INTRODUCTION
============

The discovery of microRNAs (miRNAs) in *Caenorhabditis elegans* in 1993 opened the door for the study of phenomena, such as RNA interference and paved the way for the RNA revolution. miRNAs are ∼23-nt long single-stranded RNA species that regulate post-transcriptionally protein coding genes by mRNA cleavage, direct translational repression and/or mRNA destabilization ([@gks494-B1]).

miRNAs have been deemed as key regulators of diverse biological processes, including development, stem cell proliferation, division and differentiation, regulation of innate and adaptive immunity, apoptosis, cell signaling and metabolism ([@gks494-B2; @gks494-B3; @gks494-B4]). miRNAs play an important role in a vast array of human pathologies, such as cancer, viral infections, cardiovascular diseases, metabolic disorders, autoimmune pathologies, as well as neuropsychiatric pathological conditions ([@gks494-B2],[@gks494-B3],[@gks494-B5; @gks494-B6; @gks494-B7; @gks494-B8; @gks494-B9]). They are intensely researched, not only for their role in physiology and pathology but also as potential therapeutic targets.

A long series of algorithmic tools and databases have been implemented and utilized by miRNA researching groups as tools of the trade ([@gks494-B10; @gks494-B11; @gks494-B12]). Gene target prediction applications were some of the first sectors to receive intense research focus ([@gks494-B10]). The tools that followed were designed to address the need for functional characterization of miRNAs and their predicted targets. Few of the available servers are specifically focused on the identification of miRNA targeted pathways (e.g. miTalos, DIANA--miRPath v1) ([@gks494-B13],[@gks494-B14]), while others provide a relevant functionality as an extension of a pre-existent pipeline (e.g. mirTar, Gene Trail) ([@gks494-B15],[@gks494-B16]).

miTalos ([@gks494-B13]) can be used for the analysis of a subset of human signaling pathways. It identifies targets using five different external miRNA target prediction algorithms while also considering expression data. miRTar ([@gks494-B16]) can be utilized for investigating alternatively spliced miRNA targets, which are identified by integrating external prediction algorithms. miRTar can also perform gene set enrichment analysis for the identification of miRNA targeted pathways. GeneTrail ([@gks494-B15]) is a web server hosting gene set enrichment and over-representation capabilities against various databases, such as GO and KEGG. GeneTrail has been extended with a tool, which queries miRNA identifiers against the MicroCosm Targets database for putative gene targets ([@gks494-B17]). It provides many options during the gene enrichment analysis process, such as *P*-value thresholds and multiple testing significance correction but is lacking miRNA-specific functionalities, such as information regarding binding positions and binding type.

DIANA-miRPath v1 ([@gks494-B14]) was one of the first available applications focused on the enrichment analysis of predicted target genes, capable of detecting pathways targeted by single or multiple miRNAs. Here, we present the next version of DIANA-miRPath webserver (v2.0), which was entirely redesigned. The new web server aims to significantly increase the accuracy of utilized algorithms and statistics, as well as to enhance computational speed, compared to the previous miRPath version. Importantly, DIANA-miRPath v2.0 offers for the first time a series of tools specifically focused on miRNA-targeted pathway analysis.

The user of DIANA-miRPath v2.0 can utilize predicted or experimentally validated targets; combine results with merging and meta-analysis algorithms; perform hierarchical clustering of microRNAs and pathways based on their interaction levels; as well as elaborate sophisticated visualizations, such as dendrograms or miRNA/pathway interaction heat maps, from an intuitive and easy to use web interface. The new server provides additional information regarding pathogenic SNPs in predicted miRNA target sites. Furthermore, the reverse analysis module annotates all predicted or experimentally validated miRNAs targeting a selected molecular pathway.

Specific details regarding design, implementation and use of DIANA-miRPath v2.0 are presented in the following section.

METHODS AND RESULTS
===================

miRPath v2.0 database
---------------------

DIANA-miRPath v2.0 is based on a new relational schema, specifically designed to accommodate this as well as future miRPath updates. miRNA and pathway related information was obtained from miRBase 18 ([@gks494-B11]) and Kyoto Encyclopedia of Genes and Genomes (KEGG) v58.1 ([@gks494-B18]), respectively, for *Mus musculus* and 'homo sapiens'.

In DIANA-miRPath v2.0, the user can select between *in silico* predicted miRNA gene targets and a large set of experimentally validated targets, or both. The *in silico* target prediction is performed using DIANA-microT-CDS ([@gks494-B19]), the latest version of the DIANA-microT algorithm, which computes a miRNA--gene interaction score for predicted targets in 3′-UTR and coding sequence (CDS) transcript regions. DIANA-microT-CDS has been tested against a variety of high-throughput experimental data, exhibiting the highest sensitivity and specificity in comparison with other broadly used miRNA target prediction algorithms ([@gks494-B19]). DIANA-microT-CDS is fully integrated in the new database schema, enabling the filtering of miRNA--gene interactions based on a user defined threshold. The server is using 0.8 score as a default threshold, which provides an average of 350 targets per miRNA. Information regarding the number of targets and the derived predictive accuracy for different thresholds, as calculated against experimentally verified miRNA targets ([@gks494-B20]) is provided in [Supplementary Table S1](http://nar.oxfordjournals.org/cgi/content/full/gks494/DC1).

TarBase v6.0 database ([@gks494-B12]) is also incorporated into the new schema. Tarbase v6.0 is currently the largest manually curated, experimentally validated miRNA--gene interactions database, hosting more than 65 000 miRNA--gene interactions; 16.5- to 175-fold more than any other available manually curated database.

### Pathogenic single nucleotide polymorphisms identification in predicted miRNA target sites

The coincidence of clinically significant single nucleotide polymorphisms (SNPs) and predicted miRNA target sites was calculated, in order to relate miRNA gene targets in molecular pathways to pathogenic polymorphisms. A total of 9899 experimentally verified human SNPs, specifically indicated as 'pathogenic' or 'probable pathogenic' and with known genomic coordinates were derived from dbSNP BUILD 135 ([@gks494-B21]). The SNPs' coordinates are overlapped with all miRNA target binding sites predicted with DIANA-microT-CDS, resulting in 16 578 miRNA target sites containing a pathogenic or probable pathogenic SNP. The user has access to the results of the pathogenic SNP analysis directly from the DIANA-miRPath v2.0 web server ([Supplementary Figure S2](http://nar.oxfordjournals.org/cgi/content/full/gks494/DC1)). The web server provides the dbSNP id, as well as a direct link to the relevant dbSNP entry, enabling the user to further assess the available evidence supporting the pathogenicity of the detected SNP.

Algorithms, implementation and results computation
--------------------------------------------------

The DIANA-miRPath v2.0 website is implemented by combining PHP and AJAX. It is specifically designed to provide results in real-time, offering an application-like user experience. All the statistical and analysis algorithms are implemented in R.

### Filtering based on expression data

DIANA-miRPath v2.0 offers the option to filter miRNA targets based on expression data. The user can upload a predefined list of genes that are expressed in investigated tissues. The program will filter all miRNA targets based on this list and will use only the expressed subset of genes for the pathway enrichment analysis.

### Enrichment analysis

The user can select the desired microRNAs by the web interface or by uploading a file with the desired miRNA identifiers.

Following the selection of miRNAs and (optional) genes sets, the server subsequently performs an enrichment analysis of microRNA gene targets in KEGG pathways ([Table 1](#gks494-T1){ref-type="table"}). The default algorithm utilized is the one-tailed Fisher's exact test, which is often performed in such context ([@gks494-B22],[@gks494-B23]). The one-tailed test is selected because the initial hypothesis was to detect enriched (and not depleted) pathways with targets of specific miRNAs. This test is often encountered in relevant literature also as hypergeometric test. It provides exact probabilities and is appropriate even for small number statistics ([@gks494-B23]). DIANA-miRPath v2.0 can also calculate a more conservative adjustment of Fisher's exact test ([@gks494-B24]). The derived score represents the upper bound of the distribution of the jack-knife Fisher exact probabilities and it favors pathways supported with more gene targets. Table 1.Over-representation analysis performed by the DIANA-miRPath web server∈ Pathway A∉ Pathway ATotalTargetedn~1+~n~2+~N~+~Non-targetedn~1−~n~2−~N~−~Totaln~1~n~2~N[^2]

The server offers to the user the option to perform the false discovery rate (FDR) method, as a correction for multiple hypothesis testing. The FDR algorithm is implemented as described by Benjamini and Hochberg ([@gks494-B25]). In both cases (corrected or uncorrected significance levels), the user can specifically set the desired level of significance and to filter out all pathways with an associated *P*-value \> threshold from visualizations or further analyses.

### Multiple miRNA effect analysis

The new server can accommodate many different analysis scenarios. Specific attention has been paid to the methodologies used for combining and merging predicted and/or experimentally validated gene targets of multiple miRNAs. The user can now select how gene targets or targeted pathways will be combined and even if the results combination will take place *a priori* (Union and Intersection of Genes) or *a posteriori* of the statistical analysis (Union and Intersection of Pathways). Currently, the supported analysis scenarios are as follows.

Union of Genes: this option utilizes the union of targeted genes by the selected microRNAs (genes targeted by at least one selected miRNAs) prior to the statistical calculation. The resulting targeted genes superset is used for the over-representation statistical analysis.

Intersection of Genes: in this analysis, only the intersection of targeted genes (genes targeted by all selected miRNAs) is utilized for the over-representation statistical analysis.

Union of Pathways: in this mode, the server identifies all the significantly targeted pathways by the selected microRNAs.

Intersection of Pathways: the final option provides the intersection of targeted pathways by the selected microRNAs. The resulting subset contains only the pathways with statistically significant results for all the selected microRNAs.

In the first two options (Intersection and Union of Genes), the server combines the gene targets of the selected microRNAs into a common subset (intersection) or a superset (union). The resulting set is then incorporated in the enrichment analysis. In the last two options (Union and Intersection of Pathways), the server initially calculates the significance levels between all possible microRNA--pathway pairs, by performing repeatedly the enrichment analysis against the selected microRNAs and all available pathways. In the second step of the process, the server combines the previously calculated significance levels and provides a merged *P*-value for each pathway, by applying Fisher's combined probability method (Fisher's method).

Fisher's method is a meta-analysis algorithm, which can be used to combine the results of more than one independent tests bearing upon the same hypothesis. It exhibits asymptotical optimality and has been successfully used in studies of medical as well as biological context ([@gks494-B26; @gks494-B27; @gks494-B28]). The meta-analysis' null hypothesis is that all of the separate null hypotheses are true; while the alternative hypothesis is that at least one of the separate alternative hypotheses is true. The resulting *P*-values depict the probability that the examined pathway is significantly enriched with gene targets of the selected miRNAs. By adopting this technique, DIANA-miRPath v2.0 provides accurate statistical results and *P*-values in all available analysis options.

All provided results can be also corrected in the combined enrichment analysis for multiple hypotheses testing, by applying Benjamini and Hochberg's FDR.

### Results visualization

The new DIANA-miRPath v2.0 interface ([Figure 1](#gks494-F1){ref-type="fig"}) has been designed to be highly adaptable to different use-case scenarios and to provide results in real time. In order to perform the analysis, the user can select one or more microRNAs and the source of gene targets for each miRNA (*in silico* predicted or experimentally validated). Optionally, a list of expressed genes can be also loaded. Subsequently, the server presents the significantly enriched pathways, the targeted genes in each pathway and the number of miRNAs with positively identified targets for each pathway in the form of an interactive table. Figure 1.From the DIANA-miRPath v2.0 interface, the user can select the microRNAs that will be included in the analysis or upload miRNA lists in the form of text files. The user can select if miRNA gene targets will be experimentally validated (derived from TarBase 6) or predicted (derived from DIANA-microT-CDS). Optionally, the user can upload a predefined list of genes expressed in investigated tissues, which will be used to focus the enrichment analysis only on the specified subset. Subsequently, the user can determine the result merging method and statistics/enrichment calculation methodologies. The number of provided results, as well as the sensitivity and specificity of the DIANA-microT-CDS prediction algorithm can be set by user-defined thresholds. By selecting pathways union/intersection merging methods, the user obtains access to the advanced visualizations, which include miRNA/pathway clusters and miRNAs versus pathways heat maps. All significantly targeted pathways, with *P*-values lower than the user-defined threshold are presented in the interactive table. Pathway names, KEGG ids, significance levels, number of miRNAs targeting each pathway and targeted genes are some of the provided information. The table provides also access to enriched KEGG representations, DIANA-microT-CDS prediction details and experimental validation information, in the case of TarBase derived targets. The reverse search module can be used to detect miRNAs targeting (experimentally validated or predicted) a specified pathway. All results can be downloaded in a portable .csv format.

In the case of predicted miRNA--gene interactions, the server provides a link to the relevant DIANA-microT-CDS server entries. There, the user can further inspect the predicted miRNA--gene interaction. Such interactions include the binding region, position and type. If a miRNA--gene interaction is experimentally validated, the server provides a link to the specific section of the TarBase 6.0 website. The relevant entry provides information regarding the implemented experimental method used for validation and the supporting literature.

DIANA-miRPath v2.0 offers enriched KEGG pathway visualizations, where the targeted genes are specifically marked for easier inspection ([Figure 2](#gks494-F2){ref-type="fig"}). Figure 2.DIANA-miRPath v2.0 offers enriched KEGG pathway visualizations, where the targeted genes are specifically marked for easier inspection. The server provides three levels of gene labeling: yellow (gene targeted by 1 selected miRNA), orange (gene targeted by \>1 selected miRNAs) and red (gene specifically marked by the user). The user can also enable/disable gene marking and hide/show targeted genes. By simply hovering over a target gene (tooltip), the web server provides information regarding the source of the interaction (TarBase or DIANA-microT-CDS) and the implicated miRNAs. Selection of any of the pathway's constituents will lead the user directly to the relevant entry on the KEGG website.

### Targeted pathways (reverse search module)

The new reverse search module can be used to identify all miRNAs which are predicted or experimentally validated to target a specific KEGG pathway. The module takes as input a KEGG pathway name or identifier and the source of miRNA targets. It subsequently identifies all the miRNAs targeting the selected pathway. The new module can become a powerful asset to scientists studying specific pathways. It can help examining validated relationships between pathways and miRNAs expressed in the available literature (TarBase targets) or to study novel miRNA--pathway interactions (DIANA-microT-CDS targets). If the analysis is performed *in silico*, the user can determine the desired levels for sensitivity and precision by applying a DIANA-microT-CDS score threshold.

### Advanced analysis pipelines and visualizations

DIANA-miRPath v2.0 provides also advanced features, statistics and visualization aids, which significantly increase the depth of the analysis and maximize the user's influence on results' calculation and presentation.

### Hierarchical clustering and dendrograms

The new web server can perform follow-up analyses, such as hierarchical clustering of targeted pathways and miRNAs. DIANA-miRPath v2.0 realizes clustering of the selected miRNAs based on their influence on molecular pathways. It provides clustering of pathways based on the subset of miRNAs that target each pathway and the significance level of the interaction. The server performs the hierarchical cluster analysis based on a complete linkage clustering method, where squared Euclidean distances are calculated as distance measures. The web server can utilize absolute *P*-values in all calculations (option: 'Significance Clusters') or binary values (0: not targeted, 1: targeted), if the option 'Targeted Pathways Clusters' is selected. By utilizing these options, the algorithm can cluster together microRNAs targeting similar lists of pathways, as well as pathways, which are targeted by similar lists of microRNAs (Targeted Pathways Clusters); or take also into account the significance levels of the interactions (Significance Clusters) during the clustering process.

These advanced features can help the user identify relations between miRNAs or pathways depending on the effect size of the miRNA--pathway interactions. The web server provides visualizations of the hierarchical clustering in the form of miRNA and pathway dendrograms.

### miRNAs versus pathways heat maps

The new DIANA-miRPath v2.0 server enables also the user to create advanced visualizations such as miRNAs versus pathways heat maps ([Figure 3](#gks494-F3){ref-type="fig"} and [Supplementary Figure S1](http://nar.oxfordjournals.org/cgi/content/full/gks494/DC1)). Heat maps are graphical representations of data where values in a matrix are represented as colors ([@gks494-B29]). These intuitive visualizations have been proven useful in numerous fields, since they enable the users identify patterns in the data, which were not easily discernible when examining the parameters individually. Furthermore, they enable the visualization of a very large number of variables, their in-between relationships and their levels of interaction. The web server utilizes the hierarchical clustering results on both axes (pathways and miRNAs), in order to construct the heat map visualization. As in the case of cluster analysis, the web server provides two options for heat map calculation: 'Significance Heat Maps' and 'Targeted Pathways Heat Maps'. The former involves the use of absolute *P*-values in all calculations, while the latter substitutes all *P*-values lower than the user defined threshold with 0, and 1 otherwise. With the use of these advanced tools, the user can examine numerous miRNA--miRNA, miRNA--pathway and pathway--pathway relationships. Such representations can help researchers discover patterns and relationships hidden in the data. All plots are rendered in high resolution. Figure 3.miRNAs versus pathways heat map (clustering based on significance levels). Darker colors represent lower significance values. The attached dendrograms on both axes depict hierarchical clustering results for miRNAs and pathways, respectively. On the miRNA axis, we can identify miRNAs clustered together by exhibiting similar pathway targeting patterns. An analogous clustering can be observed also on the pathway axis. In this particular example, we can observe at least one pathway (fatty acid biosynthesis) that is clearly targeted by most investigated miRNAs with a very small *P*-value. More details regarding the methods and results of this example can be found in the [Supplementary Material](http://nar.oxfordjournals.org/cgi/content/full/gks494/DC1).

DISCUSSION
==========

The new web server described in this article is designed to accommodate various use case scenarios and provide results belonging to different research pipelines. For an applied demonstration of the web server's functionality, we performed a case study based on the work of Finnerty *et al*. ([@gks494-B30]), where the researchers explore the function and role of the proposed miR-15/107 miRNA group. It is a group exhibiting strong influences in human biology, highly involved in biological functions, such as cell division, metabolism, stress response and angiogenesis, in vertebrate species. In the performed analysis, the majority of the DIANA-miRPath v2.0 results are supported by the elaborate literature review of Finnerty *et al*. Detailed information regarding the methodology and the derived results from the example can be found in the provided [Supplementary Material](http://nar.oxfordjournals.org/cgi/content/full/gks494/DC1).

DIANA-miRPath v2.0 is a completely redesigned new version, implemented to provide utilities and functions specific to the analysis and identification of miRNA targeted pathways. All analyses are performed in real time, rendering possible for the user to experiment with different levels of sensitivity and specificity regarding the miRNA--gene interactions. A user researching if a specific pathway of interest is targeted by a group of miRNAs under definite conditions may utilize a more sensitive score (e.g. suggested score 0.7). Similarly, a user investigating in a more generalized experiment which pathways are mostly affected by the expressed miRNAs, may use a higher and more specific threshold (e.g. suggested score 0.9). To our knowledge, this is the first interactive web service for pathway analysis in this direction.

Another unique feature to DIANA-miRPath v2.0 is the integration of experimentally verified targets, offering validated results derived from the extensive relevant literature.

We think that the new pathological SNP discovery module, which can be used to detect SNPs on miRNA target sites and pathways, may provide in several cases 'hidden jewels' of biological information. We hope that the increased number of additional advanced analysis and visualization tools, such as miRNA versus pathways heat maps, hierarchical miRNA/pathways clustering and meta-analysis merging of results, will help users explore and understand more clearly miRNA-related research data.

SUPPLEMENTARY DATA
==================

[Supplementary Data](http://nar.oxfordjournals.org/cgi/content/full/gks494/DC1) are available at NAR Online: Supplementary Tables 1 and 2 and Supplementary Figures 1 and 2.

FUNDING
=======

The project \[09 SYN-13-1055\] 'MIKRORNA' and the project \[09SYN-13-901\] 'EDGE' by the Greek General Secretariat for Research and Technology. Funding for open access charge: Project 'EDGE'.

*Conflict of interest statement*. None declared.

The authors would like to thank the two anonymous reviewers for their constructive comments and suggestions.

[^1]: The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.

[^2]: *n*~1~: number of nodes in pathway A, *n*~1+~: number of targeted nodes in pathway A, *n*~1−~: number of non-targeted nodes in pathway A, *n*~2:~ number of nodes ∉ Pathway A, *n*~2+~: number of targeted nodes ∉ Pathway A, *n*~2−~: number of non-targeted nodes ∉ Pathway A, N~+~: all targeted nodes, N~−~ all non-targeted nodes, N: all nodes.


Last month I wrapped up my time playing at Walter Reed for patients and families. It was truly an honor to share music so I wanted to begin my last day differently. I set up my violin by the nurses’ station to play a song specifically for them. I had no idea how long they had been working that day prior to my arrival. Perhaps the last few hours of a 12-hour shift? I don’t know but when one of the nurses asked if I could play for him I didn’t hesitate to ask which song he’d like to hear. As I readied my violin a woman came from around the corner asking if I played in individual rooms and if I could come play for her Dad. She briefly shared that his father used to play the fiddle and give concerts for family and friends. I smiled and said I’d make my way.

I played Ave Maria by the nurses’ station and saw a few heads poke out of different rooms. While the nurses worked I saw people slowly make their way to the station to listen while putting a pause on the various questions they may have wanted to ask the nurses. After I finished the song, I went to the rooms of patients to play and spotted the woman from before. She ushered me into a room full of people. The woman exclaimed that I was here and told her Dad that she had a surprised for him. I looked around and had a hard time counting the number of people visiting her Dad. I introduced myself and saw family members eager to listen and wanting to record on their phones so I made a point in saying to please feel free to record and share with family and friends. I played one song after another to hear different family members sing along to Somewhere Over the Rainbow as their Dad quietly smiled from his bed and watched as I played. I finished the music and thanked everyone for my time while giving one of the daughters my card.

A few days ago, I received a phone call from one of the daughters explaining that her father had passed away and prior to passing had arranged with his family to request if I could play at the funeral. The family asked if I could perform a Hymn with the Organist and Home on the Range. I was initially baffled honestly. Why me? But I’ve learned that sometimes God puts you where you need to be so I didn’t ask questions and said of course.

At the funeral, I sat to play as people came for the gathering prior to the service. While I played, the Organist introduced herself as she arrived so I rehearsed the hymn Abide With Me by the Organ and somehow ended playing through countless hymns with her and songs in an Organ book. As the service waited for my time to play Home on the Range at the end. At that time, the room became still and quiet. The organist gave me the signal and I stood to play Home on the Range one final time. It took me back to the time I performed Edelweiss for the patient I met in Hospice. When I finished, I heard one of the daughters exhale deeply and say thank you.

During the dinner, I still had the question lingering in my head. Why me? One of the daughters sat by me and shared that she played the video recording from that day in the hospital over and over again for her Dad. When he no longer responded verbally, she played the video and he would lift his hands playing the air violin. My heart hurt but I smiled. I was thankful to be at the hospital that very day to play.

Before I left the family said they would never forget me and thanked me again for fulfilling their Father’s request. I am grateful God continues to use me in the most amazing of ways and I hope I continue to grow in humility and skill.

Last month I wrapped up my time playing at Walter Reed for patients and families. It was truly an honor to share music so I wanted to begin my last day differently. I set up my violin by the nurses’ station to play a song specifically for them. I had no idea how long they had been working that day prior to my arrival. Perhaps the last few hours of a 12-hour shift? I don’t know but when one of the nurses asked if I could play for him I didn’t hesitate to ask which song he’d like to hear. As I readied my violin a woman came from around the corner asking if I played in individual rooms and if I could come play for her Dad. She briefly shared that his father used to play the fiddle and give concerts for family and friends. I smiled and said I’d make my way.

I played Ave Maria by the nurses’ station and saw a few heads poke out of different rooms. While the nurses worked I saw people slowly make their way to the station to listen while putting a pause on the various questions they may have wanted to ask the nurses. After I finished the song, I went to the rooms of patients to play and spotted the woman from before. She ushered me into a room full of people. The woman exclaimed that I was here and told her Dad that she had a surprised for him. I looked around and had a hard time counting the number of people visiting her Dad. I introduced myself and saw family members eager to listen and wanting to record on their phones so I made a point in saying to please feel free to record and share with family and friends. I played one song after another to hear different family members sing along to Somewhere Over the Rainbow as their Dad quietly smiled from his bed and watched as I played. I finished the music and thanked everyone for my time while giving one of the daughters my card.

A few days ago, I received a phone call from one of the daughters explaining that her father had passed away and prior to passing had arranged with his family to request if I could play at the funeral. The family asked if I could perform a Hymn with the Organist and Home on the Range. I was initially baffled honestly. Why me? But I’ve learned that sometimes God puts you where you need to be so I didn’t ask questions and said of course.

At the funeral, I sat to play as people came for the gathering prior to the service. While I played, the Organist introduced herself as she arrived so I rehearsed the hymn Abide With Me by the Organ and somehow ended playing through countless hymns with her and songs in an Organ book. As the service waited for my time to play Home on the Range at the end. At that time, the room became still and quiet. The organist gave me the signal and I stood to play Home on the Range one final time. It took me back to the time I performed Edelweiss for the patient I met in Hospice. When I finished, I heard one of the daughters exhale deeply and say thank you.

During the dinner, I still had the question lingering in my head. Why me? One of the daughters sat by me and shared that she played the video recording from that day in the hospital over and over again for her Dad. When he no longer responded verbally, she played the video and he would lift his hands playing the air violin. My heart hurt but I smiled. I was thankful to be at the hospital that very day to play.

Before I left the family said they would never forget me and thanked me again for fulfilling their Father’s request. I am grateful God continues to use me in the most amazing of ways and I hope I continue to grow in humility and skill.

Last month I wrapped up my time playing at Walter Reed for patients and families. It was truly an honor to share music so I wanted to begin my last day differently. I set up my violin by the nurses’ station to play a song specifically for them. I had no idea how long they had been working that day prior to my arrival. Perhaps the last few hours of a 12-hour shift? I don’t know but when one of the nurses asked if I could play for him I didn’t hesitate to ask which song he’d like to hear. As I readied my violin a woman came from around the corner asking if I played in individual rooms and if I could come play for her Dad. She briefly shared that his father used to play the fiddle and give concerts for family and friends. I smiled and said I’d make my way.

I played Ave Maria by the nurses’ station and saw a few heads poke out of different rooms. While the nurses worked I saw people slowly make their way to the station to listen while putting a pause on the various questions they may have wanted to ask the nurses. After I finished the song, I went to the rooms of patients to play and spotted the woman from before. She ushered me into a room full of people. The woman exclaimed that I was here and told her Dad that she had a surprised for him. I looked around and had a hard time counting the number of people visiting her Dad. I introduced myself and saw family members eager to listen and wanting to record on their phones so I made a point in saying to please feel free to record and share with family and friends. I played one song after another to hear different family members sing along to Somewhere Over the Rainbow as their Dad quietly smiled from his bed and watched as I played. I finished the music and thanked everyone for my time while giving one of the daughters my card.

A few days ago, I received a phone call from one of the daughters explaining that her father had passed away and prior to passing had arranged with his family to request if I could play at the funeral. The family asked if I could perform a Hymn with the Organist and Home on the Range. I was initially baffled honestly. Why me? But I’ve learned that sometimes God puts you where you need to be so I didn’t ask questions and said of course.

At the funeral, I sat to play as people came for the gathering prior to the service. While I played, the Organist introduced herself as she arrived so I rehearsed the hymn Abide With Me by the Organ and somehow ended playing through countless hymns with her and songs in an Organ book. As the service began, I waited for my time to play Home on the Range at the end. At that time, the room became still and quiet. The organist gave me the signal and I stood to play Home on the Range one final time. It took me back to the time I performed Edelweiss for the patient I met in Hospice. When I finished, I heard one of the daughters exhale deeply and say thank you.

During the dinner, I still had the question lingering in my head. Why me? One of the daughters sat by me and shared that she played the video recording from that day in the hospital over and over again for her Dad. When he no longer responded verbally, she played the video and he would lift his hands playing the air violin. My heart hurt but I smiled. I was thankful to be at the hospital that very day to play.

Before I left, the family said they would never forget me and thanked me again for fulfilling their Father’s request. I am grateful God continues to use me in the most amazing of ways and I hope I continue to grow in humility and skill.


EVENTS

C-SPAN to Air Segments of American Atheists National Convention Saturday July 14

Portions of the 33rd annual National Convention of American Atheists held earlier this year in Seattle, Washington will be aired on the C-SPAN network program “American Perspectives” at 8:00 PM ET on Saturday, July 14.

Edwin Kagin, National Legal Director for American Atheists, will be the guest Thursday, July 12, 2007 on the GAYBC Radio Network out of Los Angeles.

Mr. Kagin, co-founder of Camp Quest will be interviewed on the John McMullen Show. Edwin will be talking about Atheism, separation of church and state in an era of rampant religious fundamentalism, the recent RALLY FOR REASON at the Creation Museum, and more. You can call in to the program via 818-746-3985, or instant message during the program through AOL via GAYBCstudio.

The John McMullen program is broadcast globally daily from 3-6 PM (PACIFIC), 6-9 PM (EASTERN), so check your time zone. Mr. Kagin’s interview segment will begin at 3:15 PM Pacific Time You can live stream the program by clicking on the appropriate icon at www.gaybc.com.

WHO & WHAT: Edwin Kagin, National Legal Director for American Atheists on the John McMullen Show

For the first time ever, Boone Fiscal Court voted Tuesday to give an industrial revenue bond tax break to a local church.

The court voted unanimously to issue up to $2.8 million in bonds on behalf of the Vineyard Christian Church in Burlington in a transaction that renewed debate over the separation of church and state.

The bonds don’t obligate the county financially in any way – they merely allow the church to get a better interest rate on its financing from Fifth Third Bank. Because the county issues the bonds, the bank doesn’t have to report the interest on them as income to the IRS.

The church plans to use the bulk of the money to build a 5,000-square-foot addition for Sunday school classrooms, as well as for the use of community groups such as Alcoholics Anonymous. The rest of the bond issue will pay for preparing the church property for further expansions and for creating more parking spaces.

The congregation has already received $1.2 million in pledges for the project and hopes to pay off the bonds in three years, said Executive Pastor Cliff Wick.

The bond issue will help Vineyard accommodate its steadily expanding congregation. The church has averaged growth of 12 percent over the past seven years and now draws a total of about 1,200 worshippers for its four weekend services.

Attorney Ian Koffler, who represented the church for the bond issue, said it was only the second one his firm had done for a congregation. The other was for a church in Lexington.

County Judge-Executive Gary Moore told the audience for Tuesday’s meeting that he was happy the county could help out the church, and congratulated the congregation on its growth.

But he advised Koffler that some residents had asked him how the county could do it without violating the constitutional separation of church and state.

Koffler told Moore that federal courts have ruled that if governments offers such a service to other nonprofits, they must also offer it to churches.

A Kentucky attorney general’s opinion from 1993 also said bond issues like the Boone County one don’t violate constitutional principles, he said.

Roger Peterman, a specialist in bonds and financing, and a former director of the Kentucky Development Finance Authority, said the courts have recently broadened their view of the church/state issue.

The U.S. Court of Appeals for the 6th Circuit in Cincinnati “had a decision about a year ago that if the government is providing a service that it would provide to a non-religious institution, it can provide the same service to a religious organization,” he said.

That decision came in a case involving a bond issue for a religiously affiliated university in Nashville, said Phillip Sparkes, who teaches state and local government at Northern Kentucky University’s Salmon P. Chase College of Law.

The court ruled that a bond issue is a benefit much like fire protection, he said, and no one would object to the county sending fire trucks to extinguish a fire at a church.

Although it may be a first for a church in Northern Kentucky, counties routinely issue such kinds of bonds, Sparkes said.

“This kind of financing has been around for 50 years or more,” he said. “A variety of projects get funded this way.”

The courts have also ruled that the government could bus children to a church-run school, for example, but not to religious services.

“The Kentucky statutes allow bonds for educational purposes. This is an educational wing of the facility,” Peterman said of the Vineyard project.

But Union attorney Edwin Kagin, national legal director for American Atheists, said that the Kentucky Constitution forbids the government from supporting religion – and that’s what the Boone County bond issue will do.

“If Camp Quest would apply for such a bond issue, do you suppose they would issue bonds for that?” he asked.

Camp Quest is a residential summer camp for the children of atheists. Kagin and his wife, Helen, have served as camp directors for 10 years.


Quantification of endocrine disruptors and pesticides in water by gas chromatography-tandem mass spectrometry. Method validation using weighted linear regression schemes.
A multi-residue methodology based on a solid phase extraction followed by gas chromatography-tandem mass spectrometry was developed for trace analysis of 32 compounds in water matrices, including estrogens and several pesticides from different chemical families, some of them with endocrine disrupting properties. Matrix standard calibration solutions were prepared by adding known amounts of the analytes to a residue-free sample to compensate matrix-induced chromatographic response enhancement observed for certain pesticides. Validation was done mainly according to the International Conference on Harmonisation recommendations, as well as some European and American validation guidelines with specifications for pesticides analysis and/or GC-MS methodology. As the assumption of homoscedasticity was not met for analytical data, weighted least squares linear regression procedure was applied as a simple and effective way to counteract the greater influence of the greater concentrations on the fitted regression line, improving accuracy at the lower end of the calibration curve. The method was considered validated for 31 compounds after consistent evaluation of the key analytical parameters: specificity, linearity, limit of detection and quantification, range, precision, accuracy, extraction efficiency, stability and robustness.


#!/usr/bin/env python3
# -*- coding: utf-8 -*-

"""
create symlink
instead of copying files with do_synch.py
"""

import os
import re
import time

CUR_TS = int(time.time())
REPO_DIR = os.path.dirname(os.path.abspath(__file__))
HOME_DIR = os.path.expanduser('~')
os.chdir(REPO_DIR)

TAB = ' ' * 4
YN = ('y', 'n')
YNI = ('y', 'n', 'i')
LINE = '\n' + '-' * 44 + '\n'

path_map = {
    "home_k": HOME_DIR,
    "local_bin": "/usr/local/bin",
}

TO_SYNC = (
    "home_k/.Xresources",
    "home_k/.agignore",
    "home_k/.config/pylintrc",
    "home_k/.config/alacritty/alacritty.yml",
    "home_k/.config/aria2/aria2.conf",
    "home_k/.config/picom.conf",
    "home_k/.config/conky/conky.conf",
    "home_k/.config/dunst/dunstrc",
    "home_k/.config/fcitx/data/punc.mb.zh_CN",
    "home_k/.config/i3/config",
    "home_k/.config/i3/conky_status.sh",
    "home_k/.config/i3/screenshot.sh",
    "home_k/.config/i3/run_oneko.sh",
    "home_k/.config/i3status/config",
    "home_k/.config/nvim/init.vim",
    "home_k/.config/rofi/config",
    "home_k/.config/shrc.ext",
    "home_k/.config/volumeicon/volumeicon",
    "home_k/.config/xfce4/terminal/terminalrc",
    "home_k/.config/mypy/config",
    "home_k/.config/pycodestyle",
    "home_k/.gitconfig",
    "home_k/.tmux.conf",
    "home_k/.tmuxinator/k.yml",
    "home_k/.vim/.ycm_extra_conf.py",
    "home_k/.vim/mysnippets",
    "home_k/.vimrc",
    "home_k/.xinitrc",
    "home_k/.zshrc",
    "home_k/.eslintrc.js",
    "home_k/.stylelintrc",
    # "local_bin/acpyve",
    # "local_bin/docker_manager",
    "local_bin/myaria2",
    "local_bin/update_hosts",
)

def ask(choices, msg='Continue?'):
    ans = None
    msg += ' (%s) ' % '/'.join(choices)
    while ans not in choices:
        ans = input(msg)
    return ans

def proc_src(src):
    ret = src
    if 'i3/config' in src:
        # manjaro
        with open('/proc/version', 'r') as f:
            version_info = f.read().lower()
            if 'manjaro' in version_info:
                ret = src + '.manjaro'
    return ret

backup_pat = f"*_backup_{CUR_TS}"

if __name__ == "__main__":
    for src in TO_SYNC:
        pref, post = re.match(r"([^/]+)/(.*)", src).groups()
        dest = os.path.join(path_map[pref], post)

        src = proc_src(src)
        print(f"\n>>> processing: {src} -> {dest}")

        src = os.path.join(REPO_DIR, src)
        if os.path.exists(dest):
            if os.path.islink(dest):
                print(os.readlink(dest))
                if os.readlink(dest) == src:
                    print(f"{dest} exists and is already symlinked to {src}. Ignored.")
                    continue
                override_msg = f"{dest} exists and is a symlink. Override it? (file will be mv to {backup_pat})"
            else:
                override_msg = f"{dest} exists and is not a symlink. Override it? (file will be mv to {backup_pat})"
            ans = ask(YN, override_msg)
            if ans == 'n':
                continue
            os.rename(dest, dest + '_backup_{CUR_TS})')
        else:
            prdir = os.path.dirname(dest)
            if not os.path.isdir(prdir):
                os.makedirs(prdir)
        os.symlink(src, dest)
        print(f"created symlink for {src}")


By submitting your personal information, you agree to receive emails regarding relevant products and special offers from TechTarget and its partners. You also agree that your personal information may be transferred and processed in the United States, and that you have read and agree to the Terms of Use and the Privacy Policy.

ADO provides a rich infrastructure for interacting with a wide variety of data, including XML. With DataSets we can now read and write to an XML file with ease.

The following code sample demonstrates how to read and write to an XML file. We are going to read and write an XML file with the details as under:

Class : xml.vbImports System
Class WriteXML
Shared Sub main()
Dim objDataSet As New System.Data.DataSet()
Dim strVirtualPath As String = "t.xml"
'Load the XML file in the data set
objDataSet.ReadXml("xmlfile.xml")
'Read the XML content on the console
Console.Write(objDataSet.GetXml)
'Get data from the user to be saved in the XML file
Console.Write("Enter Name : ")
Dim fname, age As String
fname = Console.ReadLine
Console.Write("Enter Age : ")
age = Console.ReadLine
Console.Write(fname & age)
Dim v(1) As String
v(0) = fname
v(1) = age
'Add the data to the data set
objDataSet.Tables(0).Rows.Add(v)
'Write to updated data back to the XMl file
objDataSet.WriteXml("xmlfile.xml")
Console.Write(objDataSet.GetXml)
End Sub
End Class

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---
abstract: 'The idea of viewing gravitation as a many body phenomenon is put forward here. Physical arguments supporting this idea are briefly reviewed. The basic mathematical object of the new gravitational mechanics is a matrix of operators [@pom1]. Striking similarity of the method of R-matrix (QISM) to the mathematical formulation of the new gravitational mechanics is pointed out. The s-wave difference Schrodinger equation describing a process of emission of radiation by a gravitating particle [@pom1] is shown to be analogous to the Baxter equation of the QISM [@skl1].'
address:
- 'Department of Physics and Astronomy, University of South Carolina,'
- 'Columbia, SC 29208, USA'
author:
- 'Pawel O. Mazur'
title: Gravitation as a Many Body Problem
---

-.5in

1.2cm

*[Talk given at the Conference “Beyond the Standard Model V”,]{}*

*[April 29-May 4 1997, Balholm, Norway.]{}*

Introduction
============

It is well known that the classical gravitating systems behave in the way foreign to statistical quantum mechanics. The negative specific heat of those systems and the phenomenon of gravitational collapse are different facets of the same reality. The difficulties arise which necessitate that the complete atomistic description of gravitation be sought after [@pom1; @pom2]. An effective spacetime description of phenomena would be than obtained in the thermodynamical large $N$ limit [@pom2; @gorpom]. The well known paradoxes of gravitational physics which only until recently stood apart are recognized now as intimately connected [@pom1; @pom2; @gorpom]. They are: [*i)*]{} an ultimate gravitational collapse which also leads to the breakdown of spacetime description; [*ii)*]{} a negative specific heat of gravitating systems and of black holes specifically [@bek1; @hawk1]; [*iii)*]{} unitarity nonconservation on black holes [@hawk1; @thoof1]; [*iv)*]{} information loss on black holes, paradox of nonorthodox causality structure, “breakdown of physics” in singularities; [*v)*]{} nonrenormalizability of gravitation in the usual scheme of QFT. The well known fact of nonrenormalizability of gravitation is not surprising after all because gravitons are not the right microscopic degrees of freedom. This is here where the [*non-collapse postulate*]{} and the resulting statistical mechanical arguments [@pom2; @gorpom] help to establish that the microscopic degrees of freedom are the Planckian mass [*gravitational atoms*]{} rather than gravitons. Gravitational quanta [@pom2] and gravitons must then appear as collective excitations of a bound state of many gravitational atoms. That the microscopic theory of gravitation must involve new and previously unanticipated degrees of freedom, which have nothing to do with strings or membranes [@suss2; @ban], was first proposed several years ago [@pom1; @pom2; @lect95]. The idea of introducing new kinematics, and to be specific, exactly, the generalization of the Heisenberg matrix mechanics to the matrix of operators for a gravitating particle was first described in [@pom1] and at the USC Summer 1995 Institute lecture [@lect95; @cn95]. It should be clear that kinematics is fundamental whereas dynamics depends on a system: there are many Hamiltonians but only one fundamental relation $[p,q]={h\over {2\pi}i}$. This is why my proposal for kinematics of the new gravitational mechanics [@pom1] is universal while strings and membranes are only models [@suss2; @ban].

The Fundamental Idea of The New Gravitational Mechanics
=======================================================

I will briefly present different heuristic arguments which have led me to the proposal of the new gravitational mechanics [@pom1]. In essence my argument that the fundamental object of gravitational mechanics is the matrix of operators followed from a careful examination of the GRT Kepler problem [@pom1]. The geodesic motion is uniformized by a complex$\equiv$symplectic torus. Hence the idea of a noncommutative torus replacing a symplectic torus has emerged [@lect95; @pom1]. Two sets of matrices of operators ${\bf X}^{\mu}$, ${\bf P}_{\mu}$, which now describe a geodesic motion of a test particle satisfy a matrix Heisenberg relations [@lect95; @pom3].

There exists a subtle connection between the idea of a matrices of operators describing a gravitating particle and QISM. The second symplectic structure of the KdV equation is the same as the Virasoro algebra, the algebra of classical reparametrization invariance of a geodesic action principle. Quadratic noncommutative algebras related to the Yang-Baxter equation are central to the quantum inverse scattering method (QISM) [@skl1]. QISM or R-matrix method deals directly with a matrix of operators as the fundamental object [@skl1].

I have noticed long time ago that a classical geodesic motion of a test particle (massive or massless) in the gravitational field of a Schwarzschild black hole is related to the single soliton solution of the KdV equation. This is so because

$$u=r^{-1}={1\over 2KM}({1\over 3}+4{\cal P}(\phi;\omega,\omega')),$$

where $K={G\over c^2}$ is the Einsteinian gravitational constant, and $M$ is the mass of a black hole, is a solution to the geodesic equation. This motion is described by the doubly periodic Weierstrass ${\cal P}$-function, with two periods $2\omega$, $2\omega'$ which determine a lattice on the complex $\phi$ plane. The classical geodesic motion in the Schwarzschild black hole gravitational field is uniformized by a complex torus. I have suggested that this complex torus be regarded as a symplectic torus. This has led me to the canonical Sommerfeld phase integral

$$I=\cint p_rdr$$

over a homotopically nontrivial contour on an elliptic curve uniformizing the actual physical motion (double covering of the complex $r$-plane). Similar construction can be easily carried through for the geodesic motion in the Kerr black hole gravitational field with the effect that

$$I=4{\pi}iG{\delta}{M_C}^2=i{\delta}{A_{bh}\over 4G}=i{\delta}S_{bh} ,$$

where $M_C$ is the Christodoulou irreducible mass[^1] [@christo], $A_{bh}$ is an area of a black hole horizon, and $S_{bh}$ is a black hole entropy [@bek1; @hawk1] ($\hbar=c=k=1$ is assumed here). Semiclassical quantization conditions of Sommerfeld can be easily extended to the case of the complexified KAM torus (complexified integrable systems) [@pom1; @lect95; @pom3]. The two angle variables on a complex uniformizing torus lead to the generalized Heisenberg matrix mechanics. It is essential here that the two periods are distinct in character, as one of them is complex (purely imaginary for bound orbits). I have followed the basic idea of transition to matrix mechanics as described by Dirac [@dir; @pom1]. According to Dirac [@dir] the fundamental idea of matrix mechanics was to consider [*two Bohr orbits instead of one*]{}. Now, two distinct periods in the GRT Kepler problem suggested to me the idea of considering two sets of two integers related to two periods on the complex uniformizing torus, and hence a matrix of matrices. This is the essence of the idea of generalized Heisenberg matrix mechanics applied to gravitation: a matrix of operators ${\cal O}_{mn}$ as the fundamental object. The problem of a particle moving in the gravitational field of two heavy centers (two extremally charged black holes described classically by the Majumdar-Papapetrou metric), which is the GRT Pauli problem, shows that one must now consider an object ${\cal O}_{{\bf mn}}$, where ${\bf
n}$ is a vector multi index; in the Pauli problem this vector index has only two components. The generalization to other systems is obvious [@pom3]. The action principle for the GRT Kepler and Pauli problems is the generalization of the geodesic action principle for the mathematical object ${{\bf X}^{\mu}}_{\bf mn}$:

$$I={1\over {2l^2}}\int Tr({\bf g}_{\mu\nu}({\bf X}){\partial {\bf
X}^{\mu}}{\partial {\bf X}^{\nu}}){d\xi},$$

where $l$ is the Planck length, ${\bf g}_{\mu\nu}$ is a metric tensor which is now a matrix of operators, and ${\partial {\bf X}}={d\over d\xi}{\bf X}$, with $\xi$ a complex parameter. The trace operation $Tr({\bf A}{\bf B})$ is defined as a trace over two vector spaces on which a matrix of matrices (operators) acts. In this way one recovers in an explicit mathematical form an early heuristic suggestion of quantization of a black hole area originally due to Bekenstein [@bek2; @grg19; @thoof2; @suss1]. It becomes clear now that the spacetime picture associated with the surface of a black hole horizon divided into many Planckian area cells is quite misleading. Such a spacetime picture, sometimes called [*the holographic principle*]{} [@bek2; @thoof2; @suss1], is equally incorrect as a toy idea of the noncommutative configuration space would be at the time of the old quantum theory. It is the phase space, or symplectic geometry, which becomes noncommutative upon transition to quantum mechanics. Physical arguments based on the [*non-collapse*]{} postulate and on the s-wave difference Schrodinger equation are compatible. We have found a spectrum of collective excitations of a system of gravitational atoms [@pom1; @pom2; @gorpom].

The Non-Collapse Postulate and Integrable Many Body Systems
===========================================================

The method of R-matrix or the quantum inverse scattering method (QISM) has proven quite powerful in the many body problem solving [@skl1]. It is perhaps not too naive to expect that this method could be also applied to the phenomenon of the universal gravitation once it is demonstrated that a gravitational mass behaves as a many body system.

That gravitation is a many body problem follows from the black hole thermodynamics with the non-collapse hypothesis incorporated explicitly [@pom1; @pom2; @gorpom]. The Bekenstein entropy [@bek1] of a black hole (and its negative specific heat) does not really imply that gravitation is actually a many body problem. Even though invoking the concept of entropy in the context of black holes implicitly means that some kind of atomism is assumed, the many body (atomic) nature of a gravitational mass was not uncovered until only quite recently [@pom2; @gorpom]. The concept of gravitational quanta and gravitational atoms has appeared quite naturally once the non-collapse hypothesis was introduced. Previously, the information theoretic interpretation of entropy was adopted in accord with an apparent loss of information inside black holes [@bek1]. Therefore, the concept of gravitational atoms and gravitational quanta did not appear earlier. On the other hand elementary planckian cells of black hole horizon area were almost always mentioned in the context of black hole thermodynamics [@bek1; @bek2; @thoof1; @thoof2; @suss1]. Clearly, it is a long way from the concept of the black hole horizon area cells to the idea that the physical nature of a gravitational mass is best described as a many body problem. The arguments to this effect are of physical character and were first discovered several years ago [@pom1; @pom2; @grg19]. This is to say, that our method is model independent and this conclusion was obtained long before the so-called D-brane soliton approach to certain unphysical black holes was presented in the literature [@strovaf].

The central character of the non-collapse hypothesis in the demonstration that gravitation is a many body phenomenon is difficult to overestimate. The [*gedanken experiment*]{} presented in the next section was a basis of our hypothesis that the total specific heat of a quantum black hole is positive [@pom2; @gorpom]. This is clearly connected to the problem of unitarity conservation. With the help of this single postulate we were able to demonstrate that a gravitational mass-energy behaves as a number of correlated harmonic oscillators [@pom2; @gorpom]. This is in a complete agreement with the s-wave difference Schrodinger equation presented in [@pom1]. I have called these correlated harmonic oscillators [*gravitational quanta*]{} because they are related to the gravitational mass.

Now, it became clear to me that the simplest properties of gravitational quanta (and gravitational masses) suggest that they are weakly coupled for a large total mass-energy $E$ and that the total mass-energy of this system is a sum of energies of collective excitations

$$E=\sum_{n} {\epsilon}_{n}.$$

In particular, for a large natural number $N$ a typical energy scale for collective excitations is

$${\epsilon}_{n}\sim {{\mu}\over \sqrt{N}},$$

where $\mu$ is a Planck mass. The total mass-energy scales with $N$ as follows:

$$E\sim {\mu}\sqrt{N}.$$

This is a general property of integrable quantum many body systems that a total energy is a sum over energies of collective excitations [@skl1]. In my previous work on the collective excitations of a black hole I have proposed an s-wave difference Schrodinger wave equation which describes energy levels of a black hole [@pom1]. I have taken a null shell model for the s-wave scalar particle mode in the geometric optics approximation, which is only adequate near a black hole horizon, and I have quantized the collective degree of freedom of such a shell. The energy spectrum came out a harmonic oscillator spectrum. Such a procedure is not quite unique, as the more detailed analysis has shown. On the other hand the validity of such a model is limited only to the region near a black hole horizon, and as such this model should be considered an approximation. One can conclude from this that membrane models are not to be considered valid unless qualitative agreement is reached with other independent arguments of physical nature as the one presented above. We should keep in mind that we move on a new ground here and we should seek the consistency of arguments. The formal analogy which comes to mind is based on two observations:

[*[ i)]{} Gravitation is a many body phenomenon; the total mass-energy of a gravitating mass is a sum of energies of collective excitations.*]{}

[*[ii)]{} Quantum integrable models of many body systems are leading to the same property of the total energy, and in addition to that the method of separation of variables (SOV) [@skl1] applied to such systems leads to the Schrodinger wave equation, called in this case the Baxter equation, which, in general, is a difference equation.*]{}

Our basic observation is that the s-wave Schrodinger equation describing collective excitations of a black hole [@pom1]:

$$x(\psi(x+iL)+\psi(x-iL))=(x+2{\epsilon})\psi(x) ,$$

where $\epsilon$ is an energy of a collective excitation and $L\sim {1\over M}$ in Planck units, is of the same type as Baxter equations for collective excitations of integrable quantum many body systems [@skl1]. The question which occurs naturally now is the following: What kind of mathematical structure describing a gravitating particle leads to the difference Schrodinger equation presented in [@pom1] ? If we look closer into the derivation of the Baxter equations in the QISM approach of Sklyanin [@skl1], we also notice that the basic mathematical structure is the matrix of operators constrained by some quadratic relations. Associativity of such quadratic algebras leads to the Yang-Baxter equations (YBE). Now, my idea of the second Heisenberg algebra related to the presence of the second period of Nature (the second angle variable on a complex torus) in the GRT Kepler problem [@pom1] was to consider a matrix of operators as an observable in the new gravitational mechanics [@pom1; @pom3]. This observation has a profound meaning, and it cannot be just an accident, as it is based on physical arguments. One must follow the lead which this connection has opened up [@pom3].

The Gedanken Experiment and the Non-Collapse Hypothesis
=======================================================

Consider the following situation. A large number of identical gravitating particles (mini black holes), which for simplicity will be assumed to be spinless, are contained in a large box. This large box can be considered to be filled up with a black body radiation at some temperature $T$. This cavity black body radiation is considered to be in thermodynamical equilibrium with a cavity walls which are also kept at a constant temperature $T$. The next step is to assume that a black body radiation is in statistical equilibrium with mini black holes. Unless small identical black holes are in statistical equilibrium among themselves due to collision processes the second law of thermodynamics is violated. The [*non-collapse hypothesis*]{} can be concisely formulated as the statement to the effect that in the processes of collisions between identical mini black holes inelastic processes do not happen (hence non-collapse), or that collisions are elastic with a high probability. This is quite similar to the situation considered once by Einstein [@ein1]. Our gedanken experiment is concerned with identical gravitating particles in thermodynamical equilibrium, which is, on the other hand, impossible according to general relativity (GRT). In this situation GRT predicts a merger of two or more mini black holes in the process of a head-on collision. The phenomenon of gravitational collapse precludes the possibility of statistical equilibrium to be achieved in processes of mini black hole collisions. Hence, the hypothesis of statistical equilibrium in our gedanken experiment is a qualitatively new element introduced into the physical theory. Gravitational collapse in the head-on collisions of mini black holes does not happen. If it does happen, as GRT predicts, then the second law of thermodynamics is not valid in the situation described by our gedanken experiment.

The classic argument of Einstein [@ein1] applied by him to a classical gas of atoms in statistical equilibrium with a black body radiation and among themselves leads to the Planck distribution formula for radiation once the Bohr formula $E_{m}-E_{n}=h{\nu}_{mn}$ (and the postulate of spontaneous and stimulated emission of radiation) was assumed for the processes of absorption and emission of radiation by atoms. Reversing this classic argument, when applied to our gedanken experiment, must necessarily lead to the quantized mass-energy levels of mini black holes [@bek2; @grg19; @pom1; @pom2; @gorpom]. The new postulate was made in derivation of this conclusion. This is the non-collapse postulate which logically plays the same role in our gedanken experiment as the postulate of spontaneous emission of radiation has played in the derivation of Planck formula [@ein1]. In our case we postulate the Planck formula but we want to argue for the Bohr formula. We have thus reached the conclusion that a gravitating mass behaves statistically as if it consisted of a huge number of gravitational quanta. These quanta could be identified with collective excitation of a large number of Planckian mass scale gravitational atoms [@pom2; @gorpom]. Statistical considerations are qualitative by nature and they do not lead to the definitive mathematical models for the dynamics of those gravitational atoms. The only important statement which follows from our work [@pom2; @gorpom] is the definitive argument about the physical nature of gravitating particles. The nature of a gravitational mass is now understood qualitatively. Einsteinian gravitation is by its nature the many body phenomenon.

This work was supported by the NSF grant to the University of South Carolina.

[*Acknowledgements.*]{} I wish to thank organizers of BSMV for their kind hospitality during the conference.

P. O. Mazur, Acta Phys. Polon. [**26**]{}, 1685 (1995). E. K. Sklyanin, in [*Quantum Group and Quantum Integrable Systems*]{}, pp. 63-97, ed. Mo-Lin Ge, World Scientific, Singapore, 1992. P. A. M. Dirac, in [*Directions in Physics, Development of Quantum Mechanics*]{}, pp. 2-20, especially pp. 4-5, John Wiley and Sons, New York 1978. P. O. Mazur, Acta Phys. Polon. [**27**]{}, 1849 (1996). A. Z. Gorski and P. O. Mazur, hep-th/[**9704179**]{}, submitted to Phys. Rev. Lett. (1997). J. D. Bekenstein, Phys. Rev. [**D7**]{}, 2333 (1973). S. W. Hawking, Commun. Math. Phys. [**43**]{}, 199 (1975). G. ‘t Hooft, Nucl. Phys. [**B335**]{}, 138 (1990). P. O. Mazur, lecture at the USC Summer Institute, July 1995. P. O. Mazur, [*On the Fundamental Idea of the New Gravitational Mechanics*]{}, unpublished (1996). D. Christodoulou, Phys. Rev. Lett. [**25**]{}, 1596 (1970). J. D. Bekenstein, Lett. Nuovo Cimento [**11**]{}, 467 (1974). P. O. Mazur, GRG [**19**]{}, 1173 (1988). G. ‘t Hooft, in [*Salamfest*]{}, gr-qc/[**9310026**]{}, (1993). L. Susskind, J. Math. Phys. [**36**]{}, 6377 (1995). A. Strominger and C. Vafa, Phys. Lett. [**379**]{}, 99 (1996). A. Einstein, Phys. Z. [**18**]{}, 121 (1917). A. Casher and S. Nussinov, hep-ph/[**9510364**]{}, (1995). T. Banks, W. Fischler, S. H. Shenker and L. Susskind, Phys. Rev. [**D55**]{}, 5112 (1997). T. Banks, hep-th/[**9706168**]{}, (1997).

[^1]: The Christodoulou irreducible mass is defined by the formula $M^2={M_C}^2 + {J^2\over 4G^2{M_C}^2}$.


Follow UT Dallas:

Process of Creating Green Spaces Will Affect Access to Some Buildings

Nov. 26, 2013

Renovation of the north end of campus will begin during winter break as part of the University’s Campus Landscape Enhancement Project.

Landscape architect Peter Walker’s campus enhancement plan will expand north from the Trellis to the Administration Building. The project will bring a more park-like environment to the north mall to complement the transformation of the south end of campus, which was completed in 2010.

Parking areas affected

The 220,000-square-foot Bioengineering and Sciences Building is scheduled to begin construction.

On Friday, Dec. 20, parking lots P and O on the northeast corner of Rutford and Loop Road will permanently close to accommodate construction of the new Bioengineering and Sciences Building near the Natural Science and Engineering Research Lab (NSERL). Drivers who currently use these lots will be redirected to park in lots A, B and T. Pedestrians coming from the University Commons areas are encouraged to walk on the west side of Rutford Drive as they travel toward their destinations.

Pedestrians should also be aware of utility work along the sidewalk from lots P and O to the English Language Center during the break. Additionally, partial areas of lots H and I will be closed as crews lay the groundwork for the future installment of temporary modular buildings in the berm area between the two lots.

On Friday, Dec. 20, construction crews will begin staging the green area on the map with equipment and fencing, which will remain in place throughout the duration of the project. The north mall will be closed to pedestrians for at least a year as the renovation progresses. From Dec. 20 to Jan. 13, weather permitting, crews will work to demolish and remove pavement and heavy debris to make way for more green space.

Access to the Eugene McDermott Library, Student Union and the south part of the mall will remain unaffected.

Campus community members and visitors are encouraged to allow additional travel time to reach their destinations. Drivers may experience some delays as large trucks move in and out of campus, and road flaggers will be on hand to direct traffic as necessary. The entrance to parking lot G will also be revised.

Pedestrians will be redirected to the perimeter entrances of the affected buildings and are encouraged to use the skybridges that connect the Administration Building with the Erik Jonsson Academic Center, Founders North Building, Founders Building, Cecil H. Green Hall, Lloyd V. Berkner Hall, and the North and South Engineering and Computer Science buildings.

“We appreciate everyone’s patience as we continue with the next phase of Pardon Our Progress,” said Dr. Calvin Jamison, vice president for the Office of Administration. “As with our initial phase, we know the campus community will be proud of the finished product. When completed, we will have a very attractive, inviting and pedestrian-friendly mall that will further advance us toward a Tier One infrastructure.”

As construction progresses, faculty, staff, students and visitors will be provided with updates and information to help navigate the campus. Look for increased signage throughout the buildings and announcements via News Center as well as email and text messages.

The green area will be fenced off during the renovation of the north mall, which begins Dec. 20. Pedestrians will be able to use skybridges (map) and perimeter entrances to access buildings during the project.

North Mall Enhancement Q&A

How long will construction be ongoing?

The project will continue over the next year. If weather permits, the loudest and most disruptive part of the project will be completed by Jan. 13, when classes resume after winter break.

How will I be able to get from the south end of campus to the north end?

The north mall, from the Trellis to the Administration Building, will be closed to pedestrians throughout the duration of the project. Pedestrians will be redirected to the perimeter entrances of affected buildings, which include the Administration Building, Erik Jonsson Academic Center, University Theatre, Founders North Building, and Founders Building, Cecil and Ida Green Center, and Cecil H. Green Hall.

Students, faculty and staff are encouraged to use the indoor skybridges that connect the Administration Building with the Erik Jonsson Academic Center, Founders North Building, Founders Building, Cecil H. Green Hall, Lloyd V. Berkner Hall and the North and South Engineering and Computer Science buildings. Allowing additional travel time to reach your destination is highly recommended.

How will I be able to get to the University Theatre for an event?

Temporary access will be provided for scheduled events.

How will this affect Parking and Transportation?

Depending on their destinations, drivers may need to park in different lots and plan additional travel time. Drivers may experience some delays as large trucks move in and out of campus, and road flaggers will be on hand to direct traffic as necessary. The entrance to parking lot G will also be revised.

Cyclists should remove their bikes from racks inside the north mall construction area no later than Tuesday, Dec. 17. Any bikes left in the construction area on Wednesday, Dec. 18, will be impounded; owners will have to pick up their bikes at the UT Dallas Police Department. Bike racks will be relocated to accessible locations on the perimeter of the affected buildings.

What will happen to the Love Jack and the Spirit Rocks?

The Love Jack will be moved to a temporary location and later assigned a new, permanent location. The Spirit Rocks will be moved to a temporary location until they can be moved back and incorporated into the overall design plan of the north mall. The temporary locations will be determined soon.

What will happen to the trees currently in the mall?

Most of the trees will be moved and eventually transplanted elsewhere on campus.


12 Jul Top Things Your Business Has Probably Forgotten To Clean

How clean is your office workspace? Whilst most offices have some sort of cleaning regimen, the likelihood of a thorough and methodical clean taking place on a regular basis is probably quite limited. Whilst the most common areas might get a little spray and wipe here and there, there are undoubtedly at least several areas that are either overlooked or simply popped into the ‘too hard basket.’ Although you might not visibly notice these areas as dirty or unhygienic, it’s quite likely that dust and other microscopic particles are making their way into your morning coffee, the lunch you spent an hour preparing and worst of all, your airways, which can lead to a range of health complications in the future. To help you become more aware of what’s really lurking in your office, let’s take a look at some of the most commonly overlooked areas in the office clean out.

Print and copy stations

One of the most commonly forgotten areas to clean is around work print and copy stations. Aside from the accumulation of dirt and dust, high performance printers have the tendency to emit tiny particles that can accrue around the machine itself and the wider print station as well.

Air conditioners, heating systems & vents

Throughout both summer and winter months when air conditioners and heating systems are in constant use, offices and other small spaces fill with dust, allergens and other tiny particles which then settle around the room. Whilst most of us think that a little dust never hurt anyone, inhalation of such particles can trigger asthmatic attacks, allergic reactions and even respiratory issues. For this reason, it is so important to keep on top of vent cleanliness all year round.

Ceilings, light fixtures & fan blades

Although somewhat painful to access for cleaning purposes, ceilings, light fixtures and fan blades all have a nasty habit of collecting dust. This is exacerbated in times where there might be a little extra moisture in the air as flaky dust accumulation turns into a sticky grime that can be ugly to look at and painful to remove. In addition, light fixtures often attract insects which can accumulate quite quickly if not regularly removed.

Light switches & door handles

When was the last time you sanitised your light switches and door handles? As potentially the most frequently touched parts of your office, these areas might not seem unclean to the eye but in reality, are likely to be swarming with germs and bacteria. With the touch of a single door handle, germs can be spread throughout the entire office within just a few hours.

Window tracks

While cleaning window panes is generally at the top end of the cleaning list, an area that is almost always missed is the window tracks. You might think that because they aren’t as visible, they aren’t as important to keep clean however they actually provide the perfect environment for dirt, dust and grime to build up causing a potential health hazard. If left for too long, build up can become so great that the windows are unable to close properly and thus allow for unwanted insects, moisture and temperatures to invade your office space.

Fixed cabinets and furniture

If you’ve got some filing or storage cabinets that double as a table or photo stand, chances are these will be full of unhealthy dust and dirt. Not only do draws and files attract dust, but items such as photos and awards displayed on top have a tendency to trap unwanted particles as well. This problem is made worse if the cabinet or furniture isn’t used very often and the dust begins to accumulate as a thick film (until it is disturbed and inhaled by the next unwitting person to touch it).

Upholstery

Do you remember what colour your upholstery was when you bought it? If it was quite a while ago, try turning over one of the cushions or have a look at the back where it folds in on itself. If the colour is significantly dulled or you notice unhealthy-looking stains, then it’s definitely time to get your upholstery steam cleaned.

Walls

Sometimes the most obvious things are the easiest to overlook which is why walls are quite often missed in the general office clean. Have a close look at your walls, especially in areas behind doors, in corners and other less-inhabited areas of your office space; these areas are like playgrounds for dust and dirt to accrue and can be a not-so-fun job to clean if they’ve been left unattended for long periods of time.

So what now?

It’s great to know what areas you need to be aware of in terms of keeping the office hygienic but if you don’t have the knowledge, time or skills to actually complete the clean then where does that leave you? As with most organisations, staff are too busy actually running the business to even think about deep cleaning the office, let alone actually completing the task. So what now? Get in touch with the professionals at City Property Services!

Offering ongoing Commercial Cleaning, One-off Commercial Cleaning and Property Maintenance services, our team of cleaning professionals can customise a program to meet the unique needs of you and your business. As a dedicated team of commercial cleaning specialists, we can guarantee a superior and professional clean that meet and exceeds health, safety and hygiene standards for your sector. As one of the most highly certified cleaning companies in Australia, you can rest assured that all your cleaning requirements will be completed in the most efficient and cost-effective manner possible.

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Artist's description:

Artfinder "Artist of the week" see 'About' section for link.

The series as a whole began as a loose reference to Vonnegut's ideas of hidden messages in the caves of Mercury, and forms a cerebral enquiry into the purpose of image making. Exploring image and symbol which over time will contribute to the illusion of decipherable language: of external significance.The works are conceived to be shown individually, in isolation, or in random groupings to imply 'message'. Each piece exists within an abstract framework which, although it has no visually explicit external reference, still suggests a greater purpose.

The reference here shifts through Vonnegut to Jorge Luis Borges and the Library of Babel.This work is framed, as are we all!K.

Artist's description:

Artfinder "Artist of the week" see 'About' section for link.

The series as a whole began as a loose reference to Vonnegut's ideas of hidden messages in the caves of Mercury, and forms a cerebral enquiry into the purpose of image making. Exploring image and symbol which over time will contribute to the illusion of decipherable language: of external significance.The works are conceived to be shown individually, in isolation, or in random groupings to imply 'message'. Each piece exists within an abstract framework which, although it has no visually explicit external reference, still suggests a greater purpose.

The reference here shifts through Vonnegut to Jorge Luis Borges and the Library of Babel.This work is framed, as are we all!K.