any agreement which could give an unaffiliated contractor any competitive advantage over those who were in the association. Accordingly, the association members were sheltered from the threat of outside competition as to all of the subjects covered by their agreement, including matters unrelated to wages, hours and working conditions. Because the Connell subcontracting agreement not only prohibited the use of non-union employers, but required subcontractors to have a contract with the particular local union, that union gained the power to control access to the market for mechanical *1390 subcontracting work. That power could be used for purposes unrelated to the legitimate goals of organized labor. While conceding that there was no evidence that the union sought anything other than organizing subcontractors, the Court cited United Mine Workers v. Pennington, supra and concluded: This kind of direct restraint on the business market has substantial anticompetitive effects, both actual and potential, that would not follow naturally from the elimination of competition over wages and working conditions. It contravenes antitrust policies to a degree not justified by congressional labor policy, and therefore cannot claim a nonstatutory exemption from the antitrust laws. 421 U.S. at 625, 95 S.Ct. at 1836. The union also argued that the agreement with Connell was expressly authorized by the construction-industry proviso to the prohibition of secondary activity in § 8(e) of the LMRA, 29 U.S.C. § 158(e), thereby constituting an implied statutory exemption to antitrust proscriptions. That contention was rejected by a restrictive reading of the site agreement exclusion to § 8(e) as applicable only to agreements made "in the context of collective-bargaining relationships," and, probably, to "common-situs relationships on particular jobsites as well." 421 U.S. at 633, 95 S.Ct. at 1840. Accordingly, the agreement in Connell would be illegal under § 8(e). The Court concluded that such illegality did not exempt the union from antitrust suits because the majority found nothing in the legislative history to suggest that Congress intended the remedies in the LMRA to be exclusive of antitrust remedies for the same prohibited conduct. Such separate and independent analyses of the limitations of antitrust and labor laws seem inconsistent with the Supreme Court's recognition of an implied policy exemption from antitrust liability for activity which is within the recognized purposes of labor unions as reflected in Hutcheson, supra, and in Jewell Tea, supra. One reading those opinions might have expected the Court to conclude that because the Congress had prohibited the kind of coerced "top down organizing" which the union imposed in Connell by the provisions of the LMRA, the subject was a matter of labor law and should be excluded from consideration as to its effects on competition under the antitrust statutes. That result could have been reached as a policy exemption regardless of the analysis of the scope of the private remedy granted by § 303 of the LMRA, 29 U.S.C. § 187, made in the dissenting opinion of Mr. Justice Stewart. Under any view of the holding and opinion in Connell, it is not controlling here because of significant factual differences. Of primary importance is the fact that while the individuals who compose the Signatory Negotiating Committee are appointed by the president of the Colorado Contractors Association (an incorporated trade association of contractors) the committee's representation is not for the association; it is for individual contractors who have assigned bargaining rights, whether they are members of the CCA, another trade association, or unaffiliated with any contractors' organization. Thus, there is no tendency toward restricting competition from employers who are outside of a trade association. Another significant difference is that the subcontracting provisions of Article XVI have evolved through more than thirty years of negotiations in a collective bargaining context, and are contained in the current collective bargaining agreement between the parties. A third important distinction is that while the subcontractors in this case must accept the terms and conditions of the Master Agreement, they are not required to contract with the union. Those who do sign the Short Form Agreement as a project agreement are not required to recognize the union for any purposes and on any jobs which are not connected with the particular project and site covered under the terms and within the area of the Master Agreement. While it must be accepted that the applicability of the union security clause *1391 after 31 days on the site will have some organizing effect, that is only an incidental consequence and the parties have stipulated that many subcontracts on such construction projects will not last for a full thirty days. The hiring hall provisions are also enforced only to the extent of a need for additional employees after the subcontractor has begun the work. There is no requirement for replacement of non-union employees on his payroll. If these provisions are to be condemned as "top down organizing" it is better that restrictions on such activity by unions be made in the regulatory laws governing labor organizations than by attempting to address them under antitrust principles. The Master Agreement contains a "most favored nation clause." Connell did not hold that such a clause was per se an illegal restraint of trade. The anticompetitive effect in Connell resulted from the fact that the contract containing such a clause was with an association of contractors and the inhibition of the union in granting advantages to others had the necessary consequence of benefiting members of the association. The exemption of labor union activity and of collective bargaining contracts from the antitrust laws is dependent upon an analysis of the extent to which legitimate labor objectives are advanced by that which can be considered to have anticompetitive consequences. A union and an employer in the context of collective bargaining can reach an agreement which will have anticompetitive effects if the primary benefits are to matters of wages and working conditions. The combination of employers for the limited purpose of conducting negotiations with the union through a representative committee, open to all who choose to assign their bargaining rights, does not alter this exemption from antitrust consequences. Conversely, unions cannot use the guise of protecting labor concerns to impose direct restraints on a business market through agreements or combinations with non-labor organizations. Clearly the predominant interests involved in the agreement in this case are matters which are well within the legitimate concerns of organized labor as reflected in the policy established by the enactment of national labor legislation. Accordingly, Article XVI must be held to be exempt from the antitrust laws. Having reached that conclusion, it is not necessary to consider whether there can be any additional exemption implied from the proviso in Section 8(e) of the LMRA, and it is not necessary to determine whether anything in the application of the agreement could be considered to be an unfair labor practice. Having concluded that the subject agreement is excluded from antitrust regulation, it is ORDERED that the complaint herein is dismissed and judgment shall be entered for the defendant, without costs.

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Q: Why is .ForEach() on IList and not on IEnumerable? Possible Duplicate: Why is there not a ForEach extension method on the IEnumerable interface? I've noticed when writing LINQ-y code that .ForEach() is a nice idiom to use. For example, here is a piece of code that takes the following inputs, and produces these outputs: { "One" } => "One" { "One", "Two" } => "One, Two" { "One", "Two", "Three", "Four" } => "One, Two, Three and Four"; And the code: private string InsertCommasAttempt(IEnumerable<string> words) { List<string> wordList = words.ToList(); StringBuilder sb = new StringBuilder(); var wordsAndSeparators = wordList.Select((string word, int pos) => { if (pos == 0) return new { Word = word, Leading = string.Empty }; if (pos == wordList.Count - 1) return new { Word = word, Leading = " and " }; return new { Word = word, Leading = ", " }; }); wordsAndSeparators.ToList().ForEach(v => sb.Append(v.Leading).Append(v.Word)); return sb.ToString(); } Note the interjected .ToList() before the .ForEach() on the second to last line. Why is it that .ForEach() isn't available as an extension method on IEnumerable<T>? With an example like this, it just seems weird. A: According to Eric Lippert, this is mostly for philosophical reasons. You should read the whole post, but here's the gist as far as I'm concerned: I am philosophically opposed to providing such a method, for two reasons. The first reason is that doing so violates the functional programming principles that all the other sequence operators are based upon. Clearly the sole purpose of a call to this method is to cause side effects. The purpose of an expression is to compute a value, not to cause a side effect. The purpose of a statement is to cause a side effect. The call site of this thing would look an awful lot like an expression (though, admittedly, since the method is void-returning, the expression could only be used in a “statement expression” context.) It does not sit well with me to make the one and only sequence operator that is only useful for its side effects. The second reason is that doing so adds zero new representational power to the language. A: Because ForEach(Action) existed before IEnumerable<T> existed. Since it was not added with the other extension methods, one can assume that the C# designers felt it was a bad design and prefer the foreach construct. Edit: If you want you can create your own extension method, it won't override the one for a List<T> but it will work for any other class which implements IEnumerable<T>. public static class IEnumerableExtensions { public static void ForEach<T>(this IEnumerable<T> source, Action<T> action) { foreach (T item in source) action(item); } } A: Because ForEach() on an IEnumerable is just a normal for each loop like this: for each T item in MyEnumerable { // Action<T> goes here }

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Work hard and be nice to people Over the last month, just about every aspect of my life has been altered in some fashion. I moved to a new city, a new bedroom, with new roommates. I am the new girl (one of many) in my singles ward, with two new callings and all new people to meet (so far, they are wonderful and far too athletic). I got a new (to me) car, a new commute and a new monthly budget for gas (hint: its lower!). New running routes and a decided lack of new running partners. My job also moved to said new city and new building. Most importantly, my work gave me a new convertible standing desk. (The word new is starting to look weird now … New. New. New. See? Weird.) Now, with everything in my life being so new, it has been difficult to adjust and find a new normal. I’ve been understandably stressed and miraculously only had one panic attack of uncontrollable sobbing and . Usually I carry stress in my lower back. But not anymore! I have had a standing desk for all of eight days and after only two days my low back pain is gone. I’ve had low back pain caused by stress and laziness for about ten years so this is kind of a big deal. And the best part? I’m only standing about an hour and a half daily, spread out into three chunks throughout the day. Having a desk job is hard on your body. Everyone knows this so I won’t go into detail about how sitting is killing you. But I will say that I am so very grateful that I was given a standing desk. Its amazing how much better my whole body feels, like dropping the giant bag of rocks you didn’t know you were carrying. Another new things in my life is my FitBit Ultra. Like many of my possessions, I bought it second at a bargain and it has been working great as the previous owner never really used it. And now that I’ve become part of the FitBit madness and the 10K Steps a Day Program at my work, I have a new goal: to get 10K steps just at work. And so far, I’ve done it twice. Next week, I’m going to try to make it the whole week. I have been walking on my morning and afternoon breaks regularly for a few years now but it wasn’t nearly enough to reach 10K steps in 8 hours. Cue the standing desk! I have found a way of “walking” at my desk by trying to imitate the motion of walking while keeping the balls of my feet on the ground. That’s the best way I can explain it. Anyway, I can get about 100 steps per minute while at my desk. So I only have to “walk” at my desk for about an hour a day (spread out, of course) to reach my 10K steps a day at work. It takes a bit of disciple and I can’t do all of my tasks while bouncing at my desk but there is enough mindless work that this is very possible to do every day. I’ve always found a strange reassurance in Claire Danes’s unpretty cry face. Perhaps because I feel our faces look very similar when we cry. She is the one who always comes to mind when I try to think of hollywood stars that cry like real people. The scrunched chin, twitching, snot running, etc. So check out this tumblr for a bit of fun or have yourself a good cry in great company. It’s been about four months since Disney’s Frozen was released in theaters. And I assume that most people have had the chance to see it by now or they have at least heard the song “Let It Go,” gorgeously sung by Idina Menzel. She has such a unique gift to emote through music and I credit her with half the popularity of this song. If you didn’t have much of a reaction to the movie itself, I am guessing you had a strong reaction of some kind to this song. Whether that reaction was “I love this song!” or “Disney has a hidden agenda!,” I bet your reaction was one of strong emotion. If you are like me, you silently cried and you weren’t sure why. I’ve always been an emotional person. I cry when talking about anything too personal, spiritual or uncomfortable. And its ugly crying. The snot dripping out of your nose, voice clutching crying that you can’t stop. And my whole body shook as I cried in the theater listening to “Let It Go” for the first time in theaters. And I continued to cry the next dozen times I listened to it in my car. Why was I having such an emotional reaction to this song? I have been thinking about this for four months now. And it took me this long to put a name to what I was receiving a release from when listening to this song. It was shame. Specifically shame for having depression. As many of you know, I have battled depression for almost half of my life. And to this day I feel ashamed. That shame is not always from having depression but shame that I can’t just get over it, shame that I can’t be the perfect Wonder Woman my society and culture demands that I should be, with perfectly manicured nails and never breaking a sweat over anything. Shame that I can’t fix it and be done. Shame because my depression has no end. It is important to point out that shame is different from guilt. Guilt is actually a healthy thing at time. It makes you feel bad when you break your sister’s favorite CD or lie to your parents. To quote one of my favorite TedTalk speakers Brene Brown, “Shame is a focus on self, guilt is a focus on behavior. Shame is “I am bad.” Guilt is “I did something bad.”” When we feel guilt, we can change our behavior and it goes away. When we feel shame, it isn’t that easy because it is focused on a part of who we are. So even though I manage my depression very well through my behavior, I still feel shame for having it at all. For having to make the effort to deal with it, to never let it out of my sight because it might gang up on me in an alley if I let my guard down for even a second. So when Elsa began to sing (and even now as I type this) I cried because she was telling me to let go of my shame. She was telling me that it was okay and that she felt it too: Don’t let them in, don’t let them see Be the good girl you always have to be Conceal, don’t feel, don’t let them know Well, now they know Let it go, let it go Can’t hold it back anymore Let it go, let it go Turn away and slam the door I don’t care What they’re going to say Let the storm rage on, The cold never bothered me anyway For me personally this song was about my shame for depression. But the song writers were clever enough to make the song universal. Shame for being fat. Shame for being gay. Shame for being religious. Shame for having an addiction. Shame for being a nerd. Shame for being yourself. And when you decide to accept yourself as worthwhile, the storm of society’s judgement will rage on. Loving yourself is not an easy thing and the world might tell you loving yourself is wrong because you are wrong. But you can outlast the storm if you have love (something else Frozen taught us). I will forever be indebted to Kristen Anderson-Lopez and Bobby Lopez for writing this song. If you haven’t read about them, they are parents to two little girls and wrote Let It Go for them. I began writing this essay just hours before the Oscar’s and I was touched by their acceptance speech for best original song as it confirmed my understanding of this song and what it means to them and hopefully to every little girl who has been singing it on repeat for months now. We live in a world where the expectations are ridiculous and impossible for girls (and women) to achieve; a world that is almost guaranteed to make beautiful, wonderful, unique girls who once loved themselves suddenly feel that they don’t deserve that love from themselves or others anymore. Because they are ashamed of who they are and for not being able to live up to the standards of the world. And if there is one thing I know with absolute certainty it is that everyone in this world deserves love, from themselves and from others. And Frozen did a wonderful job showing that love can mend a broken heart. Don’t let fear or shame stop you from being awesome. Just be you. So to everyone who has criticized this movie and especially this song, stop it. This song has helped me to find greater love for myself than almost any psychology book or therapist ever has. Just let it go. This year was my third NaNoWriMo and it confirmed that NaNo will be a life-long tradition. NaNo noveling has helped shape my writing life in ways I never expected. In 2010, NaNo helped me to finish my first novel (first draft anyway) which was a revelation and a wake up call. I was a finisher for the first time since I outgrew fan fiction. In 2011, I learned how to continue to plot as I made discoveries about my characters along the way. I also worked out some personal issues with that novel which really helped to heal my heart and free my writing from old cobwebbed shadows. And 2012 was skipped due to my third successive move in five months at the beginning of November. My writing this last year has suffered and I know it is due to not pushing my boundaries with NaNoWriMo. Never again. So I entered this year’s NaNoWriMo with low expectations, finally writing my old “great golden idea” from high school, which I was certain would be a throw away novel just like every NaNo novel has been. Even so, this November gave me much more than could have expected. For the first time, I wasn’t scrambling for plot to fill up the last ten thousand words, instead passing 50K before the plot had ended, finishing NaNo’s word goal a day early (miracle of miracles!). I’ve learned a lot about my process and how to handle pressure. I wrote scenes that might be usable in later drafts (completely unheard of as I write terribly messy discovery drafts). And some of the writing was actually good. I wasn’t planning to revise, as I use NaNo as more of an experimental period than anything. But this story took hold of me and is demanding a rewrite. Possibly a musical but most definitely a rewrite. Most importantly of all, I’ve found confidence when facing the blank page. Even now, my stomach bunches in tight knots in the hour leading up to writing time every day. But the physical signs of anxiety I feel are no longer overwhelming. I doubt they will ever go away completely but now I can at least get them to sit in the corner quietly while I get my work done. I have momentum for the first time in forever. My writing well is full of inspiration, ideas and hope so bright I can almost imagine away the frigid temperatures outside. Almost. I owe a lot of my success this November to all my writing friends that took the journey with me. They were fierce competition this year, most of them beating me to the finish line, but straggling behind them still pulled me forward. And to the rest of my friends and acquaintances who commented and liked my status updates on Facebook, it meant the world to me. Thank you for letting me ignore you in November. I’m finally back. I work a desk job that is more often than not, repetitive and boring. To cope with this, I listen to several podcasts during the week to distract my brain. I’ve already mention some of my favorite writing podcasts (I Should Be Writing and Writing Excuses) but I haven’t really talked about any others so here I go! Stuff You Missed in History Class is a fabulous podcast with two hosts who have extensively researched a person, event, building, or other item of interest and condensed the information into a fun and informative 30 minute podcast. The best thing about this podcast is the introduction to bits of history I didn’t even know I was missing. In school, I never did well in histroy as I have no memory for dates and names. But every once in a while a bit of history intriques me and I would study on my own. This podcast does that for me as well as introducing me to things I might never have thought interesting enough to research on my own. I think this is a beneficial podcast for anyone who has a bit of writer’s block. I’ve learned so many interesting things, quite a few tidbits that pertain to my current WIP and future novels. Not to mention how inspiring the stories are. I’ve always said, you have to have something to write about to be a writer and this podcast will give you tons of ideas. Some of the more recent ‘casts I loved are Pluto: The Demoted Dwarf Planet, The Flannan isles Disappearance, and Who was the real Robin Hood? The podcast posts twice weekly and has been going since the beginning of 2008 so there is plenty to listen to. While listening to I Should Be Writing the other day, Noel Birch’s Four Levels of Competence were explained. Not only was this new to me, it helped me to distinguish the skill levels of many writers I have met. I have applied the Four Levels to writing for your enjoyment. Level One: Unconscious Incompetence You’re terrible. Really terrible. You’re so terrible you don’t even know how terrible you are. You have TALENT and therefore don’t need hard work, skill or ability. Often, this writer thinks they are the next J.K. Rowling, Stephen King, etc. and brings up their novel in every conversation imaginable. This is not always the case but we’ve all met these people on the bus or at a writing conference. You cannot help this person. Yet. “The only reason I’m not published is that I haven’t finished anything yet.” You realize how terrible you are. This may be followed by feeling overwhelmed or hopeless. You now recognize the value of hard work, skill and ability as well as how much there is to learn. This is where many give up because they recognize their mistakes. But mistakes are your friends. Keep going. You have worked hard, practiced and now have some writing ability. You are still breaking the beast of writing into smaller steps. you still make mistakes but now have the ability to fix them. With great concentration and a lot of time, you can write something worth reading. You are on the path of learning. “Just keep swimming, swimming, swimming.” – Dory, Finding Nemo Level Four: Unconscious Competence You have internalized all that writing knowledge and can now compose with ease. Sometimes you can even write while doing other tasks or in the midst of distractions. Writing is second nature. I love this breakdown. I’ve started to analyze all sorts of trades in my life with this system. I am definitely at level four when it comes to knitting. I can knit while doing almost anything and have yet to find a pattern I cannot master. When it comes to writing, I think I’m at level three. I can write more easily than I used to but I have yet to practice certain skills, like doing line edits on the 12th draft of a novel or writing a sequel. I often panic myself back to level two. So I guess I hover. But I wonder how many professional writers would rate themselves at level four. Can you ever truly reach level four as a writer? I feel like there is always more to learn. From all the writers I’ve met, I’ve observed the best ones to be humble enough to admit they don’t know it all. Emerson put it best: Shall I tell you the secret of the true scholar? It is this : Every man I meet is my master in some point, and in that I learn of him.

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Background ========== Previous systematic reviews indicate that children and youth using active modes of transportation such as walking or cycling to travel to/from school (e.g., active school transport; AST) accumulate more daily physical activity (PA) than those who are driven by car or bus \[[@B1],[@B2]\]. In addition, children who cycle to/from school have higher cardiovascular fitness than their peers using motorized travel modes \[[@B1],[@B3],[@B4]\]. Other investigators have also reported that AST was associated with greater academic achievement \[[@B5]\] and reduced stress \[[@B6]\]. Together, these findings suggest that AST should be promoted as a strategy to improve children's health and well-being. However, the proportion of children engaging in AST has decreased markedly over the last few decades in many countries including Australia \[[@B7]\], Canada \[[@B8]\], Switzerland \[[@B9]\], and the United States \[[@B10]\]. Furthermore, interventions aimed at promoting AST have generally achieved only modest shifts from car travel to AST \[[@B11],[@B12]\]. To inform the development of more effective interventions, a better understanding of the correlates of AST is warranted. Current theoretical models that seek to predict AST are typically based on the social ecological approach \[[@B13],[@B14]\] which posits that behaviour is determined by the interactions between multiple levels of influence. These include characteristics of the individual, the social environment, the built environment, public policies, and the physical environment \[[@B15],[@B16]\]. To date, few studies have assessed school-level factors associated with AST while controlling for relevant individual characteristics and clustering within schools \[[@B17]-[@B19]\]. Rooted in a social ecological approach, such investigations have the potential to unravel interactions between multiple levels of influence and to identify promising intervention strategies \[[@B20]\]. Therefore, the present study investigated the socio-demographic and school-level correlates of AST among 10-year-old children in Ottawa, Canada. Data were collected from multiple sources (child and parent questionnaire, school administrator survey and school audit) in order to examine multiple levels of influence. The overarching goal was to identify factors accounting for the between-school variation in AST to inform the development of future interventions. Methods ======= Participants ------------ The present study used data from the Canadian site of the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE). Based on the social-ecological model, this 12-country cross-sectional study aimed to collect data on the correlates of childhood obesity at the individual, family, neighbourhood, and school environment levels. Greater details concerning the study design are available elsewhere \[[@B21]\]. The Canadian site consisted of 567 grade five students (239 boys and 328 girls; 9--11 years of age) recruited between September 2012 and May 2013 in 26 schools within the Ottawa region. The Ottawa-Gatineau region is the fourth largest census metropolitan area in Canada, and the population is predominantly English speaking, albeit with a large French speaking minority \[[@B22]\]. Schools were stratified into four groups: English Public (n = 393; 69.3%), French Public (n = 60; 10.6%), English Catholic (n = 75; 13.2%), and French Catholic (n = 39, 6.8%). The response rate was 50%. This study was approved by the research ethics boards of the Children's Hospital of Eastern Ontario, and the participating school boards. Written informed parental consent and child assent were obtained for all participants. Procedures ---------- First, trained study staff administered a child questionnaire in schools \[[@B21]\]. Travel mode was assessed with one item ("*in the last week you were in school, the MAIN part of your journey to school was by*"). Response options were: 1) walking; 2) bicycle, rollerblade, skateboard, scooter; 3) bus, train, tram, underground, or boat; 4) car, motorcycle, or moped; 5) other. Children who reported "other" were asked to specify their travel mode. Children were also asked to report their usual school journey time. Categories were: 1) \<5 minutes; 2) 5--15 minutes; 3) 16--30 minutes; 4) 31 minutes to 1 hour; 5) \>1 hour. Second, socio-demographic variables were obtained through a parent questionnaire \[[@B21]\] (Table  [1](#T1){ref-type="table"}). Information on annual household income (eight levels), mother's education (six levels), number of functioning motorized vehicles (five levels), and the child's gender and ethnicity were examined in the present analyses. Two school-level socio-demographic variables were considered in analyses: school language (English or French) and school board (Public or Catholic). ###### Socio-demographic correlates of active school transport **Variable** **Categories** **Frequency** **Percentage** **OR** **95% CI** **p** -------------------- ---------------- --------------- ---------------- ----------- ------------ ------- Gender Boys 239 42.2 1.98 1.31-2.98 .001 Girls 328 57.8 Reference School travel mode Active 199 35.1 N/A Public transport 368 64.9 School travel time \<5 minutes 134 23.6 2.39 1.24-4.63 .010 5-15 minutes 289 51.0 2.44 1.37-4.34 .002 \>15 minutes 144 25.4 Reference Household income \<\$60,000 105 19.3 0.77 0.40-1.49 .439 \$60,000-\$139,999 231 42.4 0.87 0.54-1.40 .552 ≥\$140,000 209 38.3 Reference Mother's education \<College 85 15.2 1.52 0.84-2.76 .169 College 142 25.4 0.72 0.43-1.21 .216 University 331 59.3 Reference Motorized vehicles ≤1 236 42.1 1.25 0.81-1.94 .321 ≥2 325 57.9 Reference School language French 99 17.5 0.19 0.06-0.64 .007 English 468 82.5 Reference School board Catholic 114 20.1 0.61 0.09-1.06 .061   Public 453 79.9 Reference Note: Odds ratios for engaging in active transportation were estimated using generalized linear mixed models adjusted only for school clustering. Third, the school environment was assessed with a questionnaire completed by a school administrator (e.g., the principal). Questionnaire items were taken from the School Health Environment Survey which is a component of the Canadian School Health Action, Planning and Evaluation System \[[@B23]\]. Satisfactory test-retest reliability and convergent validity between school administrators and teachers was noted in a separate purposive sample of Ontario educators, as reported in details elsewhere \[[@B24]\]. Of particular interest, administrators were questioned about the existence of school policies related to PA and healthy eating, on school facilities that may influence children's mobility (i.e., the presence and safety of bike racks) and on school-based promotion of AST (i.e., identification of safe routes to school, organization of events such as walk to school days). They were also asked whether they perceived religious tensions, litter in the streets, drugs/drinking, gangs, heavy traffic, vacant/shabby houses, and crime as a problem in the school neighbourhood on 4-point Likert scales ranging from "major problem" to "not a problem", with a "don't know" option for each question. Eighteen variables from the administrator questionnaire were considered for the present analyses (Table  [2](#T2){ref-type="table"}). ###### School-level correlates of active school transport, as reported by school administrators **Variable** **Categories** **Frequency** **Percentage** **OR** **95% CI** **p** ------------------------------------------------- -------------------------- --------------- ---------------- ------------ ------------ -------- Physical activity policies\* Existing policies 501 88.4 1.99 0.38-10.46 .415 Practices 66 11.6 Reference Healthy eating policies\* Existing policies 499 88.0 0.51 0.10-2.58 .413 Practices 68 12.0 Reference Identify safe routes to school Yes 289 51.0 3.63 1.39-9.44 .008 No 278 49.0 Reference Provides crossing guards Yes 284 50.1 5.75 2.52-13.10 \<.001 No 283 49.9 Reference Designate car free zone Yes 238 42.0 1.52 0.52-4.49 .448 No 329 58.0 Reference Allow students to bring bicycles\* Yes 534 94.2 3.29 0.48-22.42 .224 No 33 5.8 Reference Allow students to bring small wheel vehicles^†^ Yes 351 61.9 2.72 0.94-7.84 .064 No 216 38.1 Reference Encourage use of helmets and safety gear\* Yes 544 95.9 1.17 0.14-9.53 .887 No 23 4.1 Reference Organize events (i.e. walk to school days) Yes 131 23.1 1.25 0.38-4.13 .718 No/don't know 436 76.9 Reference Access to bike racks during school hours\* Yes, on grounds only 527 92.9 2.98 0.50-17.70 .229 No 40 7.1 Reference Bikes stored in a secure area Yes 383 67.5 1.38 0.45-4.22 .571 No/don't know 184 32.5 Reference Religious tension perceived as problem\* Major/moderate 43 7.6 1.73 0.29-10.13 .544 Minor 153 27.0 1.68 0.43-6.62 .459 No problem or don't know 372 65.4 Reference Garbage/litter perceived as problem\* Major/moderate 52 9.2 3.31 0.66-16.52 .145 Minor 235 41.4 1.69 0.52-5.47 .380 No problem or don't know 280 49.4 Reference Drugs/drinking perceived as problem\* Major/moderate 30 5.3 4.36 0.78-24.54 .094 Minor 92 16.2 0.72 0.14-3.56 .683 No/don't know 445 78.5 Reference Gangs perceived as problem\* Major/moderate 25 4.4 3.98 0.64-24.87 .140 Minor 45 7.9 1.47 0.27-7.99 .654 No problem or don't know 497 87.7 Reference Traffic perceived as problem Major/moderate 126 22.2 3.41 0.86-13.56 .081 Minor 254 44.8 1.30 0.39-4.37 .671 No problem or don't know 187 33.0 Reference Vacant/shabby housing perceived as problem\* Major/moderate 28 4.9 4.11 0.73-23.32 .110 Minor 43 7.6 4.26 0.58-31.15 .153 No problem or don't know 496 87.5 Reference Crime perceived as problem\* Major/moderate 33 5.8 5.99 1.24-28.87 .026 Minor 190 33.5 1.89 0.57-6.29 .302   No problem or don't know 344 60.7 Reference Note: Odds ratios for engaging in active transportation were estimated using generalized linear mixed models adjusted only for school clustering. \*Denotes that fewer than 5 schools have one of the categories being compared; these results should be interpreted with caution. ^†^Includes skateboard, rollerblades, scooters. Fourth, a school audit was performed by a single trained examiner at each participating school \[[@B21]\] to examine opportunities for PA in the school environment. A photo dictionary was created to standardize data collection procedures. Most of the included items were taken from the Sport, Physical Activity and Eating Behaviour: Environmental Determinants in Young People (SPEEDY) study audit \[[@B25]\] which has shown acceptable inter-rater reliability and construct validity (as assessed with accelerometry-measured PA). Fourteen items were retained for the present analyses (Table  [3](#T3){ref-type="table"}). Twelve items pertained to walking and cycling provisions in the school environment. The auditor was asked to indicate whether these items were visible from any school entrance. A similar item on the visibility of fast food restaurants from any of the school entrances was added by the ISCOLE team \[[@B21]\]. Finally, land use (as perceived by the auditor) was assessed with a single question ("*Is the area around the school predominantly*?"): 1) "residential"; 2) "open fields/commons/parks"; 3) "business/retail"; 4) "a mixture of different land uses". Previous research shows that land use mix is an important correlate of adults' active transport, although its influence on children's mobility remains equivocal \[[@B26]\]. ###### **School-level correlates of active school transport, as observed in the school audit**^†^ **Variable** **Categories** **Frequency** **Percentage** **OR** **95% CI** **p** ------------------------------------------------------ ---------------- --------------- ---------------- ----------- ------------ ------- Predominant land use around school\* Residential 508 89.6 0.64 0.14-2.95 .643 Others 59 10.4 Reference Place where parents can stop and drop children off\* No 8 1.4 7.69 0.72-81.90 .091 Yes 559 98.6 Reference Place where parents can park their cars\* No 88 15.5 2.32 0.44-12.16 .319 Yes 479 84.5 Reference Bus stop No 85 15.0 2.00 0.57-7.02 .276 Yes 482 85.0 Reference Cycle lane separated from the road\* No 567 100.0 N/A Yes 0 0.0 Cycle lane on the road No 531 93.7 0.46 0.03-6.48 .556 Yes 36 6.3 Reference Sidewalks on both sides^‡^ No 93 16.4 3.07 0.85-11.04 .086 Yes 474 83.6 Reference Sidewalks on one side only No 328 57.8 0.37 0.13-1.04 .060 Yes 239 42.2 Reference Marked pedestrian crossing No 104 18.3 3.17 0.98-10.27 .054 Yes 463 81.7 Reference Traffic calming measures No 333 58.7 4.05 1.52-10.79 .005 Yes 234 41.3 Reference School warning sign for road users\* No 11 1.9 1.12 0.07-19.16 .937 Yes 556 98.1 Reference Road safety sign No 56 9.9 1.29 0.32-5.12 .722 Yes 501 90.1 Reference Route sign for cyclists No 437 77.1 0.55 0.16-1.91 .345 Yes 130 22.9 Reference Fast food restaurants No 352 62.1 0.41 0.14-1.20 .102   Yes 215 37.9 Reference Note: Odds ratios for engaging in active transportation were estimated using generalized linear mixed models adjusted only for school clustering. \*Denotes that fewer than 5 schools have one of the categories being compared; these results should be interpreted with caution. ^†^For all school audit items except land uses, the auditor was asked to specify if any of the items were visible from any school entrance. ^‡^If any of the road segments observed had sidewalks on both sides, this item was coded as yes. Data treatment -------------- Children's travel mode was dichotomized as active (walk, cycle, etc.) vs. inactive (car, bus, etc.). Participants who reported 'other' modes (n = 2) indicated running or jogging; hence, they were classified as active travelers. Given the large number of categories in the questionnaires, socio-demographic variables were recoded based on the observed distributions (Table  [1](#T1){ref-type="table"}). School travel time was categorized as 1) \<5 minutes; 2) 5--15 minutes; 3) \>15 minutes. Most journeys longer than 15 minutes were done by car or bus, so collapsing the response options did not have a marked influence on the results. Annual household income was categorized as 1) \< \$60,000; 2) \$60,000-\$139,999; 3) ≥ \$140,000. Mother's education was categorized as 1) \< college; 2) college; and 3) university. Motorized vehicle ownership was dichotomized as one or none versus two or more. Given that few administrators perceived major safety problems in the school neighbourhood, their responses to these seven items were recoded as 1) major/moderate problem; 2) minor problem; and 3) not a problem/don't know. In addition, if administrators did not know whether their school identified safe routes to school, it was assumed that they did not. This assumption was based on the fact that school travel planning \[[@B27]\] is a whole-of-school intervention that mobilises school administrators, teachers, students, and the broader community; thus, administrators would be expected to know if such a scheme was in place at their school. Finally, land use was recoded as "residential" versus "others". Statistical analyses -------------------- Generalized linear mixed models (GLMM) with a binomial distribution and logit link were used to examine the socio-demographic and school-level correlates of children's travel mode (e.g., active vs. inactive) following analytical procedures described by Cerin \[[@B20]\]. First, a model was fitted with only school entered as a random effect to determine the within-school intra-class correlation coefficient (ICC). Specifically, the greater the ICC, the more students attending the same school used the same travel mode. Second, socio-demographic variables were added as fixed effects in the model adjusted for school clustering. Only variables that were significant at the 0.05 level were kept in the model, and interactions among these variables were examined. Third, school-level factors were individually added to the model developed in step 2. Only school-level factors that were significant at the 0.05 level were retained for the final model. The school audit item pertaining to bike lanes separated from the road was omitted, because this feature was absent in all schools. Fourth, a final model was fitted with the socio-demographic and school level correlates that were found to be significantly associated with AST, and interactions among these variables were examined. All analyses were performed using IBM SPSS version 21 (Armonk, United States). Results ======= Descriptive characteristics of the sample are shown in Tables  [1](#T1){ref-type="table"}, [2](#T2){ref-type="table"}, [3](#T3){ref-type="table"}. 35.1% of participants reported that they regularly engaged in AST (33.9% walking and 1.3% other active modes). Conversely, 38.6% of participants reported using public transportation (i.e., school buses) and 26.3% traveled by car. Approximately half of the participants reported school travel times between 5 and 15 minutes while the remainder was rather evenly distributed across the \<5 minutes and ≥15 minutes categories. Parents reported relatively high income and over half of the mothers had received university education. 42.1% of parents owned ≤1 motorized vehicles while 57.9% owned ≥2 vehicles. In general, most school administrators indicated having written PA and healthy eating policies in place, and their school reportedly encouraged AST through various strategies. School administrators tended to perceive the school neighbourhood as relatively safe, and the most frequently reported concern was traffic safety. Broadly speaking, the school audit revealed that most schools were located in predominantly residential areas and there was generally good infrastructure to support walking. However, provision of cycling infrastructure was very poor with few bike lanes and traffic signs for cyclists. The initial GLMM indicated large clustering of AST at the school level (ICC = 0.31; *p* = 0.005), emphasizing the importance of controlling for school clustering. In models adjusted only for school clustering, boys (OR = 1.98; 95% CI = 1.31-2.98) and participants reporting school trip durations of \<5 minutes (OR = 2.39; 95% CI = 1.24-4.63) or 5--15 minutes (OR = 2.44; 95% CI = 1.37-4.34) were significantly more likely to engage in AST compared to girls and those with travel times \>15 minutes (Table  [1](#T1){ref-type="table"}). No interactions were observed between gender and school travel time (data not shown). Income, mother's education, car ownership and school board (e.g., public or catholic) were not associated with AST. However, lower odds of AST were noted in children attending French schools (OR = 0.19; 95% CI = 0.06-0.64). Table  [2](#T2){ref-type="table"} shows that three of the administrator survey items were significantly associated with AST. Specifically, children were more likely to engage in AST if administrators reported that the school identified safe routes to school (OR = 3.63; 95% CI = 1.39-9.44) or that crossing guards were employed (OR = 5.75; 95% CI = 2.52-13.10). If administrators perceived that crime was a major or moderate problem in the school neighbourhood children were more likely to engage in AST than if crime was not perceived as a problem (OR = 5.99; 95% CI = 1.24-28.87). This effect should be interpreted cautiously given that only three administrators (representing 33 students) perceived crime as a major or moderate problem. Finally, if traffic calming measures (i.e., speed bumps, narrower lanes) were observed during the school audit, children were significantly more likely to be active travelers (OR = 4.05; 95% CI = 1.52-10.79). In the fully adjusted model (Table  [4](#T4){ref-type="table"}), the observed associations of gender and school travel time remained significant and their effect sizes remained virtually unchanged. Specifically, boys (OR = 1.99; 95% CI = 1.30-3.03) and participants reporting school trip durations of \<5 minutes (OR = 2.26; 95% CI = 1.17-4.37) or 5--15 minutes (OR = 2.27; 95% CI = 1.27-4.03) were more likely to engage in AST. The provision of crossing guards was also associated with greater odds of AST (OR = 2.29; 95% CI = 1.22-4.30). Again, if administrators perceived that crime was a major or moderate problem in the school neighbourhood, children were more likely to use AST (OR = 3.34; 95% CI = 1.34-8.32). Finally, an interaction was observed between the identification of safe routes to school and the presence of traffic calming measures (Figure  [1](#F1){ref-type="fig"}). If both features were present (i.e., safe routes to school combined with traffic calming measures), children were almost eight times more likely to engage in AST (OR = 7.87; 95% CI = 2.85-21.76). If only one of these features were present, it was not associated with a greater likelihood of AST. Differences between children attending French vs. English schools were no longer significant. The final model explained most of the clustering of AST at the school level as shown by the very small ICC of 0.01 (p = 0.718). ###### Multivariate associations of socio-demographic and school-level factors with children's engagement in active transportation **Variable** **Categories** **OR** **95% CI** **p** ----------------------------------------------------- ---------------- ----------- ------------ -------- Gender Boys 1.99 1.30-3.03 .002 Girls Reference School travel time \<5 minutes 2.26 1.17-4.37 .015 5-15 minutes 2.27 1.27-4.03 .006 \>15 minutes Reference School language French 0.71 0.31-1.62 .411 English Reference **School administrator survey variables** Identify safe routes to school Yes 1.03 0.52-2.04 .935 No Reference Provides crossing guards Yes 2.29 1.22-4.30 .010 No Reference Crime perceived as problem\* Major/moderate 3.34 1.34-8.32 .010 Minor 1.19 0.68-2.08 .543 Not a problem Reference **School audit variables** Traffic calming measures Yes 1.06 0.52-2.16 .865 No Reference Safe routes to school X Traffic calming interaction Both yes 7.87 2.85-21.76 \<.001   Both no Reference Note: Odds ratios for engaging in active transportation were estimated using generalized linear mixed models adjusted only for school clustering. Only variables that were significantly associated with active school transport in the bivariate models (e.g., Tables  [1](#T1){ref-type="table"}, [2](#T2){ref-type="table"}, [3](#T3){ref-type="table"}) were included in the multivariate model. In the empty model, the school ICC was 0.31 (p \< 0.001) while in the fully adjusted model, it was 0.01 (p = 0.718). \*Denotes that fewer than 5 schools have one of the categories being compared; these results should be interpreted with caution. {#F1} Discussion ========== The present study assessed the socio-demographic and school-level correlates of AST among 10-year-old children in Ottawa, Canada. Analyses indicated that approximately 31% of the variance in AST was explained at the school level. The final model shows that boys, children whose school journey was shorter, and those attending schools where crossing guards were employed were approximately twice as likely to engage in AST. When school administrators reported that crime in the school neighbourhood was a major or moderate problem, children were over three times more likely to engage in AST. Of particular interest, there was a synergy between the identification of safe routes to school (as reported by administrators) and the presence of traffic calming measures (ascertained by the study team). Specifically, when both of these characteristics were present, children were almost eight times more likely to engage in AST. Collectively, these findings should be relevant for policy-makers, education leaders, public health workers, and urban/transport planners interested in facilitating children's AST. To our knowledge, no previous study has reported such a synergy between the identification of safe routes to school and the presence of traffic calming measures in the vicinity of the school. Nevertheless, this finding is consistent with a recent evaluation of the Safe Routes to School program in Oregon, United States \[[@B28]\]. Specifically, McDonald and colleagues \[[@B28]\] reported that more comprehensive interventions (including education and encouragement programs combined with infrastructure improvements) were more effective, achieving 5--20 percentage points increases in walking and cycling. Together, these findings suggest substantial interactions between the social environment and the built environment, as postulated by social ecological models \[[@B15],[@B16]\]. Nevertheless, this relationship could also be driven by unmeasured variables such as the average distance between home and school \[[@B26],[@B29]\] or neighbourhood walkability \[[@B17],[@B30]\] which are known to influence travel behaviours. This underscores a need for further studies. Interestingly, neither the identification of safe routes to school nor the presence of traffic calming measures was independently associated with children's AST in the adjusted model. This finding may suggest that interventions focusing only on the promotion of AST or on infrastructure changes may be insufficient to trigger behaviour change. Of particular interest, the Canadian school travel planning model uses a comprehensive approach where school specific interventions are developed to change travel behaviours and improve safety based on input from members of the school community (e.g., students, parents, and teachers) and other stakeholders \[[@B26]\]. Recent evaluations of this approach have revealed either a modest increase in AST \[[@B26]\] or no significant differences in travel behaviours \[[@B12]\]. These somewhat disappointing results may be attributable to the fact that schools were followed for only one year, and this time frame is likely too short for comprehensive school travel plans to be fully implemented, or their impact realized \[[@B12]\]. This hypothesis is supported by the results of the New Zealand school travel planning intervention which indicated significant increases in AST after three years of implementation, but not after only one year \[[@B31]\]. Hence, there remains a need for longer investigations examining the effectiveness of this program as well as moderators and mediators of behaviour change. AST was also strongly associated with the presence of crossing guards, as reported by the school administrators. This finding is consistent with recent studies in the city of Toronto \[[@B32]\], the United States \[[@B33]\], and the United Kingdom \[[@B19]\]. Interestingly, hiring crossing guards may represent an easier (and relatively inexpensive) strategy to encourage AST compared to major built environment changes \[[@B32]\]. Notably, children were more likely to engage in AST if school principals perceived that crime was a major or moderate problem in the school neighbourhood. While counter-intuitive, this finding is in agreement with previous research reporting a greater likelihood of AST if parents did not perceive their neighbourhood as safe \[[@B34]\] or as an excellent area to raise a child \[[@B35]\]. Other researchers also reported higher rates of AST in areas characterized by greater incivilities \[[@B36]\]. Nevertheless, longitudinal studies are warranted to examine whether such associations may be attributable to reverse causality; e.g., school officials may be more concerned about neighbourhood safety if they are aware that a large proportion of students walk or cycle to/from school. In addition, several North American studies have reported higher rates of AST in low SES areas \[[@B18],[@B37],[@B38]\] where motorized travel may not be an available option. In the present study, area deprivation (as estimated using the median household income of the census tract in which the schools were located) was not associated with AST (data not shown). The observation that children who had longer journeys to school were less likely to engage in AST is consistent with previous literature reviews indicating that long distance between home and school is a major barrier to AST \[[@B26],[@B29]\]. Furthermore, Torres et al. \[[@B39]\] reported lower rates of AST among children attending English schools in Montréal and Trois-Rivières (Québec) and noted that these children traveled greater distances to/from school. Our results show a similar association whereby children attending minority language schools (in this case, French) were approximately five times less likely to engage in AST after adjustment for school clustering. This association was no longer significant in the fully-adjusted model which included school travel time as a proxy for home-school distance. While it may not be feasible for children living far away from their school to do the entire trip on foot, a drop off zone could be designated within a "walkable" distance, so that children who are driven to school by car or bus can engage in some AST \[[@B40]\]. For example, a partnership was successfully developed to allow school buses to use the parking lot of a nearby church as part of a Safe Routes to School intervention in Atlanta, United States \[[@B41]\]. In the present study, boys were twice as likely as girls to engage in AST. This observation is consistent with many North American studies reporting higher rates of AST in boys \[[@B18],[@B37],[@B42],[@B43]\]. Furthermore, at any given age, boys generally have greater independent mobility than girls \[[@B44],[@B45]\]. Independent mobility refers to "the freedom of children to travel around their own neighbourhood without adult supervision" \[[@B46]\] and it has been repeatedly shown to be associated with greater AST and PA levels \[[@B47]-[@B49]\]. However, in Denmark, where cycling to school is much more prevalent and safer, no gender gaps have been reported \[[@B3]\]. The present findings should be interpreted cautiously given the cross-sectional study design which makes it impossible to determine the direction of the observed relationships. Moreover, the correlates of children's current travel mode may differ from those of travel behaviour change, emphasizing a need for longitudinal investigations. A second limitation to consider is that all participating schools were recruited in the Ottawa region, so it is unclear whether similar associations would have been found elsewhere. However, multiple studies of correlates of AST have found associations with variables such as distance \[[@B26],[@B29]\] and the presence of crossing guards \[[@B19],[@B32],[@B33]\] in various jurisdictions. Third, although walking and cycling may have different correlates, it was unfeasible to examine them separately owing to the scarcity of cycling in the sample. Fourth, only environmental characteristics around the school were examined. Previous research suggests that characteristics of the home neighbourhood and the route between home and school may also influence children's travel behaviours \[[@B13],[@B19]\]. Fifth, the reliability and validity of the travel mode questions was not assessed. However, previous research suggests that similar questions have high test-retest reliability and convergent validity between child and parent reports \[[@B50],[@B51]\]. Furthermore, three studies have examined the test-retest reliability of school travel time questions among children of this age, and they all reported high coefficients (ICC ranging from 0.70 to 0.94), indicating that children can provide reliable estimates \[[@B52]-[@B54]\]. Finally, the relatively small number of clusters (e.g., 26 schools) may have led to lesser precision in the estimates as suggested by the large confidence intervals observed for many of the school-level factors. However, the examination of the relative influence of socio-demographic and school-level correlates of AST while controlling for school clustering is an important strength of the study. Previous Canadian studies had shown large between-school variation in AST \[[@B18],[@B55],[@B56]\]. By identifying the factors accounting for the clustering of AST at the school level, the present study provides valuable insights for future school-based interventions and policies. Second, school-level factors were examined both from the perspective of school administrators and from a school audit performed by the study team, thus providing complementary information on a wide range of potential correlates of AST. Third, the sample was stratified according to school language and school board. After adjustment for school clustering, children attending French schools were about five times less likely to engage in AST, suggesting that interventions and policies targeting this minority population may be needed. Finally, complete data were available for all of the variables included in the final model. Conclusion ========== This study found that boys, children reporting shorter school journeys, and those attending schools where crossing guards were employed or where school administrators expressed concerns about crime in the school neighbourhood were more likely to engage in AST. Furthermore, there was a strong synergy between the identification of safe routes to school and the presence of traffic calming measures in the school neighbourhood, suggesting that these strategies should be used in combination. Together, these variables explained the majority of the clustering of AST at the school level. Future longitudinal studies should examine these variables as potential correlates of travel behaviour change in the context of AST interventions. Competing interests =================== The authors declare that they have no competing interests. Authors' contributions ====================== RL, JPC and MST conceived the analysis plan. RL conducted the statistical analyses and drafted the manuscript. GL coordinated the study and CB, PB, AGL and MMB were involved in data collection. JPC and MST were the Principal Investigators for the Canadian ISCOLE site. All authors carefully reviewed and commented the first draft and approved the submitted version. Pre-publication history ======================= The pre-publication history for this paper can be accessed here: <http://www.biomedcentral.com/1471-2458/14/497/prepub> Acknowledgements ================ We would like to thank Claire Francis, Jessica McNeil, Nina Azoug-Boneault and Hadiza Amedu-Ode for their role in data collection for the Canadian site of ISCOLE, and the Coordinating Center of ISCOLE in Baton Rouge, Louisiana, specifically Drs. Peter Katzmarzyk and Timothy Church. We would also like to thank the study participants along with their parents, teachers and school principals for their involvement in the study. The ISCOLE study was funded by the Coca-Cola Company. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors also wish to thank Dr. Nick Barrowman for his advice on the statistical analyses.

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The secretary of state, John Kerry, said on Sunday that all the evidence surrounding the downed Malaysian passenger plane pointed a clear finger at Ukrainian separatists. Kerry appeared on all five major Sunday talkshows to lay out the administration's case against the separatists and to call on Russia to act and stop them from blocking an investigation into the firing of a surface-to-air missile that brought down Malaysia Airlines flight 17 on Thursday, claiming 298 lives. The secretary of state also took aim at Russia for its support of the separatists, days after the foreign minister, Sergei Lavrov, said President Barack Obama should “stop lecturing Russia”. “Russia has armed the separatists,” Kerry told ABC's This Week. “Russia has supported the separatists. Russia has trained the separatists. Russia continues to refuse to call publicly for the separatists to engage in behaviour that would lend itself to a resolution of this issue. “And the fact is that only a few weeks ago, a convoy of 150 vehicles of artillery, armoured personnel carriers, multiple rocket launchers, tanks, crossed over from Russia into this area and these items were all turned over to the separatists.” Kerry said management of the MH17 crash site was “grotesque” and Russia needed to intervene. Speaking on CNN's State of the Union, Kerry said: “We have enormous input about this that points fingers. It is pretty clear that this was a system from Russia, transferred to separatists. We know with confidence that the Ukrainians did not have such a system anywhere near the vicinity at that point of time.” He said the US knew that in the last month there had been a “major flow of arms and weapons from Russia to the eastern part of Ukraine and turned over to the separatists”. Kerry said social-media reports and US surveillance put the missile system in question in the vicinity of the crash ahead of the tragedy. “We know because we observed it by imagery that at the moment of the shootdown we detected a launch from that area,” he said. “Our trajectory shows that it went to the aircraft. “We also know to a certainty that social media immediately afterwards saw reports of separatists bragging about knocking down a plane and then the so-called defence minister of Donetsk, Igor Strelkov, posted a report bragging about the shootdown of a transport plane.” The case against the separatists was further backed by evidence from voice intercepts and a video of a launcher moving back into Russia with at least one missing missile, said Kerry. Kerry called on Russia to “step up publicly and join in the effort to make sure there is a full-fledged investigation”, and said he had spoken to Lavrov on Saturday. “It was a direct and tough conversation,” he said. On NBC's Meet the Press, Kerry said management of the MH17 crash site was “grotesque”. “What's happening is really grotesque. And it is contrary to everything that president [Vladimir] Putin and Russia said that they would do,” Kerry said. “There are reports of drunken separatist soldiers unceremoniously piling bodies into trucks, removing both bodies, as well as evidence, from the site. “The separatists are in control. And it is clear that Russia supports the separatists, supplies the separatists, encourages the separatists, trains the separatists. And Russia needs to step up and make a difference here.” Dianne Feinstein, the chair of the Senate select committee on intelligence, told CNN the type of equipment Russia had supplied to the separatists should only to go to someone with “an ethical compass. Now we find out it’s been given to separatists who are in many respects thugs. And it's been used in a very terrible way.” “The nexus between Russia and the separatists has been established very clearly,” Feinstein added. “So the issue is, where is [President Vladimir] Putin? I would say, 'Putin you have to man up. You have to say this was a mistake,' which I hope it was.”

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Some details of this accommodation and a link to the accommodation's website will be attached automatically. 10390 Languages spoken: German | Offered by: Agency | Update: 3/24/15 Description My destination on the Tuscan coast is camping Le Capanne. The course is flat and surrounded by olive trees, pines and typical for this region eucalyptus trees. This donate much in the shadow of this really sunny region of Italy. Mobilheim Chalet 11 x Contact Special offer: 14:12 = residence before 05.07.08 and down from 23.08.08 14:10 = residence from 06.09.08 21:14 = residence before 05.07.08 and from 23.08.08 The environment is incredibly rich in cultural monuments. On very short intervals, you will find the famous Bolgheri-known for its culinary specialties and to the appropriate wines. The road to Bolgheri also offers much to see. Some of the many examples are, for example, The kerzengeraden Zypressenhaine, many holiday album embellish or the beautiful location Castagneto Carducci. The area is suitable for sporting recorded tours. Many bike athletes come here early in the season to be in the mild climate of the time, preparing for competitions. A little further away are celebrities such as San Gimignano, Siena and Volterra-and a great experience certainly is a day trip to Elba. The camp itself organized after bus drivers and others Rome and Florence. He must do much more than just to offer. There are plenty of opportunities for your camping vacation an unforgettable experience to make zb The great pool, the tennis courts and the huge playground. But remember this great offer is not even from the rest of Tuscany to enjoy. • Swimming pool with slide • Playground • Animation • Volleyball • Football • Tennis • Rent a bike • Table Tennis • Restaurant • Pizzeria • meals to take away • Bar • TV • Supermarket • washing machines • 4 km from the sea Reception There will be Italian, German, French and English spoken. Water Sports In 2003, a whole new pool complex built: The system comprises 1200 m² and offers different water depths for swimming and playing, there is a children's pool, a pool, a Jacuzzi, waterfalls, a water slide and a large lawn with palm trees Open: 3.05. Until 15.09. Bathing cap duty Boxer shorts are not allowed Sports in general Bicycle rentals (mountain bikes), adults pay 42, - € / week and 6-€ / day, and children pay 42, - € / week and 5, - € / day Tennis (concrete court, 6, - € / hour) Football Miniature Golf (free, small deposit for racket) Table Tennis (3 gaming tables) Volleyball Archery Table football Playground Beaches The beach is 4 km from the square (Marina di Bibbona), but in the high season, there are two times a day with a free shuttle In the vicinity, there are more beautiful beaches (Donoratico, San Vicenzo) with good water sports facilities Beautiful places in the vicinity During the season, bus tours to Rome, and Florence offered Elba Volterra (old Etruscan town, about 48 km away) San Gimignano (medieval city, including the 'city of a thousand towers') Siena (90 km) Pisa with the famous leaning tower Bibbona (6 km) Elba (30 km) Florence (150 km) The picturesque villages and Campiglia Suvereto are within half an hour away [B] TYPE Chalet MOBILE A / B: [/ B] GOOD NIGHT GUARANTEED Average age in this age of mobile homes with 3 rooms is 2.5 years, so a new mobile home, according to the wishes of our guests was manufactured. These mobile homes are suitable for max. 6. Division Bedrooms [B] [/ B] These mobile homes are the bedrooms at the two ends of the mobile home, and that brings a maximum of privacy to me. The bedrooms are spacious and equipped with many closets. The Elterschlafzimmer has a large double bed (1.40 x 2.00 m) and in the children's room, you will find a floor bed and a single bed. All beds in the children's rooms are 70 x 2.00 m. Lang, including for larger children! If desired, one of the single beds with a free lattice ausdrüsten, so that your child does not fall out of bed. [B] living room / kitchen [/ B] The living room is centrally located and has a table with 5 to 6 seats. In the kitchen, a large refrigerator-freezer. Furthermore, there is a 4-flammigen gas cooker hood, a sink with running hot and cold water and plenty of cabinets. An electrical heating for colder evenings, the whole thing completely. Bathroom [B] [/ B] In the bathroom, you will find a large shower, a sink with running hot and cold water and a toilet. Of course, everything is connected to the sewerage, no chemical toilet or the like! [B] outdoor [/ B] You will find a complete set of garden furniture: A large oval table, chairs, 2 adjustable chairs and a sun deck. Of course includes a sunshade for the equipment. The mobile homes Type Chalet have a cozy wood-terrace. Wood Grill THE COMPLETE ORGANIZATION Living • Exterior big oval table • dining table • Chairs • 2 adjustable chairs • sunshade with stand • sockets • Electrical Dimm-Beleuchtung • Heating • Ashtray • Ventilator Sleep • double • Einzelbetten • Removable grilles (child protection) • deck beds • Pillows Bathroom • sink with mirror • Toilet • Shower Cleaning • Buckets • broom • Kehrschaufel and Kehrbesen • Mop • Drying Rack • Harness stand • cloth • Swabs • Abfalleimer • Abwaschbürste Kitchen • refrigerator with the freezer • 4-flammiger gas stove • 3-piece saucepan set • pan with high Village • frying pan • Deep dish • Flat Plate • dessert bowls • Knives • forks • tablespoons • teaspoon • Kelle • Soup creator • spoon sauce • Cooking Spoon • bread knife • Pfannenwender • Kartoffelschälmesser • Käsehobel • snow broom • Screening • doses opener • Corkscrew • 3-piece bowl set • Becher • Trinkgläser • Wine Glasses • beer glasses • kettle • tea-pot • Thermos jug • coffee filters • storage container • lemon Press • Serving tray • Plates • cutting board We have various types of mobile homes, all with a slightly different classification. It is not possible to a special Mobilheimtyp Reserve. Camping Le Capanne - Bibbona - Tuscany-type mobile home chalet for up to 6 people Prices in € Per night For 4 people Plus Kurtaxe & Deposit 50.-€ Surcharge for 5 Person 2.50 € / day for 6.Person 3.50 € / day Special offer: 14:12 = residence before 05.07.08 and down from 23.08.08 14:10 = residence from 06.09.08 21:14 = residence before 05.07.08 and from 23.08.08 General booking information: No Dogs Allowed Booking costs 15 € The tourist tax is before departure at the campsite to pay. Deposit: 50 € spot in the journey to deposit Arrival and departure Tuesday-Thursday-Samtsag selectable Wish guarantee 25-€ per unit - if you use several family want to live side by side. Minimum stay In the pre - and post-season is a minimum stay of 2 nights. This is defined by our arrival and departure days (Tuesday, Thursday and Saturday). In the high season (7 July-18 August) is a minimum stay of one week. You can book at the following flights: Gas grill in advance bookings 30 € for the entire stay (Locally 5.-€ per day) Cot 1.50 € per night-Children's chair 1.50 per day 2.50 € Laufgitterboc per night 2.50 € Zahlunsghinweise: 20% deposit to book-rest 28 days before arrival at Adria Pur. All prices without cancellation insurance, we recommend Travel Card Family Not included are: Bed linen and towels (washer and dryer for a fee at the campsite) Bed linen (but extra bookings) Kurtaxe The price includes: Kostenlsoe support by our experienced team on the spot. Water, electricity, garbage fees, gas for cooking 1 car parking Single bed pillows and blankets available Infants bicycle We also lend bed linen A Einzelset (consisting of 2 sheets for twin beds, a pillowcase and a towel costs 12, - € And a double with 2 sheets for twin beds and 2 pillow and 2 towels cost 18, - € Equipment Topics Beach Family Hiking Nature General senior accessible appropriate for family Equipment - Offers outside Barbecue Playground Garden furniture Parking Place Outdoor pool Equipment - Interior Restaurant TV Bar Sports - Summer Sports Table Tennis Tennis Diving Soccer Fishing Sailing Conditions Charges of heating incl. Charges of electricity incl. Charges of water inclusive Bedroom Full size bed Bunk bed Single bed Bathroom Toilet Shower Kitchen Kitchen Coffee machine Hot plates Refrigerator Numbers of rooms and floor area 24 m² size of living area Numbers of rooms and floor area 2 Bedrooms 3 Number of rooms in general Time Constraints 4:00 PM Earliest check-in 10:00 AM Latest check-out Prices/Availability Prices / Availabilities for Arrival Person Departure Kids Contactget price Quantity: Please enter the number of categories belonging to your accommodation. For example: If you have single room's, double room's and suite's then the number of categories is 3.

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About the Book Police powers to stop, question and search people in public places, and the way these powers are exercised, is a contentious aspect of police-community relations, and a key issue for criminological and policing scholarship, and for public debate about liberty and security more generally. Whilst monitoring and controlling minority populations has always been a feature of police work, new fears, new ‘suspect populations’ and new powers intended to control them have arisen in the face of instability associated with rapid global change. This book synthesises and extends knowledge about stop and search practices across a range of jurisdictions and contexts. It explores the use of stop and search powers in relation to street crime, terrorism and unauthorised migration in Britain, North America, Europe, Australia, Africa, and Asia. The book covers little researched practices such as road-blocks and ID checking, and discusses issues such as fairness, effectiveness, equity and racial profiling. It provides a substantive and theoretical foundation for transnational and comparative research on police powers in a global context. This book was originally published as a special issue of Policing and Society. About the Editors Leanne Weber is Larkins Senior Research Fellow at Monash University, Melbourne, Australia. Her research interests include the detention of asylum seekers in the UK and migration policing networks in Australia. Previous publications include Borders, Mobility and Technologies of Control (2006) and Globalization and Borders: Death at the Global Frontier (2011). Ben Bowling is Professor of Criminology and Criminal Justice in the School of Law at King's College London, UK. He has studied policing since the 1980s and is recognised as a leading authority on police stop and search powers. Previous publications include Policing the Caribbean: Transnational Security Cooperation in Practice (2010) and Global Policing (2012).

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--- abstract: 'We apply a new calculation scheme of a finite element method (FEM) for for solving an elliptic boundary-value problem describing a quadrupole vibration collective nuclear model with tetrahedral symmetry. We use of shape functions constructed with interpolation Lagrange polynomials on a triangle finite element grid and compare the FEM results with obtained early by a finite difference method.[^1]' --- [ Finite Element Method for Solving the Collective Nuclear Model with Tetrahedral Symmetry]{} *A.A. Gusev$^{~a}$, S.I. Vinitsky$^{~a,b}$, O.Chuluunbaatar$^{~a,c}$, A. Góźdź$^{~d}$,* *A. Dobrowolski$^{~d}$, K. Mazurek$^{~e}$, P.M. Krassovitskiy$^{~a,f}$* [*$^{a}$Joint Institute for Nuclear Research, Dubna, Russia\ $^{b}$RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russia\ $^{c}$Institute of Mathematics, National University of Mongolia, Ulaanbaatar, Mongolia\ $^{d}$Institute of Physics, University of M. Curie[-]{}Sklodowska, Lublin, Poland\ $^{e}$Institute of Nuclear Physics PAN, Kraków, Poland\ $^{f}$Institute of Nuclear Physics, Almaty, Kazakhstan*]{} Introduction ============ In recent papers the consistent approach to quadrupole[-]{}octupole collective vibrations coupled with the rotational motion was presented to find and/or verify some fingerprints of possible high-rank symmetries (e.g., tetrahedral, octahedral, ...) in the recent experimental data of nuclear collective bands [@Dobrowolski2016; @Dobrowolski2018]. A realistic collective Hamiltonian with variable mass[-]{}parameter tensor and potential obtained through the macroscopic[-]{}microscopic Strutinsky-like method with particle[-]{}number[-]{}projected BCS approach in full vibrational and rotational, nine[-]{}dimensional collective space was diagonalized in the basis of projected harmonic oscillator eigensolutions. In this approach the symmetrized orthogonal basis of zero[-]{}, one[-]{}, two[-]{} and three[-]{}phonon oscillator[-]{}like functions in vibrational part, coupled with the corresponding Wigner function [@Szulerecka2014] has been applied for solving the boundary value problem (BVP) in 6D domain. The algorithms for construction the symmetrized basis was considered in [@casc15; @casc16] w.r.t. symmetrization group [@Gozdz2011IJMPE; @Gozdz2013PhysAtNuc; @Gozdz2013PhysScr]. In paper [@Maz2011] the BVP in 2D domain describing the above quadrupole vibration collective nuclear model of $^{156}$Dy nucleus with tetrahedral symmetry [@cornwell84] has been solved by a finite difference method (FDM) that was a part of the BVP in 6D domain. However, the FDM approach did not obtain further generalization on the above multidimensional domain, where the potential energy and components of the metric tensor given by $2\times 10^{6}$ table values. In this paper we consider the alternative approach which is applicable for solving the BVP in the multidimensional domain of $d$–dimensional Euclidian space divided into the $d!$ simplexes in the framework of a finite element method (FEM) with Lagrangian elements and PI-type Gauss quadrature formulas in the simplexes [@sb; @casc17a; @casc18]. An efficiency of the applied finite element calculation scheme is shown by the benchmark calculations of the above BVP in the 2D domain. We apply shape functions on triangle finite element grid using the interpolation Lagrange polynomials of two variables with quadrature rules in triangle [@casc17b] and compare our FEM results with obtained early by the FDM [@Maz2011]. ![ The coefficients $g_{ij}(x)$ from (\[43\]) given in variables $(q_{20},q_{32})$ (a,b,c). Square root of the determinant $2g_{0}(x)/\hbar^2{=}\sqrt{{\rm det}B(q_{20},q_{32})}$ constructed out of collective inertia parameters in units $10^{-5}\hbar^2/$(MeV fm$^5$)(d). The differences $E_v^{\rm FDM}-E_v^{\rm FEM}(p)$ between eigenvalues of $E_v^{\rm FDM}$ of $^{156}$Dy nucleus calculated by the FDM [@Maz2011] and $E_v^{\rm FEM}(p)$ calculated in the present paper by FEM with triangular Lagrange elements of the order $p=1,2,3,4$ for 30 lowest states of the BVP (\[1n\])–(\[43\]) in variables $(q_{20},q_{32})$ (e). []{data-label="fignya2"}](deb11 "fig:"){width="31.00000%"}a ![ The coefficients $g_{ij}(x)$ from (\[43\]) given in variables $(q_{20},q_{32})$ (a,b,c). Square root of the determinant $2g_{0}(x)/\hbar^2{=}\sqrt{{\rm det}B(q_{20},q_{32})}$ constructed out of collective inertia parameters in units $10^{-5}\hbar^2/$(MeV fm$^5$)(d). The differences $E_v^{\rm FDM}-E_v^{\rm FEM}(p)$ between eigenvalues of $E_v^{\rm FDM}$ of $^{156}$Dy nucleus calculated by the FDM [@Maz2011] and $E_v^{\rm FEM}(p)$ calculated in the present paper by FEM with triangular Lagrange elements of the order $p=1,2,3,4$ for 30 lowest states of the BVP (\[1n\])–(\[43\]) in variables $(q_{20},q_{32})$ (e). []{data-label="fignya2"}](deb22 "fig:"){width="31.00000%"}b ![ The coefficients $g_{ij}(x)$ from (\[43\]) given in variables $(q_{20},q_{32})$ (a,b,c). Square root of the determinant $2g_{0}(x)/\hbar^2{=}\sqrt{{\rm det}B(q_{20},q_{32})}$ constructed out of collective inertia parameters in units $10^{-5}\hbar^2/$(MeV fm$^5$)(d). The differences $E_v^{\rm FDM}-E_v^{\rm FEM}(p)$ between eigenvalues of $E_v^{\rm FDM}$ of $^{156}$Dy nucleus calculated by the FDM [@Maz2011] and $E_v^{\rm FEM}(p)$ calculated in the present paper by FEM with triangular Lagrange elements of the order $p=1,2,3,4$ for 30 lowest states of the BVP (\[1n\])–(\[43\]) in variables $(q_{20},q_{32})$ (e). []{data-label="fignya2"}](deb12 "fig:"){width="31.00000%"}c\ ![ The coefficients $g_{ij}(x)$ from (\[43\]) given in variables $(q_{20},q_{32})$ (a,b,c). Square root of the determinant $2g_{0}(x)/\hbar^2{=}\sqrt{{\rm det}B(q_{20},q_{32})}$ constructed out of collective inertia parameters in units $10^{-5}\hbar^2/$(MeV fm$^5$)(d). The differences $E_v^{\rm FDM}-E_v^{\rm FEM}(p)$ between eigenvalues of $E_v^{\rm FDM}$ of $^{156}$Dy nucleus calculated by the FDM [@Maz2011] and $E_v^{\rm FEM}(p)$ calculated in the present paper by FEM with triangular Lagrange elements of the order $p=1,2,3,4$ for 30 lowest states of the BVP (\[1n\])–(\[43\]) in variables $(q_{20},q_{32})$ (e). []{data-label="fignya2"}](debq "fig:"){width="33.00000%"}d ![ The coefficients $g_{ij}(x)$ from (\[43\]) given in variables $(q_{20},q_{32})$ (a,b,c). Square root of the determinant $2g_{0}(x)/\hbar^2{=}\sqrt{{\rm det}B(q_{20},q_{32})}$ constructed out of collective inertia parameters in units $10^{-5}\hbar^2/$(MeV fm$^5$)(d). The differences $E_v^{\rm FDM}-E_v^{\rm FEM}(p)$ between eigenvalues of $E_v^{\rm FDM}$ of $^{156}$Dy nucleus calculated by the FDM [@Maz2011] and $E_v^{\rm FEM}(p)$ calculated in the present paper by FEM with triangular Lagrange elements of the order $p=1,2,3,4$ for 30 lowest states of the BVP (\[1n\])–(\[43\]) in variables $(q_{20},q_{32})$ (e). []{data-label="fignya2"}](dfem "fig:"){width="48.00000%"}e The setting of the problem ========================== Consider a self-adjoint boundary-value problem for the elliptic differential equation of the second order [@sb; @casc18]: $$\begin{aligned} ( {D}- E ) \Phi(x)\equiv \bigg(- {\frac{1}{g_0(x)}}\sum\nolimits_{ij=1}^d\frac{\partial}{\partial x_i}g_{ij}(x) \frac{\partial }{\partial x_j} + {V}(x) -E \bigg)\Phi(x)=0.\label{1n}\end{aligned}$$ It is also assumed that $g_0(x)>0$, $g_{ji}(x)=g_{ij}(x)$ and ${V}(x)$ are real-valued functions, continuous together with their generalized derivatives to a given order in the domain $x\in\bar\Omega=\Omega\cup\partial\Omega$ with the piecewise continuous boundary $S=\partial\Omega$, which provides the existence of nontrivial solutions obeying the boundary conditions of the first kind (I) [or the second kind (II)]{}: $$\begin{aligned} \label{2n} (I)~ \Phi(x)\Bigl|_{S}{=}0, \label{2a} ~ (II)~ \frac{\partial\Phi(x)}{\partial n_{D}}\Bigl|_{S}{=}0, \quad \frac{\partial\Phi(x)}{\partial n_{D}}{=}\sum\nolimits_{ij=1}^d(\hat n, \hat e_i) g_{ij}(x)\frac{\partial\Phi(x)}{\partial x_j}.\end{aligned}$$ Here $\frac{\partial\Phi_m(x)}{\partial n_{D}}$ is the derivative along the conormal direction, $\hat n$ is the outer normal to the boundary of the domain $S=\partial\Omega$, $\hat e_i$ is the unit vector of $x=\sum\nolimits_{i=1}^d \hat e_i x_i$, and $(\hat n, \hat e_i)$ is the scalar product in ${\cal R}^d$. It is also assumed that the metric tensor $g_{ij}(x)$ is positively defined what implies the positive determinant $\mathrm{det}(g_{ij}(x)) >0$. For a discrete spectrum problem, the functions $\Phi_m(x)$ from the Sobolev space $H_2^{s\geq1}(\Omega)$, $\Phi_m(x)\in H_2^{s\geq1}(\Omega)$, corresponding to the real eigenvalues $E$: $E_1\leq E_2\leq\ldots\leq E_m\leq\ldots $ satisfy the conditions of normalization and orthogonality $$\begin{aligned} \label{3} \langle \Phi_m(x)| \Phi_{m'}(x)\rangle =\int\nolimits_{\Omega}dx g_0(x){\Phi}_m(x)\Phi_{m'}(x)=\delta_{mm'}, \quad dx=dx_1\ldots dx_d.\end{aligned}$$ The FEM solution of the boundary-value problems (\[1n\])–(\[3\]) is reduced to the determination of stationary points of the variational functional [@sb; @casc18] $$\begin{aligned} \label{4} \Xi (\Phi_m,E_m) \equiv\int\nolimits_{\Omega} dx g_0(x){\Phi}_m(x) \left( {D}-E_m \right)\Phi(x) =\Pi(\Phi_m,E_m), \end{aligned}$$ where $\Pi(\Phi,E)$ is the symmetric quadratic functional $$\begin{aligned} \label{symmr} \Pi(\Phi,E)= \int\nolimits_{\Omega}dx\biggl[ \sum\nolimits_{ij=1}^dg_{ij}(x)\frac{\partial {\Phi}(x)}{\partial x_i} \frac{\partial \Phi (x)}{\partial x_j} + g_0(x){\Phi}(x) ({V}(x) -E ) \Phi (x) \biggr].\end{aligned}$$ ![The potential energy $V(x_1,x_2)$ of $^{156}$Dy nucleus given in variables $(\alpha_{20},\alpha_{32})$ (a) and in variables $(q_{20},q_{32})$ (b). The nodal points of finite element grid are intersection points of horizontal and vertical lines.[]{data-label="fignya1"}](pota "fig:"){width="44.00000%"}a ![The potential energy $V(x_1,x_2)$ of $^{156}$Dy nucleus given in variables $(\alpha_{20},\alpha_{32})$ (a) and in variables $(q_{20},q_{32})$ (b). The nodal points of finite element grid are intersection points of horizontal and vertical lines.[]{data-label="fignya1"}](potq "fig:"){width="52.00000%"}b Quadrupole-octupole-vibrational collective model ================================================ Below we solve the BVP (\[1n\])–(\[3\]) in the 2D domain $d=2$ that describe the quadrupole-octupole-vibrational collective model of $^{156}$Dy nucleus [@Maz2011] with the coefficients $g_{0}(x)$ and $g_{ij}(x)$ determined by the expressions $i,j=1,2$: $$\begin{aligned} g_{0}(x_1,x_2){=}\frac2{\hbar^2}\sqrt{{\rm det}B(x_1,x_2)}, ~ g_{ij}(x_1,x_2){=}\sqrt{{\rm det}B(x_1,x_2)}[B^{-1}(x_1,x_2)]_{ij}.\label{43}\end{aligned}$$ The mass tensor $B_{ij}(x_1,x_2)$ has been calculated [@Maz2011] in the terms of the average nuclear deformations $x=(x_1,x_2)=(q_{20},q_{32})$ determine in [@AGB], and shown in Fig. \[fignya2\]a-d. The potential energy function $V(x_1,x_2)$ has been calculated in the terms of the nuclear deformations $x=(x_1,x_2)=(\alpha_{20},\alpha_{32})$ [@Maz2011] and shown in these coordinates as well as in coordinates $x=(x_1,x_2)=(q_{20},q_{32})$ in Fig. \[fignya1\]a,b. $v$ $E_v^{\rm FDM}$ $E_v^{\rm FEM}(1)$ $E_v^{\rm FEM}(2)$ $E_v^{\rm FEM}(3)$ $E_v^{\rm FEM}(4)$ ----- ----------------- -------------------- -------------------- -------------------- -------------------- 1 0.85988 0.96000 0.91329 0.90234 0.89065 2 0.97588 1.11144 1.04808 1.03297 1.02068 3 1.53669 1.57813 1.54403 1.53371 1.52776 4 1.61774 1.67776 1.63332 1.62287 1.61571 5 1.88907 1.93560 1.87335 1.84504 1.83794 6 1.89469 1.94932 1.87706 1.84925 1.84631 7 1.93369 2.07731 1.99714 1.98486 1.98032 8 2.23907 2.41405 2.34335 2.29594 2.28444 9 2.25778 2.46383 2.35681 2.33287 2.31778 10 2.43288 2.62454 2.55679 2.54278 2.53388 : The low part of the spectrum of 10 lowest states of $^{156}$Dy nucleus counted from minimum of potential energy ($V_{\rm min}(\alpha_{20},\alpha_{32})=0.685 MeV$). $E_v^{\rm FDM}$ calculated by FDM of the second order [@Maz2011] and $E_v^{\rm FEM}(p)$ calculated by FEM with triangular Lagrange elements of the order $p=1,2,3,4$ in the present paper.[]{data-label="tabl1"} 12345 ![The first ten eigenfunctions of $^{156}$Dy nucleus in the plane $(q_{20},q_{32})$[]{data-label="fignya3"}](fun1 "fig:"){width="19.00000%"} ![The first ten eigenfunctions of $^{156}$Dy nucleus in the plane $(q_{20},q_{32})$[]{data-label="fignya3"}](fun2 "fig:"){width="19.00000%"} ![The first ten eigenfunctions of $^{156}$Dy nucleus in the plane $(q_{20},q_{32})$[]{data-label="fignya3"}](fun3 "fig:"){width="19.00000%"} ![The first ten eigenfunctions of $^{156}$Dy nucleus in the plane $(q_{20},q_{32})$[]{data-label="fignya3"}](fun4 "fig:"){width="19.00000%"} ![The first ten eigenfunctions of $^{156}$Dy nucleus in the plane $(q_{20},q_{32})$[]{data-label="fignya3"}](fun5 "fig:"){width="19.00000%"} 678910 ![The first ten eigenfunctions of $^{156}$Dy nucleus in the plane $(q_{20},q_{32})$[]{data-label="fignya3"}](fun6 "fig:"){width="19.00000%"} ![The first ten eigenfunctions of $^{156}$Dy nucleus in the plane $(q_{20},q_{32})$[]{data-label="fignya3"}](fun7 "fig:"){width="19.00000%"} ![The first ten eigenfunctions of $^{156}$Dy nucleus in the plane $(q_{20},q_{32})$[]{data-label="fignya3"}](fun8 "fig:"){width="19.00000%"} ![The first ten eigenfunctions of $^{156}$Dy nucleus in the plane $(q_{20},q_{32})$[]{data-label="fignya3"}](fun9 "fig:"){width="19.00000%"} ![The first ten eigenfunctions of $^{156}$Dy nucleus in the plane $(q_{20},q_{32})$[]{data-label="fignya3"}](fun10 "fig:"){width="19.00000%"} Table \[tabl1\] shows a low part of the spectrum of $v=1,...,10$ states of $^{156}$Dy counted from minimum of potential energy ($V_{\rm min}(\alpha_{20},\alpha_{32})=0.685 MeV$). Second column shows eigenenergies $E_v^{\rm FDM}$ calculated by the FDM code of the second order [@Maz2011]. The remaining columns show the eigenvalues $E_v^{\rm FEM}(p)$ of the BVP (\[1n\])-(\[43\]) in $\Omega(q_{20},q_{32})$ with coefficients $g_{ij}(q_{20},q_{32})$ determined by formulas (\[43\]) and the potential energy functions $V(q_{20},q_{32})$ calculated in the present paper by the FEM code with the Gaussian quadratures PI type till the eight order [@casc17b]. Calculations has been carried out with the second type (II) boundary conditions (\[2a\]) and orthonormalization condition (\[3\]) with triangular Lagrange elements of the order $p=1,2,3,4$ in the finite-element grid $\Omega(q_{20},q_{32})$. Discrepancy $E_v^{\rm FDM}-E_v^{\rm FEM}(p)$ between the results of FDM and FEM calculations in dependence of the order $p=1,2,3,4$ of the FEM approximation is shown in Fig. \[fignya2\]e. One can see that in increasing the order of the FEM approximation the discrepancy is decreased till 1%. Fig. \[fignya3\] display the corresponding eigenfunctions $\Phi_v(q_{20},q_{32})$ in the finite-element grid $\Omega(q_{20},q_{32})$. The eigenfunctions of the ground and first excited states are in good agreement with the eigenfunctions calculated in domain $\Omega(\alpha_{20},\alpha_{32})$ by the FDM [@Maz2011]. The third eigenfunction has one node line in direction $\alpha_{20}$ in contrast with the third FDM eigenfunction that has no nodes. Meanwhile, the forth function has two node lines in direction of $\alpha_{20}$ and qualitative coincides with the forth FDM eigenfunction. We can suppose that the revivable distinctions are consequence of approximation of table values of $V(\alpha_{20},\alpha_{32})$ on the FEM grid $\Omega(q_{20},q_{32})$ instead of approximation of derivatives of table values of $g_{ij}(q_{20},q_{32})$ on the FDM grid $\Omega(\alpha_{20},\alpha_{32})$ accepted in [@Maz2011]. Conclusion ========== We applied the new calculation schemes in the framework of FEM with the triangular Lagrange elements and Gaussian quadratures for analysis of the quadrupole vibration collective nuclear model with tetrahedral symmetry. We constructed of shape functions on triangle finite element grid and compared our FEM results with obtained early by FDM that are in a good agreement. This approach is generalized directly for the solving BVP in multidimensional domain by using the algorithms and their program realization [@casc17a; @casc18]. We will apply the proposed FEM for solving the BVP in the six dimensional domain describing the above quadrupole[-]{}octupole collective vibration model, in our further papers. This work was supported by the Polish–French COPIN collaboration of the project 04–113, Bogoliubov–Infeld and Hulubei–Meshcheryakov JINR programs, the grant RFBR 18–51–18005, RUDN University Program 5–100 and grant of Plenipotentiary of the Republic of Kazakhstan in JINR. [99]{} A. Dobrowolski, K. Mazurek, A. Góźdź, *Phys. Rev. C* **94**, 054322 (2016). A. Dobrowolski, K. Mazurek, A. Góźdź *Phys. Rev. C* **97**, 024321 (2018). A. Szulerecka, A. Dobrowolski, A. Góźdź, *Phys. Scr.* **89**, 054033 (2014). A.A. Gusev et al, *Lect. Notes Comp. Sci.* **9301**, 166 (2015). A.A. Gusev et al, *Lect. Notes Comp. Sci.* **9890**, 228 (2016). A. Góźdź, A. Szulerecka, A. Dobrowolski, J. Dudek, *Int. J. Mod. Phys. E*, **20**, 199 (2011). A. Góźdź, A. Szulerecka, A. Pȩdrak, *Phys. Atom. Nucl.* **76**, 1026 (2013). A. Góźdź, A. Pȩdrak, *Phys. Scr.* **154**, 014025 (2014). A. Dobrowolski, A. Góźdź, K. Mazurek, J. Dudek, Int. J. Mod. Phys. E **20**, 500 (2011). J.F. Cornwell *Group theory in physics* Academic Press, New York (1984). P. Ciarlet, *The finite element method for elliptic problems*, North-Holland Publ. Comp., Amsterdam (1978). A.A. Gusev et al, *Lect. Notes Comp. Sci.* **10490**, 134 (2017). A.A. Gusev et al, *Lect. Notes Comp. Sci.* **11077**, 173 (2018). A.A. Gusev et al, *Lect. Notes Comp. Sci.* **10490**, 151 (2017). A. Dobrowolski, H. Goutte, J.-F. Berger, *Int. J. Mod. Phys. E* **16**, 431 (2007). [^1]: Submitted to: Acta Physica Polonica B Proceedings Supplement

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Zoo Miami has a problem with some animals, but it's not the animals at their exhibits. Officials said stray cats from the outside are finding their way into the zoo and are likely spreading a sickness. "We lost a couple of animals. Several have been lost to Toxoplasmosis. Toxoplasmosis is something that is generated in cat feces," explained Ron Magill, zoo spokesperson. Magill said the stray cats sneak in at night, "We've seen them in holding areas. In exhibits using the sand in holding areas as litter boxes." Instead of having a small pack of squirrel monkeys, Zoo Miami is down to just two, because of Toxoplasmosis. "We've lost a red kangaroo. We've lost three squirrel monkeys. I cannot guarantee that these animals got Toxoplasmosis from the cats but the fact that it is transmitted in cat feces, it's our obligation to remove all the risk that we have from the park," Magill said. NBC 6 was told the cats come from the Larry and Penny Thompson Park that surrounds Zoo Miami. They've begun a program to trap the cats there and have them removed. "We love cats but we have an obligation to the species we have in our collection," Magill said. The problem is several cat activist groups say that's wrong, the cats should stay in the park. A group called Cat Network posted this on their website: "The single most effective method of protecting the zoo's animal population would be to create barriers to entrances for all other land species." One woman even sent Magill an email stating: "This zoo should have never been built near our homes in the first place. So you and the zoo are the ones invading and should be trapped and euthanized." With 740 acres of land to secure, Magill said stopping every single stray cat of an estimated 200 would be impossible. He added it's illegal for cats to be in any area of the park around the zoo in the first place. "This is Pine Rockland, the most endangered natural habitat in South Florida. There are endangered species that live in here. It's against the law for free roaming cats to be in this property," Magill explained. So far, there are 19 cats that have been trapped and until they've found new homes, Magill said they won't trap again until then. "We've had nine cats that went to rescue groups, four cats in PetSmart right now up for adoption. We've had some already adopted," he said. Magill added the cats that are trapped out of Pine Rockland are being rescued or put up for adoption. The only ones that are being euthanized are those who are found sick.

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Come check out the Underground Sports Call with Oz as he covers the 49ers vs Seahawks. The rivalry got a little hotter with Sherman joining the 49ers and this is his first game back in Seattle. As always Oz will take a shot anytime Mullens or whoever is playing QB at the time throws a pick or gets sacked, guess a challenge wrong and if the 49ers lose.

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The dual roles of Ganoderma antioxidants on urothelial cell DNA under carcinogenic attack. Ganoderma lucidum possesses significant antioxidant and anti-cancer properties. The effects of Lingzhi antioxidants on oxidative DNA damage and oxidative stress were investigated, in order to understand their roles in bladder chemoprevention. Antioxidant-enhanced extracts were tested, in terms of ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH.) inhibition, hydrogen peroxide (H(2)O(2)) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations, and cytotoxicity, using an in vitro pre-cancerous human uroepithelial cell (HUC-PC) tumorigenic model. Water-soluble extract (GLw) possesses relatively higher antioxidant capacities than the water-insoluble counterpart (GLe); however, under the challenge of carcinogenic 4-aminobiphenyl (ABP), GLw reduced the 8-OHdG concentration in HUC-PC culture, while GLe induced the formation of H(2)O(2) and 8-OHdG in a dose-dependent manner. The modern theory of antioxidant-oxidant balance seems to obey the theory of Yin-Yang in traditional Chinese medicine (TCM). Water-soluble and water-insoluble components of Ganoderma lucidum exhibited dual roles in oxidative DNA damage. Oxidative DNA damage may be an underlying mechanism of Lingzhi-induced apoptosis in bladder chemoprevention.

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Q: How to get rid of CA2000 warning when ownership is transferred? The following code generates two CA2000 warnings (among others, but that's not the point). public sealed class Item: IDisposable { public void Dispose() {} } public sealed class ItemContainer { public void Add(Item item) { } } public sealed class Test: IDisposable { private ICollection<Item> itemCollection; private ItemContainer itemContainer; private void Add(Item item) { itemCollection.Add(item); } public void Initialize() { var item1 = new Item(); // no warning itemCollection.Add(item1); var item2 = new Item(); // CA2000: call Dispose on object item2 Add(item2); var item3 = new Item(); // CA2000: call Dispose on object item3 itemContainer.Add(item3); } public void Dispose() {} } Note that there is no warning generated for item1. It seems, Code Analysis assumes the ICollection will take responsibility of the item and eventually dispose it. Is there a way to mark my Add methods, so that the warning goes away? I'm looking for something similar to ValidatedNotNullAttribute for CA1062. Edit: to make it clear: this is not my real code. In the real code, everything is properly disposed. It's just that CA does not recognize that the call to my Add methods transfers ownership. I would like it to treat my Add methods in the same way it treats ICollection.Add. Disposing in the same scope is not an option. A: Do you want to fix the code or just suppress the warnings? Suppressing the warnings is straightforward: [SuppressMessage("Microsoft.Reliability", "CA2000:DisposeObjectsBeforeLosingScope", Justification = "Your reasons go here")] public void Initialize() { // ... } A: I also asked this at connect.microsoft.com and this is what they answered: You can workaround the issue by having the container/collection object that adds the disposable object implement ICollection or ICollection<T>. The method that performs the Add must also have name starting with "Add". And sure enough: when class Test implements ICollection<Item>, then the warning goes away. This is an acceptable solution for the case in question. But it's still an open question what to do, when it's not appropriate to implement ICollection to indicate transfer of ownership. public sealed class Test: IDisposable, ICollection<Item> { public void Initialize() { var item1 = new Item(); // no warning itemCollection.Add(item1); var item2 = new Item(); // no warning ((ICollection<Item>)this).Add(item2); var item3 = new Item(); // no warning AddSomething(item3); } //... implement ICollection and Method AddSomething } A: I know this is sample code, and so whether this workaround would work in your real code, I couldn't say. In this particular case, if you move the object creation code into it's own method, that returns the new Item, then the warning will disappear, e.g. change: public void Initialize() { var item1 = new Item(); // no warning itemCollection.Add(item1); var item2 = CreateItem(); // CA2000 no longer appears Add(item2); var item3 = new Item(); // CA2000: call Dispose on object item3 itemContainer.Add(item3); } private Item CreateItem() { return new Item(); } Obviously, the CreateItem method could be passed arbitrary parameters to pass to the Item constructor. Edit Having seen Henrik's answer, and the response on Connect, all I can say is bletch. There's no guarantee that an ICollection implementation also implements IDisposable, and whilst his posted example does implement IDisposable, apparently that's not required to shut up the code analysis (I'd have been somewhat okay if you had to implement both). A class implementing ICollection but not implementing IDisposable is highly unlikely to deal with disposing of contained objects correctly.

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February 19, 2005 Terri Schiavo Speaks: Her documented vocabulary From the Empire Journal(please read the whole article), a list of Terri Schiavo's documented vocabulary references: Witness: Nurse Heidi Law * mommy * momma * help me Witness: Nurse Carla Sauerlyer * pay (meaning "pain" when she was in discomfort) * Haaaiii (meaning "Hi" in response to "Hi Terri") * mommy * help me ("Help me was, in fact, one of her more frequent utterances. I heard her say it hundreds of times." This judgment is the greatest crime I have seen in America, They have used the courts to serve their own desires over the rights of Mrs Terry Shiavo. The behaviour of these judges is abhorrent, and as far as I am concerned illegal. Totally dehumanized. We will not forget, and I will do my best to get this injustice redressed. Kurt Mejer Posted by: Kurt Mejer at March 23, 2005 9:48 AM I'm so interested in life issues here. I tried to open the video, but it did not open for me.

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1976 Longling earthquake The 1976 Longling earthquake in Yunnan Province, People's Republic of China, was a doublet earthquake, with two main shocks striking just east of Longling at 12:23:20 and 14:00:22 UTC (20:23 and 22:00 local time). The magnitudes were estimated at 6.7 and 6.6, respectively, on the scale, and 6.9 and 7.0 on the scale; Chinese sources put these at 7.4 and 7.3 on the scale. The region is noted for the quantity and intensity of its earthquakes, and the complexity of its tectonics, which are closely related to the collision between the Indian and Eurasian tectonic plates. No one died in the Longling county town Loss in the 9 counties in Baoshan, Lincang and Dehong were 98 deaths, 451 severe injuries and 1991 light injuries. 420,000 buildings collapsed in an area of 1883 square kilometers. Geology Yunnan is a mountainous region lying east of Tibet, and north of the Red River Fault that strikes southeast along the Red River into North Vietnam and the South China Sea. The Red River fault is deep – some believe it may reach the lithosphere – and forms a major tectonic boundary that separates Indochina from the South China block. The seismotectonics of Yunnan and the adjacent areas is driven by the collision of the Indian Plate with the Eurasian Plate. This has uplifted the Tibetan Plateau (and the Himalaya Mountains) and forced it eastwards, pushing the South China Block and Indochina towards the westward subducting Philippine Sea Plate and creating various extensional structures. All of this has created a complicated geological structure with many faults, which in western Yunnan has allowed heat and fluids from the subducting Indian Plate to rise into the upper crust, creating the Tengchong volcanic field to the north of Longling and the Longling fault (location of the first event), and west of the Nu River and Nu River fault (location of the second event). It appears that igneous intrusions have weakened the bedrock in this area, which has led to uneven accumulations of stress, which caused the earthquake. See also 1976 Tangshan earthquake (July 28) 1976 Songpan–Pingwu earthquake (August 16–23) List of earthquakes in 1976 List of earthquakes in China Notes Sources . . . . . . . (in Chinese with English abstract). . External links 1976 Longling Category:1976 in China Category:1976 earthquakes

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Q: NDISwrapper showing "invalid task" I am using NDISwrapper with the Netgear WN121t USB WiFi adapter and by now I think I tried almost every .inf file on the net. I got the device working so far (it gets detected by Ubuntu and it finds my network). The problem is that NDISwrapper shows: Aug 13 04:42:04 local kernel: [ 2043.438367] ndiswrapper (NdisMSetInformationComplete:2542): invalid task and the connection times out. I am using Ubuntu 12.04 Precise Pangolin 32-Bit on a Toshiba Satellite (the driver is 32-bit). I can't post the driver file because I tried about 20 different drivers and the error message is always the same. Here is the log file: syslog file link broken How can I get this working? A: This is the nature of ndiswrapper. It is pretty much broken by design, and only works with a few specifically-supported drivers. It's like running wine in the kernel, which is far, far worse than running it in userspace, because one wrong move and you kernel panic. Ndiswrapper is not really intended for production use, and by all reports, even people who get it "working" will encounter stability, bandwidth or data corruption problems. Over the years I've tried it with over a dozen wifi chipsets, and every single one of them either crashed the kernel or had some kind of show-stopping behavior at runtime. It's a bad solution to a tough problem. If no native driver at all exists for your wifi adapter, all you can do is: Try to file a bug with Ubuntu and see if anyone can get it working (extremely unlikely, as most bugs dealing with restricted drivers are ignored) Try to file a bug with ndiswrapper upstream and see if anyone is still maintaining it and looking at bug reports (extremely unlikely) Try upgrading to the latest kernel and compiling the newest ndiswrapper from source, as whatever Ubuntu is shipping is probably out of date Try googling for a Linux driver for your wireless chipset; due to licensing concerns, Ubuntu does not ship certain chipsets' native Linux drivers, even though they are open source... for example they refused to implement Ralink's rt2800 driver back before the mainline kernel developers built their own. Try another wireless chipset that is known to be natively supported on Ubuntu (best bet is Intel chipset or Qualcomm Atheros; Ralink is ok these days too)

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Q: BlackBerry - How to improve this search feature over a VerticalFieldManager that holds custom managers I have a screen with a VerticalFieldManager for holding a list of custom managers. The screen also contains a EditField that behaves as a search field, so when the user enters some text, my app loops over an array of custom managers and compares the entered text with the text from every manager in the array. If the text from a manager matches the entered string, I append that custom manager to the VerticalFieldManager. These are the relevant parts of my code : EditField _editField; TempBeanPlaces [] _placesList; VerticalFieldManager _vfmCellPlaces; .... This is the constructor of TemBeanPlaces : public TempBeanPlaces(String pPlaceName, CellPlaceManager pCellPlaceManager) { placeName = pPlaceName; cellPlaceManager = pCellPlaceManager; } ... And this codes handles the search : _editField.setChangeListener(new FieldChangeListener() { public void fieldChanged(Field field, int context) { String text = _editField.getText().toLowerCase(); _vfmCellPlaces.deleteAll(); for (int i = 0; i < _placesList.length; i++) { TempBeanPlaces tempBeanPlaces = _placesList[i]; if(tempBeanPlaces.getPlaceName().toLowerCase().indexOf(text) != -1) { _vfmCellPlaces.add(tempBeanPlaces.getCellPlaceManager()); } } updateLayout(); } }); This works ok when the array _placesList is not too large (length of 50, for example), otherwise the app becomes too slow. How could I optimize my code for large amounts of custom managers?. For example, in case the array contains 600 elements. I really need to improve this feature. I just have read about the ListField in BlackBerry, but since I have this code done, maybe I don't need to rewrite everything with ListFields. Thanks in advance! A: Answered a similar question on BB forums here: How-to-improve-this-search-feature-over-a-VerticalFieldManager There are three workable options that I would consider: use addAll() to add all the Managers at once thus significantly reducing the layout time using 'paging' so you only add the first 15, and add later selections if the user wishes you too Use ListField The first 2 options would enable you to retain the current Manager code. Try these options, in the order given, and let us know which works for you. Update Given that options 1 has not worked for you, and you are not allowed to do option 2, then perhaps I can suggest option 1.5. Add only the first 25 or so, but add some scroll control that detects when you are getting near the end of your VFM and when you are within 1 screen, it adds some more. This will cause a scrolling glitch at that point but the list will look continuous without the huge hit at the start. I don't think anyone is going to scroll through 600 entries. If your search displays the number found, that will give your users an indication, and they will probably try a different search if the number is too large. And because you have not added every single item, you have speeded up the process significantly. A variation on this is to not add al the entries until the user moves focus off the EditField onto the list. The other thing you could look at doing it having this 'search' process done in a Thread, asynchronously, and cancel it if the user updates the edit Field with some new input. Alternatively if option 1 has NOT worked for you, can I suggest you try just adding 10 at most, and see if the glitch is still present. If so, then I suspect there is an issue in the processing of your Fields, such as some paint loop or layout loop. Compare this with the time taken to add 10 LabelFields. Perhaps we can optimise the processing in your custom Managers that will overcome this. Further edit I had a random thought that perhaps restricting the height of a VFM might restrict the painting done. Not true, I've tested and the only Fields painted are those that are visible. So the performance hit is with the layout not the paint.

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Welcome to HVAC-Talk.com, a non-DIY site and the ultimate Source for HVAC Information & Knowledge Sharing for the industry professional! Here you can join over 150,000 HVAC Professionals & enthusiasts from around the world discussing all things related to HVAC/R. You are currently viewing as a NON-REGISTERED guest which gives you limited access to view discussions To gain full access to our forums you must register; for a free account. As a registered Guest you will be able to: Participate in over 40 different forums and search/browse from nearly 3 million posts. UV Light For HVAC Had a customer today inquire about adding UV lights to his duct work. Anyone have some good information as to the effectiveness of the lights ? What models are worthwhile? I do recall you have to be careful where you install them, flex connectors and filter media cannot withstand it. Should you have one in the supply and return ? Can all evaporator pans now a days tolerate it ? IMO, if everything is well sealed..there isn't anything in the duct system that needs uv lights. that said...I replaced a ductboard supply plenum that had uv light. everywhere the uv light could reach...no mold. where it didn't reach...mold. so they do stop growth they reach. if you look at the picture, on the sides of the plenum..close to uv light...no mold. further on, where light couldn't reach...mold. the question to me alway was...what is causing mold? in this case it was no seal at duct takeoffs at the plenum & poor seal @ plenums to equipment. condensation caused by hot attic air touching metal take offs caused moisture inside (and outside) of plenum. ended up changing most of the ductwork too, as mold had grown inside flex. plenums were changed to sheet metal externally insulated as per homeowner concerns. hope this helps. The cure of the part should not be attempted without the cure of the whole. ~Plato Wow the UV light subject is defiantly a frustrating issue. Seems like to there is no consistency to anything regarding UV lights and everyone seems to have a different option. At any rate I was ultimately referred to RGF Guardian Air HVAC Cell and REME HVAC Cell. I was offered a substantial discount on the REME for my house so that I can experience it and then hopefully push the sales of them. Seems like this thing is adding peroxide, plasma or whatever to the air, which im not crazy about. Anyone else use these ? Gentlemen UVGI lamps are an excellent selection for surface irradiation. But a bad selection for IAQ. Their simply isn't enough time to deactivate a biologic moving at 500 fpm. If installed correctly they will do a good job of keeping the bio slime off of the coil which will maintain the heat transfer efficiency at the evap coil. The premise of ventilation is that the OA is clean or of sufficient quality to be used for dilution. Traditional ventilation is somewhat being threatened by the fact that the EPA is changing the requirements for outdoor air quality which is creating non-attainment zones in what is now becoming a significant portion of the country. That means that buildings in those areas will need to clean up the OA before they bring it into the building.www.genesisair.com Genesis Air Inc. Gentlemen UVGI lamps are an excellent selection for surface irradiation. But a bad selection for IAQ. Their simply isn't enough time to deactivate a biologic moving at 500 fpm. If installed correctly they will do a good job of keeping the bio slime off of the coil which will maintain the heat transfer efficiency at the evap coil. Additionally, if you do install one, insure that EVERY material within about 3 feet of the light is UV rated. Any organic material that is high %RH for +24 hours has a high potiential for mold growth. Mold spores and organic dust are everywhere. A couple hours of drying out the ducts every 12 hours could stop mold spore from growing. A/c ducts in attics with moisture saturated cooling coils will keep the ducts near saturated for days on end. Completely drying out the ducts by operating the fan a couple hours twice a day stops mold. Fans in the "on" mode 24/7 are most likely to be clear of mold. There are other problems. Also ducts in attics during cold weather also have mold potiential from condensation on the ducts when the duct surface is near the dew point of interior air dew point. Again operating the fan several hours each day will dry these surfaces and prevent mold spore germination. Good indoor air quality requires fresh air change when occupied. An air change in 4-5 hours is usually adequate when occupied. Air filtering to keep the equipment clean. Merv +11 is suggested for inside and fresh make-up ventilation. Maintaining <50%RH throughout the inside of a home avoids mold and dust mites. Air ducts spend many hours with 80%-near 100%RH during cooling hours. Several hours everyday of <50%RH everyday will reduce mold/bacteria to minimable level. In green grass climates, a whole house ventilating dehumidifier like the Ultra-Aire supplys fresh filtered air, blends the filtered dry air with filtered house air, circulated the conditioned air throughout the home via the a/c ducts. This procces maintains <50%RH throughout the all of the equipment. In most cases the 100 watt fan of the dehumidifier can operate 24/7 which keeps everything dry during the "off" cycle. The real long term effects of UV lites on sensitive occupants is unknown. Fresh filtered air, keep every dry when not in use, and low circulation is effective for indoor air quality. Regards TB We always used uv resources equipment in the air handlers when I worked in mfg.. as said before keep all wireing you can away from the area, run the wireing in conduit or shield it some way and if you have to use zip ties make sure they are uv rated. they can also help design a system I have found mold growth in units,with the customers reporting feeling very weak after leaving the home each day. We tried a duct cleaning along with a UV light but after 3 months the problem got better but didn't go away. Eventually we had to replace the unit and ductwork to eliminate the mold permanently. I believe UV can inhibit new growth and odor but does very little if anything for ridding existing mold inside the ductwork and coil.

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Q: SQL: Selecting all tuples which contain a certain value in a column after using count I have the following table called Stores: Name | Category | Industry ABC appliances retail XYZ banking finance NZE clothing retail JKI tutoring education I would like to output all the Names that are the only one in their Industry (e.g. XYZ and JKI are the only Names in their Industry). I have the following query: select s.Name, s.Industry, a.Number from Stores s inner join ( select Industry, count(*) as Number from Stores group by Industry ) a on s.Industry = a.Industry; I get an output table which has an attribute called Number which gives the total number of times each Industry appears in the table Stores. How can I select all the tuples which have the value of 1 in the Number column after using the inner join? A: use where condition select s.Name, s.Industry, a.Number from Stores s inner join ( select Industry, count(*) as Number from Stores group by Industry ) a on s.Industry = a.Industry where a.Number=1

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A long standing problem in the area of heated spas and tubs has been that when air is introduced into the water of the tub, typically in the form of bubbles, such air is at a temperature considerably below that of the water in the tub. Consequently, the parties using the tub will experience discomfort or irritation by cold air bubbles passing through hot water. While the above problem could be solved by the provision of an independent supply of heated air, this approach is not cost-effective and the maintenance of such a system presents various problems. To the knowledge of the inventor, there is not known in the art a system for providing heated air bubbles to a heated spa or tub in which the heat of the hot water itself is employed as the mechanism for heating air and air bubbles to be provided to the tub or spa.

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Thoughts and Things Archive for the ‘Poetic attempts’ Category Everything is clear, Straightforward and decided Until one event Catapults The world into turbulence, Sending it ricocheting Against unseen walls, Leaving it bruised, Dizzy, exhausted. And suddenly all the ground That had been covered Turns to paper, shredded, Then incinerated, Leaving smoke, not even ashes. Time is unreal, meaningless As years are extinguished And problems that were solved Are unsolved. Images unfocus From black and white, As gates which had been bolted shut Inexorably release The ghosts which had been Laid to rest. The smoke clears Leaving a battered world, Grey with uncertainty, Alive with dancing ghosts Mocking The final conclusions, Demarcation lines, The arrogance Of what is momentarily Clear, straightforward and Decided. Certainty and confusion Lie intertwined, Gilt and serpent, Temptation and rebuke. Never again is a challenge To the gods. Forever an invitation to irony. What’s my line? Flashing phone lights and a TV screen Cigarettes and office politics Orange juice and kit-kats Messages to pass on Dictation of prices Quotations, offers, bids, The offer is x years of isolation On the trading team, The bid is integration and participation. We are not sellers. Low voices with no names audible, Obscure facts Not to be understood. What can’t be heard should not be heard. The boss pulls the final strings, The boys rule. Who’s a cheap seller? Bubbles to fill the working day, Brighten it up with fantasy To lift the dreary din Of prices, rates and shipment months, Buy ten Dec at market, Give me Sep dollars to sell, Are we sellers of April/June Lagos At fifty over …? The differential is too high, We’re too far apart. We’re too far apart.

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Friday, 6 June 2014 In the last month or so I seem to have come across a lot of discussion on how to reduce use of antibiotics. The basic claim seems to be that we are entering a worrying stage where antibiotics lose their power to stop common infections. Only by reigning back our use of antibiotics can we avoid falling into the abyss. But how do we reign back our use of antibiotics? It is typical to refer to the tragedy of the commons when exploring the options available to us. Personally, however, I feel the tragedy of the commons is a misleading way of looking at the problem with antibiotics. Let me explain. The tragedy of the commons can arise whenever there is a resource that is limited in supply (rivalrous in the jargon of microeconomics) but that can be harvested by anyone (non-excludable). Water, fish, clean air and grazing land are the textbook examples. The tragedy is that we end up overusing the resource because each individual harvests as much as he wants, ignoring the negative effect this has on others. For example, the farmer fully irrigates his land, ignoring that this leaves less water for neighbouring farms. Or, the fisherman catches a boat load full of fish, ignoring that this leaves less fish for other fisherman or future generations. Antibiotics seem to fit the tragedy of the commons story. In this case the resource in limited supply is 'infections that can be treated with antibiotics'. The more we use antibiotics, the more drug resistant infections become, and so the smaller is the pool of infections that can be treated with antibiotics. If each individual takes antibiotics ignoring the effect that this has on others then we get overuse of antibiotics. If we think of the overuse of antibiotics as resulting from a tragedy of the commons then we have a simple solution. Namely, we need individuals to take into account the effect that their use of antibiotics has on others. One way to do this is through price - if we increase the price of antibiotics then use should fall. Another way is to educate people on the problems of overusing antibiotics with the hope they reduce use for social reasons. The latter approach is the one being favoured by policymakers. But, it also seems optimistic to expect much. Increasing the price of antibiotics would seem a surer way to reduce usage. And probably is best in terms of reducing the use of antibiotics in farming. There seems, however, something inherently wrong about increasing the price of antibiotics for human use. Why? In the standard tragedy of the commons story we have complete information - everyone knows the benefits and costs of using the good. The tragedy occurs because everyone harvests too much of the good. Increasing the price of the good looks a good way to reduce use. In the antibiotic case, by contrast, we have incomplete information - it is typically unknown whether the antibiotics will help a person or not. The tragedy occurs because too many people use antibiotics when they should not. Increasing the price of antibiotics is wrong because it penalizes those who need to take the antibiotics. The overuse of antibiotics does not, therefore, fit the tragedy of the commons story as well as it may at first appear. In particular, the problem is not so much the negative externality that one person's use of antibiotics imposes on another, but more the incomplete information about whether or not to use antibiotics. If we can solve the problem of incomplete information then we probably solve the problem of antibiotic overuse. And, fortunately, it seems as though science is on top of this problem because new methods are being developed to tell whether a patient needs antibiotics or not. Whether patients will trust to science is a different question.

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Back in the late 90’s, as a young teenager in the west of Scotland, your recreational time was either drinking on the streets or attending the local under 18’s disco and asking multiple girls throughout the evening to “Nip yer pal”(kiss your friend in English). Although both these activities I had become quite fond of, something was missing from my life. I discovered Counterstrike in a local Internet cafe, and the days of hiding the smell of stale cider from my parents were behind me, no longer would I be seen with a girl with hooped earrings and rip off tracksuit bottoms, now you would find me amongst the outcasts of the town, all smelling of BO and having underdeveloped social skills, crammed into a small room playing Dust2 on repeat knowing the outside world would not bother them. This weekend, I felt similarities to myself as a teenager with Ubisoft’s Ghost Recon Wildlands Beta. Whilst I’ve enjoyed playing popular online games like Overwatch and Rocket League, something remains missing from my gaming life. With the tactics of Rainbow 6 siege, The exploration and RPG qualities of the Division and the world that Far Cry creates around you, Wildlands may just be the Ubisoft game I have been waiting for. Ghost Recon Wildlands is an open world tactical shooter set in the Tom Clancy universe of the same name. Unlike the future setting of previous titles, Wildlands has you commanding an elite team of soldiers called the Ghosts into current day Bolivia, with the hope of stopping cartels that have assumed control of the country. With a functional character creation introduction and an overdramatized cut scene, I’m ready to see what Bolivia has to offer. Wildlands looks and feels immediately like an open world Ubisoft game, I was immediately presented with a waypoint on my map of which I had to travel to start a mission. Taking a local 4×4 I proceeded to drive through the country roads with my AI squad in the car admiring the real world setting but already feeling infuriated with the poor driving mechanics the game offered. Like recent other Ubisoft titles, the driving is sluggish when driving slow, and over twitchy when at full speed. Simply the car does not always go where you want it to go and you never feel as fully as in control as you would in GTA5 for example. When I arrive at the waypoint ( a small outpost) I was presented with a small tutorial on how to pilot my drone, by far the game’s most interesting mechanic, pressing up on the D-pad allows you to pilot a drone for a short time in full 360 degrees flight, marking enemies and deciding how to approach the mission ahead. The drone itself has a battery and range of use meaning you have to decide where is best to launch whilst keeping your squad away from danger. I proceed to carefully sneak through the area taking down each enemy with a carefully placed headshot from my silenced pistol, The outpost was mine with little effort. Character Movement was quite clunky at times. The game has a different cover system to the Division. If your crouching and move near an object that can be utilised for cover, your character will press up against it. And the same goes for walking around corners or peeking around corners, There was some frustration getting used to this after hours in New York. Shooting can be done in either first or third person modes with classic recon ‘shoulder-view’ switching available. I thought this area was very well refined. Including hit-boxes on targets. I Did not experience any target clipping or scenarios where I was shooting targets but was not registering. Overall the game has some of the most satisfying shooting of any game I have played recently. When I noticed my friends coming online, I decided to invite a few of them to join me in Bolivia. The Co-op play that the game is intended for has it’s the best moments. Hours were lost as we slowly made our way through the beta’s missions including defence of a radio transmitter, freeing a hostage and a predictable fetch quest, liberating outposts and flying helicopters to our next objective. At no point did we have any connection issues and the joining to the squad was seamless and easy to activate. Overall I have enjoyed my time in the jungles of Bolivia. the beta left me satisfied and turned a game that I may have picked up, to a game I cannot wait for. I may not be the King of the internet cafe anymore, but when Wildlands releases I will be king of the jungle.

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Government (and the creatures who infest its rotten carcass) was the most important problem facing the United States in 2014, Americans tell Gallup pollsters. That's up from being the second most serious problem in 2013, and the third-ranker in 2012. Who says the American political system is stuck? This is progress! The news that Americans are un-fond of government, Congress, the president, and politicians in general comes from an average of monthly survey results throughout the year. Given officialdom's litany of stupid government tricks, the elevation of America's own flavor of Leviathan to public enemy numero uno may seem like nothing more than good common sense to many observers. Perhaps an expression of collective survival instinct. Or, at least, mass revulsion. True, government just barely edged out general economic concerns and worries over jobs and unemployment for top ranking. But still, it's impressive when the institution whose adherents bill it as the cure for life's ills wins top billing as a major disease itself. Gallup's findings hardly come out of the blue. Pew finds public trust in the government, at 24 percent, is near historic lows. A plurality of those surveyed (42 percent) tell Reason-Rupe pollsters that President Obama has expanded the power of the government too much. Majorities among younger Americans say that government is wasteful and government agencies abuse their power. Americans have felt less free year by year since 2006, and there's a evidence to back up their perceptions of eroding liberty. That includes slippage in rankings of economic freedom and a plummet in the ratings of press freedom. Distrust of government has become so pervasive that the Census Bureau thinks the only way to get cooperation from the seething masses is with threats. Probably because that always evokes warm and fuzzy feelings. The good news for politicians, not that they deserve any, is that there's enormous room here for growth, and little downside. Frankly, it would be hard for them to disappoint a public that holds them in such low regard.

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Deposition of radiocesium to the soil by stemflow, throughfall and leaf-fall from beech trees. The amount of Chernobyl-derived 137Cs transferred to the soil by stemflow, throughfall (precipitation under the tree crown), and leaf-fall from three beeches was investigated as a function of time in the growing seasons of 1991 and 1992. Up to 70 Bq/week was deposited with the stemflow, mainly in dissolved form (< 0.45 micron) rather than in particulate form (> 0.45 micron). The ratio of dissolved radiocesium to particulate radiocesium was about 10 in the stemflow. It varied considerably with time, but since these variations followed the same pattern for all three trees, they indicated a common cause to be responsible for the fractionation of radiocesium (e.g. meterological conditions for bark weathering). A significant correlation was observed for the amount of dissolved 137Cs (in Bq) and the amount of stemflow (in liters). The 137Cs concentration in the stemflow (in Bq/1), however, decreased with increasing stemflow intensity (in Bq/week). For particulate radiocesium such correlations were not detected. Up to 5 Bq/m2 per week was deposited with the throughfall from the canopy, mainly in particulate form (ratio dissolved radiocesium to particulate radiocesium = 0.34). The mean total annual amounts of 137Cs deposited to the ground (dissolved+particulate) for the three trees were: stemflow: 1991 600 Bq; 1992 460 Bq; throughfall: 1991 and 1992 approximately 100 Bq/m2 each; leaffall: 1992 approximately 10 Bq/m2. The data indicate that at present a substantial amount of the radiocesium in the leaves derives already from root uptake.

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NASA's Curiosity rover used the Mars Hand Lens Imager (MAHLI) to capture this set of 55 high-resolution images, which were stitched together to create this full-color self-portrait. Credit: NASA/JPL-Caltech/Malin Space Science Systems (Phys.org) —New findings from NASA's Curiosity rover provide clues to how Mars lost its original atmosphere, which scientists believe was much thicker than the one left today. "The beauty of these measurements lies in the fact that these are the first really high-precision measurements of the composition of Mars' atmosphere," said Sushil Atreya, professor of atmospheric, oceanic and space sciences at the University of Michigan. Atreya is co-author of two related papers published in the July 19 issue of Science, and co-investigator on Curiosity's Sample Analysis at Mars (SAM) suite of instruments, considered the rover's cornerstone lab. SAM measured the abundances of different gases and isotopes in samples of Martian air, according to NASA. Isotopes are variations of the same chemical element that contain different numbers of neutrons, such as the most common carbon isotope, carbon-12, and a heavier stable isotope, carbon-13, which contains an additional neutron. SAM analyzed the ratios of heavier to lighter isotopes of carbon and oxygen in the carbon dioxide that makes up most of Mars' atmosphere today. Measurements showed that heavy isotopes of carbon and oxygen were more abundant in today's thin atmosphere compared with the proportions in the raw material that formed the planet (which scientists can deduce from proportions in the sun and other parts of the solar system.) This provides not only supportive evidence for the loss of much of Mars' original atmosphere, but also gives clues to how the loss occurred. It suggests that the planet's atmosphere escaped from the top, rather than due to the lower atmosphere interacting with the ground, NASA's web story states. "The isotope data are unambiguous and robust, having been independently confirmed by the quadrupole mass spectrometer and the tunable laser spectrometer, two of the SAM suite instruments," Atreya said. "These data are clear evidence of a substantially more massive atmosphere, hence a warmer, wetter Mars in the past than the cold, arid planet we find today." Curiosity landed inside Mars' Gale Crater on Aug. 6, 2012, Universal Time. Explore further Curiosity rover finds clues to changes in Mars' atmosphere

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New Civil Engineer understands that the government is poised to give the go ahead to additional runway capacity at Heathrow and Gatwick. It is believed that the announcement will be made on 18 October, with government giving the green light to a third runway at Heathrow immediately and also allowing Gatwick to expand with a second runway within the next five years. Gatwick’s 30-year agreement with local authorities not to expand is due to expire in 2019. It is also understood that government will urge Birmingham airport to advance its proposals for an additional runway. The decision to encourage all three airports to expand comes after increasing demand in the London area over the last three years has far exceeded predictions used by Sir Howard Davies’ Airport Commission. Davies’ published his independent report setting out its recommendations for expanding aviation capacity in the UK in 2015. To meet the projected growth, it said that a new runway was required by 2030 and gave a new northwest runway at Heathrow Airport as the preferred option. This, however, was based on a predicted growth in passenger numbers from a Department for Transport (DfT) report. This 2013 report used passenger figures from 2010 through to 2012 which saw airport usage at a seven-year low in 2010 after the financial crash in 2008. A slow recovery in 2011 and 2012 may have influenced a low passenger estimate in 2030. In the report, Heathrow was predicted to rise from 70M passengers per annum (ppa) in 2011 to 85Mppa by 2030. Similarly at Gatwick it predicted a rise in numbers from 34Mppa in 2011 to 42Mppa by 2030. Overall London was predicted to rise from 135M ppa to 184M ppa across Heathrow, Gatwick, Stansted, Luton and London City airport. However, since 2013, actual passenger numbers have increased at a rate far above this. In 2015 the total number of passengers at Heathrow was 75M; however, without expansion it is operating at near capacity and will therefore not see a rise in passenger numbers. At Gatwick, the actual number of passengers was 41M and at growth predictions based on data from 2013 to 2015, it is predicted to surpass the 2030 estimate in 2016. Overall, it has been predicted that if the current growth continues, London would hit the 2030 passenger number of 184M in 2019, 11 years ahead of the forecast. Birmingham airport was the only non-London based airport to not be entirely discounted by the Airport Commission’s report. The interim report stated that: “It would offer the largest catchment of people within two hours of the airport of all options. This is largely dependent on the journey time assumptions of HS2, which also makes the London airport system easier to access for passengers from Birmingham’s core aviation market.” However, speaking at New Civil Engineer’s Airports conference earlier this year, UK Civil Aviation Authority (CAA) chief executive Andrew Haines said that even if either Heathrow or Gatwick was given permission to expand, they could face challenges securing the required investors. He said that because the project did not have government assurance, it would not be bailed out should costs rise and investors may find it difficult to take on the risk. “There is no track record of regulation being applied to something of this size,” he said. Haines explained that it was genuinely unprecedented for there to be a major multi-billion pound infrastructure investment of this scale with absolutely no government guarantee or assistance. He said that the nearest project in terms of scale of investment is Hinkley Point C nuclear power station, and even that comes with government guarantee.

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As Oregon Health & Science University moves to arm its police, focus is not pulling the trigger For years Greg Moawad helped review police officers' use of force for the Multnomah County District Attorney's office, including shootings. Now, as director of the Oregon Health & Science University police, the former prosecutor is leading the push to arm his force with guns – while doing everything possible so officers don't use their new weapons. On Thursday, the OHSU board is expected to approve the recommendation for armed police. The major focus of the preparation led by Moawad, however, is not on shooting, but on communication, de-escalation of potentially violent situations, and "strategic disengagement" – an approach Moawad calls the first of its kind, encouraging officers to back down if a situation threatens to lead to more harm than it prevents. "The quasi-militaristic approach that's more traditional in law enforcement doesn't always mesh well in any academic setting," he said, "let alone an academic medical center." Following the 2007 killing of dozens at Virginia Tech, an OHSU task force had recommended an armed police force. But the university decided to set up an unarmed police force instead. Moawad was brought on to OHSU to do just that, transforming the existing security force into a team of sworn police officers with arrest powers, who are certified after undergoing police training. To supplement the OHSU police with an armed presence, the university looked to contract with local police agencies such as the Portland Police Bureau, but eventually decided the idea was not a good fit in terms of the sensitive patient mix, including the mentally ill, that OHSU frequently treats. Not only that, but response times to the Southwest hills of the OHSU main campus were poor. In one incident where a man threatened to shoot medical personnel, Portland police took 14 minutes to respond. OHSU President Joe Robertson decided it was time to proceed with an armed force, and asked Moawad to work out the details, leading to two work groups to discuss training and policies. The result: A 130-hour supplemental training course assembled by looking at police around the country. How much of Moawad's focus was dictated by his past reviews of local police situations gone wrong? "Frankly, I think a lot of it," he said. The issue is "How do we want our officers approaching situations and making decisions?" He said. "That's something that as a deputy district attorney you very rarely get to weigh in on, but as the head of a police agency you have the absolute right and expectation that you control those things. " But while his goal is to improve on training offered by the Portland police bureau and other agencies, he says it's not fair to compare the forces, as municipal law enforcement has different funding and different demands. "Our policy is designed to fit in a hospital environment," he said. "Firearms are going to be a last resort as something to deal with an active shooter as opposed to the day to day activities that it's more commonly used for in traditional law enforcement." If approved the force will finish training and be armed by mid-September. The cost will be $600,000 annually, mainly in training time. His department's current budget is about $4.4 million

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Biofilm growth on polyvinylchloride surface incubated in suboptimal microbial warm water and effect of sanitizers on biofilm removal post biofilm formation. An in vitro experiment was conducted to understand the nature of biofilm growth on polyvinyl chloride (PVC) surface when exposed to suboptimal-quality microbial water (>4 log10 cfu/mL) obtained from a poultry drinking water source mimicking water in waterlines during the first week of poultry brooding condition. PVC sections (internal surface area of 15.16 cm2) were utilized in the study to grow biofilm. After a 7-d test period, test coupons with 7-day-old biofilm were transferred into autoclaved municipal water and then treated with either chlorine-based or hydrogen peroxide-based sanitizer at bird drinking water rate, to see the impact on removal of biofilm formed on test coupons. Two trials (T1 and T2) were conducted. Test coupons used in T1 and T2 had the bacterial growth of 3.67 (SEM 0.04) and 3.97 (SEM 0.11) log10 cfu/cm2 on d 7. After sanitizer application, chlorine-based sanitizer removed bacteria in biofilm completely (0 cfu/cm2) within 24 h post treatment whereas hydrogen peroxide-based sanitizer reduced the counts to 1.68 log10 cfu/cm2 (P < 0.05) by 48 h post sanitizer application. Control remained the same (P > 0.05). Results indicated that biofilm formation can occur quickly under suboptimal water condition on PVC surface, and sanitizer application helped mitigate already formed biofilm, yet chlorine proved to be more effective than hydrogen peroxide.

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Introduction {#s1} ============ Hyperglycemia and diabetes play an important role in the pathogenesis of vascular complications including macroangiopathy and microangiopathy [@pone.0067949-Li1], which lead to retinopathy, nephropathy, arteriosclerosis and increased ischemic stroke risk by 2--4 fold relative to those without diabetes [@pone.0067949-Fox1]. Diabetes mellitus (DM) induces vascular endothelial damage and dysfunction, decreases cerebral tight junction protein expression [@pone.0067949-Ye1], and promotes artery intima-media thickness (IMT) [@pone.0067949-Haley1] and atherosclerotic vascular disease. Endothelial damage [@pone.0067949-Tamura1] and reduction of tight junction protein expression are also related with cerebral aneurysm formation [@pone.0067949-Tada1]. However, DM has been related to a decreased risk of aneurysm rupture in patients 60 years or older and in women [@pone.0067949-Inagawa1] and does not predispose to the development or rupture of saccular cerebral aneurysms [@pone.0067949-Feigin1], [@pone.0067949-Adams1], [@pone.0067949-Greenhalgh1]. Patients with aneurysmal subarachnoid hemorrhages have a lower or equivalent prevalence of DM than the general population [@pone.0067949-Feigin1], [@pone.0067949-Adams1], [@pone.0067949-Greenhalgh1]. The mechanisms responsible for this negative association remain unknown. Atherosclerotic blood vessels in diabetes are associated with inflammation and remodeling of the extracellular matrix. Advanced glycation end-products (AGEs) are a complex group of compounds formed via a nonenzymatic reaction between reducing sugars and amine residues on proteins, lipids, or nucleic acids. Receptor of advanced glycation end-products (RAGE) is the receptor of AGEs [@pone.0067949-Schmidt1], [@pone.0067949-Neeper1]. The AGE/RAGE signaling pathway plays a critical role in arterial diseases that are characterized by endothelial dysfunction, accumulation of extracellular matrix proteins, intima-media thickening, and decreased elasticity, which accelerate the development of atherosclerosis in the diabetic patients and animals [@pone.0067949-Fujita1]. RAGE also promotes the development of abdominal aortic aneurysms by inducing matrix metalloproteinase 9 (MMP9) expression [@pone.0067949-Zhang1]. MMP9 degrades the extracellular matrix and is involved in control and regulation of inflammation [@pone.0067949-Kuzuya1]. Increased MMP9 expression was detected in stenotic and aneurysmal arterial remodeling [@pone.0067949-Galis1]. As a proinflammatory factor, toll-like receptor 4 (TLR4) upregulates MMP9 expression [@pone.0067949-Qiu1] and mediates inflammatory responses and also contributes to arteriosclerosis [@pone.0067949-Li2], [@pone.0067949-Michelsen1]. Our previous study has found that T1DM-MCAo rats exhibit significantly increased RAGE, TLR4 and MMP9 expression in macrophages in the ischemic brain compared to the ischemic brain of wild-type (WT) rats [@pone.0067949-Ye2]. Generally, smoking, excessive alcohol, untreated hypertension and female gender have been shown to be the most important risk factors for aneurysmal subarachnoid hemorrhage (SAH) [@pone.0067949-Feigin1], [@pone.0067949-Juvela1]. Recent, large-scale genome-wide association (GWA) studies have revealed consistent and replicable genetic markers of several complex diseases such as coronary artery disease, and type 2 diabetes may also contribute to IA development [@pone.0067949-Onda1]. In this study, we investigated the effect of T1DM on IA formation and the underlying mechanism by which T1DM induces IA formation in rats. Materials and Methods {#s2} ===================== All experimental procedures were carried out in accordance with the NIH Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee of Henry Ford Hospital (IACUC approval number: 999). All efforts were made to ameliorate suffering of animals. Diabetes Induction {#s2a} ------------------ Adult Male Wistar rats (250--275 g) purchased from Charles River (Wilmington, MA) were used. Diabetes was induced by a single intraperitoneal injection of streptozotocin into rats (STZ, 60 mg/kg, dissolved in citrate buffer, pH 4.5; Sigma Chemical Co., St. Louis, MO). The fasting blood glucose level was measured 10 days after STZ injection by using a glucose analyzer (Accu-Chek Compact System; Roche Diagnostics, Indianapolis, IN) with test strips for glucose (Polymer Technology System, Inc. Indianapolis, IN) according to the manufacturer's instructions. Diabetes was defined by a fasting blood glucose exceeding 300 mg/dl. All animals included in this study also had a fasting blood glucose exceeding 300 mg/dl ten days after streptozotocin injection and at euthanasia. Experiment Groups {#s2b} ----------------- Wild type (WT) non-diabetic rats were used as control (n = 7). T1DM rats were euthanized 4 weeks (DM4W, n = 7) or 10 weeks (DM10W, n = 7) after STZ injection. Immunostaining was performed on all rats. Histological and Immunohistochemical Assessment {#s2c} ----------------------------------------------- The brains were fixed by transcardial perfusion with saline, followed by perfusion and immersion in 4% paraformaldehyde before being embedded in paraffin. For immunostaining, a standard paraffin block was obtained from the bregma (−1 mm to 1 mm) of the brain. A series of 6 µm thick sections were cut from the block. Every 10th coronal section for a total of 5 sections was used for immunohistochemical staining. Immunostaining for Trichrome (for differentiating muscle from collagen of arteries), α-smooth muscle actin (α-SMA, a smooth muscle cell marker, mouse monoclonal IgG 1∶800, Dako) and inflammatory mediators including RAGE (1∶400; Dako, Carpinteria, CA, USA), MMP9 (1∶500, Santa Cruz Biotechnology, Santa Cruz, CA, USA) and TLR4 (goat polyclonal IgG; dilution 1∶100; Cruz Biotech Inc., Santa Cruz, California) immunostaining were performed. Elastica van Gieson staining was used to show the thinning and loss of elastic tissue fibers in aneurysmal formation [@pone.0067949-Tada2]. Control experiments consisted of staining brain coronal tissue sections as outlined above, but non-immune serum was substituted for the primary antibody. The immunostaining analysis was performed by an investigator blinded to the experimental groups. Classification of Aneurysmal Changes {#s2d} ------------------------------------ Classification of aneurysmal changes at the anterior cerebral artery-olfactory artery branching sites using microscopy findings with Elastica van Gieson staining were recorded as: (A) Normal (stage 0). (B) Endothelial damage (stage 1). (C) Moderate protrusion (stage 2). (D) Saccular aneurysm (stage 3) [@pone.0067949-Tada2], [@pone.0067949-Guerreiro1], [@pone.0067949-Aoki1]. Quantification of RAGE, MMP9 and TLR4 Expression {#s2e} ------------------------------------------------ For quantitative measurements of RAGE, MMP9 and TLR4, five slides from each brain, with each slide anterior cerebral artery and olfactory artery were digitized under a 20× objective (Olympus BX40) using a 3-CCD color video camera (Sony DXC-970MD) interfaced with an MCID image analysis system (Imaging Research, St. Catharines, Canada) [@pone.0067949-Calza1], [@pone.0067949-Chen1]. RAGE, MMP9 and TLR4 were measured and expressed as ratio of positive area to luminal area of the anterior cerebral artery and olfactory artery. Data were analyzed in a blinded manner. Trichrome Immunostaining and Measurement {#s2f} ---------------------------------------- Using Gomori One-Step Trichrome Stain (Sigma, St Louis, MO), brain sections were postfixed in Bouin fixative. Nuclei are stained with Weigert hematoxylin and then stained in Gomori trichrome stain followed by a 0.5% acetic water rinse. Connective tissue and collagen are stained blue, nuclei are stained dark red/purple, and cytoplasm is stained red/pink. Artery intimae, media, and artery diameter (minimum diameter) were measured in the internal carotid artery (ICA). 251658240αSMA-positive Coated Arterial Diameter and Wall Thickness {#s2g} ------------------------------------------------------------------ The α-SMA stained vessels were analyzed with regard to small and large vessels (≥10 µm diameter). The 10 largest arterial wall thicknesses and internal arterial diameters were measured. In addition, the total number of occluded arterioles in the bilateral hemispheres was counted. Double Immunohistochemical Staining {#s2h} ----------------------------------- To specifically identify RAGE, TLR4 and MMP9-reactive cells co-localized with macrophages (ED1), double immunofluorescence staining of RAGE/ED1, TLR4/ED1 and MMP9/ED1 were performed. Fluorescein isothiocyanate (FITC, Calbiochem, San Diego, CA, USA), 4, 6-diamidino-2-phenylindole (DAPI, Vector Laboratories) and cyanine-3 (CY3, Jackson Immunoresearch, PA, USA) were used for double-label immunoreactivity. Each coronal section was first treated with the primary anti-RAGE, anti-TLR4 or anti-MMP9 antibody with Cy3, and then followed by ED1 with FITC. Control experiments consisted of staining brain coronal tissue sections as outlined above, but using nonimmune serum for the primary antibody. To test cerebral vascular perfusion, FITC-dye (50 mg/rat in 2 ml PBS, IV) was injected at 5 min before euthanasia in another group of animals (n = 4/group). Animals were anesthetized with ketamine and fixed by 4% paraformaldehyde. The brain tissues were processed to acquire adjacent 100-µm thick coronal sections using a vibratome. Five sections from the bregma (−1 mm to 1 mm) section were used to detect vascular perfusion by laser scanning confocal microscopy (LSCM) with the use of a Bio-Rad MRC 1024 (argon and krypton) laser-scanning confocal imaging system mounted onto a Zeiss microscope (BioRad) [@pone.0067949-Chen2]. For FITC labeled coronal sections, green (FITC) fluorochromes on the sections were excited by a laser beam at 488 nm; emissions were sequentially acquired through 522 nm emission filters. Areas of interest were scanned with an ×20 objective lens in 512.2×512.2-µm format in the x-y direction and 0.5 µm in the z direction. The photos and quantification of FITC labeled vessels were processed by ImageJ (Wayne Rasband, National Institutes of Health, USA). Statistical Analysis {#s2i} -------------------- All measurements and analyses were performed by normality of distribution, and the homogeneity of variances was tested including the biochemistry, and immunostaining. One-way analysis of variance (ANOVA) was used for the immunostaining analysis. Spearman correlation coefficients were calculated to study the correlation between aneurysm formation and immunohistochemical measurements. All data are presented as mean ± standard error (SE). Results {#s3} ======= T1DM Increases Intracranial Aneurysm (IA) Formation ([Figure 1](#pone-0067949-g001){ref-type="fig"}) {#s3a} ---------------------------------------------------------------------------------------------------- To test whether diabetes regulates IA formation and alters elastic tissue fibers in the anterior cerebral artery-olfactory artery branching sites, Elastica van Gieson staining was performed [@pone.0067949-Aoki2]. We found that T1DM significantly increased aneurysmal formation identified by the classification of aneurysmal changes compared with non-DM rats ([Figure 1A--C](#pone-0067949-g001){ref-type="fig"}). The ratio of stage 1 and 2 aneurysmal formations to total artery number increased significantly in T1DM rats compared to non-DM rats ([Figure 1D](#pone-0067949-g001){ref-type="fig"}, *p\<*0.05), and all of the aneurysmal formations were in stage 1 and stage 2, but not in stage 3 ([Figure 1D](#pone-0067949-g001){ref-type="fig"}). {#pone-0067949-g001} T1DM Increases RAGE, MMP9 and TLR4 Expression ([Figure 2](#pone-0067949-g002){ref-type="fig"}) {#s3b} ---------------------------------------------------------------------------------------------- To obtain insight into the possible underlying mechanisms of T1DM-induced arthrosclerosis and aneurysmal formation, RAGE, MMP9 and TLR4 expressions were measured. [Figure 2](#pone-0067949-g002){ref-type="fig"} shows that T1DM significantly increased RAGE, MMP9 and TLR4 expression compared to non-DM rats at 10 weeks after diabetes induction (*p\<*0.05, [Figure 2A--C](#pone-0067949-g002){ref-type="fig"}). [Figure 2D--F](#pone-0067949-g002){ref-type="fig"} show that RAGE, TLR4 and MMP9 are predominantly detected in macrophages (ED1 positive cells) in the cerebral arteries. The results are consistent with previous studies [@pone.0067949-Zhang1], [@pone.0067949-Ye2]. In addition, [Figure 2G--I](#pone-0067949-g002){ref-type="fig"} show that the increase of RAGE (r = 0.532, *p\<*0.01; [Figure 2G](#pone-0067949-g002){ref-type="fig"}), TLR4 (r = 0.634, *p\<*0.001; [Figure 2H](#pone-0067949-g002){ref-type="fig"}) and MMP9 (r = 0.522, *p\<*0.02; [Figure 2I](#pone-0067949-g002){ref-type="fig"}) expression significantly correlated with IA formation in T1DM rats. {#pone-0067949-g002} T1DM Increases the ICA Intimae Thickness and Media Thickness, and Decreases the ICA Internal Diameter in Trichrome Staining ([Figure 3](#pone-0067949-g003){ref-type="fig"}) {#s3c} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------- To test why T1DM increases IA formation in stage 1 and 2, but not in stage 3, and whether T1DM induces cerebral arteriosclerosis-like changes, Trichrome staining was used. [Figure 3](#pone-0067949-g003){ref-type="fig"} shows that ICA intimae thickness and media thickness were significantly increased in T1DM rats compared with non-DM rats (p\<0.05, [Figure 3D, E](#pone-0067949-g003){ref-type="fig"}). The ICA internal diameter was significantly decreased in T1DM rats compared with non-DM rats (*p\<*0.05, [Figure 3F](#pone-0067949-g003){ref-type="fig"}). {#pone-0067949-g003} T1DM Decreases Cerebral Vascular Perfusion ([Figure 4](#pone-0067949-g004){ref-type="fig"}) {#s3d} ------------------------------------------------------------------------------------------- To test whether T1DM regulates cerebral vascular perfusion, FITC-dye was injected into rats. [Figure 4](#pone-0067949-g004){ref-type="fig"} shows that the cerebral vascular perfusion significantly decreased at both time points (DM4W and DM10W) in T1DM rats compared to non-DM rats (*p\<*0.01, [Figure 4D](#pone-0067949-g004){ref-type="fig"}), and the cerebral vascular perfusion of DM10W was more attenuated compared to DM4W(*p\<*0.05, [Figure 4D](#pone-0067949-g004){ref-type="fig"}). The data indicate that cerebral perfusion is decreased with the course of diabetes. {#pone-0067949-g004} T1DM Decreases Cerebral Arterial Internal Diameter and Cerebral Vascular Perfusion, and Increases Cerebral Arterial Wall Thickness and Occluded Cerebral Arterioles Compared to Non-DM Rats ([Figure 5](#pone-0067949-g005){ref-type="fig"}) {#s3e} -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- To test why T1DM decreases cerebral vascular perfusion, arterial internal diameter and occlusion cerebral arterioles number were measured. The cerebral arterial internal diameters were significantly decreased in T1DM rats at 4 weeks (DM4W) and 10 weeks (DM10W) after T1DM induction compared to non-DM rats (*p\<*0.05, [Figure 5D](#pone-0067949-g005){ref-type="fig"}). Concomitantly, the cerebral artery wall thickness and numbers of occluded cerebral arterioles were significantly increased in DM4W and DM10W rats compared to non-DM rats (*p\<*0.05, [Figure 5E, I](#pone-0067949-g005){ref-type="fig"}). In addition, there was no significant difference between DM4W and DM10W in arterial internal diameter and wall thickness (*p\>*0.05, [Figure 5D, E](#pone-0067949-g005){ref-type="fig"}). {#pone-0067949-g005} Discussion {#s4} ========== In this study, to our knowledge we are the first to demonstrate that T1DM promotes the formation of intracranial aneurysm as well as significantly increases RAGE, MMP9 and TLR4 expression in the intracranial arterial wall compared to WT non-DM rats. We also found that T1DM increases cerebral artery IMT and atherosclerosis-like changes identified by decreased arterial diameter and cerebral vascular perfusion, and significantly increases the arterial wall thickness compared to non-DM rats. Diabetes Increases Initial Stages of Intracranial Aneurysm Formation {#s4a} -------------------------------------------------------------------- Previous studies have found that diabetes increases vascular damage and atherosclerotic vascular disease [@pone.0067949-Creager1], [@pone.0067949-Luscher1]. Consistent with these studies, we found that T1DM significantly increased artery IMT and vascular occlusion and decreased arterial diameter. There are several studies have investigated the effects of abdominal aortic aneurysm formation in diabetic population and demonstrated that diabetes does not aggravate aortic aneurysmal development [@pone.0067949-Thompson1], [@pone.0067949-Lederle1], [@pone.0067949-Golledge1]. However, T1DM significantly increased early stage intracranial aneurysmal formation (stage1 and 2), but not stage 3 intracranial aneurysmal formation. Our data suggest that T1DM promotes early intracranial aneurism formation, but does not promote aneurysm development to stage 3. The reason for the reduced stage 3 aneurysm development in T1DM is not clear. Possible reasons may be related to: 1) dysregulation of tPA/PAI-1 signaling pathway. A previous clinical report showed that tPA thrombolysis could induce the rupture of cerebral aneurysms [@pone.0067949-Lagares1]. While hyperglycemia significantly increases PAI-1 expression [@pone.0067949-Festa1] in cerebral arteries and also downregulates t-PA expression and activity [@pone.0067949-Kittaka1], which may increase inflammatory cell accumulation in the lesioned vessels and increase arterial intima-media thickness, and thus attenuates aneurysm diameter [@pone.0067949-Dua1], and thereby decreases saccular aneurysm (Stage 3 IA formation). 2) There may be vascular remodeling after arteriosclerosis in diabetics [@pone.0067949-Galis1]. There are two major directions in which arterial remodeling may progress. Intima thickening and constrictive geometric remodeling of the artery wall are primary changes associated with the decreased lumen [@pone.0067949-Galis1]. Expansive remodeling of the wall tends to preserve the lumen in the face of increased lesion burden. Therefore, the thicker intima-media and lower wall stress in diabetics may partly explain the protective effect of diabetes against aneurysm development [@pone.0067949-Astrand1]. 3) Hypertension is considered a risk for aneurysmal rupture [@pone.0067949-Asari1], [@pone.0067949-Winn1]. Previous studies have found that hypertension is more common in the diabetic population than in the general non-diabetic population [@pone.0067949-Epstein1], [@pone.0067949-Kannel1], and hypertension and/or insulin-dependent diabetes mellitus significantly increases cerebral IA formation [@pone.0067949-Taylor1], [@pone.0067949-Kwak1]. In the current study, we investigated the effects of T1DM alone on the regulation of IA formation. The effects of diabetes in combination with hypertension on the IA formation and progression warrants further investigation. In addition, tPA thrombolysis could induce rupture of cerebral aneurysms and also increase IA formation [@pone.0067949-Thompson1], [@pone.0067949-Lagares1]. While tPA treatment of ischemic stroke in T1DM stroke rats significantly increases brain hemorrhage formation [@pone.0067949-Fan1], [@pone.0067949-Ning1], whether the brain hemorrhage formation induced by tPA treatment is related with IA formation in T1DM animals, requires further investigation. Increase Levels of RAGE, TLR4 and MMP9 Might Promote the Initiation and Formation of Intracranial Aneurysm and Atherosclerosis-like Changes in T1DM Rats {#s4b} -------------------------------------------------------------------------------------------------------------------------------------------------------- AGEs accumulate in the vessel wall and are implicated in both the microvascular and macrovascular complications of diabetes [@pone.0067949-Yamagishi1]. The expression of the AGE receptor RAGE is upregulated in endothelial cells, smooth muscle cells, and mononuclear phagocytes in diabetic vasculature, and such upregulation is linked to the inflammatory response [@pone.0067949-Schmidt2], [@pone.0067949-Schmidt3], and it accelerates the development of atherosclerosis in patients with diabetes [@pone.0067949-Fujita1]. It has been generally accepted that the occurrence of aneurysm is related to the presence of severe atherosclerosis in the circulation [@pone.0067949-Lee1]. Increased RAGE expression was detected in aneurysm formation in animal models and in human patients [@pone.0067949-Zhang1], [@pone.0067949-Huttunen1]. RAGE affects the aneurysmal formation via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway to activate MMP9 expression [@pone.0067949-Feigin1], [@pone.0067949-Takeshita1]. In addition, TLR4 initiates inflammation in diabetics and plays an important role in arteriosclerosis by inducing inflammation responses [@pone.0067949-Li2], [@pone.0067949-Michelsen1]. TLR4 expression is apparently upregulated in the endothelial cell layer and adventitia of aneurysm walls [@pone.0067949-Aoki3], and increases MMP9 expression in macrophages [@pone.0067949-Chen1], [@pone.0067949-Aoki2], which promote aneurysmal formation [@pone.0067949-Grenier1], [@pone.0067949-Kanematsu1], [@pone.0067949-Hodgkinson1]. MMP9 degrades especially type IV collagen, the main constituent of the basement membrane [@pone.0067949-NadukKik1], and contributes to development of vascular lesions [@pone.0067949-Dollery1]. MMP9 is also involved in abdominal aortic aneurysm formation [@pone.0067949-Thompson1], [@pone.0067949-Longo1], [@pone.0067949-McMillan1]. Inhibition of MMP9 therapy results in attenuation of aneurysm formation by suppression of inflammation of the aortic wall [@pone.0067949-Prall1]. We found that diabetes significantly resulted in increased expression of RAGE, TLR4 and MMP9 in damaged arteries which also correlated with intracranial formation of aneurysms. The increased intracranial aneurysm formation may be regulated by inflammatory factors RAGE, MMP9 and TLR4 [@pone.0067949-Lindeman1]. Conclusions {#s4c} ----------- In conclusion, this study demonstrates that Type-1 diabetes promotes cerebral aneurysmal formation as well as arteriosclerosis-like changes in T1DM rats. Inflammatory mediators including MMP9, RAGE and TLR4 in diabetes might contribute the increased initiation and formation of aneurysm and arteriosclerosis. This study provides mechanistic insight into how T1DM promotes initial development of intracranial aneurysm but limits further progression. [^1]: **Competing Interests:**The authors have declared that no competing interests exist. [^2]: Conceived and designed the experiments: JC MC. Performed the experiments: TY RN AZ CR. Analyzed the data: TY JC. Contributed reagents/materials/analysis tools: JC MC. Wrote the paper: TY JC.

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Weekly jobless claims for the week ended Sept. 7 fell by 31,000 to 292,000, the Labor Department reported in data released in Washington. Economists polled by Thomson Reuters were expecting claims to rise slightly to 330,000, up from the prior week's 323,000. Economists are also expecting a 0.1% month-over-month export increase and a 0.5% import increase. In company news, Pandora ( P) was surging 6.6% to $22.80 a day after the online music streaming service named Brian McAndrews its CEO and president, effective immediately. Yahoo! ( YHOO) was gaining 1.5% to 422.64 after CEO Marissa Mayer said Wednesday that the Internet portal has about 800 million worldwide users, a 20% increase since she took control of the company 15 months ago. Dell ( DELL) will finally vote on Thursday for the $24.8 billion deal that would allow founder Michael Dell to take the company private. Investors who have followed the company's timeline know that Dell and billionaire investor Carl Icahn have wrestled for months in an attempt to take the company off the public markets and offer shareholders a sweet deal. Analysts suggest that Michael Dell will win the vote as Icahn finally stepped away from the bargaining table.

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Q: Find explicit formula for $y_{n}=\frac{1}{n (\sqrt 2)^n}+\frac{n-1}{n} y_{n-2}$ Is it possible to find a explicit formula here ? This is the reduction formula of$$\int_{0}^{\frac{\pi}{4}} (\cos x)^n dx$$. If the limits are from $0$ to $\frac{\pi}{2}$ then the nice walli's formula can be obtained,however i have no idea regarding solving this kind of recurrences. Any help will be appreciated. A: Starting with $$ y_n=\frac1{n\,2^{n/2}}+\frac{n-1}{n} y_{n-2}\tag1 $$ Multiply $(1)$ by $\frac{\Gamma\left(\frac{n+2}2\right)}{\Gamma\left(\frac{n+1}2\right)}=\frac{n}2\frac{\Gamma\!\left(\frac{n}2\right)}{\Gamma\!\left(\frac{n+1}2\right)}=\frac{n}{n-1}\frac{\Gamma\left(\frac{n}2\right)}{\Gamma\left(\frac{n-1}2\right)}$: $$ \frac{\Gamma\!\left(\frac{n+2}2\right)}{\Gamma\!\left(\frac{n+1}2\right)}y_n =\frac1{2^{\frac{n}2+1}}\frac{\Gamma\!\left(\frac{n}2\right)}{\Gamma\!\left(\frac{n+1}2\right)}+\frac{\Gamma\!\left(\frac{n}2\right)}{\Gamma\!\left(\frac{n-1}2\right)} y_{n-2}\tag2 $$ Thus, we get $$ \overbrace{\frac{\Gamma\!\left(n+1\right)}{\Gamma\!\left(n+\frac12\right)}y_{2n}}^{\large\alpha_n} =\frac1{2^{n+1}}\frac{\Gamma\!\left(n\right)}{\Gamma\!\left(n+\frac12\right)}+\overbrace{\frac{\Gamma\!\left(n\right)}{\Gamma\!\left(n-\frac12\right)}y_{2n-2}}^{\large\alpha_{n-1}}\tag3 $$ and $$ \overbrace{\frac{\Gamma\!\left(n+\frac32\right)}{\Gamma\!\left(n+1\right)}y_{2n+1}}^{\large\beta_n} =\frac1{2^{n+\frac32}}\frac{\Gamma\!\left(n+\frac12\right)}{\Gamma\!\left(n+1\right)}+\overbrace{\frac{\Gamma\!\left(n+\frac12\right)}{\Gamma\!\left(n\right)}y_{2n-1}}^{\large\beta_{n-1}}\tag4 $$ Therefore, noting that $\alpha_n=\alpha_0+\sum\limits_{k=1}^n(\alpha_k-\alpha_{k-1})$, $$ y_{2n}=\frac{\Gamma\!\left(n+\frac12\right)}{\Gamma\!\left(n+1\right)}\left[\frac{y_0}{\sqrt\pi}+\sum_{k=1}^n\frac1{2^{k+1}}\frac{\Gamma\!\left(k\right)}{\Gamma\!\left(k+\frac12\right)}\right]\tag5 $$ and noting that $\beta_n=\beta_0+\sum\limits_{k=1}^n(\beta_k-\beta_{k-1})$, $$ y_{2n+1}=\frac{\Gamma\!\left(n+1\right)}{\Gamma\!\left(n+\frac32\right)}\left[\frac{y_1\sqrt\pi}2+\sum_{k=1}^n\frac1{2^{k+\frac32}}\frac{\Gamma\!\left(k+\frac12\right)}{\Gamma\!\left(k+1\right)}\right]\tag6 $$ It might be useful to recall that $\Gamma(n+1)=n!$ and $\Gamma\!\left(n+\tfrac12\right)=n!\frac{\sqrt\pi}{4^n}\binom{2n}{n}$. Unfortunately, I am not aware of closed forms for the sums in $(5)$ and $(6)$.

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Field of the Invention The present invention relates to an external resonator type light emitting system. Related Art Statement It has been generally utilized a semiconductor laser of Fabry-Perot (FP) type including an optical resonator constructed with an active layer and mirrors provided on both end faces of the active layer. However, according to such FP type laser, light is oscillated at a wavelength satisfying conditions for oscillating standing waves. The longitudinal mode thus tends to be of multi mode, and the oscillating wavelength is changed particularly when a current or temperature is changed, resulting in a change of optical intensity. Therefore, for the purpose of optical communication or gas sensing, it is required a laser capable of single mode oscillation and with good stability of wavelength. It has been thereby developed a distributed feed-back (DFB) laser and a distributed reflection (DBR) laser. According to these laser systems, diffraction gratings are provided in a semiconductor material to oscillate light having only a specific wavelength utilizing the dependency of the gratings on wavelength. According to the DBR laser, concaves and convexes are formed on a surface of a waveguide extended from a waveguide of the active layer to provide a mirror utilizing Bragg reflection for realizing a resonator (Patent Document 1; Japanese Patent Publication No. S49-128,689A; Japanese Patent Document 2; Japanese patent Publication No. S56-148,880A). Since diffraction gratings are provided on both ends of the optical waveguide layer according to the laser, light emitted from the active layer is propagated through the optical waveguide layer, and a part of the propagating light is reflected by the diffraction gratings, returned into a current injection part and then amplified. As light component having only a single wavelength is reflected at a specific direction from the diffraction grating, the wavelength of the laser light is made constant. Further, as the application, it was developed an external resonator type semiconductor laser including a diffraction grating as a part separated from the semiconductor to form an external resonator. Such type of laser provides one having stability of wavelength, stability of temperature and controllability. The external resonator includes a fiber Bragg grating (FBG) (Non-patent document 1) and a volume hologram grating (VHG) (Non-patent document 2). Since the diffraction grating is composed of a member separated from the semiconductor laser, it is characteristic that its reflectance and length of the resonator can be independently designed. And, since it does not affected by elevation of temperature rise due to heat generation caused by current injection, it is possible to further improve the stability on wavelength. Further, the temperature dependency of refractive index of the semiconductor is different, it is possible to improve the stability on temperature can be improved by designing the refractive index together with the length of the resonator. According to Japanese Patent document 6 (Japanese Patent Publication No. 2002-134,833A), it is disclosed an external resonator type laser utilizing a grating formed in a waveguide composed of quartz glass. It aims at providing a frequency-stable laser suitably used in environment under which room temperature is considerably changed, (for example, up to 30° C. or higher) without a temperature controller. It is further described to provide a laser free from temperature dependency with mode hopping prevented and without dependency of oscillating frequency on temperature.

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Q: Cordova Card.IO plugin implementation I am having some trouble implementing the Card.io plugin for Cordova. There are instructions on the github page of how to install and implement the plugin: https://github.com/card-io/card.io-Cordova-Plugin I added the plunging by doing $ cordova plugin add https:///... And added the button they tell you to add on the github page. Up to this point I'm pretty sure I'm doing everything the way I should. Here comes the issue now though, the actual implementation in the app. I use a ui framework in my app, and as such, I don't have the index.js file, nor does my code look like the code in the standard index.js with regards to the deviceReady handling. I just do... .ready(function() { // Code to fire on device ready. }): I'm somewhat familiar with callbacks, but I have no clue what's going on in their example. the whole "example : function() {..." is completely new for me. Can someone please rewrite that example so that it is a few functions that is well structured and makes a little more sense? I tried doing this, with my code now looking like this: .ready(function() { CardIO.canScan(onCardIOCheck); }); function onCardIOComplete() { var cardIOResponseFields = [ "cardType", "redactedCardNumber", "cardNumber", "expiryMonth", "expiryYear", "cvv", "postalCode" ]; var len = cardIOResponseFields.length; alert("card.io scan complete"); for (var i = 0; i < len; i++) { var field = cardIOResponseFields[i]; alert(field + ": " + response[field]); } } function onCardIOCancel() { alert("card.io scan cancelled"); } function onCardIOCheck(canScan) { alert("card.io canScan? " + canScan); var scanBtn = document.getElementById("scanBtn"); if (!canScan) { scanBtn.innerHTML = "Manual entry"; } scanBtn.addEventListener("click", function(e) { var options = { "requireExpiry": true, "requireCVV": false, "requirePostalCode": false, "restrictPostalCodeToNumericOnly": true }; CardIO.scan(options, onCardIOComplete, onCardIOCancel); }); } This does not work though. I added alert() on both sides of the call inside the .ready() function, to see if it fires. Both fire, but it's as if the Card.canScan() function does not fire at all. I added an alert() inside the onCardIOCheck function as well, to see if it is ever reached, but it's not. Any help would be greatly appreciated. (Please note: I don't use Angular.js, I only use pure Javascript with occasional jQuery) A: You need to replace .ready(function() { CardIO.canScan(onCardIOCheck); }); With document.addEventListener('deviceready', function() { CardIO.canScan(onCardIOCheck); }, false); The ready event you were using is the ready event of the DOM and not the cordova plugins. I believe that when you called CardIO.canScan(onCardIOCheck); the plugin was not loaded and that why it not working.

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Tags I came across a clever tweet recently claiming that people who say ”The Nazis were socialists, it’s in the name!” must be ”very confused by buffalo wings.” It is now the conventional wisdom that the Nazis were capitalists, not socialists, despite their misleading name “The National Socialist German Workers Party.” Anybody with a college degree knows they were capitalistic, if not in name, then at least in principle. Of course, this is all nonsense. But the question does arise, where did this myth come from? Mises, in fact, answered this question in 1951 in his essay “Planned Chaos.” During the nineteenth century, when socialism was becoming fashionable in Europe, there was no distinction between “socialism” and “communism.” There were different forms of socialism, of course, but these were not distinguished by the different terms. Different thinkers had their preference, but the terms were used interchangeably, even by Karl Marx. Mises writes, ”In 1875, in his Criticism of the Gotha Programme of the German Social Democratic Party, Marx distinguished between a lower (earlier) and a higher (later) phase of the future communist society. But he did not reserve the name of communism to the higher phase, and did not call the lower phase socialism as differentiated from communism.” According to Marx’s theory of history, socialism was an inevitability. According to his deterministic outlook, every country was destined to progress from a feudalist society, to a capitalist, and finally to a socialist society. To Marx, this progression was inevitable. In Germany, the first purveyors of “State socialism” emerged shortly prior to Marx. Johann Karl Rodbertus, like Marx, rejected many of the existing socialist theories as untenable. Rodbertus was the first socialist thinker to advocate the control of both production and distribution, and to achieve this, the socialist must use the State. The greatest expositor of his ideas was Ferdinand Lassalle, whose proselytizing led to the rapid growth in popularity of what Mises would call “socialism of the German pattern.” German socialism, as Mises defines it, differs from what he called “socialism of the Russian pattern” in that “it, seemingly and nominally, maintains private ownership of the means of production, entrepreneurship, and market exchange.” However, this is only a superficial system of private ownership because through a complete system of economic intervention and control, the entrepreneurial function of the property owners is completely controlled by the State. By this, Mises means that shop owners do not speculate about future events for the purpose of allocating resources in the pursuit of profits. Just like in the Soviet Union, this entrepreneurial speculation and resource allocation is done by a single entity, the State, and economic calculation is thus impossible. “In Nazi Germany,” Mises tells us, the property owners “were called shop managers or Betriebsführer. The government tells these seeming entrepreneurs what and how to produce, at what prices and from whom to buy, at what prices and to whom to sell. The government decrees at what wages labourers should work, and to whom and under what terms the capitalists should entrust their funds. Market exchange is but a sham. As all prices, wages and interest rates are fixed by the authority, they are prices, wages and interest rates in appearance only; in fact they are merely quantitative terms in the authoritarian orders determining each citizen’s income, consumption and standard of living. The authority, not the consumers, directs production. The central board of production management is supreme; all citizens are nothing else but civil servants. This is socialism with the outward appearance of capitalism. Some labels of the capitalistic market economy are retained, but they signify here something entirely different from what they mean in the market economy.” But the Soviets themselves also played a part in the crafting of the myth of the Nazi capitalist. The Nazis were not trying to hide their socialism (after all, snarky tweets aside, socialism was in the name); they were just implementing socialism according to a different strategy than that of the Marxist socialists. The Soviets were able to brand the Nazis as capitalists only because they had already started redefining the terms “socialism” and “communism” to fit their own political agenda. In 1912, Lenin formed his Communist Party. The members of his party, the Bolsheviks, were now distinct from the other, rival groups of socialists. The terms “communism” and “socialism” were still able to be used interchangeably, and the Soviet Union itself was just a shorthand name for the “United Soviet Socialist Republics.” But by branding his group under the title of the “Communist Party,” the title “Communist” — now meaning a member of Lenin’s party — became a way of saying that this was a “true socialist,” so to speak. “It was only in 1928,” Mises explains, “that the programme of the Communist International ... began to differentiate between communism and socialism (and not merely between communist and socialist).” This new doctrine held that, in the Marxian framework, there was another stage of development between capitalism and communism. That stage, of course, was socialism, and it was the stage that the Soviet Union was in. In his original theory, Marx made a distinction between early- and late-stage communism, where true equality would be reached only in the final stage of communism, after the State had successfully followed all of his prescriptions and humans had evolved beyond their “class consciousness.” In the new doctrine, “socialism” simply referred to Marx’s early-stage communism, while true communism — Marx’s late-stage communism — would not be achieved until the whole world was communist. Thus, the Soviet Union was merely socialist, and the party members were Communists because they were the enlightened few who were working toward the ultimate goal of communism. But the Nazis still claimed to be socialist and, in fact, were acting quite a bit like socialists with their heavy-handed economic interventions. However, there was still economic inequality among the citizens of Nazi Germany (just as there was in the Soviet Union, but that didn’t matter to the narrative). Furthermore, as Mises pointed out in his analysis of socialism of the German pattern, the Nazis retained some of the legal language of a capitalist society. Specifically, there was still the superficial existence of nominal property ownership. When the Nazis invaded the Soviet Union, Joseph Stalin and his lackeys used the new communist narrative to redefine Nazi Socialism — which was never Marxism but was based on the theories of the original German socialists who directly influenced Marx’s later ideas — as “capitalists.” According to this new narrative, the Nazis were in the final and worst stage of capitalism. At a time when many members of the European intelligentsia were still enamored with the Soviet Union, this narrative of the Nazis as capitalists was a welcome lie. But this idea is one that comes not from any grounding in economic principles, but rather the Soviet interpretation of the Marxian framework. The Nazis, who touted their socialism proudly and implemented socialist policies with great consistency, were now being referred to as capitalists for no reason other than they did not fit cleanly into the Soviet-Marxist worldview, and this false narrative survives today.

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This is a project that I began about a year ago when i started learning Perl. Since then, it has been rotting in a folder until today, when I fixed up some of the code, commented it out, and so on. The web crawler will start from whatever URL you feed it. After that, you can grab a cup of coffee and sit back, because it will run until there are no more links left to explore on the World Wide Web... or at least that's the idea It scans each web page for e-mail addresses and puts them in a neat little file for you (because why the fuck not?). I'm unsure how useful it is unless you sell e-mail lists, but I'm posting it mostly so that people who know better can critique my code. And who knows? Maybe someone here will find a use for it. ########### -- STARTING THE MAIN LOOP -- ##########MAIN: while (@urls) { # Set the number of milliseconds to sleep between each page crawled. # This is randomized to a value between 12 and 17 seconds by default $sleep = rand(500000) + 12000000; # print to both the email database file and the console. select(STDOUT); print $&."\n"; open $emailfile,">>", ("emails.txt"); select($emailfile); if($firstmail == 0){ printf "\n-------------------- $curtime --------------------\n"; $firstmail = 1; } print $&."\n"; close $emailfile; $oldemail{$&} = 1; } } # The loop is almost done, upon a successful crawl through a link, it will sleep for the amount of time # set at the start of the loop. select(STDOUT); print "\nProgram waits for ". $sleep/1000000 ." seconds before next request.\nThis is to prevent blacklisting.\n"; usleep($sleep);} # Function to be called if user does not use the terminal flags or there is a mistake in the URLsub getInput { # Get the URL to start crawling print "\nPlease enter a URL to start crawling. \n(Example: 'http://google.com' or 'yahoo.com')\n\n"; print "http://"; $startingURL = <>; chomp $startingURL; print "\n\nDo you want the links that appear to be only the ones in the same domain that you typed in?\n". "This is useful to avoid following links to advertising sites as these usually do not contain e-mail addresses\n\n". "Domain = $domain \n\n". "1) Yes\n". "2) No\n". "3) Exit Program\n\n";

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Weary Workers When Prime Minister Narendra Modi declared nationwide lockdown on 24 March 2020 thousands of migrant workers in different cities became restless due to lack of food and essentials for their daily living. Neither the Government officials nor those who employed them bothered about their livelihood when they lost their daily work. Thousands of them started moving out leaving the large cities to reach their homes in far away villages in different states. Neither the lack of transport facilities nor the long distance stopped them. They started walking through roads. But when police started beating them for breaking the lockdown rules they took the railway tracks to walk. Men and women ventured out carrying their little children and luggage. Neither those who were running the government nor their employers were sensitive to them. If the politicians and bureaucrats who were running the government had sensitivity and foresight they could have first arranged transport for those who wanted to leave the cities for their homes before declaring the lockdown. Despite thousands walking hundreds of kilometres neither the political leaders nor those in government bothered about their hardships. Reports say that 42 workers were killed in road accidents within a few days. When 16 workers were run over by a goods train at Satana village near Aurangabad on 8th May morning governments and politicians were woken up. It is an insult that the MP Chief Minister fixed Rs. 5 lakh as the price for the life of each dead person. May be because they were poor. The irony is that the Government decided to send a special train to ferry the dead bodies to their village. Despite thousands of workers started walking from different cities those who run the government were not sensitive to make arrangements for their transportation for many weeks. At last when the trains were arranged for the workers to go home they were charged heavily. Different state governments were prompt to arrange hundreds of buses to bring the students back from the coaching centres of Kota in Rajasthan. Was it because the children belonged to rich families ? As per the records India has 487 million workers in unorganized sector which contribute largely for the economic growth of the country. Half of them belong to the category of migrant workers. Neither those who employ them nor the labour department of the Government bother to provide them decent living conditions and other essential facilities in the cities where they are employed and exploited. Hence they wanted to escape and reach their homes. While discussing about the problems of migrant workers walking in the hot sun one of my friends asked, “where are the social workers and church organisations? Why can’t they do something for their transportation?” This question provided food for contemplation. I realized that many of us may not be able to intervene in this major issue of millions of migrant workers in our individual capacity for various reasons. However I felt that this issue need to be addressed at our community and institutional level. We are quick to criticise the Government and politicians for their failures . Each one of us have much to look into our way of life and value system at this time. The religious communities and institutions employ workers. Many of them are from far away villages of the same state or from other states. They leave their dear and near ones in search of employment and livelihood. Many who work with us also are migrant workers. We may be paying them wages, giving a place to stay and food to eat. The most important question we need to answer is, “what are the ways we make them feel at home? Do we provide them freedom, love and individual dignity which make them even to forget their home in a distant region?” When many priests and religious come to USM community for exposure and training they are inspired to see the responsibility with which the workers who serve in the house behave ; the freedom, dignity and joy they experience in the community. They eat the same food at the same table like anybody else in the community. They have the freedom to watch TV whenever they wish, they have the freedom to laugh and sing as they wish. They decide the menu of each meal. They themselves purchase the provisions. There is no one to supervise them yet they manage their work well with self discipline and punctuality. They also join all the prayers like all others in the community , lead the prayers and operate the music system as in their homes. They experience dignity and receive very decent and just salary. They welcome the guests and make them at home as responsible community members. Another point of reflection and introspection would be about the responsibility and loyalty of Sisters and Priests to their community. Whenever I have asked to many religious Sisters and Priests about their emotional attachment to the mission , a vast majority promptly of them have said that they were more emotionally attached to their families than to their religious community . The members of a religious community also belong to different states and regions of this vast country. After long years of formation they make their commitment to the Congregation. The question is, why don’t they feel at home in the religious community and always thinking of the near and dear ones at home? Superiors of the communities always complain that the members do not have loyalty and commitment to the community and mission. Rules are made to control the ‘misuse’ of freedom and resources by the members who have made life commitment to the community. Superiors often make the so called ‘visitation’ to communities more to supervise and control than to motivate. When the members of the community do not experience dignity, freedom, love and compassion they will not know how to express the same values to the workers in their communities and institutions. Neither they are aware of the plight of the millions of migrant workers in different parts of India nor will they give dignity and justice to those who work for them. Where there are more rituals, rules, imposed austerity and violation of individual dignity, there workers and members suffer more injustice and exploitation. Though we cannot intervene in the case of millions of migrant workers in the country to improve their condition, religious communities and members could resolve to create an atmosphere where every worker may feel at home and experience the freedom , individual dignity and justice. Why don’t the communities create an atmosphere of feel at home for all their members and experience freedom and facilities of a home? The criteria of all practices should be based on this test : What would Jesus do if He were here ? What is the mind of Christ? What is the heart of Christ? This is the way to return to Christo centric way of life and mission. Then the distinction of workers and members will disappear and the community mission will be more fruitful . Neither the workers who have come from far away states feel helpless to stay and work in the community nor the community members look for emotional attachment to their family staying in far away regions . The plight of millions of migrant workers in the country should help us to review our commitment to renew and reinvent ourselves for building the kingdom of God here and now.

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Q: How to make a pdf Generator with ionic? I want to make a pdf of the current page so the user can print it out but every page is dynamic so I will need a sort of a text to pdf generator to make it work. It is an ionic2 app and is for like a recipe page so you can click on a button and it just makes a pdf out of the text. Do you guys know how I can achieve that? A: Your best bet is probably this plugin: https://github.com/cesarvr/pdf-generator give your dynamic page section an id like 'pdf-area' and then select it in your .ts file like this: let content = document.getElementById('pdf-area').innerHTML you can then turn that into a file or print it like this cordova.plugins.pdf.htmlToPDF({ data: content, type: "base64" }, (success) => { // you might have to turn the base64 into a binary blob to save it // to a file at this point }, (error) => console.log('error:', error); ); }

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Low vitamin D ups kids' anemia risk New study is believed to be the first one to extensively explore the link between the two conditions in children. Johns Hopkins Medicine | Oct 22, 2013 Low levels of the “sunshine” vitamin D appear to increase a child’s risk of anemia, according to new research led by investigators at the Johns Hopkins Children’s Center. The study, published online Oct. 10 in the Journal of Pediatrics, is believed to be the first one to extensively explore the link between the two conditions in children. The researchers caution that their results are not proof of cause and effect, but rather evidence of a complex interplay between low vitamin D levels and hemoglobin, the oxygen-binding protein in red blood cells. The investigators say several mechanisms could account for the link between vitamin D and anemia, including vitamin D’s effects on red blood cell production in the bone marrow, as well as its ability to regulate immune inflammation, a known catalyst of anemia. To capture the interaction between the two conditions, researchers studied blood samples from more than 10,400 children, tracking levels of vitamin D and hemoglobin. Vitamin D levels were consistently lower in children with low hemoglobin levels compared with their non-anemic counterparts, the researchers found. The sharpest spike in anemia risk occurred with mild vitamin D deficiency, defined as vitamin D levels below 30 nanograms per milliliter (ng/ml). Children with levels below 30 ng/ml had nearly twice the anemia risk of those with normal vitamin D levels. Severe vitamin D deficiency is defined as vitamin D levels at or below 20 ng/ml. Both mild and severe deficiency requires treatment with supplements. When investigators looked at anemia and vitamin D by race, an interesting difference emerged. Black children had higher rates of anemia compared with white children (14 percent vs. 2 percent) and considerably lower vitamin D levels overall, but their anemia risk didn’t rise until their vitamin D levels dropped far lower than those of white children. The racial difference in vitamin D levels and anemia suggests that current therapeutic targets for preventing or treating these conditions may warrant a further look, the researchers say. “The clear racial variance we saw in our study should serve as a reminder that what we may consider a pathologically low level in some may be perfectly adequate in others, which raises some interesting questions about our current one-size-fits-all approach to treatment and supplementation,” says lead investigator Meredith Atkinson, M.D., M.H.S., a pediatric kidney specialist at the Johns Hopkins Children’s Center. Untreated, chronic anemia and vitamin D deficiency can have wide-ranging health consequences, including organ damage, skeletal deformities and frequent fractures, and lead to premature osteoporosis in later life. Long known for its role in bone development, vitamin D has recently been implicated in a wide range of disorders. Emerging evidence suggests that low vitamin D levels may play a role in the development of certain cancers and heart disease and lead to suppressed immunity, the researchers note. Anemia, which occurs when the body doesn’t have enough oxygen-carrying red blood cells, is believed to affect one in five children at some point in their lives, experts say. Several large-scale studies have found severe vitamin D deficiency in about a tenth of U.S. children, while nearly 70 percent have suboptimal levels. “If our findings are confirmed through further research, low vitamin D levels may turn out to be a readily modifiable risk factor for anemia that we can easily tackle with supplements,” says senior study investigator Jeffrey Fadrowski, M.D., M.H.S., also a pediatric kidney specialist at Johns Hopkins. The research was funded by the National Institute of Diabetes, Digestive and Kidney Diseases under grant number K23 DK084116.

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The Girl From Scary Movie Naked Directed by David Ren. With Jason Yee, Samantha Streets, Ron Yuan, Dominique Swain. When Sandy, a call girl at "The Naked Eye", ends up dead, her friend and only ally in the world, Jake, goes on a manhunt to find out who killed her. LATEST HEADLINES ‘Spider-Man: Homecoming’ Sequel Will Have Spidey Slinging Web Around the World 14 hours ago | Slash Film ‘Scary Mother’ Named Top . The Clingy Jealous Girl trope as used in popular culture. She's often cute, sometimes to the point of twee. She's affectionate, too but she also has a grip . Can you believe these angel faced filipinas have become cock sucking little devils? ADULT DATING SERVICE The Philippines hottest bargirls! Helena in A Midsummer Night's Dreamthough to what extent is determined by the actress playing The Girl From Scary Movie Naked. Anyone willing to show kindness to her beyond her status as a Butt-Monkey will become an object of her obsession. Rise Kujikawa as well, though she's sweeter about it than Ai is, given that she'll accept a rejection without a complaint. In later episodes she responds to Isabella's mere presence by sulking, and later after Move Relationship Upgrade with Robin tries to actively kill her every time they cross paths, either by her own hand, or by indirect means at one stage encouraging Robin to abandon Isabella to her murderous husband.

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ROPONEN AND GLOERSEN CLAIM VICTORY AT THE ENGADINER SKIMARATHON The weather couldn’t have been better. While Riitta-Liisa Roponen (FIN, Fischer skis and boots) repeated her victory from last year, Anders Gloersen (NOR, Fischer) claimed victory already at his first start at the Engadiner Skimarathon over 42 kiloemeters in free technique ahead of Jean-Marc Gaillard (FRA, Fischer skis and boots). Like almost every year at the Engadiner Skimarathon a big leading group stood together for a long time. Not until five kilometers before the finish it was Anders Gloersen who was able to open a gap. His brand mate Jean-Marc Gaillard was the only one who was able to close the gap one kilometer before the finish. However Gloersen, known as a very good sprinter, secured the victory in the final sprint on the home stretch. „I am really happy. When Jean-Marc caught me I was almost sure that he would beat me in the finish as I was already pretty tired. But somehow he was tired, too, I guess and so I was able to make it,“ said the overwhelmed winner. Shortly behind these two a group of 13 racers sprinted for the following places. So Remo Fischer (SUI, Fischer) gained sixth plase and Petr Novak (CZE, Fischer skis, boots and poles) finished in eighth. On the women’s side Riitta-Liisa Roponen was able to repeat last years victory. The Finn arrived just 3:35 minutes behind the fastest men and was exhausted, but happy: “It was a very tough race today. I didn’t feel so good. Somewhen I decided to just concentrate on myself and I didn’t check if there was someone coming from behind. So at the finish I was even more suprised about my victory.“ With todays victory Riitta-Liisa Roponen also took the victory in the FIS Marathon Cup ahead of Antonella Confortola Wyatt (ITA, Fischer), who achieved ninth and Seraina Boner (SUI, Fischer), who finished in sixth place today.

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24 Cal.3d 199 (1979) 595 P.2d 91 155 Cal. Rptr. 657 THE PEOPLE, Plaintiff and Respondent, v. LAWRENCE RAYMOND PIERCE, Defendant and Appellant. Docket No. Crim. 20003. Supreme Court of California. May 10, 1979. *203 COUNSEL Appellate Defenders, Inc., under appointment by the Supreme Court, Handy Horiye and Stephen J. Perrello, Jr., for Defendant and Appellant. Evelle J. Younger, Attorney General, Jack R. Winkler, Chief Assistant Attorney General, Daniel J. Kremer, Assistant Attorney General, Karl J. Phaler, Harley D. Mayfield and John W. Carney, Deputy Attorneys General, for Plaintiff and Respondent. OPINION MOSK, J. Defendant Pierce appeals from a judgment on a jury verdict convicting him of second degree murder. (Pen. Code, §§ 187, 189.) He contends that (1) prejudicial jury misconduct occurred during the course of the trial, (2) the evidence was insufficient to support the verdict, and (3) the court erred in refusing a certain jury instruction on reasonable doubt and in admitting a photograph of the fatal injury. We conclude the first of these contentions is meritorious and requires reversal of judgment. Because there is an attack on the sufficiency of the evidence, the facts will be set forth at some length. Pierce is the coowner of a gas station in El Cajon. On the night before the murder he played poker at his home until 4:30 a.m., losing about $1,300. During the course of the game, one of Pierce's employees telephoned to report that the attendant scheduled to work the midnight shift had called in sick. Pierce told the employee to contact Dale Huffington, a new employee, and ask that Huffington cover for the ill man. In a subsequent phone call, Pierce learned that Huffington had refused to come in at midnight. Pierce then directed that Huffington report for the day shift at 8 a.m. Both Pierce and Huffington arrived at the gas station at 8 o'clock. Huffington went to work pumping gas and Pierce busied himself about the office. Shortly after 9, Pierce told Bruce Ballard, a mechanic working in the lube area of the station, that he had received a service call for a yellow Cougar automobile needing assistance on a nearby street. No one else had heard the phone ring. Ballard entered the station's tow truck to answer the call, but noticed the vehicle was almost out of gas. He drove the truck to the gas pumps, and then returned to the lube bay to report to Pierce. When he arrived, he saw Pierce behind a flight of stairs in the *204 storage room, bent over and clutching what Ballard thought was a red-handled windshield squeegee. Pierce dropped the instrument and walked out to the gas pumps with Ballard. According to Ballard, Pierce was acting strangely. They fueled the truck and, as Ballard was about to leave, Pierce said one or two armed men had entered the station over the back fence. He told Ballard to notify the police. Pierce went back into the station and Ballard drove around the corner, out of sight of the station. After an unsuccessful attempt to use the phone at a nearby residence, Ballard managed to contact the police on his CB radio. He then drove to an adjacent gas station to await the arrival of patrol officers. Meanwhile, a customer had pulled up to the gas pumps at Pierce's station and had begun to put gas into his car. He saw no one, but heard hammering sounds, like metal on metal, coming from the lube bay. Shortly thereafter the police arrived, surrounding the station. Neither Ballard, the customer, nor the officers saw anyone leave the premises. The police cautiously entered the storage room. Pierce was on the floor, crawling towards the door; Huffington was slumped in a corner, a hammer embedded in his skull. There were blood spatters on Pierce's hands and clothing. Paramedics transported Pierce and Huffington to the hospital. The hammer, by now dislodged from Huffington's skull, had been handled by several people at the scene. Huffington died in the emergency room. There were no visible injuries to Pierce, although one physician found swelling and evidence of a muscle spasm in his lower back. Pierce told the police, and testified at trial, that after he sent Ballard on the service call, Huffington called out from the back room. Pierce went to investigate, and on entering the storeroom, saw a man wearing a red windbreaker jacket and stocking mask. The man had a .38 caliber revolver in his left hand, and with his right hand was hitting Huffington, who apparently had become hysterical. Pierce could not recall if he was using his fist or a weapon. Meanwhile, Ballard had returned to the lube bay after discovering the tow truck needed gas. The assailant instructed Pierce to get rid of Ballard. After Pierce complied, the robber ordered him into the office and emptied the cash register. Pierce was then led back to the storeroom; just after entering, he was assertedly struck from behind with a blunt instrument and fell on top of Huffington's nearly supine body. Pierce testified he believed there may have been an accomplice in the storeroom. *205 Police investigators could find no sign that anyone had climbed the fence at the rear of the station, nor could they locate anyone remembering a disabled yellow Cougar. They did learn Pierce was having financial difficulties. Pierce carried robbery insurance with coverage to $1,000. At trial, there was conflicting testimony as to the amount of money, if any, missing from the cash register. There was also expert testimony that the bloodstains on Pierce's clothing were consistent with his being in the storeroom when the fatal blows were struck. I (1) Pierce's primary contention is that he was prejudiced by jury misconduct occurring during the course of trial. On voir dire a prospective juror named Seymour acknowledged that he was "Very, very familiar" with the case and that one of the first policemen to arrive on the scene, Officer Carl Case, was a neighbor and "very personal friend of mine." The prosecutor advised the court that he intended to call Case as a witness. The court and defense counsel immediately proposed to excuse Seymour, but the prosecutor suggested further inquiry. Although Seymour admitted he had previously spoken with Case about the crime, he asserted that he would give no special weight to Case's testimony and in particular that he could refrain from having any conversations outside the courtroom about the trial. Seymour was eventually seated without challenge, and was later elected foreman. At adjournment the court fully admonished the jurors against talking about the case among themselves or with third persons, emphasizing their solemn obligation to avoid any such contacts. The jurors all agreed to remember and obey the admonition, which the court thereafter repeated to them at the end of each day of the proceedings. Despite the foregoing promises and warnings, Seymour subsequently approached Case at his home and talked with him about the trial. In the course of the conversation Seymour asked and Case answered several questions about the state of the evidence and the district attorney's method of presenting his case. The incident took place after Case had testified for the prosecution and the People had rested, and while Pierce was putting on his defense. Some two weeks later, after the jury had returned its verdict of guilty, one of Case's supervisors overheard him discussing his prior contact with Seymour. The supervisor reported the matter to the police chief, and the police department and the district *206 attorney's office conducted a joint investigation into the incident. Their reports were furnished to the court and to defense counsel. The reports disclosed four matters relating to the trial that Seymour had discussed with Case. Thus Seymour asked Case why fingerprints had not been taken from the murder weapon. Case replied that the surface of the handle was such as to make it difficult to lift latent prints; and he further suggested that any such prints would be of debatable value because Pierce owned the hammer and both he and his employees had undoubtedly handled it in the course of their work. Seymour also asked Case why the jury had not been shown all the photographs used in the trial. Case did not know which photographs he was referring to, but explained that they may have been withheld from the jury because they were "gruesome."[1] Two lesser matters were also discussed. According to Case, Seymour asked him why the district attorney would bring up a point and then drop it, and Case replied that he did not know what the prosecution's tactic was; Seymour denied asking this question. Also according to Case, Seymour queried the adequacy of the police sketch of the crime scene and said that he and other jurors wanted to see the room where the murder took place; Case could not recall his answer, and Seymour stated he did not remember asking the question.[2] Upon receipt of this information, Pierce immediately moved for a new trial. (Pen. Code, § 1181, subd. 3.) Rather than hold an evidentiary hearing, however, the court relied exclusively on the investigatory reports prepared by the police and the district attorney.[3] The court denied the motion, ruling that Seymour's act of discussing the trial with Case did not result in a miscarriage of justice because it was not "reasonably probable *207 that a result more favorable to the defendant would have been reached in the absence of the error." (See People v. Watson (1956) 46 Cal.2d 818, 836 [299 P.2d 243].) As will appear, the court used an incorrect standard of prejudice in the circumstances. There is no question that juror Seymour committed serious misconduct. Penal Code section 1122 commands that at each adjournment prior to submission the court must admonish the jurors that "it is their duty not to converse among themselves or with anyone else on any subject connected with the trial...." The jury herein were so instructed. Nevertheless, in derogation of his oath as a juror and his specific promise on voir dire not to engage in any such conversations, Seymour held the above-described consultation with Officer Case during the course of the trial. In People v. Honeycutt (1977) 20 Cal.3d 150, 156-157 [141 Cal. Rptr. 698, 570 P.2d 1050], we unanimously ruled that it was serious misconduct when a juror — also, as in the case at bar, the foreman — contacted an attorney acquaintance during deliberations and asked him questions of law pertaining to the trial then in progress. The same rule is here applicable: a discussion of the state of the evidence is no less a "subject connected with the trial" within the meaning of section 1122 than is a discussion of the governing law. In either event, "Such conduct in clear violation of the trial court's admonitions interjects outside views into the jury room and creates a high potential for prejudice." (Honeycutt, at p. 157.) In determining the extent of that prejudice, moreover, the test is not the Watson standard applied by the trial court. That test is appropriate when the court is judging the effect of an error of law that it committed during the trial, such as misdirection of the jury or an incorrect evidentiary ruling. (Pen. Code, § 1181, subd. 5.) (2) By contrast, as we reiterated in Honeycutt (at p. 156), jury misconduct raises a presumption of prejudice; and unless the prosecution rebuts that presumption by proof that no prejudice actually resulted, the defendant is entitled to a new trial. (See also In re Winchester (1960) 53 Cal.2d 528, 534-535 [2 Cal. Rptr. 296, 348 P.2d 904]; People v. Wong Loung (1911) 159 Cal. 520, 528-529 [114 P. 829]; People v. Conkling (1896) 111 Cal. 616, 628 [44 P. 314]; People v. Guzman (1977) 66 Cal. App.3d 549, 559 [136 Cal. Rptr. 163]; accord, Remmer v. United States (1954) 347 U.S. 227, 229 [98 L.Ed. 654, 655-656, 74 S.Ct. 450].) (3a) The People failed to sustain that burden. First, the prosecution submitted an investigative report of an interview with Seymour in which *208 the juror told the police that his conversation with Case had not influenced his vote on the verdict of guilt. Even if such evidence had been offered in the proper form of an affidavit or testimony by Seymour, however, it would not have been "admissible to show the effect of such ... conduct ... upon a juror either in influencing him to assent to ... the verdict or concerning the mental processes by which it was determined." (Evid. Code, § 1150, subd. (a).) The prosecution also presented investigative reports reciting that each of the 11 other jurors had signed declarations asserting that at no time during the trial or deliberations did Seymour mention he knew a police officer or had any information other than that presented in court. If the declarations themselves had been offered (see Evid. Code, § 1500), they would have been admissible under Evidence Code section 1150 to prove the fact asserted.[4] But that evidence would not have rebutted the presumption that the 12th juror, Seymour, was not impartial. Pierce was "entitled to be tried by 12, not 9 or even 10, impartial and unprejudiced jurors." (Parker v. Gladden (1966) 385 U.S. 363, 366 [17 L.Ed.2d 420, 423, 87 S.Ct. 468].) It would be sheer speculation to assume that absent his conversation with Case, Seymour would necessarily have voted to convict; rather, he might well have held out for acquittal, or even succeeded in persuading his fellow jurors that a reasonable doubt as to Pierce's guilt existed. (4) Because a defendant charged with crime has a right to the unanimous verdict of 12 impartial jurors (People v. Wheeler (1978) 22 Cal.3d 258, 265-266 [148 Cal. Rptr. 890, 583 P.2d 748]), it is settled that a conviction cannot stand if even a single juror has been improperly influenced. (See, e.g., People v. Honeycutt, supra, 20 Cal.3d at p. 158; accord, id., at pp. 161-162 (conc. opn. of Richardson, J.).) (3b) Finally, in his brief on appeal the Attorney General seeks to rebut the presumption of prejudice by addressing the content of the communication from Officer Case. He contends that the communication could not have affected the outcome of the trial because it either had no probative value (see, e.g., People v. Crosby (1956) 139 Cal. App.2d 101, 106 [292 P.2d 922] [juror asked police witness for a cup with which to take an aspirin]) or was cumulative of evidence already introduced (see, e.g., People v. Martinez (1978) 82 Cal. App.3d 1, 20-25 [147 Cal. Rptr. 208] [juror brought government topographical survey maps into jury room]). The record, however, is otherwise. The questions that Seymour asked of Officer Case did not deal with mere social amenities unrelated to the trial, *209 nor were his answers wholly duplicative of evidence properly admitted. On the contrary, it clearly appears from these inquiries that several days after the prosecution had rested, Seymour had doubts about the sufficiency of the People's case. In particular, he was concerned with the fact that no fingerprints had been lifted from the handle of the murder weapon. As noted above, Officer Case replied by explaining to him that the surface of the handle was such as to make that procedure difficult and in any event that prints would be of little value because several persons had used the hammer. The communication could have improperly influenced the outcome of the trial in several ways. First, after holding the conversation Seymour could reasonably attribute the absence of fingerprints not to Pierce's innocence but to technical or practical difficulties in obtaining the evidence. The officer thus assuaged his doubts before Seymour even had the opportunity to express them to and discuss them with his fellow jurors. Second, in giving his explanation Officer Case was obviously speaking in large part as an expert; yet because the conversation was kept secret throughout the trial the defense was deprived of its right to confront the witness, inquire into his qualifications as an expert, and test the basis of his opinion on cross-examination. Finally, Case's explanation nullified as to Seymour one of the closing arguments of the defense, to wit, that the absence of Pierce's fingerprints on the murder weapon should raise a reasonable doubt in the minds of the jurors.[5] We conclude, as in Honeycutt (20 Cal.3d at p. 158), that "Under these circumstances the presumption of prejudice was not rebutted but rather was reinforced by the evidence." Defendant is therefore entitled to a new trial, free from such serious jury misconduct as the record here reveals. II (5a) Pierce next attacks the sufficiency of the evidence, contending it was legally inadequate to establish his guilt and to support the finding of second degree murder. (6) The United States Supreme Court has recently held that the double jeopardy clause of the Fifth Amendment bars retrial of a federal *210 criminal defendant after a reversal of his conviction ordered on the ground that the evidence introduced at trial was insufficient to support the verdict. (Burks v. United States (1978) 437 U.S. 1 [57 L.Ed.2d 1, 98 S.Ct. 2141].) An appellate determination of insufficient evidence, reasoned the court, is tantamount to a finding that the trial judge should have directed a verdict of acquittal; since a retrial would be barred by such a verdict, a new trial is also improper after the equivalent decision on appeal. (Id., at pp. 10-11, 16 [57 L.Ed.2d at pp. 9-10, 12-13].) In a companion case the high court held that the same rule also applies in state prosecutions when a claim of insufficient evidence is sustained on appeal under the same criteria as those used by a trial court in ruling on a motion for directed verdict. (Greene v. Massey (1978) 437 U.S. 19 [57 L.Ed.2d 15, 98 S.Ct. 2151].) Under California law these criteria are essentially the same (see, e.g., People v. Reyes (1974) 12 Cal.3d 486, 496-497 [116 Cal. Rptr. 217, 526 P.2d 225]); accordingly, the rule of Burks applies to trials conducted in our courts. In the case at bar we must therefore address Pierce's contention as to the sufficiency of the evidence because a retrial, which we here order, would be improper if his claim were meritorious. (7) When a defendant challenges the sufficiency of the evidence, the test on appeal is whether there is substantial evidence to support the conclusion of the trier of fact. (People v. Caudillo (1978) 21 Cal.3d 562, 570-571 [146 Cal. Rptr. 859, 580 P.2d 274], citing People v. Redmond (1969) 71 Cal.2d 745, 755 [79 Cal. Rptr. 529, 457 P.2d 321].) (8) Circumstantial evidence may be sufficient to connect a defendant with the crime and to prove his guilt beyond a reasonable doubt. (People v. Reilly (1970) 3 Cal.3d 421, 424-425 [90 Cal. Rptr. 417, 475 P.2d 649].) (5b) Here, there was adequate circumstantial evidence to establish that Pierce killed Huffington with malice aforethought. No person present saw the alleged "robbers" leaving the scene. Expert witnesses testified that the bloodstains on Pierce's clothing were consistent with his close proximity to the attack. The jury could reasonably have inferred that Pierce was tired and distraught from suffering a large loss at poker the preceding evening, and angry at Huffington for refusing to work the midnight shift. They could also have inferred that Pierce invented the disabled yellow Cougar as a pretext to get Ballard out of the station; that Ballard, when he discovered the tow truck needed fuel, interrupted Pierce as the first blows were struck; and that Pierce, after sending Ballard on his way with a false story of a robbery in progress, returned to the storeroom to inflict the fatal wounds. Evaluation of the credibility of Pierce's *211 testimony was within the sole province of the jury, and they were free to disregard his version of the killing. III Finally, Pierce contends the court erred in refusing a particular jury instruction and in admitting into evidence a color photograph of the victim's head injuries. We briefly discuss each point for the benefit of the trial court on remand. (9) Pierce requested an instruction on reasonable doubt that focused on identification of the defendant as the person responsible for the crime. The trial court refused the instruction and instead gave CALJIC No. 2.90, derived from Penal Code section 1096. Penal Code section 1096a provides, "In charging a jury, the court may read ... section 1096 of this code, and no further instruction ... defining reasonable doubt need be given." Notwithstanding section 1096a, a defendant upon proper request has a right to an instruction that directs attention to specific evidence from which the jury could infer a reasonable doubt. (People v. Granados (1957) 49 Cal.2d 490, 496 [319 P.2d 346], and cases cited.) The instruction requested here did not focus on specific evidence, however, but simply restated the presumption of innocence; accordingly, the court did not err in refusing it. (Cf. People v. Gomez (1972) 24 Cal. App.3d 486, 490 [100 Cal. Rptr. 896].) (10) Pierce's contention that the trial court erred in admitting a graphic photograph of Huffington's injuries is similarly without merit. Evidence Code section 352 vests the court with broad discretion to weigh the prejudicial effect of proffered evidence against its probative value. (People v. Brawley (1969) 1 Cal.3d 277, 295 [82 Cal. Rptr. 161, 461 P.2d 361].) No abuse of that discretion appears: the photograph was not cumulative, and was highly relevant evidence on the issue of malice. As the Court of Appeal said in People v. Long (1974) 38 Cal. App.3d 680, 689 [113 Cal. Rptr. 530], "murder is seldom pretty, and pictures, testimony and physical evidence in such a case are always unpleasant...." (Fn. omitted.) The judgment is reversed. Bird, C.J., Tobriner, J., Clark, J., Richardson, J., Manuel, J., and Newman, J., concurred. NOTES [1] The adjective that Case used in this regard was variously reported by different investigators as "gruesome," "shocking," "inflammatory," and having "a traumatic effect" on the jury. In his own interview with the investigators Seymour claimed it was Case who brought up the issue by asking if he had seen the photographs used in the trial; Seymour replied he had not, but assumed he would see them in the jury room; and Case then explained that the jurors are often not shown the "gory" photographs because it might "influence" them. [2] During their deliberations, the jury, speaking through their foreman Seymour, asked the court for permission to view the scene. The court denied the request. [3] Although "incompetent testimony, such as hearsay ..., if received without objection takes on the attributes of competent proof" (Berry v. Chrome Crankshaft Co. (1958) 159 Cal. App.2d 549, 552 [324 P.2d 70]), we strongly disapprove of the substitution of unsworn police reports and summaries for affidavits or testimony of the percipient witnesses. A hearing in open court would have been particularly appropriate to ascertain the relevant facts in this matter, because both Seymour and Case were initially evasive about the scope and content of their conversation. (But cf. Linhart v. Nelson (1976) 18 Cal.3d 641 [134 Cal. Rptr. 813, 557 P.2d 104] [stating rule in civil cases].) [4] Most of the jurors also alleged that Seymour "did not influence" their verdict. Such allegations, of course, would have been inadmissible under section 1150. [5] Thus defense counsel argued to the jury as follows: "What about fingerprints? Larry [Pierce] wasn't wearing any gloves. He had a hammer. We had something that should have been taken off of that. We had no evidence of fingerprints.... Why not? There ought to be. People leave fingerprints, but there's no fingerprints here."

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UPDATED: 1:10 p.m. CLEVELAND -- Cleveland Browns wide receiver Donte' Stallworth today received a 30-day jail sentence after pleading guilty to DUI manslaughter in a Miami courtroom. Stallworth was charged in the death of Mario Reyes, a pedestrian who was struck and killed by Stallworth's Bentley on March 14 in Miami Beach. The Miami Herald reported that Stallworth was immediately taken into custody and that after he gets out he will serve two years of house arrest followed by eight years of probation, according to his plea deal. He will also lose his driving privleges for life and have to perform 1,000 hours of community service. Stallworth had faced four to 15 years in prison before the plea agreement. Stallworth also reached a confidential financial settlement with the Reyes' family, according to the Herald and the Associated Press. "I will continue to bear this burden the rest of my life," Stallworth told Miami-Dade Circuit Judge Dennis Murphy, who imposed the sentence, according to the Herald. One of Stallworth's lawyers, David Cornwell, released a statement Tuesday morning indicating Stallworth has every intention of playing football again: "Donte' has a debt to repay and awesome responsibilities to fulfill. We have kept NFLPA Executive Director DeMaurice Smith, Commissioner Goodell, and the Cleveland Browns apprised of developments as they occurred. Whenever it is appropriate to do so, we are prepared to discuss the circumstances under which Donte' will resume his career." The NFL will most likely also discipline Stallworth under terms of its personal conduct policy once the legal process has played out. Stallworth, 28, was driving drunk when he struck and killed Reyes, 59, at 7:15 a.m. on March 14. Miami-Dade police said Stallworth was driving drunk and a toxicology report showed he had a blood-alcohol level of .126, which is above Florida's legal limit of .08. Miami Beach police said that prior to the crash, Stallworth had been drinking at Liv Nightclub at the Fontainebleau in Miami Beach before leaving to go to a home in Miami, where he arrived about 6:15 a.m. He was returning to Miami Beach about an hour later when he struck Reyes, who was crossing the MacArthur Causeway, which connects Miami and Miami Beach. Reyes was trying to catch a bus and was not in the crosswalk. According to police, Stallworth admitted he had been driving the car and said, "I hit the man lying in the road." Stallworth later told police at the Miami Beach police station that he had time to honk his horn and flash his headlights to warn Reyes. Stallworth has been excused from all Browns off-season workouts and a mandatory minicamp while he focused on his legal problems. He was signed to a seven-year, $35 million contract as a free agent by the Browns before last season, but was injured much of the year and caught just 17 passes for 170 yards and a touchdown. Stallworth earned a $4.5 million roster bonus from the Browns the day before the accident.

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Q: Remove ÿþ from string I'm trying to read ID3 data in bulk. On some of the tracks, ÿþ appears. I can remove the first 2 characters, but that hurts the tracks that don't have it. This is what I currently have: $trackartist=str_replace("\0", "", $trackartist1); Any suggestions would be greatful, thanks! A: ÿþ is 0xfffe in UTF-8; this is the byte order mark in UTF-16. You can convert your string to UTF-8 with iconv or mb_convert_encoding(): $trackartist1 = iconv('UTF-16LE', 'UTF-8', $trackartist1); # Same as above, but different extension $trackartist1 = mb_convert_encoding($trackartist1, 'UTF-16LE', 'UTF-8'); # str_replace() should now work $trackartist1 = str_replace('ÿþ', '', $trackartist1); This assumes $trackartist1 is always in UTF-16LE; check the documentation of your ID3 tag library on how to get the encoding of the tags, since this may be different for different files. You usually want to convert everything to UTF-8, since this is what PHP uses by default.

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Q: Rails iterate for huge db table I have huge db table, and i need to do something with here, but how i can do this? if i write: @person = Person.all @person.each do |p| //something end It's loads, loads system, and took time. Are any ways to iterate for table by not loading all data to some variable? A: This is a use case to use find_in_batches or find_each. This will load data chunk by chunk, see doc.

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Q: Prolog doesn't terminate after goal reordering I'm currently working through the Learn Prolog Now examples and for the one exercise I have a KB that runs out of local stack if I just have a tiny change in one rule. this is the KB: byCar(auckland,hamilton). byCar(hamilton,raglan). byCar(valmont,saarbruecken). byCar(valmont,metz). byTrain(metz,frankfurt). byTrain(saarbruecken,frankfurt). byTrain(metz,paris). byTrain(saarbruecken,paris). byPlane(frankfurt,bangkok). byPlane(frankfurt,singapore). byPlane(paris,losAngeles). byPlane(bangkok,auckland). byPlane(singapore,auckland). byPlane(losAngeles,auckland). travel(X,Y) :- byCar(X,Y). travel(X,Y) :- byTrain(X,Y). travel(X,Y) :- byPlane(X,Y). and the relevant rule: travel(X,Y) :- travel(X,Z), travel(Z,Y). and this is the query in question which runs out of stack: ?- travel(valmont,losAngeles). But if I change the rule to travel(X,Y) :- travel(Z,Y), travel(X,Z). Then it works. If I trace the query I get quickly stuck like this: Redo: (17) travel(raglan, _6896) ? creep Call: (18) byPlane(raglan, _6896) ? creep Fail: (18) byPlane(raglan, _6896) ? creep Redo: (17) travel(raglan, _6896) ? creep Call: (18) travel(raglan, _6896) ? creep Call: (19) byCar(raglan, _6896) ? creep Fail: (19) byCar(raglan, _6896) ? creep Redo: (18) travel(raglan, _6896) ? creep Call: (19) byTrain(raglan, _6896) ? creep Fail: (19) byTrain(raglan, _6896) ? creep Redo: (18) travel(raglan, _6896) ? creep Call: (19) byPlane(raglan, _6896) ? creep Fail: (19) byPlane(raglan, _6896) ? creep Redo: (18) travel(raglan, _6896) ? creep ... But I don't see why. Shouldn't it just understand that raglan is an endstation and thus it has to backtrack one level more? Thanks! Edit: I use SWI Prolog Edit: I found the problem after going through it step by step. In the case of raglan, there is no rule to anywhere at all. Therefore, after trying byPlane, byTrain, byCar, it tries travel(raglan, X) again (the first goal of the last rule), thus looping. But I don't see how the other rule is any better. A: You need to clarify what you mean by "it works". In fact, both versions of the predicate travel/2 do not terminate. But one happens to find a solution for a highly specific query. Now ask ?- travel(hamilton, losAngeles). which loops for both. So your fix only works for some queries but not for others. Isn't there a more reliable way out? In general, the very precise sequence of answer substitutions produced by Prolog is difficult to predict. You will have to simulate every tiny step Prolog takes. On the other hand, there is a very related notion called (universal) termination which is much easier to predict as it is independent of many details in your program like the order in which your facts appear. The easiest way to query for universal termination is to add the goal false at the end of your query. But you can go even further adding goals false wherever you want1. Such a modified program is called a failure-slice. No matter how you insert false the following holds: If the failure-slice does not terminate, then also your original program does not terminate. Now consider failure-slices for the two variants of travel/2: travel(X,Y) :- false, byCar(X,Y). travel(X,Y) :- false, byTrain(X,Y). travel(X,Y) :- false, byPlane(X,Y). travel(X,Y) :- travel(X,Z), false, travel(Z,Y). And your other version: travel(X,Y) :- false, byCar(X,Y). travel(X,Y) :- false, byTrain(X,Y). travel(X,Y) :- false, byPlane(X,Y). travel(X,Y) :- travel(Z,Y), false, travel(X,Z). In both, neither X nor Y is considered at all! So the two arguments do not influence termination. And thus both versions do not terminate. That is, they never terminate. Now compare this conclusion to the more traditional approach of looking at a trace. While failure slices permitted us to make general conclusions ("... never terminates") a particular trace can only show you details of one particular execution. In order to fix this you need to change something in the visible part. My suggestion would be to use closure/3. That is: travel(X, Y) :- closure(connexion, X, Y). connexion(X,Y) :- byCar(X,Y). connexion(X,Y) :- byTrain(X,Y). connexion(X,Y) :- byPlane(X,Y). Or use the more general path/4. 1 Actually, this only works in pure monotonic programs. Your program is one of those A: Obviously, goal ordering is really important in this case. As you figured out, your first formulation allows for finding another hypothetical connection from raglan to anywhere by going via a hypothetical another city Z, whose nonexistence is never proven because you keep looking for it be recursing infinitely. Really, the trace is your best friend here, but this is not trivial to get right. You also have to think about all the cases where one, both or none of the arguments are bound. Your second formulation is not better at all, it just happens to fail on different cases: travel(losAngeles, valmont). ERROR: Out of local stack I would propose to make your logic safer by distinguishing between a direct connection and a multi-stop journey: connection(X,Y) :- byCar(X,Y). connection(X,Y) :- byTrain(X,Y). connection(X,Y) :- byPlane(X,Y). travel(X,Y) :- connection(X,Y). travel(X,Y) :- connection(X,Z), travel(Z,Y). Goal order doesn't matter now because travel always requires some physical connection to exist (rather than a recursion) in order to proceed. This also makes it easier to record the journey, which you would want anyway (right?): connection(X,Y, car(X,Y)) :- byCar(X,Y). connection(X,Y, train(X,Y)) :- byTrain(X,Y). connection(X,Y, plane(X,Y)) :- byPlane(X,Y). travel(X,Y,[Part]) :- connection(X,Y,Part). travel(X,Y,[Part|Parts]) :- connection(X,Z,Part), travel(Z,Y,Parts). ?- travel(valmont, losAngeles, Journey). Journey = [car(valmont, saarbruecken), train(saarbruecken, paris), plane(paris, losAngeles)] And for the case where there is no valid trip: travel(losAngeles, valmont, Journey). false.

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New Porsche 911 RSR successfully concludes test drives The development of the new Porsche 911 RSR based on the current generation 991 model is nearly complete. On the Sebring International Raceway in Florida/USA the GTE race car from Weissach completed another successful test on Thursday. The successor to the Porsche 911 GT3 RSR will be run exclusively by the Porsche AG Team Manthey works squad at the 24 Hours of Le Mans and in the World Endurance Championship (WEC). The vehicle celebrates its race debut on April 14 at the WEC season-opener in Silverstone. Sharing driving duties at Sebring were Porsche works drivers Richard Lietz (Austria) and Patrick Pilet (France). Lietz contests the WEC including Le Mans with Marc Lieb (Germany) at the wheel of the 911 RSR with the starting number 92. Patrick Pilet joins forces with Joerg Bergmeister (Germany) in the number 91 vehicle. At the first two WEC rounds in Silverstone and Spa-Francorchamps as well as at Le Mans, they receive backup from their factory pilot colleagues Romain Dumas (France/No. 92) and Timo Bernhard (Germany/No.91). “We are very pleased with how the testing has gone so far,” said Porsche’s Head of Motorsport Hartmut Kristen. “Our goal is to be well prepared for the challenges of the very strong GTE class in the WEC and at Le Mans. The circuit in Sebring is very well suited to put a new vehicle through some demanding trials. For this reason, a test in Sebring is a very good rehearsal for one of the toughest races of all, the 24 Hours of Le Mans. Until the season kicks off in Silverstone, we will conduct some final tests on other race tracks so that our new 911 RSR is well and truly ready for the World Endurance Championship season.” The new Porsche LMP1 racing car is currently being put through its paces in test drives on international circuits. Following its successful launch in June on the Porsche test track in Weissach, the prototype sports car ... Porsche 911 resolves apparent contradictions like no other sports car – such as between tradition and innovation or between exclusivity and high social acceptance, and of course between performance and efficiency...

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The invention concerns the technical sector of packaging machines, which are arranged downstream of machines for producing articles in order to receive the articles, order them and insert them into corresponding packagings. In particular, the invention refers to the packaging of articles constituted by sachets or pouches for granular or liquid products, known in the trade as stickpacks, a predetermined number of which are piled and then placed in relative cartons. In this technical sector, machines for producing stickpacks are part of the category known as “sachet-filling machines”, while the machines for placing them in cartons are known as “cartoning machines”. The most commonly used type of stickpack filling machine is a vertical machine. The taut band which will form the stickpack is unwound from a spool and brought to the upper part of the machine. Suitable cutters divide the band longitudinally into a predetermined number of strips, all having a same width. Each strip is fed into a relative dropping channel, in which the following are provided, in order: folding organs, which roll the strip in the direction of its width so as to form a continuous tubular packaging; longitudinal sealing organs, which seal the overlapping edges of the continuous tubular packaging and close the packaging; transverse sealing organs, which are activated horizontally in a phase relation with the stepped descent of the continuous tubular packaging, dividing the internal volume of the underlying sealed stickpack from the upper stickpack in formation, which operation defines the bottom of the stickpack; pouring organs located above the transverse sealing organs, which project into the continuous tubular packaging and dispense dosed quantities of granular or liquid product into the stickpack being formed; cutting organs, which are activated in a phase relation with the descent of the continuous tubular packaging and separate the lowest stickpack from the continuous tubular packaging, which stickpack has been filled with the product and sealed. The various dropping channels, each being provided with the above-listed organs, are arranged side by side, and distanced by a constant interaxial measurement which is equal to the width of the strips; obviously the same interaxial measurement separates one stickpack from the stickpack adjacent to it, at the exit zone in the lower part of the machine. The vertically-arranged stickpacks exiting from the machine are collected by handling organs, for example of the “pick and place” type, which have a same number of heads as there are dropping channels, and are arranged with the same interaxial measurement, which handling organs insert the horizontally arranged stickpacks into corresponding queued walled compartments of a conveyor line associated to the cartoning machine which is arranged downstream. The pick and place cycle is repeated until a predetermined number stickpacks has been placed in each compartment. The compartments are distanced from each other by the same interaxial measurement as the dropping channels; the walls of each compartment, as is known, are arranged at right angles relative to the direction of advancement of the line and are positioned, in the above-described application, at a slightly lower height than the height of the carton in which the batch of stickpacks will be placed. Given the same interaxial measurement however, the distance between the walls of each compartment can vary according to the format of the carton which, in turn, will be larger or smaller according to the number of stickpacks it has to contain. Consequently, there is no control over the position of the stickpacks when they are being placed in the compartments, therefore each batch of stickpacks arranges itself differently, firstly in the relative compartments and subsequently in a relative carton, while remaining within the same overall area. Thus it is clearly impossible to form an ordered pile of stickpacks and keep their arrangement under control up to the moment when they are placed in the carton; this precludes the following operating modalities: placing an ordered pile inside a precisely-sized format of carton, that is, a carton having dimensions only slightly greater than the pile itself; placing more than one ordered pile into a precisely-sized carton; placing more than one ordered pile into a precisely-sized carton which is provided with separators between one pile and the next.

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Introduction {#s1} ============ Recently, an increasing number of patients are found to have thyroid nodules accidentally by computed tomography (CT) examination, magnetic resonance imaging (MRI) examination and carotid ultrasonography \[[@R01]\]. Traditional screening for nodular thyroid disease is palpation during screening \[[@R02]\]. However, screening has recently been conducted using an ultrasound system \[[@R01]\]. In a study of human subjects, it has been reported that thyroid ultrasound showed thyroid nodules in 22.8% of patients \[[@R03]\]. Most of these thyroid nodules were benign, and only a few were malignant nodules. Therefore, in the treatment of thyroid nodule lesions, it is important to properly diagnose and distinguish malignant thyroid nodules from other thyroid nodules. Thyroid ultrasound is cheaper and simpler than CT and MRI, and is the primary tool for diagnosing thyroid diseases as it is noninvasive. In recent years, with the improvements in the resolution of ultrasonography equipment, it has become possible to diagnose nodules of several millimeters, and the number of thyroid ultrasound examinations performed has increased accordingly. As a result, many thyroid nodules are discovered and diagnosed, and the high incidence of thyroid nodules is a growing public health concern \[[@R04]\]. The previously reported ultrasound findings useful for differentiating benign from malignant thyroid nodule lesions are fine calcification, borderline obscurity or septate, intranodal blood flow increase, aspect ratio \> 1, solid nodules and hypoechoic nodule findings \[[@R05]\]. In addition, many studies have evaluated the relationship between thyroid cancer and blood thyroglobulin (Tg) concentration. However, it is difficult to distinguish malignant thyroid nodule lesions from benign thyroid nodule lesions based only on serum Tg concentration \[[@R06]\]. Previous studies have extensively reported the number of individuals from various countries diagnosed with thyroid nodule lesions, mainly in the West, and these data are being accumulated. On the other hand, people from Japan have higher iodine intake than those from other countries, and this affects the incidence of thyroid diseases. Hence, the use of existing thyroid disease data remains controversial \[[@R07]\]. Moreover, the morbidity rate of follicular thyroid carcinoma is lower, while that of papillary thyroid carcinoma is higher, in Japan than in other countries \[[@R08]\]. With regard to differentiating benign from malignant thyroid nodular lesions, none of the previous retrospective studies included multiple specialists performing ultrasound image analysis in a single institution, used identical ultrasound diagnostic devices and investigated the usefulness of serum Tg values. Careless fine needle aspiration biopsy cytology (FNAC) should be avoided in the diagnosis of thyroid nodules. Therefore, in this study, we aimed to examine the characteristic ultrasound findings of patients with papillary thyroid carcinoma (PTC), which is the most frequent thyroid carcinoma. We also aimed to determine the usefulness of measuring serum Tg concentration in differentiating benign from malignant nodules. Materials and Methods {#s2} ===================== Study design and patient population {#s2a} ----------------------------------- This retrospective study included 327 patients who underwent FNAC for thyroid nodule lesions at Saitama Medical University Hospital from 2014 to 2016. The institutional review board at our university approved the study (approval number: 17018). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. FNAC was performed for 457 thyroid nodules, and the Japanese Society of Thyroid Surgery (RSJSTS) 2015 reporting system \[[@R9]\] was used to differentiate benign from malignant nodules. This reporting system is based on the 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) \[[@R10]\], and the individual cytological results of this study were finally evaluated against the criteria of TBSRTC \[[@R10]\]. Nineteen nodules were determined to be atypia of undetermined significance or follicular lesions of undetermined significance, while 103 nodules were determined to be follicular neoplasms or suspected follicular neoplasms; these lesions were excluded from the analysis. We also excluded three nodules from patients who had thyroid malignant lymphoma and excluded one suspected medullary thyroid carcinoma. Ultimately, the malignant group (i.e., malignant and suspected malignant lesions) included 26 patients with 33 nodules, while the benign group included 210 patients with 298 nodules ([Fig. 1](#F1){ref-type="fig"}). The malignant nodules were diagnosed as PTC. {#F1} Furthermore, we investigated the usefulness of measuring serum Tg concentration for differentiating benign from malignant thyroid nodules. Serum Tg concentrations, anti-Tg antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb) levels were measured using an electrochemiluminescence immunoassay in all patients in this study (SRL Inc., Tokyo, Japan). In Japan, TgAb and TPOAb levels are used to diagnose Hashimoto's thyroiditis \[[@R11]\], whereby the TgAb of ≥ 28 IU/mL and/or TPOAb of ≥ 16 IU/mL are considered diagnostic of Hashimoto's thyroiditis \[[@R12], [@R13]\]. These values are based on the results of a Japanese study, which reported the correlation between the pathological findings in the isolated thyroid gland and TgAb/TPOAb levels measured in the patient's serum \[[@R12]\]. In this study, the cutoff values of TgAb and TPOAb levels for the diagnosis of Hashimoto's thyroiditis were 28 and 16 IU/mL, respectively, and it was therefore concluded that Hashimoto's thyroiditis should be diagnosed at values of TgAb ≥ 28 IU/mL and/or TPOAb ≥ 16 IU/mL \[[@R11], [@R13]\]. In Japan, these research results have been adopted into clinical practice; consequently, in this study we considered TgAb ≥ 28 IU/mL and/or TPOAb ≥ 16 IU/mL to be outside the normal range, and therefore, an additional 82 patients were excluded. All 82 of the excluded patients had TgAb ≥ 28 IU/mL, and 32 of them had TPOAb ≥ 16 IU/mL. No patients had an isolated abnormally high value of ≥ 16 IU/mL. For analysis of the relationship between serum Tg concentration and nodule size, 34 patients with multiple nodules were excluded, leaving a total of 120 patients (104 patients, benign subgroup; 16 patients, malignant subgroup) to be included in this analysis. Researchers who performed image analysis and interpretation {#s2b} ----------------------------------------------------------- Three doctors specializing in endocrine diabetes internal medicine who are engaged in performing thyroid ultrasonography at Saitama Medical University participated in the image analysis. These doctors have an average of 10 years of experience. For all cases, at least two doctors performed image analysis and unified the evaluation of the ultrasound images. Evaluation method of ultrasonic test results {#s2c} -------------------------------------------- All the ultrasonic diagnostic imaging devices used Hi vision Ascendus uniformly (Hitachi Ltd, Tokyo, Japan). For the ultrasonographic inspection, a probe including a high-frequency band of 9 - 15 MHz was used. The blood flow inside the thyroid nodule was also evaluated using color Doppler. The items evaluated by B-mode ultrasonography were thyroid volume, thyroid nodule volume, thyroid nodule properties (solid or mixed (solid with cystic structures)), shape (arranged or irregular), boundary properties (smooth or coarse), boundary clarity (clear or unclear), boundary hypoechoic zone (regular, irregular or none), internal properties (uniform or non-uniform), internal echo level (isoechoic or hypoechoic), coarse internal calcification (presence or absence) and microcalcifications (presence or absence). Color Doppler was used to evaluate internal blood flow (abundant, small amount, or none) as shown in [Table 1](#T1){ref-type="table"} and [Figure 2](#F2){ref-type="fig"}. The microcalcifications and other evaluation items were classified according to the report of Kwak et al \[[@R14]\]. The volumes of the thyroid gland and nodules were calculated using the method used in Suzuki et al's study \[[@R15], [@R16]\]. For thyroid volume (milliliters), the width, thickness and height of each lobe were measured, and the volume of each lobe was calculated using the mean of the elliptical shape volume formula (π/6 × width × thickness × height) \[[@R15]\]. Thyroid nodule volume (milliliters) was calculated as follows: depth (cm) × width (cm) × length (cm) × π/6 \[[@R16]\]. ###### Characteristics of Thyroid Nodules on Ultrasonography Characteristics of thyroid nodules ------------------------------------ ------------------------------------------------------------------------------------------------------- Shape An integer indicates a circle or an ellipse. Irregularity indicates an irregular shape. Boundary property Edge of the lesion is linear (smooth) versus serrated (coarse). Boundary clarity Clear versus unclear boundary. Internal echo property Echo properties with uniform internal echo (homogeneous) versus uneven internal echo (heterogeneous). Internal echo level The solid part of the thyroid is evaluated by comparing it to the surrounding thyroid tissue. Internal coarse calcification Lesion contains coarse (≥ 1 mm) high echo findings. Microcalcifications Lesion contains fine (\< 1 mm) high echo findings. Internal blood flow The internal blood flow on color Doppler imaging is visible. Boundary hypoechoic zone A low echo band is visible at the boundary. Nodule type Solid (no cystic areas) versus mixed (solid and cystic areas). {#F2} When the utility of measuring serum Tg concentration was examined, the difference in serum Tg levels between the benign and malignant subgroups was analyzed, and the value of the serum Tg value/nodule volume ratio was also analyzed in the same way. Statistical analyses {#s2d} -------------------- Data were shown as mean ± standard deviation or median (interquartile range), and missing values were excluded from the analysis. Pearson's χ^2^ test, Fisher's exact test and Welch's *t*-test were used for the analysis of the ultrasonography test results, and a P value of \< 0.05 was considered significant. In Pearson's χ^2^ test, the results of the comparisons among the three groups were evaluated using residual analysis. Residual analysis was used to determine which of the three groups had a significant difference in the observed values in the Pearson's χ^2^ test. It was confirmed that each item had a significant difference using the adjusted standardized residue value. Adjusted standardized residue value of ≥ 1.96 or ≤ -1.96 was considered significant. With regard to the ultrasonographic findings, the sensitivity, specificity and positive likelihood ratio were analyzed. Wilcoxon's test was used to compare the differences in serum Tg level and serum Tg/nodule volume ratio between the benign subgroup and malignant subgroup. Serum TgAb and TPOAb levels were also analyzed in the same way. All analyses were performed using SPSS statistics software package (IBM Corp., NY, USA). Results {#s3} ======= Background of the study patients {#s3a} -------------------------------- [Table 2](#T2){ref-type="table"} shows the background of the study patients. The age of 26 patients with malignant nodules was 52.8 ± 16.7 years, while that of 210 patients with benign nodules was 60.2 ± 13.4 years. The mean age was significantly lower in the malignant nodules group than in the benign nodules group (P \< 0.05). In total, 11 men and 15 women had malignant nodules, whereas 46 men and 164 women had benign nodules. The proportion of men was significantly higher in the malignant nodules group than in the benign nodules group (P \< 0.05). Regarding the laboratory parameters, serum Tg, TgAb and TPOAb levels were also shown in [Table 2](#T2){ref-type="table"}. Serum Tg concentration was 91.6 (17.7 - 138.0) ng/mL in the malignant nodule group, and 52.4 (20.8 - 114.6) ng/mL in the benign nodule group, and the TgAb level was 17.5 (10.8 - 80.0) IU/mL in the malignant nodule group and 15.0 (10.0 - 34.0) IU/mL in the benign nodule group. The TPOAb level was 7.5 (5.8 - 11.0) IU/mL in the malignant nodule group, and 8.0 (6.0 - 11.0) IU/mL in the benign nodule group. Serum Tg, TgAb and TPOAb levels did not differ significantly between the benign and malignant groups. ###### Profiles of Patients With Thyroid Nodules Total (331 nodules, 236 patients) Malignant nodules (33 nodules, 26 patients) Benign nodules (298 nodules, 210 patients) P-value\* ------------------------------------------------------- ----------------------------------- --------------------------------------------- -------------------------------------------- ------------ Age, years 59.4 ± 13.9 52.8 ± 16.7 60.2 ± 13.4 \< 0.05^†^ Sex, n (male/female) 57/179 11/15 46/164 \< 0.05^†^ BMI, kg/m^2^ 23.6 ± 4.2 24.2 ± 4.1 23.5 ± 4.2 0.45^†^ History of thyroid disease, n (yes/no/unknown) 18/215/3 0/25/1 18/190/2 0.12^‡^ Family history of thyroid disease, n (yes/no/unknown) 42/173/21 6/15/5 36/158/16 0.08^‡^ Laboratory parameters   Tg, ng/mL 55.3 (20.8 - 115.6) 91.6 (17.7 - 138.0) 52.4 (20.8 - 114.6) 0.42^§^   TgAb, IU/mL 15.0 (10.0 - 35.0) 17.5 (10.8 - 80.0) 15.0 (10.0 - 34.0) 0.44^§^   TPOAb, IU/mL 8.0 (6.0 - 11.0) 7.5 (5.8 - 11.0) 8.0 (6.0 - 11.0) 0.99^§^ Values are expressed as mean ± standard deviation, count or median (interquartile range). \*Malignant nodules versus benign nodules according to Welch's *t*-test, Fisher's exact test, or Wilcoxon's test. ^†^Welch's *t*-test. ^‡^Fisher's exact test. ^§^Wilcoxon's test. BMI: body mass index; Tg: thyroglobulin; TgAb: anti-thyroglobulin antibody; TPOAb: anti-thyroid peroxidase antibody. Differentiating benign and malignant based on ultrasonography results {#s3b} --------------------------------------------------------------------- The results are shown in [Table 3](#T3){ref-type="table"}. Thyroid volume was 37.3 ± 27.3 mL in the benign nodule group and 25.5 ± 11.0 mL in the malignant nodule group, and the thyroid volume was significantly smaller in the malignant nodule group (P \< 0.01). Moreover, the volume of benign thyroid nodules was 11.7 ± 7.1 mL and that of malignant thyroid nodules was 3.9 ± 2.4 mL. The malignant nodule was significantly smaller than the benign nodule (P \< 0.01). Malignant thyroid nodules showed significantly lower echoes than benign nodules (P \< 0.01). With regard to internal microcalcifications, malignant nodules showed significantly more microcalcifications than benign nodules (P \< 0.01). With regard to internal blood flow findings, nodules rich in blood flow seemed to be malignant, while nodules with no blood flow seemed to be benign (P \< 0.05). With regard to nodule type, solid nodules suggested malignant nodules and mixed nodules suggested benign nodules (P \< 0.01). There was no significant difference between the benign and malignant nodules in the low-echo band at the boundary (regular, irregular, or none), shape (arranged or irregular), boundary property (smooth or coarse), boundary clarity (clear or unclear), internal echo property (uniform or non-uniform) and internal coarse calcification (presence or absence). [Table 4](#T4){ref-type="table"} shows the inspection accuracy of the ultrasonographic findings. The sensitivity, specificity and positive likelihood ratio of internal echo level (hypoechoic) were 53.1%, 68.1% and 1.67, respectively. With regard to internal microcalcifications, the sensitivity, specificity and positive likelihood ratio were 62.5%, 75.9% and 2.6, respectively. ###### Comparison of Ultrasonography Results Between Benign and Malignant Nodules Benign nodule Malignant nodule P value ------------------------------------------------------------- --------------------- --------------------- ------------ Volume of the thyroid gland, mL (n) 37.3 ± 27.3 (181) 25.5 ± 11.0 (22) \< 0.01\* Volume of thyroid nodule, mL (n) 11.7 ± 7.1 (283) 3.9 ± 2.4 (31) \< 0.01\* Shape, % (n) 0.10^†^   Arranged 53.9% (159) 38.7% (12)   Irregular 46.1% (136) 61.3% (19) Boundary properties, % (n) 0.29^†^   Smooth 56.7% (166) 46.9% (15)   Coarse 43.3% (127) 53.1% (17) Boundary clarity, % (n) 0.51^†^   Clear 62.2% (184) 56.3% (18)   Unclear 37.8% (112) 43.8% (14) Internal properties, % (n) 0.74^†^   Uniform 31.5% (93) 34.4% (11)   Non-uniform 68.5% (202) 65.6% (21) Internal echo level, % (n) \< 0.01^†^   Isoechoic 68.1% (201) 46.9% (15)   Hypoechoic 31.9% (94) 53.1% (17) Coarse internal calcification, % (n) 0.09^‡^   Presence 12.5% (37) 3.1% (1)   Absence 37.5% (259) 96.9% (31) Microcalcifications, % (n) \< 0.01^†^   Presence 24.1% (71) 62.5% (20)   Absence 75.9% (224) 37.5% (12) Internal blood flow, % (n), \[Adjusted standardized value\] \< 0.05^†^   Abundant 27.1% (79) \[-2.0\] 43.8% (14) \[+2.0\]   Small amount 49.8% (145) \[0\] 50% (16) \[0\]   None 23% (67) \[+2.2\] 6.23% (2) \[-2.2\] Boundary hypoechoic zone, % (n) 0.28^‡^   Regular 14.0% (41) 9.4% (3)   Irregular 12.3% (36) 21.9% (7)   None 73.6% (215) 68.8% (22) Nodule type, % (n) \< 0.01^‡^   Solid 59.1% (176) 97.0% (32)   Mixed 40.9% (122) 3.0% (1) Values of the thyroid gland and nodule are expressed as mean ± standard deviation. \*Welch's *t*-test. ^†^Pearson's χ^2^ test. ^‡^Fisher's exact test. ###### Diagnostic Accuracy of the Ultrasonographic Findings Sensitivity (%) Specificity (%) Positive likelihood ratio ---------------------------------- ----------------- ----------------- --------------------------- Internal echo level (hypoechoic) 53.1 68.1 1.67 Microcalcifications (presence) 62.5 75.9 2.6 Internal blood flow (abundant) 43.8 72.9 1.61 Nodule type (solid) 96.9 41.4 1.65 Usefulness of serum Tg concentration measurement in benign and malignant nodule differentiation {#s3c} ----------------------------------------------------------------------------------------------- After examining the subgroup of patients with a single nodule and those who tested negative for TgAb, the median (interquartile range) serum Tg concentration was 32.7 (11.0 - 83.8) ng/mL in the subgroup of patients with benign nodules and 104.5 (22.6 - 182.0) ng/mL in the subgroup of patients with malignant nodules. Serum Tg values were not significantly different between the two subgroups. Serum Tg was significantly positively correlated with nodule volume (r = 0.40, P \< 0.0001). Based on this result, we compared the serum Tg value/nodule volume ratios between the two subgroups ([Fig. 3](#F3){ref-type="fig"}). The serum Tg value/nodule volume ratio, expressed as median (interquartile range), was 13.3 (4.2 - 51.3) in the benign nodule subgroup and 29.7 (15.0 - 340.6) in the malignant nodule subgroup. When compared between these subgroups, the serum Tg/nodule volume ratio was significantly higher in the subgroup of patients with malignant nodules than in the subgroup of patients with benign nodules (P \< 0.05). {#F3} Discussion {#s4} ========== In recent years, the incidence of differentiated thyroid cancer has increased dramatically around the world, and a Korean study in 2014 confirmed a 15-fold increase in the incidence from 1993 to 2011 \[[@R04]\]. One reason for this is that cancer screening in Korea is offered free of charge, but it is also owing to the fact that the ultrasound diagnostic device can obtain higher-resolution images. On the contrary, the mortality rate remains low, and it is necessary to reconsider the diagnosis process for the possibility of overdiagnosis. For thyroid cancer, if a thyroid nodule is suspected by palpation, puncture aspiration cytology is performed directly without performing ultrasonography. However, at present, thyroid ultrasonography is performed first, and puncture aspiration cytology is only performed when necessary. When thyroid nodule lesions are observed, thyroid nodules are evaluated based on the ultrasound diagnostic criteria in order to differentiate benign from malignant nodules \[[@R17], [@R18]\]. In addition, several previous studies have reported the thyroid ultrasonographic findings of patients with PTC \[[@R17]-[@R20]\]. However, there is no Japanese study in which two or more doctors interpret and evaluate the same case using a uniform ultrasonography system. We used this method to classify the nodule properties based on the abovementioned items by discussing each one with all the readers and selecting similar findings, so that classification was made more accurately. In the present study, hypoechoic nodules, presence of microcalcification and solid nodules suggested malignant nodules in B-mode images of nodules, and findings of abundant internal blood flow using color Doppler tests ([Table 3](#T3){ref-type="table"}) also indicated malignancy. In addition, malignant nodules had significantly higher serum Tg/volume ratios than benign nodules ([Fig. 3](#F3){ref-type="fig"}). However, no clear cutoff value could be suggested; thus, the utility of measuring serum Tg/volume of nodule ratio in clinical practice remains questionable. With regard to the findings of B-mode images, the diagnosis of PTC could be further enhanced if multiple findings suggesting the abovementioned malignant nodules are observed. Using B-mode ultrasound to confirm the presence of nodules and to determine presence or absence of the abovementioned findings is a useful method for differentiating PTC from many benign nodules in actual clinical practice. Bastin et al reported that B-mode images may show microcalcifications that are unclear or lobulated; increased blood flow in the nodule; aspect ratio \> 1; solid nodules; and low-echo nodules \[[@R05]\]. In Japan, Shimura et al reported that the nodule shape, internal echo level and nodule boundary were considered useful findings suggesting malignancy, and that there was no significant difference in microcalcifications \[[@R20]\]. With regard to microcalcifications, the results of B-mode imaging examinations differed depending on the study and are regarded as minor findings based on the ultrasound diagnostic criteria for thyroid nodules in Japan \[[@R21]\]. In this study, however, the presence of microcalcifications suggested malignancy, and it was considered to be a useful finding to determine papillary cancer. With regard to blood flow, many of the currently used ultrasonic diagnostic apparatuses have a color Doppler function and can be used at the screening stage. Previous studies have examined the prediction of malignant findings combining the B-mode and Doppler methods. Frates et al reported that color Doppler findings were subdivided into 0 - 5 stages, and blood-rich nodules were common in patients with malignant nodules \[[@R22]\]. Appetecchia et al reported that color Doppler studies were divided into types I-III in terms of blood flow findings, and that nodules rich in internal blood flow comprised mainly of malignant nodules \[[@R23]\]. These results are consistent with the results of this study. On the contrary, Moon et al reported that blood flow in the nodule was detected even in benign nodules. Therefore, color Doppler is not superior to B-mode imaging. Moreover, the Korean Radiological Society consensus statement also reported that the use of color Doppler during normal examinations is not recommended \[[@R24], [@R25]\]. However, based on the results of this study, the combination of B-mode imaging results and color Doppler findings may prove to be a useful tool for distinguishing PTC from benign lesions. Horvath et al proposed the Thyroid Imaging Reporting and Data System (TIRADS) as a useful thyroid ultrasound diagnostic system \[[@R26]\]. We considered TIRADS to be a breakthrough system that can confirm malignant tumors by combining multiple echo findings. In addition, TIRADS was evaluated in a prospective study as well as in a meta-analysis \[[@R27], [@R28]\]. However, based on the results of these studies, TIRADS was considered to be ineffective in Japan \[[@R29]\]. This may be due to the differences in thyroid tumor ultrasound findings between patients in the US and Europe, who were the subjects in TIRADS studies, and patients in Japan. In the present study, the diagnostic accuracy of ultrasonographic findings was analyzed. Although the individual findings were not very sensitive or specific, it was thought that combining multiple findings would be useful for diagnosis. In future studies, we hope to increase the sample size and establish a similar system appropriate for the Japanese patient cohort. Serum Tg measurement is currently not considered useful for distinguishing benign nodules from malignant thyroid nodules \[[@R06]\]. Serum Tg levels are thought to increase with increasing nodule size, both in benign and malignant nodules \[[@R30]\]. Our study also showed a significant positive correlation between serum Tg and nodule volume in 120 patients with benign or malignant single nodules and those who tested negative for TgAb (P \< 0.05). Therefore, we calculated the value of serum Tg/nodule volume ratio and compared the results between benign and malignant nodules in order to determine the influence of serum Tg value. We speculated that if the measurement of serum Tg/nodule volume ratio is useful for differentiating benign from malignant nodules, it could be easily calculated even in the actual clinical setting; therefore, it was considered a very good discrimination method. The results of the comparative study showed a significant difference in the value of serum Tg/nodule volume ratio between benign and malignant nodules. However, this parameter cannot be used to differentiate between benign and malignant in actual clinical practice. Future studies incorporating a larger sample size and prospective study design will be required to further validate our results and determine whether serum Tg/nodule volume ratios can serve as a useful diagnostic aid. This study has some limitations. If thyroid ultrasound is performed and thyroid nodules suspected of lymph node metastasis are observed or if there is a sudden increase in thyroid nodules in a short period of time, a thyroid puncture should be considered by the attending physician. Aspiration cytology was not performed in our department, and some patients were directly referred for thyroid surgery, and thus, were excluded from this study. In the present study, when investigating ultrasonographic findings, we did not investigate the evaluation by detailed categories; that is, by the evaluation of intermediate existence, such as mild and moderate, and we evaluated only in the two categories of presence and absence. This was because we wanted to conduct a survey using the simplest evaluation method possible and to identify an evaluation that is easy to use in actual clinical situations. However, it is very important to conduct detailed evaluation by category as mentioned above, and we are considering increasing the sample size in the future to investigate this by such a detailed categorical study. There may also be a bias in this study due to missing values of the thyroid ultrasonography findings. In addition, the number of patients with thyroid cancer other than PTC was small, and thus, meaningful statistical analysis could not be performed in these patients. Conclusions {#s4a} ----------- In the present study, we examined the findings of B-mode and color Doppler ultrasonography for thyroid nodules. In B-mode, the thyroid nodule was hypoechoic, showed microcalcification and was a solid nodule suggesting malignancy. In color Doppler examination, the blood flow inside the nodules was abundant, suggesting malignancy. By combining these image findings, in the diagnosis of PTC, it is possible to reduce the number of unnecessary invasive FNAC examinations and to consider PTC as an easy and cost-effective method. In the future, we intend to further increase the number of target patients and use ultrasound imaging to investigate findings that suggest malignant nodules. We will investigate not only PTC but also other thyroid cancers to determine how combining the findings that suggest malignancy on the ultrasound image can improve the cancer diagnosis rate. The authors would like to express their gratitude to Kazuyuki Inoue, MD, for his role in the data collection. We would also like to thank Ikuo Inoue, MD, PhD, Mitsuhiko Noda, MD, PhD, and Akira Shimada, MD, PhD, for discussing some aspects of the manuscript. Financial Disclosure {#s4a1a} ==================== This research received the 2017 Young Researcher Training Research Fund (Saitama Medical University). Conflict of Interest {#s4a1b} ==================== The authors declare that they have no conflict of interest. Informed Consent {#s4a1c} ================ Informed consent was obtained from all participants. Author Contributions {#s4a1d} ==================== DS and SY conceptualized and designed the study, collected the data, conducted initial analyses and drafted the initial manuscript. RN collected the data, SY and RN critically reviewed the manuscript and SY approved the final manuscript as submitted. Data Availability {#s4a1e} ================= The authors declare that data supporting the findings of this study are available within the article.

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Electrophysiologic effects of mexiletine in children. The effects of intravenous administration of mexiletine on the refractory periods of the atrium and atrioventricular (AV) node were studied using His bundle recordings and the extrastimulus technique with atrial pacing. The drug was administered to 10 children with heart disease in an intravenous bolus dose of 3 mg/Kg, injected over a 5-min period, followed by an infusion of 1 mg/Kg/hr of mexiletine, achieving a mean therapeutic plasma concentration of 0.762 +/- 0.270 microgram/ml. The AH and HV intervals, the resting sinus cycle length, and the functional and effective refractory periods of the atrium and AV node were measured before and 5 min after initiation of the mexiletine infusion. The sinus cycle length was reduced significantly. However, neither the refractory periods nor the AH and HV intervals changed in a significant manner. Except for the heart rate, these results are similar to those reported in adults without conduction disturbances. In adults, mexiletine did not affect the sinus cycle length. However, in children, it consistently increased the heart rate. The lack of side effects in children is in contrast to adults, who usually suffer from gastrointestinal and neurologic symptoms upon receiving comparable doses parenterally.

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1998 Internationaux de Strasbourg The 1998 Internationaux de Strasbourg was a women's tennis tournament played on outdoor clay courts in Strasbourg, France that was part of Tier III of the 1998 WTA Tour. It was the 12th edition of the tournament and was held from 18 May until 24 May 1998. Second-seeded Irina Spîrlea won the singles title. Finals Singles Irina Spîrlea defeated Julie Halard-Decugis 7–6, 6–3 It was Spîrlea's only title of the year and the 7th of her career. Doubles Alexandra Fusai / Nathalie Tauziat defeated Yayuk Basuki / Caroline Vis 6–4, 6–3 It was Fusai's 2nd title of the year and the 6th of her career. It was Tauziat's 2nd title of the year and the 20th of her career. References External links ITF tournament edition details Tournament draws Internationaux de Strasbourg 1998 Internationaux de Strasbourg Category:May 1998 sports events in Europe

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Behaviour of leukocyte membrane fluidity in presence of anaesthetic drugs. Comparison between allergic patients and control subjects. 1. In this study we compared the effects of two anaesthetic drugs on the leukocyte membrane fluidity in allergic patients versus control subjects. 2. Fluidity was assessed by means of the fluorescence polarization technique. 3. We report that the treatment of the whole leukocytes with thiopental or pancuronium enhanced membrane fluidity in the allergic group as well as in the control one, but the effect was more pronounced in allergics. 4. This finding suggests a different biophysical behaviour of the leukocyte membrane towards anaesthetic drugs in allergic diseases. 5. This agrees with the hypothesis of the existence of an intrinsic abnormality in allergic cells, expressed as an initial hyperreactive state.

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Integration of human papillomavirus type 11 in recurrent respiratory papilloma-associated cancer. The main objective was to demonstrate that human papillomavirus (HPV) type 11 is an aggressive virus that plays a significant role in the development of laryngeal cancer in patients with a history of recurrent respiratory papillomatosis (RRP). We have done so by preliminary investigation into the molecular mechanism underlying the malignant transformation of RRP to invasive squamous cell carcinoma. An experimental, nonrandomized, retrospective study using tissue specimens from nine patients with a history of RRP that progressed to laryngeal or bronchogenic cancer was performed. DNA and RNA were extracted from 20 formalin-fixed, paraffin-embedded specimens from six patients with a history of early onset RRP and laryngeal cancer and from three patients with early onset RRP and bronchogenic cancer. Polymerase chain reaction (PCR) was performed on DNA to determine the HPV type in each specimen. Reverse-transcriptase PCR specific for virus transcripts was performed on RNA to determine whether the viral genome was integrated into the host genome. HPV-11 but not HPV-6, 16, or 18 was found in all of the laryngeal and bronchogenic cancers in patients with a history of early onset RRP in this study. RNA, sufficiently intact for examination, was obtained from seven patients. Analysis of HPV 11 transcripts revealed integration of the viral genome in three of seven patients. HPV type 6 and 11 are considered "low-risk" viruses and are not associated with genital cancers, as are HPV types 16 and 18. However, our data suggests that HPV type 11 is an aggressive virus in laryngeal papilloma that should be monitored in patients with RRP.

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Introduction {#s1} ============ Preterm birth is the single most important cause of perinatal mortality and morbidity and a major contributor to perinatal and infant mortality worldwide. Annually, there are more than 15 million preterm births, which contribute to more than 1 million deaths globally ([@B1], [@B2]). The neonatal sequelae of preterm birth can be significant and lead to long-term disability, cognitive impairment, blindness, and pulmonary complications ([@B3]--[@B6]). There is a differential impact upon the small subset of early preterm births before 32 weeks gestation (1--2% of all births, 16% of preterm births), because these infants account for the majority of neurological morbidity and perinatal mortality ([@B7], [@B8]). Although progesterone supplementation was shown to prevent preterm birth in women with a history of a prior preterm birth, more recent trials have not shown benefit ([@B9]--[@B13]). Clearly, new approaches are urgently needed to prevent perinatal mortality and serious morbidities associated with preterm birth. Mechanisms leading to the onset of labor involve a complex series of fetal and placental endocrine events that act to prime the myometrium. In a healthy and normal pregnancy, the uterus transitions from a quiescent organ to one that is able to efficiently propagate electrical signals to generate contractions near term ([@B14], [@B15]). Both term and preterm labor (PTL) is known to be an inflammatory process with immune cells and inflammatory proteins (cytokines, chemokines) playing a key role in parturition ([@B16]--[@B20]). We and others have demonstrated that inflammation within the myometrium and decidua *precedes* the onset of spontaneous and PTL, thereby implicating an inflammatory process as a labor inciting event ([@B19], [@B21]--[@B26]). Choriodecidual tissues at the maternal-fetal interface represent a primary site for the synchronized infiltration of peripheral leukocytes ([@B21], [@B27], [@B28]) that could have a direct effect on the myometrium ([@B24], [@B27], [@B29]) to promote uterine contractions and cervical ripening ([@B16], [@B29]--[@B31]). A pharmacologic block of inflammation within the myometrium, decidua and placenta may represent a useful therapeutic approach for preventing preterm birth. Recruitment of leukocytes from the peripheral circulation to the decidua and myometrium is mediated by chemokines, a class of cytokines that act as chemoattractants ([@B32], [@B33]). Chemokines include \~50 endogenous chemokine ligands and 20 G protein-coupled receptors \[reviewed in ([@B32])\]. In women with PTL, several chemokines are elevated in the amniotic fluid, placenta, decidua and/or myometrium including monocyte chemotactic protein 1 (MCP-1/CCL-2), chemokine (C-X-C motif) ligand 1 (CXCL1), interleukin-8 (IL-8/CXCL8), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF) ([@B28], [@B34]--[@B41]). Chemokine receptor antagonists might inhibit PTL and have been used in clinical trials to prevent cancer metastasis ([@B42], [@B43]) and as an early stage HIV therapy ([@B44]). In rodent models, chemokine receptor antagonists have been used to prevent or ameliorate kidney disease ([@B45]--[@B47]), bowel inflammation ([@B48], [@B49]), and brain injury or stroke ([@B50]). Broad Spectrum Chemokine Inhibitors (BSCI) have also been developed that can simultaneously block multiple chemokine signaling pathways ([@B51]). In this study, we used a BSCI, which specifically binds the cell-surface type-2 somatostatin receptor (SSTR2) and results in a potent suppression of chemokine signaling without directly affecting chemokine receptors ([@B52]--[@B54]). Our previous work showed that pre-treatment with the BSCI (BN83470) resulted in reduced uterine inflammation and partially prevented preterm birth induced by lipopolysaccharide (LPS) in a mouse model of preterm labor ([@B55]). The efficacy of a BSCI to ameliorate disease has been demonstrated in a wide range of animal models (e.g., allergic asthma, surgical adhesion formation, rheumatoid arthritis, and HIV replication) ([@B51], [@B53], [@B56]--[@B60]). This data provided the basis for this study that uses a new BSCI compound (FX125L) with superior pharmaceutical properties including pharmacokinetics, safety and toxicology with the potential for greater therapeutic efficacy \[([@B61]) and Dr. David Fox, Warwick University, personal communication\]. Whether a BSCI, like FX125L, might prevent PTL by limiting leukocyte recruitment and inflammatory cascades within the chorioamniotic membranes and myometrium is unknown. We hypothesized that prophylaxis with a BSCI would downregulate the inflammatory microenvironment induced by Group B Streptococcus (GBS, *Streptococcus agalactiae*) to suppress PTL, but still allow for bacterial resolution. GBS is a common lower genital tract bacteria associated with fetal injury, stillbirth, and preterm birth ([@B62]--[@B71]). To test our hypothesis, we used a unique chronically catheterized pregnant non-human primate (NHP; *Macaca nemestrina*, pigtail macaque) in which we have previously studied the pathogenesis of GBS-induced inflammation and preterm birth ([@B72]--[@B76]). In this model, we inoculate GBS into the choriodecidual space, between the uterine muscle and the chorioamniotic membranes, where bacteria are first thought to come in contact with the choriodecidual tissues and myometrium after ascending from the vagina ([@B72], [@B75], [@B77]). Herein, we demonstrate that prophylactic BSCI administration reduced the rate of PTL, but failed to limit bacterial invasion of the amniotic cavity and fetus, which led to greater fetal inflammation and injury. Materials and Methods {#s2} ===================== Ethics Statement ---------------- All animal experiments were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Research Council and the Weather all report, "The use of non-human primates in research." The University of Washington Institutional Animal Care Use Committee approved the protocol (Permit Number: 4165-01). All surgery was performed under general anesthesia and all efforts were made to minimize suffering. Written informed consent for donation of adult human blood was obtained from subjects, per the Principles in the WMA Declaration of Helsinki and Dept. of Health and Human Services Belmont Report. The study was approved by the Seattle Children\'s Research Institute Institutional Review Board (protocol \#11117). Children under the age of 18 were not recruited for donation of human blood. Study Design and the Chronically Catheterized NHP Model ------------------------------------------------------- We used a chronically catheterized pregnant NHP (*Macaca nemestrina*) model, in which we surgically implanted catheters via laparotomy into the maternal femoral vein, amniotic cavity, and choriodecidual interface in the lower uterine segment (between uterine muscle and fetal membranes, external to amniotic fluid). For inducing PTL, we used a hyperhemolytic and hyperpigmented GBS strain (GBS COH1Δ*covR*), lacking the hemolysin repressor CovR, which is associated with PTL ([@B63], [@B75]). In this study, animals received choriodecidual infusions of GBS COH1Δ*covR* with pre-treatment and daily infusions of a BSCI (*N* = 4; 10 mg/kg intravenous and 10 mg/kg intra-amniotic). These results were compared to two other groups of animals receiving either a choriodecidual inoculation of GBS COH1Δ*covR* (*N* = 5; hypervirulent, hyperpigmented strain, 1--5 × 10^8^ CFU/ml) or saline (*N* = 6). The GBS COH1Δ*covR* (*N* = 5) and some of the saline control (*N* = 4) experiments were performed and published previously ([@B19], [@B72], [@B73]). Other saline control experiments (*N* = 2) were performed as part of this study. Our chronically catheterized NHP model has been previously described ([@B75]). Briefly, between days 114--125 of pregnancy (term = 172 days), catheters were surgically implanted via laparotomy into the maternal femoral artery and vein, amniotic cavity, and choriodecidual interface in the lower uterine segment (between uterine muscle and fetal membranes, external to the amniotic cavity). After surgery, the animal was placed in the jacket and tether with catheters tracked through the tether system. Cefazolin, indomethacin and either terbutaline sulfate or atosiban were administered to reduce postoperative infection risk and uterine activity, but stopped at least 72 h before experimental start (\~5 half-lives for terbutaline, 40 half-lives for cefazolin, \>97% of both drugs eliminated). Experiments began \~2 weeks after catheterization surgery to allow recovery (\~30--31 weeks human gestation). Intra-amniotic pressure was continuously recorded, digitized, and analyzed using custom software. The integrated area under the intrauterine pressure curve was used as a quantitative measure of uterine activity and reported as the hourly contraction area (HCA; mmHg-s/h) over 24 h. PTL and Cesarean Section ------------------------ PTL was defined as progressive cervical dilation associated with increased uterine activity (\>10,000 mmHg-s/h). Cesarean section was performed at the following endpoints to allow for tissue collection: (1) PTL, (2) 3 days after GBS inoculation if no PTL was observed, or (3) 7 days after saline inoculation ([@B72]). A 3-day endpoint to assess the effects of GBS on placental tissues and fetal injury was chosen in order to study the earliest events in the pathway of infection/inflammation associated preterm birth. The 7-day endpoint for saline controls was chosen at the inception of our research program and provides a close gestational age match for the current study. After Cesarean section, fetuses were euthanized by barbiturate overdose followed by exsanguination and fetal necropsy. BSCI ---- The BSCI (FX125L) was obtained as a gift from Dr. David Fox at the University of Warwick. A dose of 10 mg/kg, administered both intra-amniotically and intravenously, was chosen based on murine studies showing efficacy with an equivalent dose for the inhibition of LPS-induced PTL ([@B55]). The first infusion of BSCI was administered 24 h before GBS inoculation. The second infusion was given \~1 h prior to GBS inoculation. Subsequently, BSCI infusions were administered daily until Cesarean section. Bacterial Growth and Confirmation of GBS From Infected Animals -------------------------------------------------------------- GBS strains used in this study were derived from a clinical isolate known as COH-1 (ST-17 clone, capsular serotype III), which was obtained from an infected newborn ([@B78], [@B79]). The hyperhemolytic and hyperpigmented Δ*covR* was derived from wild type (WT) GBS COH-1 ([@B63]) was previously tested in our NHP model ([@B75]). Routine cultures of GBS were grown in tryptic soy broth (TSB) or tryptic soy agar (TSA, Difco Laboratories) at 37°C in 5% CO~2~. For inoculations in the NHP model, GBS strains were grown to mid-log phase (O.D~600~ = 0.3) and \~1--5 × 10^8^ CFU in 1 mL PBS was inoculated into the choriodecidual space, as described previously ([@B72]). For bacterial enumeration, amniotic fluid (100 μL) was serially diluted and 10-fold dilutions were plated on TSA, incubated overnight at 37°C, 5% CO~2~ and enumerated to determine bacterial invasion. Quantities of GBS were reported as colony forming units (CFU). To confirm that bacteria recovered from infected animals was GBS, we took advantage of the fact that the hyperpigmented GBSΔ*covR* strain exhibits an orange color on TSA ([@B63]). We also tested for CAMP factor activity on sheep blood agar plates with the inoculum strain included in parallel. PCR and DNA sequencing for 16S ribosomal RNA was performed as needed. These tests confirmed that GBS did not change phenotype during the course of the experiment. NHP Sample Collection --------------------- Amniotic fluid (AF) and maternal blood were sampled frequently i.e., before (−24 and −0.25 h) and after pathogen inoculation (+0.75, +6, +12, +24 h and then every 12 h until Cesarean section for fetal necropsy) to culture for GBS and assay for inflammatory mediators. At the time of Cesarean section, fetal blood was obtained. For cytokine and prostaglandin (PG) analysis, samples of amniotic fluid and blood were collected in heparin and EDTA tubes, respectively. Samples were centrifuged for 5 min at 1,200 rpm immediately after collection and the supernatant was frozen and stored at −80°C. For analysis of bacterial dissemination in fetal organs, fetal tissues were weighed at necropsy, homogenized in sterile PBS and 10-fold serial dilutions were plated on TSA and incubated overnight at 37°C, 5% CO~2~ and enumerated as described ([@B80]). For inflammatory cytokine analysis, fetal organ homogenates were diluted 1:1 in lysis buffer \[150 mM NaCl, 15 mM Tris, 1 mM MgCl~2~, 1 mM CaCl~2~, 1% Triton X-100, supplemented with Complete Mini, EDTA-free protease inhibitor cocktail (Roche)\] and incubated overnight at 4°C. Lysates were centrifuged at 4,000 rpm for 20 min at 4°C, and the supernatants were stored at −80°C or used immediately for analysis. About 100 μl of sample was used in Luminex or ELISA assays as described above. Cytokine and Prostaglandin Analysis ----------------------------------- Cytokines \[interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin (IL-8), and tumor necrosis factor-alpha (TNF-α)\] levels were determined using Luminex multiplex cytokine kits (Millipore, Billerica, MA) for maternal plasma, fetal plasma and AF samples. Prostaglandin E2 (PGE2) and Prostaglandin F2-alpha (PGF2α) were determined using commercially available human EIA kits (Cayman Chemical, Ann Arbor, MI). In the tissues, we quantitated cytokines using a Luminex multiplex cytokine kit designed for NHP samples covering 37 cytokines/chemokines (37-plex ProcartaPlex™ NHP panel; Thermo Fisher Scientific, Waltham, MA). Values are reported as pg/mL in the amniotic fluid and maternal and fetal plasma or pg/g in fetal tissues. Histopathology, Immunohistochemistry and Quantitative Image Analysis -------------------------------------------------------------------- A board-certified veterinary pathologist (A.B) peformed histopathologic examination of the fetal and placental tissues. H&E-stained, full-thickness paraffin sections (placental disc, umbilical cord, fetal membrane roll) were examined from each case to exclude inflammation, necrosis, fetal vascular thrombosis, or other histopathological findings. Chorioamnionitis was diagnosed by the presence of a neutrophilic infiltrate at the chorion-decidua junction (mild) or amniochorion junction (moderate or severe). For histologic examination of the fetal lung, two to three randomly selected fixed fetal lung tissues were embedded in paraffin and sections stained with hematoxylin and eosin (H&E). We also performed immunostaining for myeloperoxidase (MPO, granulocyte marker) and CD68 (macrophage marker) on the chorioamniotic membranes and fetal lung tissues. For the chorioamniotic membrane analyses, we included an additional two controls ([@B81]). The University of Washington Histology and Imaging Core performed the immunohistochemistry optimization and staining for MPO and CD68. We used the following primary, secondary and tertiary antibodies: rabbit polyclonal MPO (Clone Ab-1, ThermoScientific, Catalog Number RB-373-A1), mouse monoclonal CD68 (Clone 514H12, Leica, Catalog Number PA0273), Leica Post-Primary linker and goat anti-rabbit horseradish peroxidase polymerized antibody (Leica Catalog Number DS9800). Utilizing the Leica Bond Rx Automated Immunostainer (Leica Microsystems, Buffalo Grove, IL), slides were first deparaffinized with Leica Dewax Solution at 72°C for 30 s. For MPO staining, antigen retrieval was heat-mediated using citrate, pH 6, at 100°C for 20 min. For CD68 staining, antigen retrieval was performed with EDTA, pH 9, at 100°C for 20 min. All subsequent steps were at room temperature. Blocking was performed with 10% normal goat serum (Jackson ImmunoResearch, Catalog Number 005-000-121) in tris-buffered saline for 20 min followed by blocking with Leica Bond Peroxide Block for 5 min. Slides were then incubated with either the MPO (1:100) primary antibody in Leica Primary Antibody Diluent or CD68 (no dilution) primary antibody for 30 min. For MPO, a secondary antibody (goat anti-rabbit horseradish peroxidase polymerized antibody) was applied for 8 min. For CD68, the Leica Post-Primary linker was applied for 8 min and tissues were then incubated with a tertiary antibody (goat anti-rabbit horseradish peroxidase polymerized antibody) for 8 min. Antibody complexes were visualized using DAB (3,3′-diaminobenzidine), detection 2 × for 10 min. Tissues were counterstained with hematoxylin. Slides were removed from the automated stainer, dehydrated and coverslipped. Unless otherwise specified all reagents were obtained from Leica Microsystems. Quantitative imaging was the performed using Visiopharm image analysis software (Visiopharm, Inc., Hoersholm, Denmark). Regions of interest within each tissue were outlined corresponding to the amnion, chorion and decidua within the chorioamniotic membranes and alveoli within the fetal lung. The ratio of the immunostained area of tissue to the area of the entire tissue within the region of interest was calculated and compared across groups using one-way ANOVA with adjustment for multiple comparisons using Tukey\'s test. NET Immunostaining ------------------ We performed immunostaning as previously described ([@B75]). Briefly, full thickness paraffin sections of fetal roll were deparaffinized and epitopes were revived overnight at 60°C in citrate buffer (10 mM sodium citrate, 0.05% Tween 20, pH 6.0). After epitope revival, slides were washed, blocked for 1 h at 23°C in 5% (v/v) goat serum and 1% (w/v) BSA, then incubated overnight at 4°C with rabbit anti-neutrophil elastase antibody (1:2000, Abcam).Anti-neutrophil elastase antibody was detected using anti-rabbit IgG antibody conjugated to Cy3 (1:2500, Abcam). Extracellular and nuclear DNA was detected using DAPI (4′,6-diamidino-2-phenylindole) in Vectashield (Vector Laboratories). Images were captured using a DM4000B Fluorescent upright microscope (Leica) under 20 × magnifications. The microscope was attached to a DFC310FX camera (Leica) and the acquisition software used was the Leica application suite (version 4.0.0). Isolation of Neutrophils From Adult Human Blood ----------------------------------------------- Neutrophils were isolated from fresh human adult blood as described ([@B75]). Briefly, \~20--30 mL of blood was collected from independent healthy human donors in EDTA tubes (BD Bioscience). Neutrophils were then isolated using a MACSxpress neutrophil isolation kit following manufacturer\'s instructions (Miltenyi Biotec). Following neutrophil isolation, the cells were pelleted and any residual red blood cells (RBC) were removed using the RBC lysis solution (0.15 nM NH~4~Cl, 1 mM NaHCO~3~) as per manufacturer\'s instructions. Cells were then washed with RPMI 1640 containing L-glutamine (Corning Cellgro; hereafter referred to as RPMI-G). Cells were counted and resuspended at appropriate concentrations in assay-specific buffers. Neutrophil Killing Assays ------------------------- Neutrophils isolated as described above were washed in RPMI-G. GBS were grown to early log phase (OD~600~ = 0.3) in TSB (Tryptic Soy Broth) and washed twice with PBS. Approximately 2.2 × 10^4^ neutrophils were incubated with GBSΔ*covR* at an MOI of 10 in RPMI-G in the presence and absence of 100 μg BSCI in nuclease-free water (Ambion Nuclease-Free Water; hereafter referred to as NFW). After 1 h of incubation at 37°C, Triton X-100 was added at a final concentration of 0.025% to release intracellular bacteria, and total bacteria (intracellular and extracellular bacteria) were enumerated by serial dilution and plating. The survival index was calculated as the ratio of CFU recovered in the presence of neutrophils to CFU recovered in the absence of neutrophils. Data shown are representative of two independent experiments with neutrophils isolated from three different donors in each experiment, which was performed in duplicate. Neutrophil Reactive Oxygen Species (ROS) Assays ----------------------------------------------- ROS production in neutrophils was measured as described previously ([@B75]). Briefly, human neutrophils were isolated as described above and washed in RPMI-G. GBS were grown to early log phase (OD~600~ = 0.3) in TSB and washed twice with PBS. Neutrophils were resuspended in HBSS (Corning) and incubated with 84 μM dihydrorhodamine123 (DHR123) for 30 min at 37°C. Approximately 5 × 10^5^ DHR123-pre-treated neutrophils were incubated with either GBSΔcovR at an MOI of 100 in PBS in the presence and absence of 100 μg BSCI in NFW. Controls included neutrophils (cells only) and neutrophils treated only with BSCI. At various times post incubation (0, 60 min) at 37°C, cells were analyzed on a LSR II flow cytometer to determine oxidation to fluorescent mono-hydrorhodamine 123 (MHR). Statistical Analysis -------------------- The primary study outcome was PTL, which was hypothesized to be inhibited by pre-treatment with the BSCI. Secondary outcomes were rates of MIAC, fetal sepsis, and adverse pregnancy outcomes (composite of PTL and MIAC/fetal sepsis). Other secondary outcomes included quantities of uterine activity (peak mean daily hourly contraction area), GBS in the amniotic fluid and fetus (CFU), amniotic fluid cytokines and prostaglandins (PGE2, PGF2α), and the myeloperoxidase (MPO; neutrophil marker) and CD68 (macrophage marker) immunohistochemical staining area within the amnion, chorion, decidua and fetal lung. Outcomes were compared using the Fisher\'s exact test (categorical variables), Wilcoxon rank sum (continuous variables) as appropriate. We pre-specified two comparisons of interest (1) Saline group vs. BSCI and (2) GBS vs. BSCI. We did not adjust our *p*-values *post-hoc* due to the small sample size. Statistical analysis was performed using GraphPad Prism version 8.0 (GraphPad Software, [www.graphpad.com](http://www.graphpad.com)) or STATA/IC 14.2 (StataCorp LLC, College Station, TX). Results were considered significant if the *p*-value was ≤ 0.05. However, due to the limited number of samples per group, we also report trends (*p*-values between 0.05 and 0.1) as described previously with NHP experiments ([@B82]). Results {#s3} ======= BSCI Prevents PTL, but Not MIAC or Fetal Sepsis During GBS Infection -------------------------------------------------------------------- We tested whether pre-treatment with a BSCI might suppress GBS-associated PTL and allow for bacterial resolution in a chronically catheterized pregnant NHP model. In our saline controls (*N* = 7), there were no cases of PTL by 7 days post-inoculation ([Figure 1A](#F1){ref-type="fig"}; [Table 1](#T1){ref-type="table"}). As we previously reported, choriodecidual inoculation of GBS alone induced PTL in 4 of 5 cases (80%) by 3 days post-inoculation ([Figure 1B](#F1){ref-type="fig"}) ([@B75]). In contrast, PTL did not occur in any cases inoculated with GBS and treated with the BSCI within this time-frame (0/4, 0%; *p* = 0.02; [Figure 1C](#F1){ref-type="fig"}). Two BSCI animals were delivered 1 day early due to discoloration of the amniotic fluid indicating a significant bacterial burden, which was a pre-defined study endpoint to avoid stillbirth. In one case, clinical microbiological methods to identify bacteria recovered from the amniotic fluid, revealed that contaminating bacteria (*Staphylococcus epidermidis*) was present in one BSCI case prior to GBS inoculation (BSCI case 2, [Table 2](#T2){ref-type="table"}). We chose to include this case, because it represented a further test of the ability of the BSCI to inhibit microbial-infection associated PTL and biased our study toward the null hypothesis. Notably, despite the presence of at least two different bacterial strains in BSCI case 2, PTL did not occur. {#F1} ###### Summary of pregnancy outcomes, uterine activity, cytokines, and prostaglandins. **Outcome or cytokine** **Saline (*N* = 6)** **GBS (*N* = 5)** **BSCI+GBS (*N* = 4)** ***P*****-value** --------------------------------------------------------- ---------------------- ------------------- ------------------------ -------------------------------------- --------------------------------------- **MATERNAL AND FETAL OUTCOMES** PTL 0 (0%) 4 (80%) 0 (0%) NS 0.02 MIAC 0 (0%) 3 (60%) 4 (100%) 0.005[\*](#TN2){ref-type="table-fn"} NS Fetal Bacteremia 0 (0%) 3 (60%) 4 (100%) 0.005[\*](#TN2){ref-type="table-fn"} NS Adverse outcomes[^‡^](#TN1){ref-type="table-fn"} 0 (0%) 5 (100%) 4 (100%) 0.005[\*](#TN2){ref-type="table-fn"} NS **UTERINE CONTRACTILITY** Peak Mean HCA (mm Hg∙s/h) 1,327 (507) 4,008 (763) 3,654 (964) 0.06 NS Final HCA (mm Hg∙s/h) 607 (434) 3,843 (847) 2,427 (1,189) 0.06 NS **AMNIOTIC FLUID CYTOKINES AND PROSTAGLANDINS (ng/mL)** IL-1β 0.03 (0.02) 5.1 (3.1) 5.8 (2.1) 0.01[\*](#TN2){ref-type="table-fn"} NS TNF-α 0.03 (0.01) 2.0 (1.2) 1.0 (0.2) 0.01[\*](#TN2){ref-type="table-fn"} NS IL-6 7.1 (2.6) 22.7 (1.5) 11.8 (7.6) NS NS IL-8 0.9 (0.3) 15.7 (4.2) 3.6 (1.6) 0.06 0.03[\*](#TN2){ref-type="table-fn"} PGE2α 0.5 (0.2) 4.5 (4.1) 3.7 (1.3) 0.03[\*](#TN2){ref-type="table-fn"} NS PGF2α 0.4 (0.2) 98.5 (98.0) 1.6 (0.8) NS NS **FETAL CYTOKINES (pg/mL)** IL-1β 0.9 (0.6) 42.3 (23.2) 3.6 (1.0) 0.02[\*](#TN2){ref-type="table-fn"} 0.05 TNF-α 2.3 (1.1) 7.8 (0.8) 3.2 (1.8) NS \<0.05[\*](#TN2){ref-type="table-fn"} IL-6 3.6 (1.9) 675.3 (413.0) 241.8 (218.0) 0.01[\*](#TN2){ref-type="table-fn"} NS IL-8 574 (314) 4,721.7 (1745.0) 1,098.4 (885.0) NS 0.09 *BSCI, broad spectrum chemokine inhibitor; GBS, Group B Streptococcus; HCA, hourly contraction area; IL, interleukin; PTL, preterm labor; MIAC, Microbial invasion of the amniotic cavity; PGE2, prostaglandin E2; PGF2α, prostaglandin F2 alpha; TNF-α, tumor necrosis factor alpha*. *Adverse outcomes represent PTL and/or MIAC*. *Maternal and fetal outcomes are shown as number (%) and are compared using Fisher\'s exact test. Amniotic fluid cytokines and prostaglandins are shown as mean peak (standard error of the mean) in ng/mL. Fetal plasma cytokines (pg/mL) represent the mean quantity at delivery (GBS and BSCI+GBS) or at their peak (saline controls) with standard error of the mean shown in parentheses. Cytokines and prostaglandins are compared between the saline and BSCI+GBS group and the GBS and BSCI+GBS group*. *P \< 0.05 are considered significant, but p ≤ 0.1 are shown due to the small sample size*. ###### Primary outcomes and time course for MIAC and delivery by animal. **Animal** **MIAC and fetal sepsis** **Timepoint[^\*^](#TN3){ref-type="table-fn"} when GBS first detected in AF** **PTL** **Days from inoculation[^\*\*^](#TN4){ref-type="table-fn"} to delivery** **Notes and figure correspondence** ------------ --------------------------- ------------------------------------------------------------------------------ --------- -------------------------------------------------------------------------- ------------------------------------------------------------------------------------- Saline 1 N/A N/A N/A 7 Saline 2 N/A N/A N/A 7 Saline 3 N/A N/A N/A 7 Saline 4 N/A N/A N/A 7  [Figure 1A](#F1){ref-type="fig"} Saline 5 N/A N/A N/A 7 Saline 6 N/A N/A N/A 7 GBS 1 Yes 0.25 h Yes 0.3 (7 h) GBS 2 Yes 0.75 h Yes 1  [Figure 1B](#F1){ref-type="fig"} GBS 3 Yes 12 h No 2 AF brown and cloudy, but no PTL. Delivered due to concern for impending stillbirth. GBS 4 No N/A Yes 3 Lowest GBS inoculum (5 × 10^7^ CFU) GBS 5 No N/A Yes 1 BSCI+GBS 1 Yes 6 h No 2 AF brown and cloudy BSCI+GBS 2 Yes Non-GBS contaminant detected at −1 h No 2 AF brown and cloudy; also had a non-GBS contaminant BSCI+GBS 3 Yes 6 h No 3  [Figure 1C](#F1){ref-type="fig"} BSCI+GBS 4 Yes 6 h No 3 PTL, preterm labor; MIAC, microbial invasion of the amniotic cavity; AF, amniotic fluid. *Indicates the first time point when GBS was cultured from amniotic fluid. For example, a positive value at 6 h indicates that bacterial trafficking occurred sometime between 45 min and 6 h*. *The day of inoculation is considered day 0*. Analysis of the uterine contraction pattern revealed that GBS inoculation alone resulted in a building contraction pattern within 6 h of inoculation that typically culminated in PTL. In contrast, BSCI prophylaxis was associated with a transient increase in uterine activity following GBS inoculation that decreased over time, but did not result in cervical change or PTL. A quantitative analysis of peak mean uterine contraction strength and frequency (hourly contraction area, HCA) revealed that BSCI+GBS and GBS groups had similar peak mean HCA ([Table 1](#T1){ref-type="table"}); however, at the end of the experiment, uterine contractility was lower in the BSCI+GBS compared to the GBS group ([Table 1](#T1){ref-type="table"}). Overall, BSCI prophylaxis was associated with inhibition of PTL by 3 days post-GBS inoculation compared to GBS alone. Next, we sought to determine whether BSCI administration can prevent MIAC and fetal sepsis due to GBS inoculation. Neither MIAC nor fetal sepsis occurred in the saline controls (0/6; 0%). As previously reported, choriodecidual inoculation of GBS alone frequently led to MIAC and fetal bacteremia (3/5, 60%) ([@B75]). Notably, in all cases, BSCI administration followed by GBS inoculation was associated with MIAC and/or fetal bacteremia (4/4, 100%). In contrast to our hypothesis, an increased bacterial burden in AF and fetal tissues was noted in the BSCI+GBS group ([Figure 2A](#F2){ref-type="fig"}, 10-fold median increase in AF, *p* = 0.1; [Figure 2B](#F2){ref-type="fig"}, 1,000-fold median increase in fetal blood, *p* = NS) compared to the GBS only group. In all BSCI cases, MIAC occurred by 6 h following choriodecidual GBS inoculation whereas bacteria was detected in the AF by 1 h in 2 GBS cases and in a third GBS case by 12 h post-inoculation ([Table 2](#T2){ref-type="table"}, [Figure 2](#F2){ref-type="fig"}). Taken together, these data indicate that while administration of BSCI inhibits PTL, it was associated with bacterial dissemination into the amniotic cavity and fetus. {#F2} BSCI Dampens IL-8 in the Maternal Plasma and AF, but Not in Fetal Plasma ------------------------------------------------------------------------ Our chronically catheterized NHP model allows for the serial sampling of amniotic fluid and maternal blood throughout the course of the experiment. We therefore examined the effect of BSCI administration on cytokine and chemokine profiles in the maternal blood, amniotic fluid and fetal blood using a luminex assay. BSCI prophylaxis was associated with lower levels of IL-8 in the maternal plasma compared to the GBS group at multiple time points throughout the experiment ([Figure 3A](#F3){ref-type="fig"}). IL-1β levels in maternal plasma were also lower in the BSCI+GBS vs. GBS group ([Figures 3B](#F3){ref-type="fig"}). IL-6 and TNF-α levels in the maternal plasma were not affected by BSCI prophylaxis ([Figures 3C,D](#F3){ref-type="fig"}). In the AF, BSCI+GBS compared to GBS group was associated with significantly lower IL-8 levels for the first 12 h of the experiment ([Figure 4A](#F4){ref-type="fig"}) and significantly lower peak mean levels compared to the GBS group (*p* = 0.03, [Table 1](#T1){ref-type="table"}); similarly, IL-6 levels were significantly lower for the first 12 h following GBS inoculation ([Figure 4C](#F4){ref-type="fig"}). Levels of AF IL-1β and TNF-α ([Figures 4B,D](#F4){ref-type="fig"}) and AF prostaglandin E2 and F2α ([Figure 5](#F5){ref-type="fig"}) were unaffected by BSCI treatment. In fetal plasma from the BSCI+GBS compared to the GBS group, the peak mean levels of many cytokines were lower including TNF-α (*p* \< 0.05), IL-1β (*p* = 0.05), and IL-8 (*p* = 0.09; [Table 1](#T1){ref-type="table"}). Levels of fetal plasma IL-6 were similar between the GBS and BSCI+GBS groups. {#F3} {#F4} {#F5} BSCI Diminished Fetal Chemokines and Cytokines in Tissues but did Not Prevent Bacterial Dissemination ----------------------------------------------------------------------------------------------------- We next asked whether tissue levels of chemokines and cytokines were altered as a result of fetal exposure to the BSCI and focused investigation on the fetal lungs, brain and chorioamniotic membranes at the GBS inoculation site. BSCI prophylaxis was associated with a significantly lower level of IL-7 and IFN-α in the fetal lung ([Figure 6A](#F6){ref-type="fig"}, *p* = 0.02 for both) and significantly lower IL-2, IL-7, and IL-18 in the fetal brain ([Figure 6B](#F6){ref-type="fig"}; *p* = 0.02 for IL-2 and IL-18; *p* = 0.03 for IL-7) compared to GBS alone. Notably, statistical power was limited for these comparisons as we had fewer chorioamniotic membrane inoculation site samples available for Luminex analysis (GBS group, *N* = 3; BSCI+GBS, *N* = 4). The quantities of many other cytokines and growth factors were also lower at the GBS inoculation site within the chorioamniotic membranes with BSCI exposure compared to the GBS only group ([Figure 6C](#F6){ref-type="fig"}; IP-10, IL-7, FGF2, VEGF-A, *p* = 0.06 for all). A trend toward a lower IL-1β and I-TAC concentration at the GBS inoculation site of the chorioamniotic membranes was also observed in the BSCI+GBS group vs. GBS only ([Figure 6D](#F6){ref-type="fig"}, *p* = 0.1). {#F6} Diminished levels of pro-inflammatory cytokines may have an adverse effect in controlling bacterial dissemination. We also noted a trend toward a higher bacterial burden in all tissues from BSCI-treated animals compared to GBS alone, particularly in the fetal brain and at the GBS chorioamniotic membrane inoculation site ([Figure 6E](#F6){ref-type="fig"}). These data suggest that treatment with BSCI may dampen inflammatory cytokines at the cost of increased bacterial burden. This may be due partially to decreased neutrophil recruitment at the membrane inoculation site and in fetal tissues. To investigate the impact of BSCI treatment on neutrophil infiltration of the chorioamniotic membranes and fetal tissues, we compared histopathology of the membrane inoculation site and fetal lungs across the treatment groups. BSCI Treated Animals Exhibited Increased Neutrophil and Macrophage Recruitment in the Chorioamniotic Membranes and Fetal Lungs ------------------------------------------------------------------------------------------------------------------------------ To gain further insight into the effect of BSCI on chemokine inhibition, we performed immunostaining on the chorioamniotic membranes at the GBS inoculation site ([Figures 7](#F7){ref-type="fig"}, [8](#F8){ref-type="fig"}). In the saline controls, there was minimal to no neutrophil infiltration \[[Figure 7A](#F7){ref-type="fig"}, H&E stain; [Figure 7E](#F7){ref-type="fig"}, myeloperoxidase (MPO) stain of granulocytes\] or CD68 immunostaining ([Figure 7I](#F7){ref-type="fig"}). GBS inoculation led to an accumulation of neutrophils in the decidua at 24 h post-inoculation ([Figures 7B,F](#F7){ref-type="fig"}) and throughout the chorioamniotic membranes by 48 h ([Figures 7C,G](#F7){ref-type="fig"}). Albeit unexpected, we observed that inhibition of chemokines by BSCI did not significantly dampen neutrophil migration into the chorioamnion. Rather, increased neutrophil migration was observed in the BSCI+GBS group when compared to the GBS group ([Figures 7D,H](#F7){ref-type="fig"}), which may in part reflect the longer latency until delivery in the BSCI+GBS group as these animals did not develop PTL. Quantitation of the immunostained regions of the membranes revealed a significantly higher area of MPO+ stained cells in the amnion and chorion, but not the decidua, in the BSCI+GBS compared to the GBS only group ([Figures 8A--C](#F8){ref-type="fig"}). CD68 immunostaining was similar across groups in the amnion, chorion and decidua ([Figures 8D--F](#F8){ref-type="fig"}); although CD68 immunostaining in the decidua appeared greater in the BSCI vs. GBS and saline groups ([Figures 7I--L](#F7){ref-type="fig"}), this was not significant and driven mainly by staining in 2 of the 4 BSCI cases ([Figure 8F](#F8){ref-type="fig"}). These results suggest that although BSCI dampened the levels of certain chemokines, this did not impact neutrophil recruitment into the membranes. Despite the increase in neutrophil recruitment, BSCI was also unable to limit bacterial invasion of the amniotic cavity and fetal organs. {#F7} ![Quantitation of immunostaining for MPO and CD68 in the chorioamniotic membranes. The area of immunostaining for MPO **(A--C)** and CD68 **(D--F)** are shown in the amnion **(A,D)**, chorion **(B,E)**, and decidua **(C,F)**. The area of MPO immunostaining in the BSCI vs. GBS alone group was significantly greater in the amnion **(A)** and chorion **(B)**, but not decidua. No significant differences were observed in the area of CD68 immunostaining between the BSCI and GBS alone groups in the chorioamniotic membranes. The outlier in the saline group in **(D,F)** was a newer saline control performed as part of this study and the next two highest controls were previously published ([@B72]). \**p* \< 0.05, \*\**p* \< 0.01, \*\*\**p* \< 0.001, one-way ANOVA with Tukey\'s *post-hoc* correction.](fimmu-11-00770-g0008){#F8} We also investigated the effect of BSCI exposure on the fetal lungs ([Figures 9A--D](#F3){ref-type="fig"}), which are in direct contact with the amniotic fluid, a site of BSCI inoculation. Recruitment of neutrophils and CD68+ cells into the fetal lungs followed a similar pattern as in the chorioamniotic membranes with a significantly increased immunostaining area of MPO+ cells in the BSCI+GBS group ([Figures 9H,10A](#F9){ref-type="fig"}) vs. GBS alone ([Figures 9F,G](#F9){ref-type="fig"}, [10A](#F10){ref-type="fig"}) or saline ([Figures 9E](#F9){ref-type="fig"}, [10A](#F10){ref-type="fig"}). There was no change in the area of CD68 immunostaining in the BSCI compared to either the GBS or saline groups ([Figures 9I--L](#F9){ref-type="fig"}, **10B**). Notably, the GBS bacterial burden in the fetal lungs was similar or higher in the BSCI+GBS group compared to the GBS group ([Figure 6E](#F6){ref-type="fig"}). Therefore, increased neutrophil recruitment was not effective in reducing the GBS burden within the fetal lung at 3 days post-inoculation suggesting either ineffective bacterial killing or insufficient time for neutrophils to clear bacteria by the study endpoint. {#F9} {#F10} BSCI did Not Impact Neutrophil Function --------------------------------------- Our previous studies indicate that the GBS strain, used in this study, induced the formation of neutrophil extracelluar traps (NET) ([@B75]). Extracellular release of neutrophil contents such as neutrophil elastase and DNA has been associated with formation of NETS and bacterial entrapment ([@B83], [@B84]). Co-localization of neutrophil elastase and DNA in the chorioamnion of GBS infected animals previously revealed the presence of NETs ([@B75]). Therefore, we examined whether BSCI impacted formation of NETs induced by choriodecidual GBS infection ([Figure 11](#F11){ref-type="fig"}). We used human adult neutrophils as a model for how BSCI might impact maternal and fetal neutrophils. Immunofluorescence staining for neutrophil elastase indicates that while NET formation is seen in the GBS infected animals, there was no difference in NET staining density in the chorioamniotic membranes of the BSCI+GBS and GBS only groups ([Figure 11](#F11){ref-type="fig"}). {#F11} We also tested whether neutrophil function was impaired in the context of BSCI treatment. To measure production of reactive oxygen species (ROS), human adult neutrophils were pre-treated with di-hydro-rhodamine 123 (DHR) before exposure to GBS. In the presence of ROS, DHR is oxidized to mono-hydro-rhodamine (MHR) which can be quantitated using flow cytometry. The number of ROS positive cells was not significantly different between neutrophils exposed to GBS vs. neutrophils exposed to GBS and BSCI ([Figures 12A,B](#F12){ref-type="fig"}). Finally, GBS survival in the presence of adult human neutrophils was not significantly different as a result of BSCI exposure ([Figure 12C](#F12){ref-type="fig"}). Together, these data suggest that the increased bacterial burden observed in the BSCI treated animals was not due to a BSCI-mediated suppression of neutrophil function or bacterial killing, but may reflect a generalized impairment of the innate immune response and/or insufficient time to clear a rapidly progressing bacterial infection. {#F12} Discussion {#s4} ========== In this study, our primary objective was to determine if the BSCI could inhibit PTL and whether there was a beneficial or detrimental effect on bacterial trafficking in the amniotic cavity. Our results demonstrate that administration of a BSCI during an invasive microbial infection, led to the powerful suppression of uterine activity and a complete blockade of PTL at 3 days post-inoculation. Although the inhibition of PTL was remarkable, BSCI did not prevent bacterial trafficking to the amniotic cavity and fetal infection. The simultaneous progression of infection into the fetal compartment represents a serious adverse outcome for the pregnancy. Fetal bacteremia occurred in all of the experiments involving BSCI treatment, compared to only 20% of animals receiving GBS alone. In the BSCI+GBS group, there was a significant reduction in IL-8 in the maternal blood and amniotic fluid compared to the GBS only group; many other cytokines (e.g., IL-6, IL-1β, IL-7) were reduced in either the fetal plasma, lung, or brain compared to GBS alone. Although one might expect a reduction in neutrophilic infiltration due to the BSCI, there was a significantly greater quantity of neutrophils in the chorioamniotic membranes and fetal lungs of the BSCI animals compared to the GBS only group. Overall, the lack of uterine contractile activity in the BSCI+GBS group was remarkable, particularly in the context of the significant infectious burden in the chorioamniotic membranes, amniotic fluid, and fetal compartment. BSCIs are an attractive therapeutic class of drugs for the inhibition of PTL, because they have the capability to simultaneously block multiple cytokine signaling pathways ([@B51], [@B55]). BSCIs are unlike other anti-inflammatory drugs in that they do not antagonize the classical pathway of chemokines binding to their receptors, but rather they act as agonists by binding to cell-surface type-2 somatostatin receptors (SSTR2). A total of five sub-types of human SSTR have been cloned and detected in human tissues with splice variants SSTR2A and SSTR2B ([@B85], [@B86]). SSTRs (mainly SSTR2 and SSTR5) are reported to be highly expressed on inflammatory cells, including activated lymphocytes, monocytes, and endothelial cells ([@B52], [@B87]). Interestingly, it was shown that binding SSTR2 inhibits adenylyl cyclase and calcium entry by suppressing voltage-dependent calcium channels, which can affect several organ-specific functions (i.e., inhibiting secretion of glucagon and insulin in the pancreas, inhibiting neurotransmitter in the brain) ([@B88]--[@B91]). BSCIs are partial agonists of SSTR2, which stimulate signals that diminish pathways generated by the related chemokine receptors; without classical SSTR2 agonist effects (e.g., effect on growth hormone levels or the hypothalamic-pituitary axis) ([@B53], [@B54]). Partial agonism of SSTR2 has been hypothesized to dampen directional signals from the chemokine receptors leaving cells effectively "blinded" to the chemokine gradient. There are at least three possible explanations for why the BSCI treatment was so effective in preventing preterm labor ([Figure 13](#F13){ref-type="fig"}, conceptual model). First, we speculate that binding of BSCI to SSTR2 could have inhibited calcium entry by suppressing voltage-dependent calcium channels, which prevented the increase in intracellular calcium (\[Ca^2+^\]~i~) and thus precludes elevated \[Ca^2+^\]~i~ to act on the contractile filaments of myometrial smooth muscle cells, and generate uterine contractions. Secondly, it is plausible that the BSCI may have inhibited the expression or function of gap junction proteins, in particular Connexin 43. Propagation of an action potential can only be generated when individual cells are electrically coupled to allow elevated Ca^2+^ to spread between neighboring cells. In the myometrium, this coupling occurs through intercellular bridges formed by gap junction proteins (connexins) through which ions and certain small molecules pass. Connexin 43 is the most abundant connexin in the uterus and its expression is increased with term and preterm labor in all mammals ([@B92]). Finally, there was also a significant reduction in the major neutrophil chemokine IL-8 in the maternal plasma and amniotic fluid in the BSCI compared to the GBS only group; many other cytokines (e.g., IL-6, IL-1β, IL-7, TNF-α) were also reduced in either the fetal plasma, chorioamniotic membranes, lung, or brain tissues compared to GBS alone. As IL-8 infusion *alone* does not induce PTL in a pregnant rhesus macaque model ([@B93]), this suggests that a broader suppression of chemokines may be a promising approach to inhibiting PTL if microbial infections are properly diagnosed and treated. Altogether, these factors acting individually or in concert may explain why the BSCI+GBS group did not develop PTL. .](fimmu-11-00770-g0013){#F13} Interestingly, the cytokine pattern observed in the NHP model is remarkably different from what was observed in our murine model of LPS-induced preterm birth ([@B55]). In the NHP model, IL-7 was inhibited in the chorioamniotic membranes, as well as in fetal brain and fetal lungs. IL-7 is a hematopoietic growth factor, produced and secreted by neurons, epithelial, and other cells and is crucial for the maturation of lymphocytes. Further, pro-inflammatory cytokines IL-2 and IL-18 (both capable of regulating adaptive and innate immunity) were also inhibited in the fetal brain. In contrast to the NHP model with many cytokines in the AF and fetal tissues showing decreased levels, only maternal tissues exhibited diminished cytokines in response to BSCI treatment in the murine systemic LPS-induced model of preterm birth ([@B55]). This may be due in part to the fact that the BSCI was given to mice intraperitoneally, but not intra-amniotically and intravenously similar to the NHP model. In our previous study, the BSCI (BN83470) compound needed to cross two layers of syncytiotrophoblast cells (mouse placental barrier), which is unlikely due to the chemical structure of the BSCI. Therefore, we speculated that BN83470 was not able to cross the placenta, as we could not detect any effect of this drug on the chemokine profile in the amniotic fluid of mice systemically challenged with LPS. However, in the current study, we administered FX125L both intra-amniotically and intravenously with effects detected within fetal tissues. These data also highlight the many differences between the two models of PTL with the NHP model more closely resembling human pregnancy. Given our observations that the BSCI treated animals exhibited increased bacterial burden, it is possible that diminished chemotaxis and recruitment of leukocytes early during infection, might inadvertently allow for greater bacterial growth and burden. Alternatively, it is possible that the greater time achieved *in utero* due to BSCI administration and suppression of PTL allowed for a natural progression of infection that would have occurred normally in the GBS only group if given sufficient time; however, PTL in the GBS only group resulted in early delivery in nearly all cases, which truncated the experimental time course. It is also possible that a combination of greater time *in utero* and delayed or blunted leukocyte action contributed to the microbial invasion of the amniotic cavity seen in every animal in the BSCI+GBS group. Interestingly, the striking neutrophilic infiltration of the chorioamniotic membranes and fetal lungs in the BSCI+GBS group suggests that the BSCI despite blunting some inflammatory responses, did not ultimately prevent neutrophil recruitment; further, the increased neutrophil infiltration was not sufficient to contain bacterial growth or induction PTL. Our *in vitro* data indicate that the BSCI did not impact the microbicidal function of neutrophils. Therefore, it is likely that the suppression of certain chemokines by BSCI while delaying PTL promoted increased bacterial replication in the animals inoculated with GBS and treated with the BSCI. Whether a combination of BSCI and antibiotics might inhibit PTL and eradicate the infection is unknown, but represents an important question and could be an approach to translate to human pregnancy. A second and critical question arising from our results is the precise mechanism of PTL inhibition, which would best be studied by analyzing inflammatory and immune responses regionally within the myometrium and placental tissues. It is notable that suppression of IL-8 was a recurring finding in our cytokine analyses within the amniotic fluid and maternal plasma placental, which represents an attractive focal point for further experiments to define the expression of genes promoting parturition. Future studies to analyze the expression of genes promoting labor within the placenta and myometrial tissues, in particular, may address why PTL was absent following BSCI treatment despite a significant infection. The strength of our study is in the use of a unique chronically catheterized NHP model, which represents the closest animal model to human pregnancy. Humans and NHP share a number of features in pregnancy, which enables a direct comparison. These experiments in an NHP model afford a rare opportunity to determine how a PTL therapeutic can affect maternal-fetal immune responses, as well as the health of the fetus. Further, this model allows for serial analyses of maternal blood, amniotic fluid, and uterine contraction data over time, which is not possible in lower mammalian models. Our study was limited by the small number of animals within each group, which is typical of NHP studies where conservation is necessary for ethical reasons and experimental costs are typically 1,000--2,000-fold\> that of murine studies. This precluded us from studying the direct effect of BSCI on pregnant animals in the absence of infection. Important questions remain as to whether a therapeutic for PTL can safely inhibit labor without jeopardizing the health of the fetus. Our results strongly suggest that inhibition of PTL using a BSCI may be effective, but it is imperative for the obstetrician to rule out intra-amniotic infection for the safety of the fetus and the mother. Several new studies suggest that an intra-amniotic infection, in some cases, can be treated successfully with antibiotics ([@B94]--[@B98]). Further research is needed to determine if antibiotic therapy with an immunomodulator, similar to the BSCI, can eradicate an intrauterine infection and prevent PTL. As immunomodulators to prevent preterm birth move from the laboratory into clinical trials, it will be critical that intra-amniotic infections are properly diagnosed and treated with antibiotics to prevent progression of the infection. Data Availability Statement {#s5} =========================== The datasets generated for this study are available on request to the corresponding author. Ethics Statement {#s6} ================ The studies involving human participants were reviewed and approved by Seattle Children\'s Research Institute Institutional Review Board (protocol \#11117). The patients/participants provided their written informed consent to participate in this study. The animal study was reviewed and approved by the University of Washington Institutional Animal Care and Use Committee. Author Contributions {#s7} ==================== MC, LR, and KA drafted the initial manuscript. MC, NK, AB-R, OS, SL, LR, and KA critically edited the manuscript. MC, AO, T-YW, MD, SM, JO, AB, JM, LR, and KA provided technical assistance with the experiments. The funding was obtained by OS, SL, and KA. Conflict of Interest {#s8} ==================== The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We thank Dr. David Fox for the generous gift of the BSCI and the Histology and Imaging core at the University of Washington for assistance with immunostaining and quantitation. We also thank Shyala Nguyen for technical assistance. **Funding.** This work was supported by the National Institutes of Health Grant \#AI133976 (LR and KA), AI145890 (LR and KA), and the Burroughs Wellcome Fund (\#1013759, SL, OS, and KA). This study also used resources supported by the National Institutes of Health Office of Research Infrastructure Programs to the Washington National Primate Research Center (P51 OD010425). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. [^1]: Edited by: Nardhy Gomez-Lopez, Wayne State University, United States [^2]: Reviewed by: Thaddeus Golos, University of Wisconsin-Madison, United States; Elizabeth Ann Bonney, University of Vermont, United States [^3]: This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology

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Everyone knows Lambert’s. It’s the home of throwed rolls, the home of southern cookin’, the home sides on demand. It’s a great restaurant that thousands of people have come to love over the years. Lambert’s is a great restaurant. But, it’s not the only restaurant in Ozark. There are tons of great place to get your munch on in Ozark. There’s something for whatever kind of mood you’re in. Let’s take a look at 10 awesome locally-owned restaurants in Ozark! The town of Ozark just got a little taste of Europe close to home! David Pruneau, owner, operator, and chef of the new local restaurant, Little Danube, is bringing Eastern European Tradition to his community. Drawing heavily from his own upbringing in Europe, Pruneau hopes to expand the palette of many Ozarkians. Even the unique name of his new venture has an inspiring story behind it. Its meaning derives from the second-longest river in Europe and the events in 1987 in which David’s Father fought for his freedom by fleeing an oppressive political landscape of Romania. Davids love for his homeland and the Ozarks is is clearly present at Little Danube, making him a standout individual in the community. Maru brings Japanese cuisine to the culinary palettes of our neighbor to the south like no other restaurant does in the area. It features a robust sushi menu, too. Plenty of things to try each time you visit! Don’t get this restaurant confused with the now closed Mr. Yen’s. Yen Ching is still open and dishing out some sweet (and sour) meals to Chinese food lovers in Ozark. If you love Springfield-style cashew chicken, this is a great place to go. They also have a pretty tasty Imperial Chicken, Teriyaki Chicken and if you’re in an adventurous mood, try the hot squid & veggies! Yen Ching also has awesome decor and a great environment for dates or family dinners. Check it out! A contemporary Latin-American restaurant with locally sourced ingredients? YES PLEASE! Iguana Roja serves up unique and delicious dishes that are handmade by chef Brian Taylor and the staff. You might’ve heard that they won best wings at Wingapalooza, but they’re much more than just a wing restaurant. This place goes the extra mile to provide a wonderful dining experience. They’ll even make guac right there at the table. This place pulls out all the stops and some world famous musicians are taking notice! If that’s not enough, it’s also a great place to grab a frosty, local beverage! That’s right. Iguana Roja serves Mother’s brews on tap, along with a bunch of other unique kinds of oat soda. Check them out on their Thirsty Thursdays for 1/2 price draft beers! They don’t put fresh in the name for nothing. Salvatore’s makes everything from scratch and you can really taste the difference. They have a robust menu with sandwiches, paninis, burgers, salads, and of course, plenty of pasta dishes. Salvatore’s also has a great wine menu with plenty of choices and advice on which wines to have with what you’re ordering for dinner! If you’re looking for a cozy place to enjoy some breakfast, brunch or lunch, Market House is a great choice! It comes with the feeling of a classy bistro and the delicious menu of one, too! Market house makes things from scratch, which really gives you a taste of gourmet home cooking inspired by a Midwestern pizazz. Market House features soups, sandwiches, salads, quiches and plenty more. Some of their house specialities are pretty great, too. Try the Deputy Fire Stacker for breakfast. It’s a scrumptious combination of eggs, crispy hashbrowns and biscuits and gravy. Nothing like a hearty breakfast to start of a weekend! The ultimate bar and grill in Southwest Missouri, Big Whiskey’s has carved out a niche in Ozark as well! Serving up it’s famous appetizers, burgers, steaks and brews, it’s quickly become a go-to spot to grab some comfort food. It’s the perfect environment for a night on the town or the venue to watch a big game. You can’t go wrong with a Viking Burger or a New York Strip at any of Big Whiskey’s locations. Oh, and the fries…they’re really, really good. The East Coast has found a home on the Ozark square at Mama’s Style Kitchen. They make NY style pizza and cheese steaks inspired by Philadelphia. Their customer rave about the environment and service they receive and the quality of the food served. The menu is loaded with awesome dishes like Stromboli, Gyros, and Chicken Pesto to name a few. What an absolutely perfect place to have lunch in downtown Ozark. The Spring Creek Tea Room is an adorable spot for soups, salads, quiches and plenty more. The choices for dessert are equally amazing. These folks have the best cakes and pies in town. Just look at ’em! Not fast food. Just good food. Rosie Jo’s is fast, but it’s not a burger in a wrapper, this is Southern Soul food. This is a great place to get a pork tenderloin sandwich and a side of hand-cut fries or fried chicken and mashed potatoes with white gravy. If you’re looking for a heart meal and friendly environment, look no further! What’s your favorite Ozark restaurant? Let us know in the comments on Facebook!

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count Count InCommon-Law PleadingorCode Pleading, the initial statements made by a plaintiff that set forth aCause of Actionto commence a civil lawsuit; the different points of a plaintiff's declaration, each of which constitute a basis for relief. InCriminal Procedure, one of several parts or charges of an indictment, each accusing the defendant of a different offense. The term count has been replaced by the word complaint in the Federal Rules of Civil Procedure and many state codes of civil procedure. Sometimes count is used to denote the numbered paragraphs of a complaint, each of which sets out an essential element of the claim. Federal and state rules of criminal procedure govern the standards that a criminal count must satisfy in federal and state criminal matters. count n. each separate statement in a complaint which states a cause of action which, standing alone, would give rise to a lawsuit), or each separate charge in a criminal action. For example, the complaint in a civil (non-criminal) lawsuit might state: First Count (or cause of action) for negligence, and then state the detailed allegations; Second Count for breach of contract, Third Count for debt, and so forth. In a criminal case each count would be a statement of a different alleged crime. There are also so-called common counts which cover various types of debt. (See: common counts) count a paragraph in an indictment containing a distinct and separate charge. COUNT, pleading. This word, derived from the French conte, a narrative, is in our old law books used synonymously with declaration but practice has introduced the following distinction: when the plaintiff's complaint embraces only a single cause of action, and he makes only one statement of it, that statement is called, indifferently, a declaration or count; though the former is the more usual term. 2. But when the suit embraces two or more causes of action, (each of which of course requires a different statement;) or when the plaintiff makes two or more different statements of one and the same cause of action, each several statement is called a count, and all of them, collectively, constitute the declaration. 3. In all cases, however, in which there are two or more counts, whether there is actually but one cause of action or several, each count purports, upon the face of it, to disclose a distinct right of action, unconnected with that stated in any of the other counts. 4. One object proposed, in inserting two or more counts in one declaration, when there is in fact but one cause of action, is, in some cases, to guard against the danger of an insufficient statement of the cause, where a doubt exists as to the legal sufficiency of one or another of two different modes of declaring; but the more usual end proposed in inserting more than one count in such case, is to accommodate the statement to the cause, as far as may be, to the possible state of the proof to be exhibited on trial; or to guard, if possible, against the hazard of the proofs varying materially from the statement of the cause of action; so that if one or more or several counts be not adapted to the evidence, some other of them may be so. Gould on Pl. c. 4, s. 2, 3, 4; Steph. Pl. 279; Doct. Pl. 1 78; 8 Com. Dig. 291; Dane's Ab. Index, h.t.; Bouv. Inst. Index, h.t. In real actions, the declaration is most usually called a count. Steph. Pl. 36, See Common count; Money count. All content on this website, including dictionary, thesaurus, literature, geography, and other reference data is for informational purposes only. This information should not be considered complete, up to date, and is not intended to be used in place of a visit, consultation, or advice of a legal, medical, or any other professional.

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Q: Stopping Raspberry Pi display sleep I'm using my raspberry pi displayed on a tv through HDMI. It boots up into the terminal and is fine, however, when I leave it for a few minutes, the display goes to sleep. I'm using an application called conspy to control the console from another computer, but the display does not wake once I start typing (I can still ssh and everything else). Is there a command that will wake the display or just prevent it from sleeping? I'm not using the GUI, just the console it boots into. Edit: I sometimes use the standard video output as well, so a fix for either hdmi or video will be appreciated. A: You could try you@yourpi:~$ setterm -powersave off -blank This should prevent the screen from sleeping for the current session. Put it in your .bashrc to make it permenant.

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Applicant claims priority under 35 U.S.C. xc2xa7119 of German Application No. 101 18 886.2 filed Apr. 18, 2001. 1. Field of the Invention The invention relates to a device for optically scanning a moving web of material. The device is formed by at least one CCD camera directed against the material web. The camera includes a lens and a CCD receiving element scanning an area of the material web. The invention also relates to a method for adjusting the moving web of material. 2. The Prior Art A device for scanning and analyzing the surface of a moving web of material is known from German Patent No. 37 09 500 C2. This device is formed by a CCD camera, which is directed against the web of material. The CCD camera includes a lens and a CCD receiving element. To completely analyze the surface of a very wide web of material, a plurality of such devices must be mounted next to one another. It is important in this connection that the scanned areas of the CCD receiving elements are coordinated so that they are exactly aligned with each other. A device for measuring the speed of a jet of fluid and the detected length in a combined manner is known from German Patent No. 32 00 508 C2. From these two measured quantities, it is possible to determine the volume flow over the cross section of the jet. For this purpose, the devices include a receiving element that is formed by a plurality of diodes. Light reflected by the jet of fluid acts upon the diodes via a lens and a beam divider. By displacing the receiving element axially relative to the lens, it is possible to vary the area of the jet of fluid detected by the receiving element and to measure the illuminated area of the fluid. An object of the present invention is to provide a device for optically scanning a moving web of material that permits a simple and highly sensitive adjustment of the area scanned by the CCD camera. Furthermore, the aim of the invention is to specify a simple method for adjusting the scanned area. In accordance with the invention, these and other objects are accomplished by providing a device for optically scanning a moving material web formed by at least one CCD camera directed against the material web. The camera includes a lens and a CCD receiving element scanning an area of the material web. For adjusting the scanning range of the device, a template can be fixed in the area of the plane of the material web. The template has at least one structure extending transversely in relation to the direction of movement of the material web, which is detectable by the CCD camera. The CCD receiving element can be adjusted in relation to the lens transversely to its optical axis by at least one drive. The drive is actively connected with a controlling device responsive to signals from the CCD camera. The template may include a digital coding detectable by the CCD camera. This coding is formed by a sequence of bits, in which any desired partial sequence of an xe2x80x9cnxe2x80x9d number of directly successive bits of the sequence supplies a clear n-bit code for the absolute position of the CCD camera along the template. The device as defined by the invention serves for optically scanning a moving web of material. In particular, the device serves to control the surface of the moving web of material optically so as to detect any weaving, printing and dying defects. The device may also be used to detect the marginal edge or a printed marking of the web of material in order to detect the course along which the material web is moving. The device is formed by at least one CCD camera that is directed against the web of material and includes a lens and a CCD receiving element. Because the web of material is moving past the camera, the CCD receiving element may take the form of a line receiving element, with all light-sensitive photodiodes in the element arranged next to each other. By generating a plurality of images of the line that are offset in terms of time, it is possible to obtain a complete image of the surface of the web of material due to the movement of the material web. In particular in connection with wide webs of material, the range scanned by one single CCD camera is not adequate for detecting the surface of the web of material over the entire width of the material. Several CCD cameras generally are employed for that reason that are distributed over the width of the web of material. These CCD cameras have to be coordinated with each other. Specifically, their scanning ranges will be aligned with one another, so that the individual CCD cameras combined will supply a through-extending scanning line extending transversely in relation to the direction in which the web is running. In this way it is assured that the images generated by the individual CCD cameras can be correctly assembled to obtain an overall image, so that defects located in the area of transition between two CCD cameras can be correctly detected as well; so that the CCD cameras may scan the web of material without any gaps, it is important that the scanning ranges are correctly adjusted to one another, with a minor overlap, and to a narrow marking illuminated along the web of material. But even if only one single CCD camera is used, it is important that the CCD camera be positioned so that the area of the material web illuminated along a line is located within the range scanned by this CCD camera. To permit very fine adjustment of the areas of the web scanned by the CCD cameras, in accordance with the invention, the CCD receiving element of the CCD camera is adjusted transversely to the optical axis of the lens of the camera. In this way, adjusting the relatively lightweight CCD receiving element alone is sufficient without also having to drive the lens along with the help of an automatically focusing (xe2x80x9cautofocusxe2x80x9d) control device that may be installed. Because the lens of the CCD camera is not driven with the CCD receiving element, the CCD receiving element will be shifted away from (or to the outside of) the optical axis of the lens; however, this shifting is acceptable, particularly for finely adjusting the scanning range. So that the CCD cameras can be correctly aligned, a template can be fixed at the level of the plane of the material web with at least one structure aligned transversely to the direction of movement of the material web. In particular, the template is provided with a line extending transversely in relation to the direction in which the web of material is moving. This line supplies an adequately high optical contrast vis-à-vis the rest of the template, so that this line can be easily detected by the CCD camera. So that the adjustment process can be carried out in the simplest manner possible, the CCD receiving element is set by drives that are actively connected with a controlling device. This controlling device is influenced or regulated by the signals emitted by the CCD receiving elements. In this way, the CCD receiving elements are automatically adjusted to the structure on the template, so that adjustments are executed quickly and always with a constantly high quality. So as to achieve an exact alignment of the scanning ranges of the CCD camera, it is sufficient to displace the CCD receiving element in the direction in which the material web is running, as well as transversely to the optical axis of the lens. Any additional transverse displacement of the CCD receiving element relative to the moving direction of the material web is unnecessary because these alignment errors can be taken into account by selecting a suitable amount of overlap between the CCD cameras. So that the individual image lines generated by the CCD receiving elements can be easily assembled to form an image, it is important that the receiving elements be aligned in parallel with one another. However, the overall structure of the holding devices for mounting the CCD cameras contain manufacturing tolerances with respect to the alignment of the receiving line of the CCD receiving element. Such tolerances lead to a deviation of the alignment from the ideal parallelism that is relevant to the evaluation of the received image. It is therefore favorable if the CCD receiving element is supported so that it can be rotated about an axis of rotation that extends approximately parallel to the optical axis of the lens. Turning the CCD receiving element by one to three degrees generally suffices because the aforementioned manufacturing tolerances are minor. This arrangement enables the light source to emit a particularly narrow band of light, yet nonetheless assures that the CCD cameras will detect only the illuminated section of the material web. So that the required adjustability of the CCD receiving element can be realized in the simplest possible way, it is advantageous if the CCD receiving element is mounted on a revolving table that is rotatably supported on a sliding carriage. In this way, the CCD receiving element can be both rotated and displaced transversely in relation to the optical axis in a very simple manner while nonetheless keeping the mechanical expenditure at a low level. To achieve a precise displacement or turning of the CCD receiving element, it is important that the revolving table or the sliding carriage be driven with as little play as possible. Since the driving of the revolving table or sliding carriage requires gears that are always subject to play, it is favorable if such play is excluded by means of at least one spring engaging the revolving table or the sliding carriage. So as to assure that the revolving table and the sliding carriage are driven in a simple and precise way, it is favorable if two spindle nuts engage the revolving table. Each spindle nut is engaged by a threaded spindle driven by a servo-motor, preferably an adjusting or stepping motor. By synchronously turning the two threaded spindles in the same sense of rotation, the sliding carriage is displaced along a guide without rotation of the revolving table. On the other hand, by synchronously turning the two threaded spindles in opposite directions of rotation, the revolving table is turned without moving the sliding carriage. When the revolving table is turned, the threaded spindles do not perform a pure sliding movement but are slightly pivoted at the same time. Because the required angles of rotation for turning the revolving table are very small, to simplify the structure of the device, the threaded spindle may be designed to pivot to a limited extent in the nut of the spindle or in the servo-motor. In this way, no additional means is necessary to compensate for the pivotal movement of the threaded spindle. Preferably, the threaded spindle engages the nut of the spindle or the servo-motor with play, so that the required pivotal movement of the threaded spindle can be absorbed by the spindle. By biasing the revolving table or sliding carriage in one direction with a spring in the proposed manner, such play will have no bearing on the precision of the movement of the CCD receiving element. So that the scanning ranges of the individual CCD cameras can be adjusted to each other with a slight, preset amount of overlap, it is important to detect the absolute position of the individual CCD cameras on the web of material. For this purpose, the template is provided with a digital coding that is detected by the CCD receiving element. The coding consists of a sequence of bits that are scanned by the CCD receiving element. Because too much time and effort is required for start-up by first focusing the individual CCD cameras on a zero point of the measurement range, the coding contains an xe2x80x9cnxe2x80x9d number of bit codes that clearly reflect the absolute position of the CCD receiving element. It is important in this connection that any desired partial sequence of an xe2x80x9cnxe2x80x9d number of successive bits directly following each other supplies a clear n-bit code. In this case, reading of the xe2x80x9cnxe2x80x9d number of bits can be started at any desired point within the sequence while nonetheless assuring that the code that has been so read is suitable for clearly determining the position of the CCD receiving element. In this way, detecting the xe2x80x9cnxe2x80x9d number of successive bits of the sequence is sufficient to determine the position, so that only a very small portion of the sequence of bits has to be evaluated. The method as defined by the invention has been successfully tested for adjusting the device specified above for optically scanning a moving web of material by means of at least one CCD receiving element. In this process, a template is first fixed in the area of the plane of the material web. The template has a structure that extends transversely in relation to the direction in which the web of material is moving. This structure can be detected by the CCD receiving element. The structure is preferably formed by a printed line that extends crosswise in relation to the direction in which the material web is moving. The photodiodes of the CCD receiving element generate signals that are dependent upon whether these photodiodes detect the structure or an area of the template located next to the structure. For example, the structure may be formed by a white line that is imprinted on an otherwise black template. The light reflected by the white line generates in the respective photodiodes a photo-signal, whereas the black surface of the template results substantially in a zero level on the receiver diodes. The signals generated by the photodiodes are evaluated as to which ones of the photodiodes detect the structure and which ones detect the areas located next to the structure. Depending on the result of the evaluation, the CCD receiving element is adjusted so that it is aligned with the structure. This adjustment is carried out automatically without any activity required by the operating personnel. The adjustment process is carried out rapidly with no change in the high quality of the adjustment. After the adjustment has been made, the CCD receiving element is maintained in the adjusted position. With the CCD receiving element in the adjusted position, the template may be subsequently removed in order for the CCD receiving element to scan surface structures of the moving web of material. So that the CCD receiving element can be adjusted as precisely as possible, it is necessary to provide the structure applied to the template with a relatively narrow configuration. The consequence thereof, however, is that before the adjustment process starts, the structure most likely will be disposed completely outside of the detection range of the CCD receiving element. In that case, it is advantageous if the CCD receiving element is first displaced transversely to the structure until it is located within the scanning range of at least one of the photodiodes. Following this rough adjustment, clues at least can be obtained from the signals generated by the photodiodes about the possible configuration of the structure of the template in relation to the CCD receiving elements. Such clues are important for the further adjustment of the CCD receiving element. In particular, the point where the structure on the template intersects the scanning line of the CCD receiving element can be determined by evaluating the position of those photodiodes within the CCD receiving element that supply a corresponding active signal. Based on the number of the photodiodes that supply an active signal, it is then possible to deduce the angle that is enclosed by the two aforementioned lines between each other. To obtain an adjustment algorithm that is simple yet nonetheless efficient, it is favorable if the CCD receiving element is turned and displaced so that the number of photodiodes detecting the structure of the template is maximized in each case. This maximization specification generally suffices for aligning the CCD receiving elements with the structure with a finite number of steps. The CCD receiving element is preferably turned and displaced in an alternating manner so that the two modes of adjustment will exert the smallest possible influence on each other. By rotating the CCD receiving element, the greater the number of receiving elements detecting the structure, the smaller the angle between the two receiving elements will be. If the axis of rotation of the CCD receiving element fails to coincide with the range of detection of the CCD receiving element, rotating the CCD receiving element will result in an apparent displacement of the structure in relation to the photodiodes. Such an apparent shift is corrected between each two rotations by a corresponding displacement of the CCD receiving elements. Finally, to improve the efficiency of the adjustment algorithm, it is advantageous if the CCD receiving element is displaced so that the template structure extends approximately symmetrically through the axis of rotation. If the CCD receiving element is arranged approximately symmetrically with respect to the axis of rotation, it is generally sufficient if the axis of rotation is shifted so that the photodiodes supplying an active signal will be distributed approximately symmetrically around the center photodiode of the CCD receiving element. What is achieved with this measure is that the axis of rotation is approximately located within the range of detection of the CCD receiving element. In turn, the consequence thereof is that after the CCD receiving element has been turned, it has to be displaced only very slightly, so that the adjustment process will lead to an overall optimal adjustment of the CCD receiving element in just a few adjustment steps. The CCD receiving element may also be turned and displaced at the same time. In that case, maximizing of the number of photodiodes detecting the structure will have a bearing substantially only on the rotation of the CCD receiving element. Any detected asymmetry of the signals generated by the photodiodes will effect a displacement of the CCD element that will compensate for such rotation.

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Originally written December 8. Yesterday was a good day. Woke up when I felt like it; opened Christmas presents with my fiancée Ellen; lounged around all day munching candy, listening to Christmas carols and doing a puzzle; had the traditional Christmas dinner of spaghetti carbonara; made and ate an entire batch of chocolate chip cookies; and fell asleep watching “It’s a Wonderful Life.” “But it’s not yet December 25!” you exclaim. “This is madness!” Madness? THIS. IS. CHRISTMAS! As you may have realized, I’ve been re-watching the movie “300” and enjoying the story of the ragtag band of Spartans taking on the hordes of Persians trying to conquer them. Though they ultimately lost the battle, it is the struggle against a seemingly insurmountable force that makes the combat so entertaining. That, and the seething badassedness of King Leonidas and his warriors. For the Lehmans, 2008 proved a similarly difficult task, but you’ll be happy to know we emerged victorious. You may be wondering why I’m celebrating Christmas before Christmas. I could tell you it’s because I’ve been living in Germany from October until December 20, but then you’d just ask why I’m living in Germany, so let me explain by telling you about my year. I spent as much of ’08 as possible staying out of Los Angeles, my disdain for the traffic, the people, and even the constant sunshine getting the better of me. Through my job as a supervisor with SkyWest Airlines, it cost literally nothing to fly, so February I went to Orlando, March I went to Thailand, April was Phoenix, May I saw Vegas, July I outdid myself with Salt Lake City then Dallas then Des Moines, and August found me in Colorado for our family vacation (more on that later). So when October came, I decided it was time for a break, quit my job, and moved to Germany. Okay, so it wasn’t that simple. Ellen got a Fulbright scholarship to teach English in a little town near the Swiss border called Meersburg, so I took the opportunity to live out here until the end of the year with almost no expenses and even fewer commitments. We’ve taken a couple short trips to Vienna and Slovakia, as well as day trips throughout southern Germany, but for the most part I’ve been working on independent writing and projects. For more on that, check out misusingecards.blogspot.com. But right before Germany, I flew up to Portland and asked Ellen to marry me, to which she of course said “Hell yes.” To victory! To save up for my life abroad, Daniel let me crash on his couch for the summer, effectively cutting my cost of living by about a grand. Plus, it gave me the chance to see how the other half lives. He still works at WaMu, he’s still going to school for his Master in Psychology, and he’s still surfing, despite a small mishap where his board attacked him and gashed open his face. But he just shouted, “Nobody makes me bleed my own blood!” and got back on it. Some new things he’s doing: worrying about whether or not he’ll still be working at WaMu tomorrow; preparing to do his practicum for school, meaning actual psychology stuff like “it’s obvious you’re subconsciously in love with your dog and this love is manifesting itself in the brightly-colored ties you wear”; and accompanying me to the great state of Iowa for a visit with our old friend Becky, where we drank beer out of Das Boot and saw a Moose on the Loose (it’s exactly what you think it is, as long as you think it’s a store full of Midwestern doodads). It wouldn’t be a year in the life of Daniel without some risky behavior, so in September, he and I drove up north to Whitney Portal, where we met up with Dave (dad), Roger (uncle) and Dennis Reibold (friend) and hiked all the way up to the 14,505 ft summit of Mt. Whitney, the tallest peak in the lower 48. It was breathtaking, truly. We could barely breathe. Then just a week later, Daniel took me hang gliding for my 24th birthday at Dockweiler Beach in LA, and we ran up and down hills with wings attached, trying desperately to fly. Each time Daniel gripped the glider, and each time something went slightly awry. Finally, the last attempt: his hands were steady, his aim—perfect! And by the end, we each caught at least 10 feet of air for at least 5 seconds. By now you must be wondering: did Dave make it down off the mountain alive? Surprisingly, yes, and so did Roger and Dennis. For a few old fogies, they really held their own as mountain men, especially considering that only 1 out of every 3 people who attempt to climb to the top of Whitney don’t make it. (Don’t make it as in can’t get to the top, not as in die.) We each just put one foot in front of the other, trudging every step of the way, even when darkness came and we were still on the mountain. But it wasn’t fear that gripped us, only a heightened sense of things. And yes, I may have dropped in that statistic just to brag, but can you blame me? Aside from several practice hikes, Dad spent the rest of ’08 in the usual manner: deaconing, real estate brokering, and music group singing with Michelle (mom). He took a few trips, including one with Michelle and I to Orlando for the annual Century 21 convention, and we enjoyed an air boat ride through an alligator infested swamp and a day at the Experimental Prototype Community of Tomorrow (or EPCOT, for you philistines out there). He also celebrated being cancer free for two years, and he took on a post as spiritual advisor for St. Vincent De Paul Council of Northern California. In his position, he is sure to usher in a future brighter than anything we can imagine. With their traveling buddies, the Reibolds, Dave and Michelle went to Arizona in April to see our good friend Corry, and I tagged along for a couple days. We all went to see feathered dinosaurs at the Mesa Natural History museum, then I flew back for work and the rest of them did all the stuff I didn’t care about like botanical gardens and Sedona. A couple months later, Michelle met up with me in Salt Lake City because I had a free hotel room for a work conference, so she spent a couple days exploring and we enjoyed some good old fashioned Mormon culture. And because they have a million timeshares and had to use one up, Dave and Michelle just spent a week in San Francisco pretending they haven’t been there a bunch of times by riding cable cars, taking a Bay Cruise, and visiting Golden Gate Park, Fisherman’s Wharf, the Ferry Building, Pier 39, the Aquarium, China Town, Union Square, and St. Mary’s Cathedral. Other than excessive travel, mom kept herself busy trying to stay afloat in the midst of real estate craziness, but with her “never retreat, never surrender” attitude and the help of His Holiness the Deacon Dave, she managed to close enough deals to keep putting food on the table. Since real estate wasn’t so busy, she also took the opportunity to get elected to the Board of Directors for the Sacramento Association of Realtors, as well as be reappointed to the Deacon Advisory Council for a second 3 year term. Who really knows what either of those do, but it’s important to note that she, too, is sure to usher in a future brighter than anything we can imagine. Of course, what would a year be without a Lehman family vacation? Worthless, that’s what. Last December, just before Christmas, we all flew down to Cancun for a week full of ancient Mayan ruins and deadly ball games, aquatic zoos with pooping pumas (pictures available online), and a tour guide named Jesus that constantly reminded us to “trust in Jesus.” But that was last year’s vacation that just didn’t make it into the newsletter before deadline. This year, we stayed closer to home by getting Rocky Mountain high in Breckenridge, Colorado. We drank some brews at the Coors factory in Golden and did a lot of hiking. Dave, Daniel and I drove out to Quandary Peak, where we did what we were trained to do, what we were bred to do, what we were born to do. Three hours and several meetings with mountain goats later, we reached the top, and enjoyed the view that only 14,265 ft can afford. I couldn’t get an entire week off, so I had to fly back early and missed the second hike of 12000 ft up to Black Powder Pass. I can’t imagine anything being fun that doesn’t involve the possibility of blacking out from lack of oxygen and falling thousands of feet to one’s death, but the pictures made it seem like Dave, Michelle and Daniel had a good time. So all in all, Colorado was good to us. And that’s our story for 2008. We faced some challenges, but only the hard, only the strong may call themselves Lehmans, and we triumphed in the end. As for me, I’ll be headed home December 21 just in time to enjoy my second Christmas of the month, then the 25th I get to have a third. With three days of gifts and celebration, I feel like I’m three-eighths of the way to becoming a Jew. However many days of festivities you and your family have, we Lehmans hope they’re everything you wish for this season. And if there’s one piece of advice I can leave you with, it’s this: Prepare for glory! Love, Dave, Michelle, Daniel and Mark (me) P.S. For Michelle’s website, visit www.fairoakshomes.net. Dave and Daniel can be reached via e-mail at [email protected] and [email protected], respectively. And we are such a high-tech family we can all be found on Facebook and LinkedIn. I leave tomorrow morning early to take the bus to the train to the plane to Dublin, Ireland, where I stay until Sunday morning and fly out to San Francisco and get in just in time for Christmas with the Lehman extended family. If I make it through this weekend alive and in one piece, I'll write observations on my final days in Germany. My time here is almost up, as I leave on Saturday to head back home in time for Christmas, and it seems Europe has decided to say "good riddance" by making my money worth so much less. When I arrived three months ago, the exchange rate was around $1.25 = 1 euro, and it stayed pretty steadily there until last week, when it started rising. Since then, it's been going up by about 3 cents per day, and today it's at $1.44 = 1 euro. I just finished doing 51 straight pushups, and I’m only halfway to my goal. When I arrived in Germany a couple months back, I was determined to improve on some areas of my life that had been lacking, one of which was exercise. So I started doing some pushups, doing my own routine and feeling good. Then I heard from my friend Mindy about this thing called the Hundred Pushups Challenge, and I knew it was my destiny. I’ve just finished Week 5 of a 6-week program, and at the end of this week, I’m supposed to be able to do 100 pushups in a row. Somehow, I don’t see that happening, since it’s taken me 5 weeks to go from 25 pushups to 50. But if it takes another 5 or even 10 weeks, I’m going to hit that 100 goal. There are about 100 stairs total, right around the corner from our apartment here, and at one point I was going up and down those bad boys about 16 times in a 30-minute session. It was quite a workout, plus I got the added bonus of having all the German people using them to get from the bottom to the top or vice versa give me weird looks. Three months into my stay, though, I’m used to weird looks from Germans. I took this little video the other day to further illustrate the magnitude of this task: Sadly, since it’s been snowing and raining, the steps have iced over and are basically a death trap, so I’ve discontinued that part of my workout. To sum up, when I get out of bed in the morning, something new hurts every time. (The music in the video, if you're wondering, is a friend from high school, Eric, playing the theme song from the old Nintendo game "Mike Tyson's Punch Out." Download it at http://ericslittleshack.tripod.com/.) So much so that I pulled out my old Apple //e emulator and played some Oregon Trail. I decided to be a carpenter; being a banker afford way too much money and not enough difficulty, but the life of a farmer is harsh and often unsanitary. Me being an impatient man, I bought the maximum oxen I could (18) and was plugging along at 30 miles a day. Just after crossing the first two rivers, a thief came in the night and stole 16 oxen. 16! How could all five of us in my party have missed the sounds of 16 oxen leaving camp?! Well, our pace slowed considerably and a few of us came down with some nasty diseases (Buddha got typhoid, Jesus got the measles). Then Ellen caused all kinds of problems when she broke her arm, then got lost for 4 days, then broke her leg, then got cholera, then got lost for another 5 days. You'll be happy to know, though, that we all made it alive and in fair health to the beautiful Willamette Valley. Since I was in a nostalgic mood, I did a quick Google search and found another classic: Where in the World is Carmen Sandiego. I had a few missteps when first I caught up to the thief and had forgotten to issue a warrant, but got my groove back and was busting heads quick. However, something I noticed disturbed me. The detective (me, I guess) sleeps from 11pm until 9am. It seems the game makers were trying to teach kids that 10 hours of sleep is very important, even when on the hunt for a major criminal who just stole the elevator out of the Eiffel Tower (I’m not making this up). Lesson learned. I, however, would rather put in the extra effort and guard the safety of all other famous monuments’ elevators. I don't even remember how I found this game, but every time I use the internet now I find myself on their site, playing it. It's called Flood-It. Instructions from the site: The object of the game is to flood the whole board with one color in less than 25 steps. You start from the top left corner and progress by selecting one of the colored balls on the left. When you change your current area color, every adjacent square with the same color also changes, that way you can flood other areas on the board. The snow continued to fall overnight, covering the landscape in another couple inches of fresh powder, and Ellen and I took advantage. But before I detail our adventures, let me relay a short story to you of a budding architect and a horrible (but also maybe brilliant) Christmas present. When I was about 10 years old, I decided it was time that I started giving my extended family Christmas presents. Having no stable source of income other than a meager $3 a week allowance, I found the most economical place to shop would the the old 98 Cent Clearance Center, where everything was 98 cents. (I believe they’ve since been bought out by the dollar tree, where everything costs $1. Inflation is tough.) The woman in the family all got lovely 98 cent earrings, and the men got anything from mugs to cassette tapes of awful music, and everyone feigned gratefulness. However, my two cousins I idolized, so I wanted to make something special for them. One cousin, Todd, had been attending the US Military Academy at West Point, so I took a pioneer wagon that I had made out of popsicle sticks in cub scouts, painted it camouflage, and then led him on a treasure hunt to find it. When he finally did, he certainly had little idea of what to say, but acted like it was the best gift in the world and was able to fool me. I felt bad, though, because I only had one popsicle stick creation and two cousins. So, for my cousin Jeff, I took the remaining popsicle sticks and made the best possible structure: a wall. Of course, even my 10-year-old mind knew a popsicle stick wall wasn’t much of a Christmas present unless it was marketed correctly, so I painted in large red letters on it “The Wall 2000.” You can probably guess that he loved it; so much so, in fact, that he still talks about it as the best present he’s ever gotten. (A close second is another of my masterpieces: a beer can wrapped with a home-printed label saying “can of whupass.”) So without further ado, I present “The Wall 3000.” Sadly, because there were only about 5 inches of snow, we had to resort to trick photography. Here’s how high “The Wall 3000” is. * * * We also had another baby. Looks like our snowman has a new baby sister. Of course, sometimes the classic is drizzled with chocolate syrup, or sprinkled with carmelized sugar on top. In other words, Nutella filled awesome, drizzled with drops of liquid and/or sprinkled awesomeness. And lastly, the football-shaped croissant. Very similar to the classic, this one usually comes packaged and sold in grocery stores. Not amazing, but a solid dessert. Not into French pastries? That's okay, I saved the best for last. I always thought Rice Krispie Treats Cereal were the most amazing cereal ever in the world. (Breaking News: I was searching for a picture of Rice Krispie Treats Cereal to put on here, and found that they are sold on Amazon.com. I know what I want for Christmas.) I thought wrong. Nougat Kissen These are small chocolate squares filled with a Nutella-like hazelnut/chocolate filling. I get a small stomach ache every time I eat them, and then I black out from happiness overload. I never expected I would like chocolate in Germany so much. When I was a kid, every time I was in the cake mix aisle, I would look at the German chocolate cake mix and be supremely disgusted because it looked like vomit. To this day, I still think it does. I'll spare you by not posting a picture, but click here to see one if you're curious. * * * And thus ends my dessert manifesto. Now you can see why 8:30-9:00 pm has become my favorite time of day. I'm trying again. Before getting on the plane to come to Germany, I started reading W. Somerset Maugham's "Of Human Bondage" on the recommendation of a friend from work, a spunky English lady who raved on and on about it. After reading about 50 pages and still not having any notion of who any of the characters were or why I should care, I tossed it aside and picked up "Twilight" instead. And then I grabbed "How Animals Have Sex" from a British bookshop in Vienna. Finally, I'm trying again. No more animal sex or vampires, it's time for some real, adult fiction. And not "adult fiction" as in erotica, either, because I'm sure after 50 pages of erotica I would know exactly what was happening in almost-medical detail. Although with a title containing the word "Bondage," I don't blame you for thinking that way. Incidentally, I'd advise against Googling that book; putting "bondage" in a Google search doesn't return the most wholesome results. I can assure you, Ellen and I didn't see anything of that sort around here. Christmas markets start in towns all over Germany on Thanksgiving weekend, and we visited three different ones in three different towns. Instead of clamoring over neighbors for the last copy of "WALL-E" or throwing a few elbows to try to grab a cheap digital camera, Germans suffered through the cold to graze through outdoor craft fairs, sipping alcoholic gluhwein and eating pizzas and bratwursts and kebabs, singing and dancing traditional German carols. And while I didn't actually find anything good to buy at any of those markets, they were still a good old time and I was able to do some present shopping on Amazon to snag some decent deals without risking my life or my health. We'll be heading to Nuremberg this coming weekend to check out their market, which is supposed to one of the best in the country, so hopefully I can snag some cool stuff there I've seen them live in LA a few times, so if anyone has a chance, you should definitely check them out. Then just today I got an e-mail update from them with another glorious Christmas video, this time featuring a whole cast of stars like Doogie Howser / Barney Stinson / Neil Patrick Harris, Meg Ryan, Faizon Love (Dr. Turk from "Scrubs"), etc.

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[Computer simulation of the isolated lesion of tibiofibular an syndesmosis using the finite element method]. The aim of this study was to construct a computed simulation of an isolated lesion of tibiofibular syndesmosis on typical clinical range of value. The analysis was made using the method of finite elements with a simplified plain model of a bone and assuming material of bone and ankle joint as isotropic and homogeneous. The distraction processes were modelled by external generalized forces. The computed programme ANSYS was used. For evaluation obtained was the computed image of changes of anatomy in relation to forces.

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[On the activity of the Japanese Research Society for Surgical Cancer Immunology]. The recent progress in immunology has shown depression of immunological competence, especially cellular immunity in tumor bearing host due to anesthesia, blood transfusion and operative trauma itself and disappearance of host's concomitant immunity caused by removal of primary tumor, resulting the enhancement of growth of residual tumor or metastatic foci. The prophylactic lymph node dissection in cancer operation must be reconsidered through immunological studies of lymph node as immunological surveillance system. Splenectomy combined with the operation of stomach cancer must also be reconsidered. Therefore, the main aims of this society are to suppress the negative aspect in connection with the cancer operation by means of immunotherapeutic approach and to prevent the recurrence and/or metastasis of cancer. Research society, met for the first time in 1980, and has since discussed the following main themes at 9 occasions of meetings up to 1988: 1. Pre- and postoperative immunological competence in cancer patients. 2. Surgery and immunological competence for cancers. 3. Antitumor activity of regional lymph nodes. 4. Splenectomy and tumor growth. 5. Surgical treatment and immunochemotherapy. 6. Serum immunosuppressive factors in cancer patients. 7. BRM and immunotherapy. 8. Diagnosis and treatment of cancer using monoclonal antibody. 9. Cancer treatment using IL-2, TNF. 10. Host defense factors and cancer metastasis. In addition, 14 educational lectures dealing with recent immunology have been given by immunological specialists.

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A survey conducted by Pew Research Center shows that the 1.3 million asylum seekers that entered Europe in 2015 are overwhelmingly male– not widows and orphans as President Barack Obama claimed last year. Pew’s research shows that four out of 10 refugees in Europe are young men, aged 18 to 34. Approximately three-fourths (73 percent) of refugees entering Europe in total were male, while 53 percent of all refugees were young adults between the ages of 18 and 34. Individuals hailing from war-torn countries making up a large portion of all refugees were also overwhelmingly male. Syrian refugees were 71 percent male, Iraqi refugees were slightly higher at 75 percent, while Afghan refugees were a remarkable 80 percent male. Refugees from these three countries made up over half of Europe’s refugees in 2015. Research found that young male refugees make up a large portion of asylum applicants in certain countries. Italy’s applicants were heavily young and male, at 74 percent. Germany, which fell victim to a spat of terror attacks committed by refugees last month, saw 39 percent of asylum applications come from young men. Germany has seen the most applications for resettlement, with 442,000– or 33 percent of all applications in Europe. The European Union has attempted to disperse refugees evenly across its member states, though Pew’s research shows that the endeavor has largely failed. Eighty-four percent of Syrian refugees traveling to Europe applied for asylum in Germany, Hungary, Sweden, Austria and the Netherlands. The E.U. plans to fine member countries an astronomical $280,000 for each refugee a member country refuses to accept as part of the plan. Obama lambasted Republican politicians who opposed allowing Syrian refugees into the U.S. after the Paris attacks last November, claiming they were “scared of widows and orphans.” He also accused several former Republican presidential candidates of engaging in rhetoric that serves as a “potent recruitment tool” for the Islamic State. Follow Russ Read on Twitter Send tips to [email protected]. Content created by The Daily Caller News Foundation is available without charge to any eligible news publisher that can provide a large audience. For licensing opportunities of our original content, please contact [email protected].

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U.S. oil workers begin the largest national strike since 1980 Fonte/Source, Time, Oil workers in the U.S. began the largest national strike since 1980 on Sunday, after failing to agree on new labor contracts. The United Steelworkers Union (USW) called for about 3,800 employees to strike in nine sites across the country, affecting plants that account for 10% of the total U.S. refining capacity, reports Bloomberg. USW failed to agree on five contracts offered by lead negotiators Royal Dutch Shell PLC on behalf of several major oil companies including Chevron Corp. and Exxon Mobil Corp. When the current contract expired on Sunday, USW said it “had no choice” but to call the walkout after no further deal was reached. If a full strike of union workers is called, USW says it could disrupt as much as 64% of U.S. fuel production. Shell said it remained committed to reaching a deal with the union. But USW, which has been in talks since Jan. 21, feels the oil companies can afford to make the changes it is demanding, which include substantial pay raises and improved safety measures. “The problem is that oil companies are too greedy to make a positive change in the workplace,” said Tom Conway, USW international vice president of administration. “They continue to value production and profit over health and safety, workers and the community.” The strike comes at a difficult time in the market as companies cut costs amid a collapse in crude oil prices. Bloomberg says more refineries are standing by to join the industrial action.

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Seed mixtures as a resistance management strategy for European corn borers (Lepidoptera: Crambidae) infesting transgenic corn expressing Cry1Ab protein. Dispersal of neonate European corn borers, Ostrinia nubilalis (Hübner), in seed mixtures of transgenic corn expressing Cry1Ab protein (Bt+) and nontransgenic corn (Bt-) was evaluated in a 2-yr field study. The main objective was to determine if larval dispersal limits the effectiveness of seed mixtures as a resistance management strategy. Mixtures evaluated included (1) all Bt+ plants, (2) every fifth plant Bt- with remaining plants Bt+, (3) every fifth plant Bt+ with remaining plants Bt-, and (4) all Bt- plants. The transformation events MON 802 (B73 BC1F2 x Mol7) and MON 810 (B73 BC1F1 x Mo17), which express the Cry1Ab endotoxin isolated from Bacillus thuringiensis subsp. kurstaki, were used as the sources of Bt+ seed in 1994 and 1995, respectively (YieldGard, Monsanto, St. Louis, MO). At corn growth stage V6-V8, subplots within each mixture (15-20 plants each) were infested so that every fifth plant in mixtures 1 and 4, every Bt- plant in mixture 2, and every Bt+ plant in mixture 3 received two egg masses. Larval sampling over a 21-d period indicated increased neonate dispersal off of Bt+ plants, reduced survival of larvae that dispersed from Bt+ plants to Bt- plants, and a low incidence of late-instar movement from Bt- plants to Bt+ plants. Computer simulations based on mortality and dispersal estimates from this study indicate that seed mixtures will delay the evolution of resistant European corn borer populations compared with uniform planting of transgenic corn. However, resistant European corn borer populations likely will develop faster in seed mixes compared with separate plantings of Bt and non-Bt corn.

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How do we contribute to OpenStack? We are a team of 4 highly driven developers who want to contribute to OpenStack in some way. We have read some documentation but really have no idea about the research/latest-work going on in here. How can we get to know the right people and choose what aspect to work on? Thanks!

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