On May
9, 2017, President Donald Trump fired James Comey as Director
of the Federal Bureau of Investigation. In the fallout from
that event, news rapidly circulated about numerous private
conversations between the two men over the preceding months.
The exchanges left the former Director feeling unnerved and,
apparently, wanting a paper trail. On June 8, Comey testified
publicly that while still in office, he had created several
contemporaneous memoranda documenting up to nine
conversations with the President. The content of those memos
has since been the subject of intense public speculation and
is the focus of these consolidated cases.

Plaintiffs,
which include various news organizations and non-profits, all
sought copies of the so-called Comey Memos via a
tried-and-true method: The Freedom of Information Act, 5
U.S.C. § 552 et seq. The Government denied each
request, claiming that the release of these documents would
interfere with the Office of Special Counsel's ongoing
investigation into links between Russia and Trump's 2016
campaign team. Plaintiffs then brought these suits, and both
sides now seek summary judgment. After reviewing the Memos
in camera, as well as receiving a sealed ex
parte proffer from the Special Counsel's Office, the
Court agrees with the Government's assessment. As it
prevails here, the Comey Memos, at least for now, will remain
in the hands of the Special Counsel and not the public.

I.
Background

Drawing
from public reports, the Court begins by recounting the
now-familiar story of Comey's termination, as well as his
much-discussed Memos. (The appointment of and investigation
by the Special Counsel will be covered in Part III,
infra.) It then outlines the procedural history of
this case.

A.
Factual Background

On
March 20, 2017, then-Director Comey confirmed in public
testimony “that the FBI, as part of our
counterintelligence mission, is investigating the Russian
government's efforts to interfere in the 2016
presidential election, and that includes investigating the
nature of any links between individuals associated with the
Trump campaign and Russia's efforts.” Statement
Before the House Permanent Select Committee on Intelligence,
available at https://www.fbi.gov/
news/testimony/hpsci-hearing-titled-russian-active-measures-investigation.
He added, “As with any counterintelligence
investigation, this will also include an assessment of
whether any crimes were committed.” Id. Two
months later, the President fired Comey, citing, among other
reasons, frustration with the ongoing probe into Russian
interference, which he saw as “an excuse by the
Democrats for having lost [the] election.” CNN
Statement of Undisputed Material Facts, ¶ 29.

On May
16, 2017 - one week after Comey left office - news of his
Memos first broke. The New York Times published a
report about an Oval Office meeting between President Trump
and the then-Director, said to have taken place on February
14 of that year. During this one-on- one conversation, the
President allegedly referenced a potential investigation into
his former National Security Advisor Michael Flynn's
contacts with Russia, telling Comey, “I hope you can
see your way clear to letting this go, to letting Flynn
go.” Michael S. Schmidt, Comey Memo Says Trump
Asked Him to End Flynn Investigation, N.Y. Times (May
16, 2017), available at
https://www.nytimes.com/2017/05/16/us/politics/james-comey-trump-flynn-russia-investigation.html.
The Times report was based on “a memo Mr.
Comey wrote shortly after the meeting.” Id.
According to the newspaper, “Mr. Comey shared the
existence of the memo with senior F.B.I. officials and close
associates, ” one of whom “read parts of [the
Memo] to a Times reporter.” Id.

Spurred
by this report, the Senate Select Committee on Intelligence
held a hearing, during which Comey corroborated the
Times account. On June 8, he testified under oath
for nearly three hours, fielding myriad questions about his
Memos. See Hearing with Former FBI Director James
Comey, 115th Cong. (June 8, 2017) (Statement of James B.
Comey), available at
https://www.intelligence.senate.gov/sites/default/files/documents/os-jcomey-060817.pdf.
He there explained that after his first conversation with
then-President-Elect Trump, he “felt compelled to
document” their encounter in a memo, which he
“began to type . . . on a laptop in an FBI vehicle
outside Trump Tower the moment [he] walked out of the
meeting.” Id. at 2.

According
to Comey, “Creating written records immediately after
one-on-one conversations with Mr. Trump was [his] practice
from that point forward.” Id. He thought he
had done so “after each of [his] nine
conversations” with the President, or at least
“for nearly all of them, especially the ones that were
substantive.” Transcript of Comey Hearing,
available at
https://www.intelligence.senate.gov/hearings/open-hearing-former-fbi-director-james-comey#.
Comey said he had memorialized these conversations out of
concern that President Trump “might lie about the
nature of our meeting.” Id. In such a
scenario, he wanted a contemporaneous account “to
defend the FBI and our integrity as an institution and the
independence of our investigative function.”
Id.

B.
Procedural Background

The
same day that news spread of Comey's memoranda, Plaintiff
Cable News Network submitted a FOIA request for copies of
“all records of notes taken by or communications sent
from FBI Director James Comey regarding or documenting
interactions (including interviews and other conversations)
with President Donald Trump.” Def. MSJ (First
Declaration of David M. Hardy), ¶ 6; see also
id., Exh. CNN-B (CNN FOIA Request). CNN was not the only
one interested in the Comey Memos. Plaintiffs Daily Caller
News Foundation, non-profit organizations Judicial Watch and
Freedom Watch, and USA Today (the business name of Gannett
Satellite Information Network), along with its reporter Brad
Heath, the James Madison Project, and journalists Garrett
Graff and Lachlan Markay, all submitted FOIA requests to the
same end. See First Hardy Decl., ¶¶ 14,
21, 30, 37, 44. Some Plaintiffs (including the USA Today
group and Freedom Watch) sought additional related records,
which are outside the scope of the instant summary-judgment
motions. See, e.g., id., ¶ 44.

The
Department of Justice responded to each request by letter
dated June 16, 2017, invoking Exemption 7(A) to withhold all
documents. To wit, it stated: “The records responsive
to your request are law enforcement records. There is a
pending or prospective law enforcement proceeding relevant to
these responsive records, and the release of the information
could reasonably be expected to interfere with enforcement
proceedings.” Id., Exhs. CNN-F, USA Today-D,
JMP/Graff-D, JMP/Markay-C, JW-D, FW-D. Undeterred, all
Plaintiffs timely brought actions in this Court, suing,
variously, the FBI and DOJ. The Court consolidated their
cases on July 31, 2017. See Minute Order.

Four
months later, the Government moved for partial summary
judgment as to all requests related to the Comey Memos, and
Plaintiffs, in turn, filed cross-motions for the same. To
bolster its case, the Department of Justice also sought leave
to introduce an ex parte and in camera
affidavit from David W. Archey, a Deputy Assistant Director
with the Counterintelligence Division, who currently
supervises all FBI personnel assigned to the investigation
into Russia's interference with the 2016 Presidential
election. See ECF No. 23. After the parties finished
briefing, the Court granted the Government's request and
ordered, at Plaintiffs' behest, that it also produce all
withheld Memos for in camera review. See
Minute Order of Jan. 11, 2018.

The
Court reviewed those submissions and, out of an abundance of
caution, thought it helpful to seek more specifics as to the
Memos' connection with an ongoing investigation. It
therefore asked that an attorney from the Office of Special
Counsel proffer such information. Michael R. Dreeben, who
serves as Counsel to the Special Counsel, did so in a sealed,
on-the-record ex parte session. Finally, in response
to this Court's follow-up questions about that sealed
proffer, the Government submitted the Third Declaration of
David W. Archey in camera and ex parte.
See ECF No. 47. (The agency previously moved to
submit the Second Declaration of David W. Archey regarding
records other than the Memos, see ECF No. 46, and
the Court has not yet ruled on that motion.) Although none of
this material is currently available to Plaintiffs, all forms
part of the record that could be reviewed on appeal or in any
subsequent litigation.

II.
Legal Standard

Summary
judgment may be granted if “the movant shows that there
is no genuine dispute as to any material fact and the movant
is entitled to judgment as a matter of law.”
Fed.R.Civ.P. 56(a); see also Anderson v. Liberty Lobby,
Inc., 477 U.S. 242, 247-48 (1986); Holcomb v.
Powell, 433 F.3d 889, 895 (D.C. Cir. 2006). A fact is
“material” if it is capable of affecting the
substantive outcome of the litigation. See Liberty
Lobby, 477 U.S. at 248; Holcomb, 433 F.3d at
895. A dispute is “genuine” if the evidence is
such that a reasonable jury could return a verdict for the
non-moving party. See Scott v. Harris, 550 U.S. 372,
380 (2007); Liberty Lobby, 477 U.S. at 248;
Holcomb, 433 F.3d at 895. “A party asserting
that a fact cannot be or is genuinely disputed must support
the assertion” by “citing to particular parts of
materials in the record” or “showing that the
materials cited do not establish the absence or presence of a
genuine dispute, or that an adverse party cannot produce
admissible evidence to support the fact.” Fed.R.Civ.P.
56(c)(1). The moving party bears the burden of demonstrating
the absence of a genuine issue of material fact. See
Celotex Corp. v. Catrett, 477 U.S. 317, 323 (1986).

FOIA
cases typically are decided on motions for summary judgment.
See Brayton v. Office of U.S. Trade Rep., 641 F.3d
521, 527 (D.C. Cir. 2011). In a FOIA case, the Court may
accept an “agency's affidavits, without pre-summary
judgment discovery, if the affidavits are made in good faith
and provide reasonably specific detail concerning the methods
used to produce the information sought.” Broaddrick
v. Exec. Office of the President, 139 F.Supp.2d 55, 64
(D.D.C. 2001). “Agency affidavits are accorded a
presumption of good faith, which cannot be rebutted by purely
speculative claims about the existence and discoverability of
other documents.” SafeCard Servs., Inc. v.
SEC, 926 F.2d 1197, 1200 (D.C. Cir. 1991) (internal
quotation marks and citation omitted). “Summary
judgment may not be appropriate without incamera review, ” however, “when agency
affidavits in support of a claim of exemption are
insufficiently detailed.” Armstrong v. Exec. Office
of the President, 97 F.3d 575, 578 (D.C. Cir. 1996). In
such a circumstance, “district court judges [have]
broad discretion in determining whether in camera
review is appropriate.” Id. at 577-78.

III.
Analysis

The
country (or at least the Beltway) has spent months abuzz
about the Comey Memos and what they might reveal. Despite
rampant media speculation, however, the Memos themselves have
remained out of public view. The Government hopes to keep it
that way, but to withhold release under FOIA, it must satisfy
two elements. First, it must “demonstrate the . . .
adequacy of the search” for relevant documents.
Perry v. Block, 684 F.2d 121, 127 (D.C. Cir. 1982).
Second, it must show that the withheld material “falls
within one of nine statutory exemptions.” People
for the Ethical Treatment of Animals v. Nat'l Institutes
of Health,745 F.3d 535, 540 (D.C. Cir. 2014).
Plaintiffs attack the Government's efforts at each step.

         A.
Adequ ...

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ERROR: -o argument was empty string


torsdag 31 oktober 2013

Rachelle Lefevre set to star in Thriller "Reclaim"

deadline EXCLUSIVE: John Cusack, Ryan Phillippe, Rachelle Lefevre, Jacki Weaver and Luis Guzman are starring in Reclaim, a suspense thriller inspired by true events. The film is just getting underway in Puerto Rico, directed by Alan White (Erskineville Kings). The most recent script draft is by Luke Davies, from an original script by Carmine Gaeta.

Phillippe and Lefevre (The Twilight Saga) play an American couple who head to Puerto Rico to finalize the adoption of their new 7-year-old daughter, a Haitian orphan named Nina. When take the time to explore the idyllic coast to bond as a new family, Steven clashes with an intimidating local (Cusack), and Nina disappears from her bed one night.

The film is being produced by Paradox Entertainment’s Fredrik Malmberg and Silvio Muraglia, and Brian and Josh Etting of Paradox Entertainment. Arclight Films is handling international sales and Paradox will make the domestic deal.


Hemolymph and tissue-bound peptidase-resistant analogs of the insect allatostatins.
While neuropeptides of the allatostatin family inhibit in vitro production of juvenile hormone, which modulates aspects of development and reproduction in the cockroach, Diploptera punctata, they are susceptible to inactivation by peptidases in the hemolymph, gut, and bound to internal tissues. Patterns of peptidase cleavage were investigated in two allatostatin analogs in which sterically bulky components were incorporated into the active core region to block peptidase attack. The results were used to design and synthesize the first pseudopeptide analog of an insect neuropeptide resistant to degradation by both hemolymph and tissue-bound peptidases. This pseudotetrapeptide allatostatin mimetic analog represents a valuable tool to neuroendocrinologists studying mechanisms by which the natural peptides operate and the physiological consequences of challenging an insect with an allatostatin that is not readily degraded via peptidase enzymes. Disruption of critical physiological processes modulated by neuropeptides such as the allatostatins via peptidase-resistant mimetic analogs could form the basis for novel pest insect management strategies in the future.


Blockchain, HR & Payroll: What does the future hold?

Is blockchain in your future planning for HR and payroll? It should be!

If you are in payroll, you’ll need to develop an understanding about blockchain. It won’t directly affect your work today, but it certainly will make an impact in the near future. How near? That depends on where you work.

So what is blockchain?

If your first thought was ‘bitcoin’, then you’re not wrong: Cryptocurrencies like bitcoin are the most prominent use of blockchain technology, and the one that grabs a lot of headlines. Blockchain is the technology that enables bitcoin. But blockchain is so much more.

Think about how an employer pays her employees today: after payroll is run, a bank file containing all payments is created and sent to the bank. The bank processes this file and takes money out of the employer’s bank account to deposit it in the accounts of the employees. It can take several days to move money from one account to another. In other countries, employees receive paper checks, which they take to the bank to receive their money.

In both cases you use a trusted middle man (“the bank”) to move money around. The bank stores information about each account in a database on its own servers. But the bank is not a charitable organization and charges both parties for its services.

While money is being moved, it’s unclear where the money resides or how long it takes. And finally, end-users can’t check the validity or security of the underlying databases and must trust the bank to ensure correctness and protection against falsification.

What if we could remove the “trusted third-party” from the equation while ensuring that the authenticity of each transaction is securely captured and validated?

Distributed Ledger Technology

That is where blockchain comes in: it builds a secure and trusted ledger across a decentralized infrastructure, also called Distributed Ledger Technology (DLT). When someone makes a transaction, that is broadcasted to all parties in the network (nodes), who validate and approve it.

The data is encrypted and anonymous to those who aren’t directly involved in the transaction. Once the transaction is complete, a new block is created and added to the existing chain of transaction records (that’s why it’s called blockchain).

The hash or signature of previous blocks is added to the current block and then encrypted – as such the blocks can’t be changed or tampered with. The chain provides a permanent and transparent ledger, ensuring that the historical record of data becomes unchangeable. The distributed ledger guarantees the security of this technology.

When data changes, all nodes receive a fully synchronized copy of the data – and so each member is essential in establishing the integrity of every transaction.

There is no centralized version, and if an intruder wants to break into that system, they must break in on all the same blocks on all nodes at the exact same time, which is virtually impossible. Distributed ledgers can be public or private and vary in structure and size.

When using DLT, a “transaction” can mean different things:

a payment between 2 parties;

a validation of a document;

a verification of someone’s identity, etc.

All transactions are captured, but instead of storing them in a centralized database (remember the bank), transactions are encrypted, and an update is send across the decentralized network.

Every time a transaction takes place, the blocks are updated, so the chain accurately reflects the change. And because transactions are recorded as a ‘public ledger’, every user of the blockchain can trust that the blocks are secure.

How will blockchain change payroll?

When your employees live in the same country, the process is straightforward, and you need the bank to issue payments. It gets more complex when you need to make cross-border payments because you employ expats.

There is additional wait time when money travels via the banking system from one country to the next. When you send a check, the employee pays a fee to the bank to cash it. And when currency exchanges are involved, the bank charges additional fees as exchange rates. Because of these complexity, companies typically engage 3rd parties to handle international payments.

Suppose you use DLT to issue that same payment? What would change?

When using blockchain, you can achieve the following benefits:

Money moves faster: when the employer initiates the payment there is a direct connection via DLT to the account balance of the employee, so employees receive their payments quicker

Eliminate the middle man: you don’t need a trusted 3rd party in the middle, because the DLT guarantees the security and validity of each transaction thus enabling peer-to-peer payments. When making cross-border payments, it also reduces currency volatility, where (hourly) changes in exchange rates can be taken advantage of by intermediaries.

Lower transaction costs: Using DLT there are fewer parties involved and when you move money the transaction fee is a fraction of banking fees

Payment flexibility: employees can redirect payments and share wages earned with (overseas) family, with no or low remittance fees

Transparency: with DLT you know the exact status of the payment at all times.

Better security: because DLT is encrypted and distributed, it is virtually impossible to falsify content.

Blockchain payments enable the gig economy

An employer can enter into a smart contract stored on DLT, and when the work is delivered, the payment happens immediately. Same day payments are important for these workers, as they want to be paid in real time to eliminate dependency on payday lenders.

And it’s not limited to these workers: permanent employees welcome the flexibility to receive instantaneous payments too.

A further benefit is that blockchain allows payment to people who don’t have a bank account. These individuals (estimated at 2B people globally) would have an opportunity to create a digital bio-identification straight from their smartphones and use that to access a digital wallet platform and accept payments.

A word of caution

As often with new technologies, it takes a while for governments to catch up.

Paying for work is subject to taxation, social security and other contributions and regulations. In many countries it’s illegal to pay someone who does not have a bank account or use a payment system that is not visible to the authorities for reasons of fraud detection. While it’s good to experiment with new technologies like blockchain, always verify that you are compliant.

As a payroll provider, how will NGA HR use DLT?

The examples above give you some background on the benefits of using DLT in the payroll process. As global payroll provider, NGA HR is piloting several use cases on DLT, to ensure that we take full advantage of this exiting technology in our client service delivery. Johan Bosschaerts, SVP Technology, Innovation and Solutions, adds the following insights:

If you take the payroll process, security is fundamental, but security is only as strong as the weakest point in the whole chain. So, when you redesign the payroll process on DLT, it’s crucial to apply security consistently throughout the whole process.

In the case of payroll, from the moment NGA HR receives data via the client’s cloud HRIS, DLT enables us to put this data in a secure and trusted ledger. This allows us to log all events, so they can’t be tampered with. We can also introduce contextual access security, depending on access keys: when NGA HR as data processor uses its key, that provides a different type of data access than the client (employer) has using their key.

Similarly, when an employee calls with a payroll question, they can use their key to allow the service agent read-access to the data. When the call ends, and the agent closes the tickets, the access is revoked.

Throughout the whole payroll lifecycle (except for the black box payroll run itself), employee data and transactions are only stored in and referenced via the ledger, ensuring single data storage, that all dependent systems, like MyHRW (case management system) or PEX would reference to.

So instead of copying data between systems and holding copies in a number of databases, the DLT would work as a trusted source of data that is referenced by other systems when data access is required. In redesigning the payroll process using DLT, NGA HR can provide a secure service to clients, who can trust that PII (Personally Identifiable Information) is in authorized hands.

While NGA HR is exploring blockchain/DLT as a promising technology for payroll, we are also pursuing other use cases in the HR domain, like for personal data and recruitment. We’ll discuss those in a next blog post.

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Malcolm Bennett

Malcolm Bennett has been NGA Human Resources Group Counsel and Company Secretary since January 2015. He was previously Associate General Counsel for over 13 years with IBM and previously held legal positions with CMS Cameron McKenna and BHP Billiton prior to that.

Malcolm has experience in managing teams/departments and structuring and negotiating complex commercial transactions in multiple jurisdictions – he now leads a small team of legal, compliance and security professionals for NGA HR across the globe.

He studied Law at the University of Cape Town and now resides in Manchester with wife and son.

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Welcome to Charlie's Restaurant of Saint Clair Shores, where we’re always happy to see you. We work hard to provide you with the best dining experience using a quality preparation to make sure you always have a great meal.

Here at Charlie's your satisfaction is always guaranteed. If you’re not happy with some aspect of your meal just let us know and we’ll make it right.


2015 was a spectacular year for CS:GO fans. We have seen the rise of Team Solo Mid and the fall of the Ninjas in Pyjamas. Virtus Pro was once again able to proof that they are a top four team with multiple top finishes.

EnvyUs suffered from internal problems and with the exchange of Smithzz and Shox for KennyS and Apex from Titan got back to old form and closed out a really impressive year. Fnatic had arguably the best year with two major wins. Team Kinguin started slowly but shined after moving to G2 and picking up Dennis and Jkaem, crowning their year with a stellar 3/4th place at Dreamhack Cluj-Napoca. Cloud9 picked up fREAKAZOiD and Skadoodle and managed to grab three consecutive second-place finishes.

Hundreds of frag movies were released throughout the year and these ten were probably the best. They let you relive some of the greatest moments of 2015 and show once again that CS:GO keeps on growing.

1: Team SoloMid: Dawn by Frank Garnett Welsh

2: NiP – Dubai | CS:GO | by akidosEU

3: CS:GO | Counter-Strike: Passion | Motivational Movie by AncientElg

4: Team SoloMid : Ascend by Frank Garnett Welsh

5: CS:GO G2 – Believe (Tournament Fragmovie) DreamHack Open Cluj-Napoca 2015 by Phinx CSGO

6: CS:GO – FACEIT Stage 2 Finals Fragmovie (DreamHack Open Valencia) by DreamHack

7: ESL One Cologne 2015 | Official Aftermovie by ESL

8: CS:GO – A LIGHT (DreamHack Open 2015 Highlights) by HeartlessOne

9: CS:GO – Team Kinguin by Virre CSGO

10: THIS IS CS GO by Jon HDEAN

Thanks for watching.

Credit goes to:

Frank Garnett Welsh – https://www.youtube.com/user/FGWCSS

akidosEU – https://www.youtube.com/user/akidosEU

AncientElg – https://www.youtube.com/channel/UCLuSwZVY_8m3fm-obmkTazw

Phinx CSGO – https://www.youtube.com/user/qhin1

Faceit – https://www.youtube.com/user/FACEITcom

ESL – https://www.youtube.com/channel/UC0G2qz-hoaCswQNgoWU_LTw

Virre CSGO – https://www.youtube.com/user/AsSisT1337

HeartlessOne – https://www.youtube.com/channel/UC3wJ-MknhmLLTO0H-qm6fJA

Jon HDEAN – https://www.youtube.com/channel/UCfG1Wo7AN1gUDklJIXq3a_Q


<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN" "http://www.w3.org/TR/html4/loose.dtd">

<title>FieldGenerator</title>
<meta name="date" content="2019-04-08">
<link rel="stylesheet" type="text/css" href="../../../../../../dev_javadoc.css" title="Style">

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com.google.appengine.api.search.dev

Class FieldGenerator

java.lang.Object

com.google.appengine.api.search.dev.FieldGenerator

public class FieldGenerator
extends java.lang.Object

Class contains information about new fields we are going to generate for
 the current search request.

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Constructor and Description

FieldGenerator(java.lang.String name,
              Expression expression)

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getExpression()

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getName()

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Q:

Javascript modification security?

As my website depends a lot on Javascript, I would like to know: Is it possible for the user to edit .js files? Because this way they can delete condition checks and get access to stuff they shouldnt have. And mess the whole site. What is the chance of something like this happening and how to avoid it?

A:

No, the user cannot edit the js files. They can however edit the javascript returned from said files and execute as much additional javascript as they wish within the browser. anything you can do with javascript (in the browser), so can the client. This includes anything that is within a conditional that would have normally kept the user out of specific content that they aren't allowed to access.
Do not do security checks client-side, otherwise the client will be able to change said checks to gain access.


Q:

For loop does not work appropriate for the function

Here is a for loop contains a function which specify whether the port is open or closed by using checkPort function.
var IPAdress = '192.168'; //Local area network to scan (this is rough)
var Portadd = 80;
var Newip;
var i=0;
var j=0;
//scan over a range of IP addresses and execute a function each time the port is shown to be open.
for(i=0; i <= 1; i++){
for(j=0; j <= 3; j++){
Newip = IPAdress+'.'+i+'.'+j;

checkPort(Portadd, Newip, function(error, status, host, port) {
// Status should be 'open' since the HTTP server is listening on that port
if(status == "open"){
        console.log("IP" , Newip, "on port" , Portadd, "is open");
    }
else if(status == "closed"){
        console.log("IP" , Newip, "on port" , Portadd, "is closed");
    }
});

console.log(Newip);
}
}

and this is the result:
192.168.0.0
192.168.0.1
192.168.0.2
192.168.0.3
192.168.1.0
192.168.1.1
192.168.1.2
192.168.1.3
IP 192.168.1.3 on port 80 is closed
IP 192.168.1.3 on port 80 is closed
IP 192.168.1.3 on port 80 is closed
IP 192.168.1.3 on port 80 is closed
IP 192.168.1.3 on port 80 is closed
IP 192.168.1.3 on port 80 is closed
IP 192.168.1.3 on port 80 is closed
IP 192.168.1.3 on port 80 is closed

since the NewIp as it is printed out works properly, I expected the result to be for example something like this:
IP 192.168.0.0 on port 80 is closed
IP 192.168.0.1 on port 80 is closed
IP 192.168.0.2 on port 80 is closed
IP 192.168.0.3 on port 80 is closed
IP 192.168.1.0 on port 80 is closed
IP 192.168.1.1 on port 80 is closed
IP 192.168.1.2 on port 80 is closed
IP 192.168.1.3 on port 80 is closed

Does anybody have an idea that why it shows the IPs like that in the actual result part?

A:

checkPort is using a callback function that is executed later, and by the time it is executed all the IP addresses have been changed in the variable NewIP.
So the result is the callback function prints the last value of NewIP, because it's referencing that value.
You have two alternatives:

You can use the parameter host that is passed to the callback function instead.
Define var NewIP inside the inner for loop by changing var Newip = IPAdress+'.'+i+'.'+j;. This will create a variable that is scoped to the callback function.


Inside story: SAF kept military out of the loop


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The chronic use of beta-blockers and proton pump inhibitors may affect the rate of bacterial infections in cirrhosis.
Bacterial infections are among the most common and life-threatening complications in cirrhosis. Qualitative and quantitative modifications of the gut microbiota, dysfunction of the intestinal barrier and multiple immune defects are factors that contribute to a pathological 'bacterial translocation' (BT), leading to a higher susceptibility to infections in cirrhotic patients. Long-term therapies, commonly adopted in cirrhotic patients, may influence BT and modify the risk of infection in these patients. To investigate the influence of chronic therapies on the prevalence and microbiological characteristics of infections in cirrhosis. Consecutive cirrhotic patients hospitalised from 2008 to 2013 were enrolled. All previous treatments were carefully recorded. Infections were actively sought out, patients were actively monitored for infection, and possible risk factors were evaluated. Four hundred cirrhotic patients were included. The most frequent therapies were proton pump inhibitors (PPIs) (67%), non-absorbable-disaccharides (44%), beta-blockers (BBs) (39%) and non-absorbable-antibiotics (10%). Child-Pugh C (P < 0.001; OR 5; 95%CI: 2.6-9.9) and PPI therapy (P = 0.008; OR 2; 95% CI: 1.2-3.2) were found to be independent predictors of infection, and the use of BBs was a protective factor (P = 0.001; OR 0.46; 95%CI: 0.3-0.7). Cirrhotic patients with bacterial infection showed lower morbidity and mortality when taking BBs. Proton pump inhibitors increase the risk of infection in cirrhosis and should not be prescribed in these patients without specific indications. In contrast, the use of BBs is associated with a lower rate of infection and attenuates the consequences of infections in cirrhotic patients.


Pregnant Jehovah Witness in bikini protest

Pregnant Jehovah Witness in bikini protest against independent school

A pregnant Jehovah's Witness has launched a bikini-clad protest against an independent school after it cut down the hedge that separated their properties.

By Auslan Cramb

2:53PM GMT 19 Mar 2009

Naghme King, 39, staged the unusual demonstration after claiming that the head teacher had "stripped her of her assets".

Following a long-running boundary dispute, which has involved council officials and lawyers, she took to the streets of Milton Keynes, Bucks, this week carrying placards calling for the school principal Deborah Berkin to be "a bit more loving" and to realise that "God is love".

Mrs King, a mother-of-five who is six months pregnant, said there was nothing wrong with her bikini protest and she was merely spreading the gospel according to Jehovah.

Some neighbours in Redland Drive, Loughton, took a less charitable view, with one remarking that local children thought she was "mad".

Mrs King's dispute with the £10,300-a-year Grove Independent School began five years ago and according to its lawyers, the 176-pupil school has done everything possible to reach an amicable agreement over the boundary.

The neighbours' dispute started after Mr and Mrs King complained that staff had chopped down a 6ft wide hedge that divided their six-bedroom detached home from the school.

She said: "The hedge belonged to us and was on our property, on our land and the school chopped it down. It had no right to do this and take away our privacy." She added that they put up a wooden fence in its place, but it was also taken down.

"Since then I have walked up and down outside the school with my placards between eight and nine o'clock every morning," said Mrs King. Her protests are timed to coincide with the arrival of parents delivering their children.

The family is also said to have strung up an unsightly washing line visible to pupils and staff, put out bags of rubbish on the line where the hedge used to be, and played loud Salsa music directed at the principal's office.

A neighbour who asked not to be named, said: "It all started over a hedge but now it's gone crazy. The school has tried reasoning with her but she keeps launching these incredible protests.

"Yesterday she was pacing up and down outside wearing a witch's hat and carrying her placards with sayings from the bible on them.

"She times her protests for when parents are dropping off their children at school. On the last occasion she was very pregnant and a strange sight to see."

Milton Keynes Council said the rubbish dumping did not warrant legal action but environmental health officers were monitoring music levels.

Zoe Wright, a lawyer representing the school, said it had no objection to the Kings erecting a fence, provided it was on their own land.

LMAO... wait ... wait.... so there is a 39 year old annointed JW (I guess she either replaced an unfaithful one, or she is insane, according to the WT), ticked off that a school next to her home cut down her hedge, and she is protesting by walking around in a bikini and leaving underwear out on a clothes line... lol...

That's a little too funny.... oh wait, this was back in 2009. Was this real?


Isolated direct-current (DC) to DC switching voltage converters use transformers to convert power from an input source into power for an output load. Such a voltage converter includes primary-side power switches that convert DC input power into alternating-current (AC) power that is fed to the primary side of a transformer. AC power supplied on the secondary side of the transformer is rectified to convert it back into DC power which, in turn, is provided to the output load.
In order to prevent damage to the primary-side power switches or the transformer itself, care must be taken to ensure that the core of the transformer does not magnetically saturate. This is typically accomplished by oversizing the transformer and/or using the current in the primary-side power switches to detect transformer core saturation. Should transformer core saturation be detected thusly, power transfer through the transformer is curtailed. More advanced techniques may track the transformer core flux, e.g., using a volt-second measure based upon a voltage of the transformer. A controller of the voltage converter may use the tracked transformer core flux to keep the flux well-balanced between positive and negative excursions, and to curtail power transfer if the tracked flux is approaching a level corresponding to a core saturation limit of the transformer.
A load transient, e.g., a step increase in the power required by the load, is preferably handled by increasing a current output from the voltage converter at a high rate until the voltage provided to the output load approaches a desired output level. The output current must be increased such that it does not cause saturation of the transformer core. Furthermore, the voltage converter components including, in particular, an output inductor must be sized such that a maximum output current is accommodated.
Techniques are desired for providing fast transient response within a voltage converter while avoiding transformer core saturation and without increasing the size of the transformer or an output inductor of the voltage converter.


Call: Reconceiving Cognition conference

The cognitive sciences, including its neural branches, continue to flourish. But what exactly is cognition? Recent developments in Embodied, Embedded and Enactive approaches to cognition, or E-cognition, have drawn attention to the numerous ways in which embodied situated interaction might be more intimately related to cognition than previously acknowledged. E-cognition is often taken to raise concerns about the tenability of a conception of cognition according to which in-the-head representational and/or computational mechanisms breathe cognitive life into organismic activities that would otherwise be mere bodily motion. But do E-factors call for a replacement or merely a reform of standard conceptions of cognition? And what exactly should be the new concept of cognition? Relatedly, the arrival of E-cognition leads to such questions as whether or not we need to reconsider the relation between cognition (including perception) and behavior, what explanations of cognition consist of, and what role the brain should play in such explanations.

The conference will offer the opportunity to engage with these questions, in the light of, inter alia, the views of the authors of recent books on conference themes-Michael Anderson’s After Phrenology, MIT Press 2014; Louise Barrett’s Beyond the Brain, Princeton University Press 2011; Giovanna Colombetti’s The Feeling Body, MIT Press 2013, and Daniel D. Hutto and Erik Myin’s Evolving Enactivism, MIT Press 2017.

Besides invited presentations (see list below), the conference program has room for contributed presentations. Please send a 250-500 word abstract to karim.zahidi@uantwerpen.be, with as title “Reconceiving Cognition”, before February 13, 2018. Notification of acceptance will be communicated at the latest March 1.


Oh, to be free-agent right-hander Zack Wheeler.

His stuff is elite. His career innings total is low. His recent durability is encouraging.

Any day now, he will be a $100 million man.

Wheeler, 29, has received at least one $100 million offer and will land a five-year deal in excess of that amount, according to major-league sources.

The White Sox, Twins, Reds, Rangers and Blue Jays are among the clubs pursuing Wheeler, who is the leading free-agent alternative to fellow right-handers Gerrit Cole and Stephen Strasburg even though his career ERA+ (ERA adjusted to park and league) is exactly league average.

A pitcher’s long-term health is difficult to predict. Teams craft narratives to justify whatever additions they make, believing what they want to believe. But the intense interest in Wheeler indicates that clubs view him as a No. 3 starter at worst, a No. 1 at best.

The White Sox can imagine him fronting a rotation with Lucas...


A marble palace set in the historic village of Vila Viçosa

Luxury Hotel in Vila Viçosa

Boutique hotel designed by architect Miguel Cancio Martins, set in the historic village of Vila Viçosa

Unique spa in a disused marble quarry with a number of pools, massage beds and a hammam

Alentejo terroir cuisine served in the restaurant

Alentejo Marmoris Hotel & Spa

Highlighting the marble for which Vila Viçosa is renowned, Alentejo Marmoris Hotel & Spa is a shining example of a beautiful renovation. Integral to the build of the hotel, marble features throughout the property; from intricately decorated floors to the walls of the spa. With an indoor and outdoor pool and a restaurant serving superb regional cuisine, this is the ideal setting from which to discover the beauty of the Alentejo region of Portugal.

The ambience at Alentejo Marmoris Hotel & Spa is both tranquil and comfortable. The rooms and suites are contemporary in style with streamlined furniture and the use of crisp, modern colours in the fabrics. Each one of the stunning marble bathrooms is individually designed and many of the rooms have an outdoor terrace. Head to the marble-lined spa and try an indulgent treatment using products from the famous Karin Herzog range.

Wander around Vila Viçosa and discover its architectural gems including the Royal Palace, the Castle, its numerous churches, museums and palaces. Then, head out to nearby Évora and beyond through pretty villages and follow the wine and olive oil routes. Return to Alentejo Marmoris Hotel & Spa for dinner in the hotel restaurant to savour the cuisine of the Alentejo.

44 rooms

1 restaurant

3 floors

Hotel type:

Photos

The rooms

CLASSIC ROOM

Not available for your dates

Sleeps: 3 People.

twin or double
patio landscape view- free WiFi

Classic Room with twin or double beds- patio and landscape views. The room is spacious and comfortable with a modern atmosphere contemporary design features and offers a sense of tranquillity. The room is complete with air conditioning- marble bathroom- telephone- plasma TV- safe- mini bar- hairdryer and free internet access.

Deluxe Room

Not available for your dates

Sleeps: 3 People.

Twin or double
street or pool view- free WiFi

Deluxe Room with twin or double beds- street or pool view. The room is spacious and comfortable with a modern atmosphere- contemporary design features and offers a sense of tranquility. Room is complete with air conditioning- marble bathroom- telephone- plasma TV- safe- mini bar hairdryer and free internet access. Room size is 26-33 square metres.

JUNIOR SUITE

Not available for your dates

Sleeps: 4 People.

King bed street
view- marble bathroom- free WiFi

Junior Suite with double bed and street views. The room is spacious and comfortable with a modern atmosphere, contemporary design features and offers a sense of tranquility. The Junior Suite is complete with air conditioning, marble bathroom, telephone, plasma TV, safe, mini bar hairdryer and free internet access. Room size is 36 square metres.

SUITE

Not available for your dates

Sleeps: 4 People.

King bed-street view
marble bathroom- plasma TV- free WiFi

Suite with King size bed and street views. The room is spacious and comfortable with a modern atmosphere, contemporary design features and offers a sense of tranquility. Suite is complete with air conditioning, marble bathroom, hairdryer, safe, mini bar, plasma TV, telephone and free internet access. Room size is 52 square metres.

Transport options

Points of Interest

Things to enjoy

Narcissus Fernandesii

Meals served: Breakfast, Lunch, Dinner

The Narcissus Fernandesii restaurant offers the best of Alentejo cuisine in a contemporary interpretation. Our cuisine promises to open doors to tastes never tasted before. We create dishes with authentic flavour using products from the surrounding fields of Vila Vicosa and accompanied with an excellent wine list that gives special emphasis to Alentejo wines

The Stone Spa by Karin Herzog is excavated from a marble quarry. The beauty and the strength of its original walls with the authentic formation of small stalactites make its atmosphere absolutely unique. The Stone Spa has 4 treatment rooms, an indoor and outdoor swimming pool, hammam, heated swimming pool with hydrotherapy circuit, including massage beds. The rituals use products by Karin Herzog, the leading brand in cosmetics with active oxygen from Switzerland. This is the brand chosen by dermocosmetic specialists such as Dr. Ivo Pitanguy, Dr. Paul Lorenc and Dr. Anthony Chu, and famous personalities such as Princess Kate Middleton, Madonna, Sir Elton John, Cameron Diaz among others for their effectiveness and revolutionary technology.

What I liked most :

Perfect break in a perfect location

By Christopher from SPALDING, United Kingdom

Stay date: June 2016

My Trip Type: Couple

The hotel was 5star plus, the staff were friendly & very helpful. We had an amazing room on the ground floor over looking the pool. The breakfast was lush. You can walk to most places from the hotel, and the people in the town were very friendly too. The biggest surprise was the local history & culture. We had an amazingly relaxing time in a beautiful hotel. Will definitely go back.

Top tip for other guests:

Enjoy all the culture in the town.

Hotelier reply:

Dear Mr. Thompson,
First of all, we would like to thank you for your preference and for your kind review on SLH.
We are glad to know that you enjoyed your experience with a good combination that aggregated the room, the Hotel services, the people and the Hotel surroundings.
If you decide to come back and pay us a new visit, we will be at your service to help you in any way.
Best regards,
The Alentejo Marmòris Team

Very comfortable and pleasant stay

By Carlos from Les Avants, Switzerland

Stay date: October 2015

My Trip Type: Couple

Probably the best hotel between Lisbon and the Spanish border, driving eastwards. Obviously you must not be allergic to marble, as this new hotel is an illustration of what you can do nowadays with this material to be found in this region. But it is done with style and it must give the hotel a very fresh and cool ambiance during the hot summers. Nice modern design all over, spacious and elegant lounge (lights are a bit too bright in the evening), stimulating feeling in the dining room and a very comfortable room with a large bathroom. Wonderful food, probably one of the best Chefs in Portugal, and the wines from the region are splendid. Friendly and knowledgeable service. We stayed four nights and enjoyed it thoroughly. Perfect location to explore this part of Alentejo, the city of Evora (30 minutes drive away), Vila Viçosa itself with the stunning palace of the Braganca family, Elvas, Estremoz and the local wineries. The hotel has a very nice spa, (great massage by Ana). We regretted that the outside pool was already covered, and this is not very attractive when you sit outside, but it was October. We felt really welcome from our check-in to departure. And had the pleasure to meet Mrs Alves, a warm and spontaneous owner. We really recommend her hotel.

Top tip for other guests:

Perfect getaway in a beautiful Hotel

By Youssouf from San Fernando de Henares, Spain

Stay date: August 2014

My Trip Type: Family

The hotel is pretty recent so all the facilities are clean and well taken care of generally, the customer are surrounded by marble and the decorator demonstrated a good taste specially in the entry. The personal was helpful with all the tips regarding the things and site to visit, and at the same time knew when to be discreet and leave you enjoy the calm and quietness of the hotel. The only thing I regret is the lack of space during rush hours around the pool.

Top tip for other guests:

The closest sea side spot is the one near lisbon (troia) at two hours by car, take the road rather than the ferry, the whole trip will be shorter


Q:

No need for mutex, race conditions not always bad, do they?

I'm getting this crazy idea that mutex synchronization can be omitted in some cases when most of us would typically want and would use mutex synchronization.
Ok suppose you have this case:
Buffer *buffer = new Buffer(); // Initialized by main thread;

...

// The call to buffer's `accumulateSomeData` method is thread-safe
// and is heavily executed by many workers from different threads simultaneously.
buffer->accumulateSomeData(data); // While the code inside is equivalent to vector->push_back()

...

// All lines of code below are executed by a totally separate timer
// thread that executes once per second until the program is finished.

auto bufferPrev = buffer; // A temporary pointer to previous instance

// Switch buffers, put old one offline
buffer = new Buffer();

// As of this line of code all the threads will switch to new instance
// of buffer. Which yields that calls to `accumulateSomeData`
// are executed over new buffer instance. Which also means that old
// instance is kinda taken offline and can be safely operated from a
// timer thread.

bufferPrev->flushToDisk(); // Ok, so we can safely flush
delete bufferPrev;

While it's obvious that during buffer = new Buffer(); there can still be uncompleted operations that add data on previous instance. But since disk operations are slow we get natural kind of barrier.
So how do you estimate the risk of running such code without mutex synchronisation?

Edit
It's so hard these days to ask a question in SO without getting mugged by couple of angry guys for no reason.
Here is my correct in all terms code:
#include <cassert>

#include "leveldb/db.h"
#include "leveldb/filter_policy.h"

#include <iostream>
#include <boost/asio.hpp>
#include <boost/chrono.hpp>
#include <boost/thread.hpp>
#include <boost/filesystem.hpp>
#include <boost/lockfree/stack.hpp>
#include <boost/lockfree/queue.hpp>
#include <boost/uuid/uuid.hpp>            // uuid class
#include <boost/uuid/uuid_io.hpp>         // streaming operators etc.
#include <boost/uuid/uuid_generators.hpp> // generators

#include <CommonCrypto/CommonDigest.h>

using namespace std;
using namespace boost::filesystem;

using boost::mutex;
using boost::thread;

enum FileSystemItemType : char {
    Unknown         = 1,
    File            = 0,
    Directory       = 4,

    FileLink        = 2,
    DirectoryLink   = 6
};

// Structure packing optimizations are used in the code below
// http://www.catb.org/esr/structure-packing/
class FileSystemScanner {
private:
    leveldb::DB *database;

    boost::asio::thread_pool pool;

    leveldb::WriteBatch *batch;

    std::atomic<int> queue_size;
    std::atomic<int> workers_online;
    std::atomic<int> entries_processed;
    std::atomic<int> directories_processed;
    std::atomic<uintmax_t> filesystem_usage;

    boost::lockfree::stack<boost::filesystem::path*, boost::lockfree::fixed_sized<false>> directories_pending;

    void work() {
        workers_online++;

        boost::filesystem::path *item;

        if (directories_pending.pop(item) && item != NULL)
        {
            queue_size--;

            try {
                boost::filesystem::directory_iterator completed;
                boost::filesystem::directory_iterator iterator(*item);

                while (iterator != completed)
                {
                    bool isFailed = false, isSymLink, isDirectory;

                    boost::filesystem::path path = iterator->path();

                    try {
                        isSymLink = boost::filesystem::is_symlink(path);
                        isDirectory = boost::filesystem::is_directory(path);

                    } catch (const boost::filesystem::filesystem_error& e) {
                        isFailed = true;
                        isSymLink = false;
                        isDirectory = false;
                    }

                    if (!isFailed)
                    {
                        if (!isSymLink) {
                            if (isDirectory) {
                                directories_pending.push(new boost::filesystem::path(path));

                                directories_processed++;

                                boost::asio::post(this->pool, [this]() { this->work(); });

                                queue_size++;
                            } else {
                                filesystem_usage += boost::filesystem::file_size(iterator->path());
                            }
                        }
                    }

                    int result = ++entries_processed;

                    if (result % 10000 == 0) {
                        cout << entries_processed.load() << ", " << directories_processed.load() << ", " << queue_size.load() << ", " << workers_online.load() << endl;
                    }

                    ++iterator;
                }

                delete item;
            } catch (boost::filesystem::filesystem_error &e) {

            }
        }

        workers_online--;
    }

public:
    FileSystemScanner(int threads, leveldb::DB* database):
        pool(threads), queue_size(), workers_online(), entries_processed(), directories_processed(), directories_pending(0), database(database)
    {
    }

    void scan(string path) {
        queue_size++;

        directories_pending.push(new boost::filesystem::path(path));

        boost::asio::post(this->pool, [this]() { this->work(); });
    }

    void join() {
        pool.join();
    }
};

int main(int argc, char* argv[])
{
    leveldb::Options opts;

    opts.create_if_missing = true;
    opts.compression = leveldb::CompressionType::kSnappyCompression;
    opts.filter_policy = leveldb::NewBloomFilterPolicy(10);

    leveldb::DB* db;

    leveldb::DB::Open(opts, "/temporary/projx", &db);

    FileSystemScanner scanner(std::thread::hardware_concurrency(), db);

    scanner.scan("/");
    scanner.join();

    return 0;
}

My question is: Can I omit synchronization for batch which I'm not using yet? Since it's thread-safe and it should be enough to just switch buffers before actually committing any results to disk?

A:

You have a serious misunderstanding. You think that when you have a race condition, there are some specific list of things that can happen. This is not true. A race condition can cause any kind of failure, including crashes. So absolutely, definitely not. You absolutely cannot do this.
That said, even with this misunderstanding, this is still a disaster.
Consider:
buffer = new Buffer();

Suppose this is implemented by first allocating memory, then setting buffer to point to that memory, and then calling the constructor. Other threads may operate on the unconstructed buffer. boom.
Now, you can fix this. But it's just one the many ways I can imagine this screwing up. And it can screw up in ways that we're not clever enough to imagine. So, for all that is holy, do not even think of doing this ever again.


**Specifications Table**Table*Subject areaNeuroscienceMore specific subject areaPeripheral nervous system, neurobiology, redox biologyType of dataImmunohistochemistry imagesHow data was acquiredImmunohistochemistry for redoxins, counterstaining with hematoxylin, microscopy on an Leica Diaplan microscope equipped with a MicroPublisher camera (QImaging, Surrey, BC, Canada)Data formatTables, microscopy imagesExperimental factorsMice subjected to sciatic nerve injury versus control.Experimental featuresThe data were obtained from mice with a specific deletion of hypoxia inducible factor 1 alpha (SNS-HIF1α*^−/−^*) in sensory neurons of the dorsal root ganglia (DRGs) and floxed control mice.Data source locationFrankfurt, GermanyData accessibilityData is with this paper*

Value of the data {#s0005}
=================

•The immunohistology of redoxins may be used for comparison of the expression and regulation of these enzymes in models of nerve, brain or spinal cord injury.•The Hif1α dependent regulation of redoxin expression may be used for comparison of redoxin regulation in other tissues e.g. in cancer or cardiovascular tissue.•The rainbow pseudocolor conversion of quantitative immunhistology data of dorsal root ganglia and spinal cord may be used as an example for quantitative assessment and presentation of immunohistology data.

1. Data {#s0010}
=======

The present DiB paper shows immunohistochemistry of redoxins including peroxiredoxins (Prdx1--6), glutaredoxins (Glrx1, 2, 3, 5), thioredoxins (Txn1, 2) and thioredoxin reductases (Txnrd1, 2) in the DRGs [Figs. 1](#f0005){ref-type="fig"} and [2](#f0010){ref-type="fig"}), spinal cord ([Fig. 1](#f0005){ref-type="fig"}, [Fig. 2](#f0010){ref-type="fig"}, [Fig. 7](#f0035){ref-type="fig"}), sciatic nerve ([Fig. 3](#f0015){ref-type="fig"}, [Fig. 4](#f0020){ref-type="fig"}, [Fig. 5](#f0025){ref-type="fig"}, quantification [Fig. 6](#f0030){ref-type="fig"}) and thalamus ([Fig. 8](#f0040){ref-type="fig"}) in naïve mice and 7 days after Spared sciatic Nerve Injury (SNI) in control mice (Hif1α-flfl) and in mice with a specific deletion of hypoxia inducible factor 1 alpha (SNS-HIF1α^−/−^) in DRG neurons. The sciatic nerves were immunostained for the respective redoxins and counterstained with hematoxylin. The redoxin immunoreactivity was quantified with ImageJ. For the DRGs and spinal cord the data show the quantitative assessment of the intensity of redoxin immunoreactivity [@bib1] transformed to rainbow pseudocolors ([Fig. 2](#f0010){ref-type="fig"}). In addition, some redoxin examples of the ipsi and contralateral dorsal and ventral horns of the lumbar spinal cord ([Fig. 7](#f0035){ref-type="fig"}) and some redoxin examples of the thalamus ([Fig. 8](#f0040){ref-type="fig"}) are presented. Characteristics of the antibodies are listed in [Table 1](#t0005){ref-type="table"} along with some features of the redoxins.

2. Experimental design, materials and methods {#s0015}
=============================================

2.1. Mice and surgery {#s0020}
---------------------

The data were obtained from mice with a specific deletion of hypoxia inducible factor 1 alpha (SNS-HIF1α^−/−^) in sensory neurons of the dorsal root ganglia (DRGs). The deletion was achieved by mating floxed mice (Hif1α-flfl) with SNScre mice, which express cre-recombinase under control of the Nav1.8/SNS promoter, which is specific for small and medium sized DRG and trigeminal neurons [@bib2]. Hif1α-flfl littermates were used as controls.

Mice were subjected to a sciatic nerve during isoflurane anesthesia using the SNI model [@bib3]. Two of the three peripheral branches of the sciatic nerve, the common peroneal and the tibial nerves, were ligated with silk and distally transected, leaving the sural nerve intact. Seven days after nerve injury mice were terminally anesthetized with isoflurane and cardially perfused with ice cold 1× phosphate buffered saline (PBS), pH 7.4 followed by 4% paraformaldehyde (PFA) in PBS for fixation. Naïve mice were used as controls.

2.2. Immunohistochemistry {#s0025}
-------------------------

Tissues were excised, postfixed in 4% PFA for 2 h, cryoprotected overnight in 20% sucrose at 4 °C, embedded in small tissue molds in cryomedium and cut on a cryotome (12 µm for DRGs and sciatic nerves; 18 µm spinal cord). Slides were air-dried and stored at −80 °C. After thawing, slides were immersed and permeabilized in 1× phosphate buffered saline (PBS) with 0.3% Triton-X-100 (PBST), incubated in 3% hydrogen peroxide for 10 min to quench endogenous peroxidase, then blocked with 1% blocking reagent (Roche) or with 10% normal goat serum (Sigma) in PBST, subsequently incubated overnight with the primary antibody in PBST at 4 °C. Primary antibodies are listed in [Table 1](#t0005){ref-type="table"}, validated in [@bib4]. Sections were then washed with PBST, incubated with a biotinylated species specific secondary antibody diluted 1:500 for 1--2 h at room temperature. Vectastain HRP streptavidin was used for antigen detection according to the manufacturer׳s recommendations using red aminoethyl carbazole HRP substrate (AEC, Invitrogen). Subsequently, slides were counter-stained with Mayer׳s hematoxylin and mounted with Mowiol. Negative control slides were incubated with 10% goat serum in PBST, examples of negative control stainings are shown in [Fig. 1](#f0005){ref-type="fig"}.

2.3. Quantitation of immunohistology images {#s0030}
-------------------------------------------

The WCIF plugin bundle of ImageJ was used for quantification of immunohistology images [@bib5]. After background subtraction the RGB image was split into its channels to separate the immunoreactive red from the blue hematoxylin counterstain. The single channel image was then inverted, the intensity threshold set to automatic detection, the intensity distribution plotted as histogram and the mean intensity was used for statistical comparisons. The intensities were transformed to rainbow pseudocolor for visualization ([Fig. 2](#f0010){ref-type="fig"}). The analysis did not differentiate between different types of cells, e.g. neuronal fibers, Schwann cells and immune cells in the nerves. The analysis was based on 2 images per mouse and tissue of 3 mice per group. Mean pixel intensities were submitted to analysis of variance followed by post hoc analysis between treatment groups employing a Sidak correction for multiple testing. *P* was set to 0.05 for all comparisons.

The thioredoxin system consists of the cytosolic Txn1, which can be shuttled to the nucleus and can be secreted [@bib6] or the mitochondrial Txn2 and the respective thioredoxin reductases (Txnrd1 or Txnrd2) [@bib7]. Following disulfide reduction by the respective Txn, Txnrd reduces the disulfide in the active site using electrons provided by NADPH. Glutaredoxins (Glrx) do not depend on a specific reductase for catalysis. Instead, Glrxs use glutathione (GSH) as electron source [@bib8], [@bib9], [@bib10], which is synthesized in two steps by glutamate cysteine ligase (Gclc) and glutathione synthetase [@bib11]. Oxidized GSH, glutathione disulfide (GSSG), is subsequently reduced by glutathione reductase (Gsr) at the expense of NADPH. Peroxiredoxins reduce peroxides rather than protein disulfides [@bib12]. During the peroxidase reaction, the 2Cys Prdxs (1, 2 and 3 and atypical Prdx4 and 5) form a sulfenic acid intermediate, which reacts with a second resolving cysteine, resulting in a disulfide bond, which is subsequently reduced by Txns. The 1Cys Prdx6 uses glutathione (GSH) for the reduction of the sulfenic acid intermediate. Sulfiredoxins prevent the over-oxidation of peroxiredoxins.

We acknowledge the financial support of the Deutsche Forschungsgemeinschaft (SFB815 A12 to I.T. and CRC1080 A9). We thank Rohini Kuner for SNScre mice.

![Control stainings of DRGs, dorsal and ventral horns of the spinal cord, sciatic nerve and thalamus. Slides were incubated with anti-Ig *G* without primary antibody and developed with the Streptavidin--HRP system using red AEC as substrate and then counterstained with hematoxylin (blue). Scale bar 20 µm or 50 µm.](gr1){#f0005}

![WCIF-ImageJ was used for quantification of histological images. After substraction of background, the RGB image was split into its channels, the channel representing the redoxin-immunoreactivity was then inverted, the threshold set to auto, and intensities transformed to rainbow colors as shown in the images. The mean pixel intensity and distribution were plotted as histograms and the mean intensity was used for statistical comparisons. The quantification is based on results of 3 animals in each group.](gr2){#f0010}

![Immunohistology of peroxiredoxins, Prdx1--6 (in red) in the ipsilateral sciatic nerve proximal of the nerve lesion 7 days after Spared Nerve Injury (SNI) in SNS-HIF1α^−/−^ and HIF1α-flfl mice. SNS-HIF1α^−/−^ have a cre/loxP mediated deletion of hypoxia inducible factor 1 alpha specifically in sensory neurons of the dorsal root ganglia (DRGs). Naïve mice were used as controls. Slides were developed with the Streptavidin--HRP system using red AEC as substrate and then counterstained with hematoxylin (blue). Results are representative results of 3 mice per group. Scale bar 50 µm.](gr3){#f0015}

![Immunohistology of glutaredoxins, Glrx1, 2, 3 and 5 (in red) and of the catalytic subunit of glutamate--cysteine ligase, Gclc (red) in the ipsilateral sciatic nerve proximal of the nerve lesion 7 days after Spared Nerve Injury (SNI) in SNS-HIF1α^−/−^ and HIF1α-flfl mice. SNS-HIF1α^−/−^ have a cre/loxP mediated deletion of hypoxia inducible factor 1 alpha specifically in sensory neurons of the dorsal root ganglia (DRGs). Naïve mice were used as controls. Slides were developed with the Streptavidin--HRP system using red AEC as substrate and then counterstained with hematoxylin (blue). Results are representative results of 3 mice per group. Scale bar 50 µm.](gr4){#f0020}

![Immunohistology of thioredoxins (Txn1, 2) and thioredoxin reductases (Txnrd1, 2) (in red) in the ipsilateral sciatic nerve proximal of the nerve lesion 7 days after Spared Nerve Injury (SNI) in SNS-HIF1α^−/−^ and HIF1α-flfl mice. SNS-HIF1α^−/−^ have a cre/loxP mediated deletion of hypoxia inducible factor 1 alpha specifically in sensory neurons of the dorsal root ganglia (DRGs). Naïve mice were used as controls. Slides were developed with the Streptavidin--HRP system using red AEC as substrate and then counterstained with hematoxylin (blue). Results are representative results of 3 mice per group. Scale bar 50 µm.](gr5){#f0025}

![Quantification of redoxin histology of the sciatic nerve with WCIF ImageJ. Mean pixel intensities were determined after substraction of background, RGB split into its channels and threshold settings based on negative control images using "auto" settings. The analysis did not differentiate between different types of cells and is a global readout for immunoreactivities in axonal fibers, Schwann cells and infiltrating immune cells. Pixel intensities were compared with one-way ANOVA for each redoxin separately. In case of significance, groups were mutually compared employing a Sidak correction of alpha, which was set at 0.05 for all comparisons. Asterisks indicate significant differences versus the respective naive animals. The analysis was based on results of 3 animals per group.](gr6){#f0030}

![Exemplary immunohistology of redoxins (red, hematoxylin counterstain in blue) in the contralateral and ipsilateral lumbar spinal cord 7 days after Spared Nerve Injury (SNI) of the ipsilateral sciatic nerve in SNS-HIF1α^−/−^ and HIF1α-flfl mice. SNS-HIF1α^−/−^ have a cre/loxP mediated deletion of hypoxia inducible factor 1 alpha specifically in sensory neurons of the dorsal root ganglia (DRGs). Scale bar 50 µm.](gr7){#f0035}

![Exemplary immunohistology of redoxins (red, hematoxylin counterstain in blue) in the thalamus 7 days after Spared Nerve Injury (SNI) of the sciatic nerve in SNS-HIF1α^−/−^ and HIF1α-flfl mice. SNS-HIF1α^−/−^ have a cre/loxP mediated deletion of hypoxia inducible factor 1 alpha specifically in sensory neurons of the dorsal root ganglia (DRGs). The right panel shows a higher magnification. Slides were developed with the Streptavidin--HRP system using red AEC as substrate. Scale bars 50 and 20 µm.](gr8){#f0040}

######

Characteristics of redoxins and antibody specifications.

Table 1

  Name                                          Gene     GO molecular function                                                                                GO cellular component   Type                                    Catalytic activity                                                                                [a](#tblfna){ref-type="table-fn"}Arnt, Ahr or HIF1 sites   Phosphosites                                         Antibody
  --------------------------------------------- -------- ----------------------------------------------------------------------------------------------------------------------------------------------- ----------------------- --------------------------------------- -------------------------------------------------------------------------------------------------------------------- ---------------------------------------------------------- ---------------------------------------------------- -------------------------------------------
  Peroxiredoxin 1                               Prdx1    Thioredoxin peroxidase activity, heme binding, antioxidant activity, oxidoreductase activity                                                    N, C, S                 2Cys-intermolecular --S--S--            2R′--SH+ROOH=R′--S--S--R׳+H~2~O+ROH                                                                                \-                                                         Thr90                                                [@bib4]
  Peroxiredoxin 2                               Prdx2    Thioredoxin peroxidase activity, antioxidant activity, oxidoreductase activity                                                                  C, S                    2Cys-intermolecular --S--S--            2R′--SH+ROOH=R′--S--S--R׳+H~2~O+ROH                                                                                48                                                         Ser112, Thr182                                       Santa Cruz Biotechnology, Inc. (sc-33572)
  Peroxiredoxin 3                               Prdx3    Thioredoxin peroxidase activity, antioxidant activity, oxidoreductase activity                                                                  M, C, E                 2Cys-intermolecular --S--S--            2R′--SH+ROOH=R′--S--S--R׳+H~2~O+ROH                                                                                \-                                                         Thr146                                               [@bib4]
  Peroxiredoxin 4                               Prdx4    Thioredoxin peroxidase activity, antioxidant activity, oxidoreductase activity                                                                  S, C, ER, M, L          atypical 2Cys, intramolecular--S--S--   2R′--SH+ROOH=R′--S--S--R′+H~2~O+ROH                                                                                121, 211                                                   Ser68, Tyr266                                        Abcam plc (ab59542)
  Peroxiredoxin 5                               Prdx5    Thioredoxin peroxidase activity, antioxidant activity, oxidoreductase activity, RNA polymerase and receptor binding                             C, M, N, P              atypical 2Cys, intramolecular--S--S--   2R′--SH+ROOH=R′--S--S--R׳+H~2~O+ROH                                                                                125, 404, 221                                              Ser34, Thr97, Ser101, Ser182                         [@bib4]
  Peroxiredoxin 6                               Prdx6    Glutathione peroxidase activity, phospholipase A2 activity, antioxidant activity, oxidoreductase activity                                       C, L, S                 1Cys                                    2R′--SH+ROOH=R′--S--S--R׳+H~2~O+ROH; 2 glutathione+H2O2=glutathione disulfide+2 H2O.                                 102                                                        Ser32, Thr44, Ser83, Tyr89, Ser146, Thr177, Ser186   Abcam plc (ab59543)
  Glutaredoxin 1                                Glrx1    Glutathione disulfide oxidoreductase activity                                                                                C, N, M, S              dithiol                                 2 Glutathione+H2O2=glutathione disulfide+2 H2O, in the presence of NADPH and Gsr                                     \-                                                         Tyr25                                                [@bib4]
  Glutaredoxin 2                                Glrx2    Glutathione disulfide oxidoreductase activity, protein disulfide isomerase activity                                                             M, N                    dithiol                                 2 Glutathione+H2O2=glutathione disulfide+2 H2O, in the presence of NADPH and Gsr                                     \-                                                         Ser20, Tyr103, Tyr113                                [@bib4]
  Glutaredoxin 3                                Glrx3    Protein disulfide oxidoreductase activity, protein disulfide isomerase activity, protein kinase C binding                                       C, N                    monothiol 2×                            2 Glutathione+H2O2=glutathione disulfide+2 H2O, in the presence of NADPH and Gsr                                     34                                                         Ser32, Ser117, Ser120, Ser196                        [@bib4]
  Glutaredoxin 5                                Glrx5    Protein disulfide oxidoreductase activity, 2 iron, 2 sulfur cluster binding, metal ion binding                                                  M, N, C                 monothiol                               2 Glutathione+H2O2=glutathione disulfide+2 H2O, in the presence of NADPH and Gsr                                     \-                                                         Ser41, Ser145                                        [@bib4]
  Glutamate cysteine ligase, catalytic domain   Gclc     Glutamate--cysteine ligase activity, glutathione synthase activity, ATP binding                                                                 C                                                               ATP+[l]{.smallcaps}-glutamate+\>[l]{.smallcaps}-cysteine=ADP+phosphate+gamma-\>L-glutamyl-[l]{.smallcaps}-cysteine   317, 328                                                   Ser5, Ser8, Ser621                                   Santa Cruz Biotechnology, Inc. (sc-22755)
  Thioredoxin 1                                 Txn1     Protein disulfide oxidoreductase activity, poly(A) RNA binding, dithiol--disulfide exchange                                                     C, N, S                 cytopslasmic                            Dithiol--disulfide exchange                                                                                \-                                                         Ser44, Ser46, Ser67                                  [@bib4]
  Thioredoxin 2                                 Txn2     Protein disulfide oxidoreductase activity, dithiol--disulfide exchange                                                                          M, C, N                 mitochondrial                           Dithiol--disulfide exchange                                                                                155 (mouse)                                                \-                                                   [@bib4]
  Thioredoxin reductase 1                       Txnrd1   Selenium-dependent oxidoreductase activity, thioredoxin--disulfide reductase activity, NADP(H) oxidase activity                                 C, N                    cytopslasmic                            Thioredoxin+NADP^+^=thioredoxin disulfide+NADPH.                                                                     461                                                        Tyr161, Tyr163, Tyr277, Tyr281                       [@bib4]
  Thioredoxin reductase 2                       Txnrd2   Selenium-dependent oxidoreductase activity, thioredoxin--disulfide reductase activity, acting on a sulfur group of donors, NAD(P) as acceptor   M                       mitochondrial                           Thioredoxin+NADP^+^=thioredoxin disulfide+NADPH.                                                                     118                                                        Tyr40                                                Santa Cruz Biotechnology, Inc. (sc-67127)

M, Mitochondria; C, Cytoplasm; N, Nucleus; V, Vesicular structure (endosome, peroxisome, lysosome); E, Endosome; P, Peroxisome; S, Secreted; ER, Endoplasmic reticulum; L, Lysosome.

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EC Issues Report on Recommendations for Sustainable Financing in EU

ByRegulatory News

January 31, 2018

EC published a report that sets out strategic recommendations for a European financial system that supports sustainable investments. EC welcomes this report by its High-Level Expert Group on Sustainable Finance.

The report maps out challenges and opportunities that the EU faces in developing a sustainable finance policy. It identifies the ways in which the financial sector can re-connect with the real economy to support the transition to a more resource-efficient and more circular economy. The Expert Group argues that reorienting investment flows into long-term, sustainable projects will also improve the stability of the financial system. The report contains the following proposals:

A classification system, or taxonomy, to provide market clarity on what is sustainable

Clarifying the duties of investors toward achieving a more sustainable financial system

Improving disclosure by financial institutions and companies on how sustainability is factored into their decision-making

An EU-wide label for green investment funds

Making sustainability part of the mandates of ESAs

A European standard for green bonds

EC plans to work on finalizing its strategy on sustainable finance, on the basis of the recommendations in this report. Delivering an EU strategy on sustainable finance is a priority action of the EC Capital Markets Union Action Plan, in addition to being a key step toward implementing the historic Paris Agreement and the EU's Agenda for sustainable development. EC will discuss the findings of the report, along with a comprehensive action plan, at a high-level conference in Brussels in March 2018.

FHFA published, in Federal Register, the final rule to adopt, as its own, portions of the regulations of the Federal Housing Finance Board pertaining to the capital requirements for the Federal Home Loan Banks.

PRA published a policy statement (PS4/19) that provides feedback on responses to the consultation paper (CP27/18) on adjusting for the reduction of loss absorbency where own fund instruments are taxed on write down under Solvency II.

The framework provides independent valuers and the general public with an indication of the expectations of SRB on the principles and methodologies for valuation reports, as set out in the legal framework.


by on

The Seattle 2018 Annual Parking Study is out – helping you to play like a parking pro! Every year since 2010, the Performance-Based Parking Pricing Program assesses supply and demand, to help drivers more reliably find short-term parking.

The effort supports downtown mobility by reducing circling and cruising for an open street parking spot. Over the years, SDOT has made 300 different adjustments to parking rates and other parking elements, addressing parking demand changes as Seattle grows.

Parking use determines rates.

The Performance-Based Parking Pricing Program hones in on street blocks with more than 85% and less than 70% occupancy. Paid parking rates are then adjusted annually.

In areas and times where parking occupancy is low and spaces easy to find, rates are decreased by $0.50 an hour. Where parking occupancy is high and spaces hard to find, rates are increased by $0.50 an hour.

Goal: 1 – 2 open spaces per block.

The goal is 1 to 2 street parking spaces open per block, on average. Pricing helps to direct travelers to lesser used areas, and to consider the use of other travel options. This can ultimately reduce traffic congestion in areas where parking spaces are hard to find.

For details on street parking by City area, click on the map above. We also have a citywide map showing parking regulations across Seattle, to help you plan your trip.

Timing matters.

SDOT manages street parking by the time of day, with the potential for different rates in the morning, afternoon, and evening, based on local conditions.

For this latest study, combining parking areas with different times of day, there were 92 areas/time periods reviewed for changes:

61 of these will have no rate changes

17 will have $0.50 rate increase

14 will have $0.50 rate decreases

For example, parking occupancy in the Uptown Core (aka, Lower Queen Anne) is traditionally low in the mornings and high in the evenings.

The trend continued in 2018, so we will lower the morning rate before 11 AM to $0.50/hour (down from $1.00), and increase the evening rate after 5 PM to $2.00/hour (up from $1.50).

Rate and timing changes citywide are now in progress, through the end of 2018. The next analysis is expected to begin in the spring of 2019.

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Hello World.
I'm Imagination.
Today I'm going to talk about Genome Editing.
Genome editing, or genome engineering, or
gene editing, is a type of genetic engineering
in which DNA is inserted, deleted, modified,
or replaced in the genome of a living organism.
Unlike early genetic engineering techniques
that randomly insert genetic material into
a host genome, genome editing targets the
insertions to site-specific locations.
Nine genome editors were available as of 2017.
In 2018, the common methods for such editing
used engineered nucleases, or "molecular scissors".
These nucleases create site-specific double-strand
breaks at desired locations in the genome.
The induced double-strand breaks are repaired
through nonhomologous end-joining or homologous
recombination, resulting in targeted mutations
edits.
In May 2019, lawyers in China reported, in
light of the purported creation by Chinese
scientist He Jiankui of the first gene-edited
humans, the drafting of regulations that anyone
manipulating the human genome by gene-editing
techniques, like CRISPR, would be held responsible
for any related adverse consequences.
A cautionary perspective on the possible blind
spots and risks of CRISPR and related biotechnologies
has been recently discussed, focusing on the
stochastic nature of cellular control processes.
In February 2020, a US trial safely showed
CRISPR gene editing on 3 cancer patients.
Genetic engineering as a method of introducing
new genetic elements into organisms has been
around since the 1970s.
One drawback of this technology has been the
random nature with which the DNA is inserted
into the host's genome.
This can impair or alter other genes within
the organism.
Methods were sought which targeted the inserted
genes to specific sites within an organism
genome.
As well as reducing off-target effects it
also enabled the editing of specific sequences
within a genome.
This could be used for research purposes,
by targeting mutations to specific genes,
and in gene therapy.
By inserting a functional gene into an organism
and targeting it to replace the defective
one it could be possible to cure certain genetic
diseases.
Researchers have used CRISPR-Cas9 gene drives
to modify genes associated with sterility
in A.gambiae, the vector for malaria.
This technique has further implications in
eradicating other vector-borne diseases such
as yellow fever, dengue, and Zika.
The CRISPR-Cas9 system can be programmed to
modulate the population of any bacterial species
by targeting clinical genotypes or epidemiological
isolates.
It can selectively enable the beneficial bacterial
species over the harmful ones by eliminating
pathogens, which gives it an advantage over
broad-spectrum antibiotics.
In January 2019, scientists in China reported
the creation of five identical cloned gene-edited
monkeys, using the same cloning technique
that was used with Zhong Zhong and Hua Hua
– the first-ever cloned monkeys - and Dolly
the sheep, and the same gene-editing Crispr-Cas9
technique allegedly used by He Jiankui in
creating the first-ever gene-modified human
babies Lulu and Nana.
The monkey clones were made in order to study
several medical diseases.
In the near future, the new CRISPR system
will also be able to eradicate diseases and
conditions that humans are predisposed to.
With this new technology, scientists will
be able to take the genes of a human sperm
cell and egg and replace the genes that activate
cancer or other abnormal or unwanted defects.
This will take the stress off from parents
worrying about having a child and not able
to live a normal life.
After just one generation of this process,
the entire future of the human race would
never have to worry about the problems of
deformities or predisposing conditions.
Many transhumanists see genome editing as
a potential tool for human enhancement.
Australian biologist and Professor of Genetics
David Andrew Sinclair notes that "the new
technologies with genome editing will allow
it to be used on individuals to have healthier
children" – designer babies.
According to a September 2016 report by the
Nuffield Council on Bioethics in the future
it may be possible to enhance people with
genes from other organisms or wholly synthetic
genes to for example improve night vision
and sense of smell.
The American National Academy of Sciences
and National Academy of Medicine issued a
report in February 2017 giving qualified support
to human genome editing.
They recommended that clinical trials for
genome editing might one day be permitted
once answers have been found to safety and
efficiency problems "but only for serious
conditions under stringent oversight."
Genome editing tools such as CRISPR are beginning
to reshape the physical world around us, one
base pair at a time.
That's all for today.
Thanks for watching.