bluuebunny/crossref_metadata_2025 huggingface dataset:
Prostate angiogenesis in development and inflammation
Authors: Wong Letitia , Gipp Jerry , Carr Jason , Loftus Christopher J. , Benck Molly , Lee Sanghee , Mehta Vatsal , Vezina Chad M. , Bushman Wade
Published: November 2013

BACKGROUND

Prostatic inflammation is an important factor in development and progression of BPH/LUTS. This study was performed to characterize the normal development and vascular anatomy of the mouse prostate and then examine, for the first time, the effects of prostatic inflammation on the prostate vasculature.

METHODS

Adult mice were perfused with India ink to visualize the prostatic vascular anatomy. Immunostaining was performed on the E16.5 UGS and the P5, P20, and adult prostate to characterize vascular development. Uropathogenic E. coli 1677 was instilled transurethrally into adult male mice to induce prostate inflammation. RT‐PCR and BrdU labeling was performed to assay anigogenic factor expression and endothelial proliferation, respectively.

RESULTS

An artery on the ventral surface of the bladder trifurcates near the bladder neck to supply the prostate lobes and seminal vesicle. Development of the prostatic vascular system is associated with endothelial proliferation and robust expression of pro‐angiogenic factors Pecam1, Tie1, Tek, Angpt1, Angpt2, Fgf2, Vegfa, Vegfc, and Figf. Bacterial‐induced prostatic inflammation induced endothelial cell proliferation and increased vascular density but surprisingly decreased pro‐angiogenic factor expression.

CONCLUSIONS

The striking decrease in pro‐angiogenic factor mRNA expression associated with endothelial proliferation and increased vascular density during inflammation suggests that endothelial response to injury is not a recapitulation of normal development and may be initiated and regulated by different regulatory mechanisms. Prostate 74:346–358, 2014. © 2013 Wiley Periodicals, Inc.
Model‐based estimation of sampling‐caused uncertainty in aerosol remote sensing for climate research applications
Authors: Geogdzhayev Igor , Cairns Brian , Mishchenko Michael I. , Tsigaridis Kostas , van Noije Twan
Published: November 2013

To evaluate the effect of sampling frequency on the global monthly mean aerosol optical thickness (AOT), we use 6 years of geographical coordinates of Moderate Resolution Imaging Spectroradiometer (MODIS) L2 aerosol data, daily global aerosol fields generated by the Goddard Institute for Space Studies General Circulation Model and the chemical transport models Global Ozone Chemistry Aerosol Radiation and Transport, Spectral Radiation‐transport Model for Aerosol Species and Transport Model 5, at a spatial resolution between 1.125°× 1.125° and 2°× 3°: the analysis is restricted to 60°S–60°N geographical latitude. We found that, in general, the MODIS coverage causes an underestimate of the global mean AOT over the ocean. The long‐term mean absolute monthly difference between all and dark target (DT) pixels was 0.01–0.02 over the ocean and 0.03–0.09 over the land, depending on the model dataset. Negative DT biases peak during boreal summers, reaching 0.07–0.12 (30–45% of the global long‐term mean AOT). Addition of the Deep Blue pixels tempers the seasonal dependence of the DT biases and reduces the mean AOT difference over land by 0.01–0.02. These results provide a quantitative measure of the effect the pixel exclusion due to cloud contamination, ocean sun‐glint and land type has on the MODIS estimates of the global monthly mean AOT. We also simulate global monthly mean AOT estimates from measurements provided by pixel‐wide along‐track instruments such as the Aerosol Polarimetry Sensor and the Cloud–Aerosol LiDAR with Orthogonal Polarization. We estimate the probable range of the global AOT standard error for an along‐track sensor to be 0.0005–0.0015 (ocean) and 0.0029–0.01 (land) or 0.5–1.2% and 1.1–4% of the corresponding global means. These estimates represent errors due to sampling only and do not include potential retrieval errors. They are smaller than or comparable to the published estimate of 0.01 as being a climatologically significant change in the global mean AOT, suggesting that sampling density is unlikely to limit the use of such instruments for climate applications at least on a global, monthly scale.
Space-time symmetries and the Yang-Mills gradient flow
Authors: Del Debbio L. , Patella A. , Rago A.
Published: November 2013

Abstract

The recent introduction of the gradient flow has provided a new tool to probe the dynamics of quantum field theories. The latest developments have shown how to use the gradient flow for the exploration of symmetries, and the definition of the corresponding renormalized Noether currents. In this paper we introduce infinitesimal translations along the gradient flow for gauge theories, and study the corresponding Ward identities. This approach is readily generalized to the case of gauge theories defined on a lattice, where the regulator breaks translation invariance. The Ward identities in this case lead to a nonperturbative renormalization of the energy-momentum tensor. We discuss an application of this method to the study of dilatations and scale invariance on the lattice.
A universal equivalent circuit for carbon-based supercapacitors
Authors: Fletcher Stephen , Black Victoria Jane , Kirkpatrick Iain
Published: November 2013

A universal equivalent circuit is proposed for carbon-based supercapacitors. The circuit, which actually applies to all porous electrodes having non-branching pores, consists of a single vertical ladder network in series with an RC parallel network. This elegant arrangement explains the three most important shortcomings of present-day supercapacitors, namely open circuit voltage decay, capacitance loss at high frequency, and voltammetric distortion at high scan rate. It also explains the shape of the complex plane impedance plots of commercial devices and reveals why the equivalent series capacitance increases with temperature. Finally, the construction of a solid-state supercapacitor simulator is described. This device is based on a truncated version of the universal equivalent circuit, and it allows experimenters to explore the responses of different supercapacitor designs without having to modify real supercapacitors.
Synthesis of Poly(maleic anhydride‐co‐taurine) as a Biodegradable Detergent Builder
Authors: Pan Lihui , Guo Jianwei , Zhu Dongyu
Published: November 2013

Biodegradable poly(maleic anhydride‐co‐taurine) was synthesized by anionic ring‐opening copolymerization of maleic anhydride (MA) and taurine. The structures were characterized by elemental analysis, Fourier transform infrared spectroscopy, nuclear magnetic resonance (1H NMR) and mass spectroscopy. The weight‐average molecular weight (Mw) of the copolymers was tested using multi‐angle laser light scattering instrument. The biodegradability of the copolymers was judged by the shaking table test method. The possibility of the copolymers to be a detergent builder was assessed in terms of the calcium sequestration capacity which was evaluated in accordance with the China National Standard method (GB/T 21884‐2008) and dispersive power test. The results showed that the copolymers were biodegradable, and possessed a high calcium sequestration capacity and a good dispersancy, which were environment‐friendly detergent builders.
Fluoroscopy During Removal of 50 Upper Arm Venous Ports
Authors: Burbridge Brent , Sinclair Nicolette , Stoneham Grant , Otani Robert , Szkup Peter
Published: November 2013

Background: The Cook Vital Port system was observed with fluoroscopy before elective removal. A previous publication noted that catheter fracture with this device occurred at the entry of the catheter into the vein used for catheter deployment. We hypothesized that catheter rupture at the vein entry site may be due to ballooning of the catheter during injection, or possibly due to angulation of the catheter during arm movements.

Methods: Port system contrast injection and fluoroscopy was performed for 50 consecutive patients who attended for elective arm vein port removal. Assessment of the angle of entry of the catheter into the arm vein was performed with the arm in anatomic position and during arm movements.

Results: There was no evidence of catheter ballooning or distortion during contrast injection. There was no evidence of fibrin sheath formation at the catheter tip. One catheter was observed to leak at the vein entry site with the injection of contrast. The only arm movement that affected the angle of the catheter at the vein entry site was flexion at the elbow. The average change in the angle of the catheter between anatomic position and full elbow flexion was 22.4°C.

Conclusions: The hypothesis of ballooning of the catheter at the vein entry site during injection was not confirmed. We observed a wide variation in catheter angulation with elbow flexion. The exact cause for catheter fracture remains unknown.
The Need for Comparative Data in Vascular Access: The Rationale and Design of the PICC Registry
Authors: Girgenti Constance , Moureau Nancy L.
Published: November 2013

Approximately 4.3 million peripherally inserted central catheters (PICCs) are placed each year. Currently, there are no national-level comparative data registries to gather information regarding PICC placement, care, or maintenance, and there are no benchmarks or quality measures for vascular access specialists. As the specialty of vascular access evolves from placing peripheral intravenous catheters and administering infusions to the placement of more advanced devices such as PICCs and other central venous access devices, the lack of national comparative data becomes more significant. Without consistent, comparative data, vascular access specialists cannot demonstrate the high level of clinical outcomes provided for patients or justify the value of the specialty to hospital administrators or third-party payers. Data collection must evolve to improve quality and show cost-effectiveness. National-level comparative data collection has been used for decades by physicians to implement quality initiatives and improve patient care. Comparative data can now easily be provided using informatics technologies like the Internet to collect and analyze data for improved clinical outcomes. Vascular access teams must begin using data registries for collecting comparative data, allowing the development of benchmarks and improved quality measures.
The Effects of 3 Peripherally Inserted Central Catheter Insertion Techniques in Chinese Patients With Different Vascular Status
Authors: Yuan Ling , Fu Rong , Li Rong-Mei , Guo Miao-Miao , Chen Xiang-Yu
Published: November 2013

Objective: To provide evidence for selecting an appropriate peripherally inserted central catheter (PICC) insertion technique by comparing the insertion success rate and the incidence of complications with 3 PICC insertion techniques.

Methods: We assigned enrolled patients to 3 groups according to the insertion technique selected by the individual patient: Group A, usual insertion technique (traditional, blind insertion); Group B, Modified Seldinger Technique (MST) insertion without ultrasound guidance; and group C, ultrasound-guided MST insertion. We compared the insertion success rate and the incidence of complications among these groups.

Results: When comparing these 3 PICC insertion techniques, no significant difference was seen with respect to the insertion success rate and the incidence of catheter malposition (P > 0.05), although a significant difference existed in the incidence of bleeding at the insertion site after the PICC procedure (P < 0.05), with the ultrasound-guided MST insertion technique superior to the other 2 techniques; the incidence of mechanical phlebitis and catheter occlusion during the use of PICC had no significant difference among the 3 groups (P > 0.05); but a significant difference was seen in the incidence of thrombosis and catheter-related infections (P < 0.05), with a lower incidence in the ultrasound-guided MST insertion group than that in the other 2 groups.

Conclusions: Ultrasound-guided MST insertion technique may address the problems occurring in patients with poor vascular access during the PICC procedure, whereas the usual insertion technique is the best choice for patients with good vascular access and poor economic status. Therefore, the selection of an appropriate insertion technique should be based on the economic and vascular status of the individual patient in clinical practice.
Initial Affect of Introducing Ultrasound Guided—Long Lines to the All Wales Cystic Fibrosis Centre
Authors: Marson Ben Arthur , Davies Carole , Lee Jonathan , Ketchell Robert Ian , Duckers Jamie
Published: November 2013

Background: The insertion of a long line can be a dreaded aspect of receiving courses of intravenous antibiotics for respiratory exacerbations associated with cystic fibrosis. Our study evaluates the use of ultrasound guidance in a pilot scheme to improve the experience of line insertion.

Methods: Fifty-five patients commencing intravenous antibiotics for respiratory exacerbation had a long line inserted using conventional Seldinger technique, whereas 18 patients had a line inserted after the introduction of ultrasound guidance. Patients completed a questionnaire to score their satisfaction with line placement and longevity. Complication rates of the lines inserted were recorded prospectively.

Results: No significant difference was found in satisfaction with line placement, line longevity, or number of attempts required to insert the line. Qualitative assessment suggests that patients preferred the use of ultrasound.

Conclusions: Our study shows that routine ultrasound guidance is not associated with improvement in clinical variables, but it does have a role in the management of cystic fibrosis in adult patients.
PAINS: Relevance to Tool Compound Discovery and Fragment-Based Screening
Authors: Baell Jonathan B. , Ferrins Lori , Falk Hendrik , Nikolakopoulos George
Published: December 2013

Pan assay interference compounds (PAINS) are readily discovered in any bioassay and can appear to give selective and optimisable hits. The most common PAINS can be readily recognised by their structure. However, there are compounds that closely resemble PAINS that are not specifically recognised by the PAINS filters. In addition, highly reactive compounds are not encoded for in the PAINS filters because they were excluded from the high-throughput screening (HTS) library used to develop the filters and so were never present to provide indicting data. A compounding complication in the area is that very occasionally a PAINS compound may serve as a viable starting point for progression. Despite such an occasional example, the literature is littered with an overwhelming number of examples of compounds that fail to progress and were probably not optimisable in the first place, nor useful tool compounds. Thus it is with great caution and diligence that compounds possessing a known PAINS core should be progressed through to medicinal chemistry optimisation, if at all, as the chances are very high that the hits will be found to be non-progressable, often after a significant waste of resources.
Sociopolitical and institutional conditions for teaching Spanish as a L2 in US universities
Authors: Lacorte Manel
Published: November 2013

This article examines the teaching of Spanish as a second language (L2) in the US in recent years through a review of public documents and a synthesis of relevant literature. The main goals of the article are to compare the sociopolitical and institutional presence of Spanish with that of other languages within the US educational context, and to explore specific critical dimensions that are likely to influence the future development of Spanish as a L2 in this country. This analysis makes it clear that the current abundance of students studying Spanish does not guarantee a constantly increasing number of learners in future Spanish programs, especially in a sociopolitical and institutional climate such as the present one, in which the study of the humanities, in general, as well as the study of second or foreign languages, in particular, seem to be heading for a marked decline.
Los índices metapragmáticos, la argumentación y el caso de la participación ciudadana en juicios penales
Authors: Carranza Isolda E.
Published: November 2013

Entre los diversos tipos de índices metapragmáticos se elige estudiar las referencias explícitas a la práctica sociocultural de administrar justicia penal, sus principios y su racionalidad, que aparecen en el curso de esa misma práctica. Las manifestaciones de reflexividad no son descripciones neutrales sino que expresan o implican las concepciones normativas de los participantes. La clase de índices metapragmáticos que se examinan son las emisiones que nombran la actividad que se está desarrollando o explicitan sus reglas, procedimientos, conceptos y racionalidad. Estas emisiones son examinadas en el género ‘alegato final’ en juicios penales orales desde la perspectiva teórica del análisis del discurso social e históricamente situado. El análisis muestra que, cuando integran un movimiento argumentativo, estos índices desalientan un potencial desafío. El participante que los emplea en el curso del desempeño de su rol institucional proyecta una imagen de conocedor y respetuoso de los fundamentos y las normas de la práctica social. La función central de estos índices, ya sea que intervengan o no en una argumentación, es la de señalar la posición social de ‘experto’. El estudio también revela que la incorporación de jurados populares se concibe como destinada a legitimar ante la sociedad el funcionamiento institucional.
Tuteo and voseo in the classroom
Authors: Weyers Joseph R. , Canale Germán
Published: November 2013

This study is based on the results of an online survey of Montevidean educators on their attitude toward the tuteo and voseo in the classroom. Traditionally, tuteo was considered the only correct form of address for classroom use in Uruguay’s capital. The results of the 78 completed surveys, along with qualitative data from 11 interviews, suggest a shift in that tradition. Teachers report using voseo with almost similar frequency as tuteo; voseo is viewed by a noteworthy number of educators as acceptable for classroom use; and there is considerable acceptance of the T-V form (e.g. tú tenés) that is common in Montevideo. The results here are consistent with prior studies that point to an increasing use of voseo to the detriment of tuteo in Montevideo, the latter of which reportedly persists given, in part, its traditional role in educational domains.
Spanish/English contact in rural Puerto Rico
Authors: Holmquist Jonathan
Published: November 2013

This article presents three perspectives in the study of Spanish/English contact in a community of rural Puerto Rico. First, it presents an analysis of variation based on the presence of English forms in recorded conversational Spanish. Second, it provides a view of the social context of Spanish/English contact by examining responses to a sociological questionnaire focusing on the use of “Spanish Only” versus Spanish and English in spheres of community life. Third, it highlights speaker commentary on social factors in relation to the use of Spanish and English. The study shows that the presence of English in the recorded conversational Spanish is extremely limited and that Spanish dominates in community life. Nevertheless, the presence of English in both conversational Spanish and social spheres within the community reveals patterns in relation to social factors recognized by speakers.
Models of what processes?
Authors: Chesterman Andrew
Published: November 2013

Toury (1995, 2012) distinguishes between cognitive translation acts on the one hand, and sociological translation events on the other; a translation act is embedded in a translation event, and both acts and events are seen as processes. He also explains three senses of ‘translation problem,’ which relate to different notions of the processes involved in the translation act. The present paper analyzes and develops these ideas. It distinguishes between what are here labeled virtual, reverse-engineered, and actual processes of translation acts or events, which correlate with Toury’s three senses of ‘translation problem.’ A few examples are given of models of each kind of process, both classical and more recent ones. Also discussed is the extent to which the various models are predictive and hence testable. To designate the translation process at the historical and cultural level, alongside the mental act and the situational event, the term ‘translation practice’ is suggested.
Shared representations and the translation process
Authors: Schaeffer Moritz , Carl Michael
Published: November 2013

The purpose of the present paper is to investigate automated processing during translation. We provide evidence from a translation priming study which suggests that translation involves activation of shared lexico-semantic and syntactical representations, i.e., the activation of features of both source and target language items which share one single cognitive representation. We argue that activation of shared representations facilitates automated processing. The paper revises the literal translation hypothesis and the monitor model (Ivir 1981; Toury 1995; Tirkkonen-Condit 2005), and re-defines it in terms of findings from translation process research. On the basis of the evidence, we propose a recursive model of translation.
ELF speakers’ restricted power of expression
Authors: Albl-Mikasa Michaela
Published: November 2013

At the crossroads of English as a lingua franca (ELF) research and interpreting studies, it is paramount to examine why interpreters are at odds with ELF communication in general and with the effects of the output of the growing number of non-native English conference speakers on their work in particular. On the basis of a small-scale case study, the stumbling blocks resulting from non-native English input are examined. The findings point toward what may be a major impediment: activation and retrieval constraints can result from ELF speakers’ restricted power of expression and have an adverse effect on the interpreter’s inferential processing and target text rendering. In the discussion, it is argued that a key problem for devising compensatory (strategic or didactic) measures may lie in the unpredictable and open-ended nature of the means of expression creatively constructed by ELF speakers, which makes it extremely difficult for interpreters to build up a stock of resources that will match the ongoing input items, allowing them to function as activating cues.
The effect of interpreting experience on distance dynamics
Authors: Pavlović Nataša , Antunovic Goranka
Published: November 2013

The aim of this process-oriented study is to test the literal translation hypothesis, i.e., the frequently held view that, in their search for the most suitable translation solution, translators move from more literal towards freer renderings. The study uses keystroke-logging to investigate translation processes involving self-revision in terms of ‘distance dynamics.’ The latter term refers to the fact that each new solution to a particular translation problem can be closer or more distant from the source item than the previous one. A more specific hypothesis is also tested, namely that experience in interpreting has an effect on distance dynamics. To this end, processes of two groups of subjects — translators without substantial interpreting experience, and interpreters — are compared. The findings challenge the literal translation hypothesis, and highlight some methodological issues that should be tackled in future studies.
The impact of process protocol self-analysis on errors in the translation product
Authors: Angelone Erik
Published: November 2013

This paper presents the initial results of an exploratory study examining the efficacy of Integrated Problem and Decision Reporting (IPDR) logs, recorded verbalizations, and screen recordings when used by translation students as revision tools for purposes of recognizing problems and mitigating errors in their translations. Students were given the task of creating one of these three process protocol types in conjunction with nine translations. They were then asked to self-reflect on their problem-solving performance while paying particularly close attention to a series of concrete problem indicator types found in the respective protocols during a post-task retrospective session. The students had the chance to make any desired revisions to their translations as a result of analyses before submitting a final version. The revised versions were marked up for punctuation, spelling, lexical, syntactic, stylistic, and mistranslation errors. The frequency of errors for each of these types was calculated for each student in conjunction with the process protocol utilized. The total number of errors in conjunction with each process protocol type used, regardless of textual level, was also calculated. Screen recording consistently proved to be the most efficacious process protocol type in mitigating errors. This paper concludes by positing several possible explanations for the greater success rate of screen recording as a revision tool and calls for screen recording to be implemented as a core component of a process-oriented translator training curriculum.
Opening eyes to opera
Authors: Eardley-Weaver Sarah
Published: November 2013

In today’s rapidly developing digital age and increasingly socially-aware society, the notion of media accessibility is evolving in response to shifting audience expectations. Performing arts and media, such as opera, are called upon to include all audiences, and related audiovisual translation methods are progressing in this direction. These comprise audio description and touch tours for the blind and partially-sighted, two relatively new translation modalities which are consumer-oriented and require an original research design for the analysis of the translation processes involved. This research design follows two fundamental principles: (1) audience reception studies should be an integral part of the investigation into the translation process; and (2) the translation process is regarded as a network. Therefore, this paper explores the unique translation processes of audio description and touch tours within the context of live opera from the perspective of actor-network theory and by providing an overview of a reception project. Through discussion of the methodology and findings, this paper addresses the question of the impact of audience reception on the translation process.
Finding consistent disease subnetworks using PFSNet
Authors: Lim Kevin , Wong Limsoon
Published: November 2013

Motivation: Microarray data analysis is often applied to characterize disease populations by identifying individual genes linked to the disease. In recent years, efforts have shifted to focus on sets of genes known to perform related biological functions (i.e. in the same pathways). Evaluating gene sets reduces the need to correct for false positives in multiple hypothesis testing. However, pathways are often large, and genes in the same pathway that do not contribute to the disease can cause a method to miss the pathway. In addition, large pathways may not give much insight to the cause of the disease. Moreover, when such a method is applied independently to two datasets of the same disease phenotypes, the two resulting lists of significant pathways often have low agreement.

Results: We present a powerful method, PFSNet, that identifies smaller parts of pathways (which we call subnetworks), and show that significant subnetworks (and the genes therein) discovered by PFSNet are up to 51% (64%) more consistent across independent datasets of the same disease phenotypes, even for datasets based on different platforms, than previously published methods. We further show that those methods which initially declared some large pathways to be insignificant would declare subnetworks detected by PFSNet in those large pathways to be significant, if they were given those subnetworks as input instead of the entire large pathways.

Availability:  http://compbio.ddns.comp.nus.edu.sg:8080/pfsnet/

Contact:  kevinl@comp.nus.edu.sg

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Gene Sets Net Correlations Analysis (GSNCA): a multivariate differential coexpression test for gene sets
Authors: Rahmatallah Yasir , Emmert-Streib Frank , Glazko Galina
Published: December 2013

Motivation: To date, gene set analysis approaches primarily focus on identifying differentially expressed gene sets (pathways). Methods for identifying differentially coexpressed pathways also exist but are mostly based on aggregated pairwise correlations or other pairwise measures of coexpression. Instead, we propose Gene Sets Net Correlations Analysis (GSNCA), a multivariate differential coexpression test that accounts for the complete correlation structure between genes.

Results: In GSNCA, weight factors are assigned to genes in proportion to the genes’ cross-correlations (intergene correlations). The problem of finding the weight vectors is formulated as an eigenvector problem with a unique solution. GSNCA tests the null hypothesis that for a gene set there is no difference in the weight vectors of the genes between two conditions. In simulation studies and the analyses of experimental data, we demonstrate that GSNCA captures changes in the structure of genes’ cross-correlations rather than differences in the averaged pairwise correlations. Thus, GSNCA infers differences in coexpression networks, however, bypassing method-dependent steps of network inference. As an additional result from GSNCA, we define hub genes as genes with the largest weights and show that these genes correspond frequently to major and specific pathway regulators, as well as to genes that are most affected by the biological difference between two conditions. In summary, GSNCA is a new approach for the analysis of differentially coexpressed pathways that also evaluates the importance of the genes in the pathways, thus providing unique information that may result in the generation of novel biological hypotheses.

Availability and implementation: Implementation of the GSNCA test in R is available upon request from the authors.

Contact:  YRahmatallah@uams.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Accessibility of microRNA binding sites in metastable RNA secondary structures in the presence of SNPs
Authors: Day Luke , Abdelhadi Ep Souki Ouala , Albrecht Andreas A. , Steinhöfel Kathleen
Published: December 2013

Motivation: We study microRNA (miRNA) bindings to metastable RNA secondary structures close to minimum free energy conformations in the context of single nucleotide polymorphisms (SNPs) and messenger RNA (mRNA) concentration levels, i.e. whether features of miRNA bindings to metastable conformations could provide additional information supporting the differences in expression levels of the two sequences defined by a SNP. In our study, the instances [mRNA/3′UTR; SNP; miRNA] were selected based on strong expression level analyses, SNP locations within binding regions and the computationally feasible identification of metastable conformations.

Results: We identified 14 basic cases [mRNA; SNP; miRNA] of 3′ UTR-lengths ranging from 124 up to 1078 nt reported in recent literature, and we analyzed the number, structure and miRNA binding to metastable conformations within an energy offset above mfe conformations. For each of the 14 instances, the miRNA binding characteristics are determined by the corresponding STarMir output. Among the different parameters we introduced and analyzed, we found that three of them, related to the average depth and average opening energy of metastable conformations, may provide supporting information for a stronger separation between miRNA bindings to the two alleles defined by a given SNP.

Availability and implementation: At http://kks.inf.kcl.ac.uk/MSbind.html the MSbind tool is available for calculating features of metastable conformations determined by putative miRNA binding sites.

Contact:  kathleen.steinhofel@kcl.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
A mathematical model describing the mechanical kinetics of kinesin stepping
Authors: Khataee Hamidreza , Wee-Chung Liew Alan
Published: December 2013

Motivation: Kinesin is a smart motor protein that steps processively forward and backward along microtubules (MTs). The mechanical kinetics of kinesin affecting its stepping behavior is not fully understood. Here, we propose a mathematical model to study the mechanical kinetics of forward and backward stepping of kinesin motor based on the four-state discrete stochastic model of the motor.

Results: Results show that the probabilities of forward and backward stepping can be modeled using the mean probabilities of forward and backward kinetic transitions, respectively. We show that the backward stepping of kinesin motor starts when the probability of adenosine diphosphate (ADP) binding to the motor is much higher than that of adenosine triphosphate (ATP) binding. Furthermore, our results indicate that the backward stepping is related to both ATP hydrolysis and synthesis with rate limiting factor being ATP synthesis. Low rate of ATP synthesis under high backward loads above 10 pN is also suggested as a reason for the detachment of kinesin motor from MT in the kinetic state MTċKinesinċADPċPi.

Availability and implementation: The code for this work is written in Visual C# and is available by request from the authors.

Contact:  a.liew@griffith.edu.au
GPU linear and non-linear Poisson–Boltzmann solver module for DelPhi
Authors: Colmenares José , Ortiz Jesús , Rocchia Walter
Published: December 2013

Summary: In this work, we present a CUDA-based GPU implementation of a Poisson–Boltzmann equation solver, in both the linear and non-linear versions, using double precision. A finite difference scheme is adopted and made suitable for the GPU architecture. The resulting code was interfaced with the electrostatics software for biomolecules DelPhi, which is widely used in the computational biology community. The algorithm has been implemented using CUDA and tested over a few representative cases of biological interest. Details of the implementation and performance test results are illustrated. A speedup of ∼10 times was achieved both in the linear and non-linear cases.

Availability and implementation: The module is open-source and available at http://www.electrostaticszone.eu/index.php/downloads.

Contact:  walter.rocchia@iit.it

Supplementary information:  Supplementary data are available at Bioinformatics online
RNASurface: fast and accurate detection of locally optimal potentially structured RNA segments
Authors: Soldatov Ruslan A. , Vinogradova Svetlana V. , Mironov Andrey A.
Published: November 2013

Motivation: During the past decade, new classes of non-coding RNAs (ncRNAs) and their unexpected functions were discovered. Stable secondary structure is the key feature of many non-coding RNAs. Taking into account huge amounts of genomic data, development of computational methods to survey genomes for structured RNAs remains an actual problem, especially when homologous sequences are not available for comparative analysis. Existing programs scan genomes with a fixed window by efficiently constructing a matrix of RNA minimum free energies. A wide range of lengths of structured RNAs necessitates the use of many different window lengths that substantially increases the output size and computational efforts.

Results: In this article, we present an algorithm RNASurface to efficiently scan genomes by constructing a matrix of significance of RNA secondary structures and to identify all locally optimal structured RNA segments up to a predefined size. RNASurface significantly improves precision of identification of known ncRNA in Bacillus subtilis.

Availability and implementation: RNASurface C source code is available from http://bioinf.fbb.msu.ru/RNASurface/downloads.html.

Contact:  ruslansoldatov@gmail.com

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Chemical annotation of small and peptide-like molecules at the Protein Data Bank
Authors: Young Jasmine Y. , Feng Zukang , Dimitropoulos Dimitris , Sala Raul , Westbrook John , Zhuravleva Marina , Shao Chenghua , Quesada Martha , Peisach Ezra , Berman Helen M.
Published: November 2013

Over the past decade, the number of polymers and their complexes with small molecules in the Protein Data Bank archive (PDB) has continued to increase significantly. To support scientific advancements and ensure the best quality and completeness of the data files over the next 10 years and beyond, the Worldwide PDB partnership that manages the PDB archive is developing a new deposition and annotation system. This system focuses on efficient data capture across all supported experimental methods. The new deposition and annotation system is composed of four major modules that together support all of the processing requirements for a PDB entry. In this article, we describe one such module called the Chemical Component Annotation Tool. This tool uses information from both the Chemical Component Dictionary and Biologically Interesting molecule Reference Dictionary to aid in annotation. Benchmark studies have shown that the Chemical Component Annotation Tool provides significant improvements in processing efficiency and data quality. Database URL: http://wwpdb.org
When You Ain’t Got Nothin’, You Got Nothin’ to Lose…. Union Recognition Laws, Voluntarism and the Anglo Model
Authors: Doherty Michael
Published: November 2013

A number of recent works have assessed key outcomes of the third statutory union recognition procedure in Britain. A common feature of many of these is the concern that the machinery has failed to achieve positive collective bargaining outcomes for trade unions, due, in particular, to the wider policy environment into which the procedure has been inserted, and the inherent structural confines of the Anglo, ‘representational’, conception of collective bargaining. This article contributes further to this literature, by addressing these issues in the context of, and drawing comparisons with, Irish law on ‘the right to bargain’.
CXCR5+CD4+ follicular helper T cells accumulate in resting human lymph nodes and have superior B cell helper activity
Authors: Havenith Simone H. C. , Remmerswaal Ester B. M. , Idu Mirza M. , van Donselaar-van der Pant Karlijn A. M. I. , van der Bom Nelly , Bemelman Fréderike J. , van Leeuwen Ester M. M. , ten Berge Ineke J. M. , van Lier René A. W.
Published: November 2013

Although many relevant immune reactions are initiated in the lymph nodes, this compartment has not been systematically studied in humans. Analyses have been performed on immune cells derived from tonsils, but as this tissue is most often inflamed, generalization of these data is difficult. Here, we analyzed the phenotype and function of the human CD4+ T-cell subsets and lineages in paired resting lymph node and peripheral blood samples. Naive, central memory cells and effector memory cells as well as Th1, Th2, Th17 and Treg cells were equally represented in both compartments. On the other hand, cytotoxic CD4+ T cells were strikingly absent in the lymph nodes. CXCR5+CD4+ T cells, representing putative follicular Th (Tfh) cells were over-represented in lymph nodes and expressed higher levels of Tfh markers than their peripheral blood counterparts. Compared with the circulating pool, lymph-node-derived CXCR5+CD4+ T cells were superior in providing help to B cells. Thus, functionally competent Tfh cells accumulate in resting human lymph nodes, providing a swift induction of naive and memory antibody responses upon antigenic challenge.
RNA-dependent RNA polymerase of Japanese encephalitis virus binds the initiator nucleotide GTP to form a mechanistically important pre-initiation state
Authors: Surana Parag , Satchidanandam Vijaya , Nair Deepak T.
Published: November 2013

Flaviviral RNA-dependent RNA polymerases (RdRps) initiate replication of the single-stranded RNA genome in the absence of a primer. The template sequence 5′-CU-3′ at the 3′-end of the flaviviral genome is highly conserved. Surprisingly, flaviviral RdRps require high concentrations of the second incoming nucleotide GTP to catalyze de novo template-dependent RNA synthesis. We show that GTP stimulates de novo RNA synthesis by RdRp from Japanese encephalitis virus (jRdRp) also. Crystal structures of jRdRp complexed with GTP and ATP provide a basis for specific recognition of GTP. Comparison of the jRdRpGTP structure with other viral RdRp-GTP structures shows that GTP binds jRdRp in a novel conformation. Apo-jRdRp structure suggests that the conserved motif F of jRdRp occupies multiple conformations in absence of GTP. Motif F becomes ordered on GTP binding and occludes the nucleotide triphosphate entry tunnel. Mutational analysis of key residues that interact with GTP evinces that the jRdRpGTP structure represents a novel pre-initiation state. Also, binding studies show that GTP binding reduces affinity of RdRp for RNA, but the presence of the catalytic Mn2+ ion abolishes this inhibition. Collectively, these observations suggest that the observed pre-initiation state may serve as a checkpoint to prevent erroneous template-independent RNA synthesis by jRdRp during initiation.
Structural mechanism of transcription regulation of the Staphylococcus aureus multidrug efflux operon mepRA by the MarR family repressor MepR
Authors: Birukou Ivan , Seo Susan M. , Schindler Bryan D. , Kaatz Glenn W. , Brennan Richard G.
Published: November 2013

The multidrug efflux pump MepA is a major contributor to multidrug resistance in Staphylococcus aureus. MepR, a member of the multiple antibiotic resistance regulator (MarR) family, represses mepA and its own gene. Here, we report the structure of a MepR–mepR operator complex. Structural comparison of DNA-bound MepR with ‘induced’ apoMepR reveals the large conformational changes needed to allow the DNA-binding winged helix-turn-helix motifs to interact with the consecutive major and minor grooves of the GTTAG signature sequence. Intriguingly, MepR makes no hydrogen bonds to major groove nucleobases. Rather, recognition-helix residues Thr60, Gly61, Pro62 and Thr63 make sequence-specifying van der Waals contacts with the TTAG bases. Removing these contacts dramatically affects MepR–DNA binding activity. The wings insert into the flanking minor grooves, whereby residue Arg87, buttressed by Asp85, interacts with the O2 of T4 and O4′ ribosyl oxygens of A23 and T4. Mutating Asp85 and Arg87, both conserved throughout the MarR family, markedly affects MepR repressor activity. The His14′:Arg59 and Arg10′:His35:Phe108 interaction networks stabilize the DNA-binding conformation of MepR thereby contributing significantly to its high affinity binding. A structure-guided model of the MepR–mepA operator complex suggests that MepR dimers do not interact directly and cooperative binding is likely achieved by DNA-mediated allosteric effects.
Routes for breaching and protecting genetic privacy
Authors: Erlich Yaniv , Narayanan Arvind
Published: November 2013

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.
Genetics of single-cell protein abundance variation in large yeast populations
Authors: Albert Frank W. , Treusch Sebastian , Shockley Arthur H. , Bloom Joshua S. , Kruglyak Leonid
Published: November 2013

Many DNA sequence variants influence phenotypes by altering gene expression. Our understanding of these variants is limited by sample sizes of current studies and by measurements of mRNA rather than protein abundance. We developed a powerful method for identifying genetic loci that influence protein expression in very large populations of the yeastSaccharomyes cerevisiae. The method measures single-cell protein abundance through the use of green-fluorescent-protein tags. We applied this method to 160 genes and detected many more loci per gene than previous studies. We also observed closer correspondence between loci that influence protein abundance and loci that influence mRNA abundance of a given gene. Most loci cluster at hotspot locations that influence multiple proteins—in some cases, more than half of those examined. The variants that underlie these hotspots have profound effects on the gene regulatory network and provide insights into genetic variation in cell physiology between yeast strains.
Designing Robustness to Temperature in a Feedforward Loop Circuit
Authors: Sen Shaunak , Kim Jongmin , Murray Richard M.
Published: November 2013

‘Incoherent feedforward loops’ represent important biomolecular circuit elements capable of a rich set of dynamic behavior including adaptation and pulsed responses. Temperature can modulate some of these properties through its effect on the underlying reaction rate parameters. It is generally unclear how to design such a circuit where the properties are robust to variations in temperature. Here, we address this issue using a combination of tools from control and dynamical systems theory as well as preliminary experimental measurements towards such a design. We formalize temperature as an uncertainty acting on system dynamics, exploring both structured and unstructured uncertainty representations. Next, we analyze a standard incoherent feedforward loop circuit, noting mechanisms that intrinsically confer temperature robustness to some of its properties. Further, we explore different negative feedback configurations that can enhance the robustness to temperature. Finally, we find that the response of an incoherent feedforward loop circuit in cells can change with temperature. These results present groundwork for the design of a temperature-robust incoherent feedforward loop circuit.
Functional Annotation Signatures of Disease Susceptibility Loci Improve SNP Association Analysis
Authors: Iversen Edwin S. , Lipton Gary , Clyde Merlise A. , Monteiro Alvaro N. A.
Published: November 2013

We describe the development and application of a Bayesian statistical model for the prior probability of phenotype–genotype association that incorporates data from past association studies and publicly available functional annotation data regarding the susceptibility variants under study. The model takes the form of a binary regression of association status on a set of annotation variables whose coefficients were estimated through an analysis of associated SNPs housed in the GWAS Catalog (GC). The set of functional predictors we examined includes measures that have been demonstrated to correlate with the association status of SNPs in the GC and some whose utility in this regard is speculative: summaries of the UCSC Human Genome Browser ENCODE super–track data, dbSNP function class, sequence conservation summaries, proximity to genomic variants included in the Database of Genomic Variants (DGV) and known regulatory elements included in the Open Regulatory Annotation database (ORegAnno), PolyPhen–2 probabilities and RegulomeDB categories. Because we expected that only a fraction of the annotation variables would contribute to predicting association, we employed a penalized likelihood method to reduce the impact of non–informative predictors and evaluated the model’s ability to predict GC SNPs not used to construct the model. We show that the functional data alone are predictive of a SNP’s presence in the GC. Further, using data from a genome–wide study of ovarian cancer, we demonstrate that their use as prior data when testing for association is practical at the genome–wide scale and improves power to detect associations.