bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing Human Papillomavirus Vaccine Coverage Among Men Who Have Sex With Men—National HIV Behavioral Surveillance, United States, 2014
Authors: Oliver Sara E. , Hoots Brooke E. , Paz-Bailey Gabriela , Markowitz Lauri E. , Meites Elissa ,   for the NHBS Study Group
Published: June 2017

Background:

Human papillomavirus (HPV) can cause oropharyngeal and anogenital cancers among men who have sex with men (MSM). In 2011, the Advisory Committee on Immunization Practices (ACIP) extended HPV vaccine recommendations to males through age 21 and MSM through age 26. Because of this distinction, vaccination for some MSM might rely on sexual behavior disclosure to health care providers. Receipt of ≥1 HPV vaccination among MSM aged 18–26 in National HIV Behavioral Surveillance (NHBS) was 4.9% in 2011. We evaluated HPV vaccine coverage and associated factors among MSM in 2014.

Setting:

Twenty US metropolitan statistical areas in 2014.

Methods:

Coverage was calculated as percentage of MSM self-reporting ≥1 HPV vaccination. Adjusted prevalence ratios were calculated from Poisson regression models to estimate associations of demographic and behavioral characteristics with HPV vaccination.

Results:

Among 2892 MSM aged 18–26 years, HPV vaccine coverage was 17.2%. Overall, 2326 (80.4%) reported a health care visit within 12 months, and 2095 (72.4%) disclosed MSM attraction or behavior to a health care provider. Factors associated with vaccination included self-reported HIV infection; having a health care visit within 12 months, health insurance, or a usual place of care; and disclosing MSM attraction or behavior to a health care provider.

Conclusions:

Since the 2011 recommendation for vaccination of males, HPV vaccine coverage among MSM increased, but remains low. Most MSM reported a recent health care visit and disclosed sexual behavior, indicating opportunities for vaccination. Potential strategies for increasing MSM coverage include improving access to recommended care, and offering education for providers and patients.
Differences in Awareness of Pre-exposure Prophylaxis and Post-exposure Prophylaxis Among Groups At-Risk for HIV in New York State: New York City and Long Island, NY, 2011–2013
Authors: Walters Suzan M. , Rivera Alexis V. , Starbuck Lila , Reilly Kathleen H. , Boldon Nyasha , Anderson Bridget J. , Braunstein Sarah
Published: June 2017

Background:

Pre-exposure prophylaxis (PrEP) to reduce the risk of HIV was approved in 2012 and post-exposure prophylaxis (PEP) in 2005. We report the differences in awareness of PrEP/PEP and factors associated with awareness by examining 3 risk groups (men who have sex with men (MSM), people who inject drugs, and high-risk heterosexuals).

Methods:

National HIV Behavioral Surveillance system data collected in New York City (NYC) and Long Island, NY in 2011–2013 were used. Logistic regressions by region were developed to estimate adjusted associations [Adjusted Odds Ratios (AOR)] and determine differences in awareness of PrEP/PEP.

Results:

Awareness of PrEP/PEP was low for all groups. In multivariate analysis controlling for sociodemographic factors, noninjection drug use, HIV status, and exposure to HIV prevention, males who inject drugs in NYC had significantly decreased odds of PrEP/PEP awareness [AOR: 0.45; confidence interval (CI): 0.25 to 0.81] compared with MSM. MSM aged 18–29 years had increased awareness of PrEP (AOR: 2.94; 95% CI 1.11 to 7.80). On Long Island, females who inject drugs (AOR: 0.18; 95% CI: 0.05 to 0.62), males who inject drugs (AOR: 0.14; 95% CI: 0.05 to 0.39), female heterosexuals (AOR: 0.25; 95% CI: 0.11 to 0.59), and male heterosexuals (AOR: 0.32; 95% CI: 0.14 to 0.73) had significantly decreased odds of PrEP/PEP awareness. Black MSM had increased awareness of PrEP (AOR: 4.08 CI:1.21 to 13.73).

Conclusions:

Large proportions of groups at-risk for HIV were unaware of PrEP/PEP. When comparing risk groups to MSM, we found MSM to have greater awareness in both regions. On Long Island, people who inject drugs and heterosexuals were far less likely to have PrEP/PEP awareness than in NYC. On Long Island, Black MSM had increased PrEP awareness and in NYC MSM aged 18-29 had increased PrEP awareness. These findings suggest that awareness may be spreading through networks and highlight the importance of targeted educational and prevention efforts by group and region.
Brief Report: Nonfatal Overdose Events Among Persons Who Inject Drugs: Findings From Seven National HIV Behavioral Surveillance Cities 2009 & 2012
Authors: Robinson William T. , Kazbour Catherine , Nassau Tanner , Fisher Kiva , Sheu Shane , Rivera Alexis V. , Al-Tayyib Alia , Glick Sara Nelson , Braunstein Sarah , Barak Narquis , Shinefeld Jennifer , Poe Jonathon , Raymond Henry Fisher , Brady Kathleen
Published: June 2017

The rate of drug and opioid overdose deaths in the United States has more than tripled over the past 15 years. The ability to conduct public health surveillance on nonfatal overdoses is limited. The current study used National HIV Behavioral Surveillance (NHBS) data to estimate recent and lifetime history of nonfatal overdose events in persons who inject drugs in 7 cities. Recent and lifetime experience of overdose events ranged from 3% to 20% and from 29% to 63%, respectively. Adapting systems such as NHBS may be useful in responding to and monitoring emergent public health problems such as the overdose epidemic.
Demoralization among cancer patients in mainland China: validity of the Demoralization Scale(DS)
Authors: Deng Lisha , Pang Ying , He Yi , Zhang Yening , Fielding Richard , Tang Lili
Published: June 2017

Demoralization, characterized by hopelessness, helplessness, and loss of meaning and purpose, reflects existential distress. The objectives is To assess the validity of a Mainland Chinese versions of the demoralization scale (MC-DS) for using with Mainland Chinese cancer patients. In-patients sequentially recruited from a specialist tertiary-level cancer hospital in Beijing between January 2016-April 2016 completed Demoralization Scale, (DS) Patient Health Questionnaire-9 (PHQ-9), Revised Life Orientation Test (CLOT-R), Beck Hopelessness Scale (BHS), and provided sociodemographic and clinical information. We determined DS factor structure and convergent and divergent validity. 296/424 (70.0%) participants reported mean DS score=30.42(SD=13.00). EFA identified 3-factors explaining 21.4%, 17.8%, and 10.6% respectively of observed variance. Respective Cronbach Alphas were 0.88, 0.84, and 0.64 (0.90 full-scale). Convergent was shown by PHQ-9 scores correlating with Factor 2 (r=0.606), and BHS and C-LOT-R scores correlating (r=0.632,r=0.407 respectively) with Factor 1. Dichotomizing demoralization (high >30, low≦30) cross-tabulated against PHQ-9 score (mood) scores revealed 47% of patients exceeded demoralization cut-off, 60% of whom were not depressed. Using mean value±SD indicated demoralization cutoffs at <17.4 (low), 17.4-43.4 (medium) and >43.4 (high). Overall 71% met criteria for medium demoralization, and 15% for high demoralization. Sixty percent of all medium demoralization patients were not depressed, but only 5% of high demoralization patients were not depressed. The conclusion is that the Mainland Chinese Demoralization Scale is useful for detecting mild-to-moderate demoralization in cancer patients but at higher scores has poor specificity against depression.
Exposing the Exposome with Global Metabolomics and Cognitive Computing
Authors: Warth Benedikt , Spangler Scott , Fang Mingliang , Johnson Caroline H , Forsberg Erica M , Granados Ana , Martin Richard L , Domingo Xavi , Huan Tao , Rinehart Duane , Montenegro-Burke J Rafael , Hilmers Brian , Aisporna Aries , Hoang Linh T , Uritboonthai Winnie , Benton Paul , Richardson Susan D , Williams Antony J , Siuzdak Gary
Published: June 2017

Concurrent exposure to a wide variety of xenobiotics and their combined toxic effects can play a pivotal role in health and disease, yet are largely unexplored. Investigating the totality of these exposures, i.e. theexposome, and their specific biological effects constitutes a new paradigm for environmental health but still lacks high-throughput, user-friendly technology. We demonstrate the utility of mass spectrometry-based global exposure metabolomics combined with tailored database queries and cognitive computing for comprehensive exposure assessment and the straightforward elucidation of biological effects. The METLIN Exposome database has been redesigned to help identify environmental toxicants, food contaminants and supplements, drugs, and antibiotics as well as their biotransformation products, through its expansion with over 700,000 chemical structures to now include more than 950,000 unique small molecules. More importantly, we demonstrate how the XCMS/METLIN platform now allows for the readout of the biological effect of a toxicant through metabolomic-derived pathway analysis and further, cognitive computing provides a means of assessing the role of a potential toxicant. The presented workflow addresses many of the outstanding methodological challenges current exposome research is facing and will serve to gain a deeper understanding of the impact of environmental exposures and combinatory toxic effects on human health.
Transcriptome Deconvolution of Heterogeneous Tumor Samples with Immune Infiltration
Authors: Wang Zeya , Cao Shaolong , Morris Jeffrey S. , Ahn Jaeil , Liu Rongjie , Tyekucheva Svitlana , Gao Fan , Li Bo , Lu Wei , Tang Ximing , Wistuba Ignacio I. , Bowden Michaela , Mucci Lorelei , Loda Massimo , Parmigiani Giovanni , Holmes Chris C. , Wang Wenyi
Published: June 2017

Transcriptomic deconvolution in cancer and other heterogeneous tissues remains challenging. Available methods lack the ability to estimate both component-specific proportions and expression profiles for individual samples. We presentDeMixT, a new tool to deconvolve high dimensional data from mixtures of more than two components.DeMixTimplements an iterated conditional mode algorithm and a novel gene-set-based component merging approach to improve accuracy. In a series of experimental validation studies and application to TCGA data,DeMixTshowed high accuracy. Improved deconvolution is an important step towards linking tumor transcriptomic data with clinical outcomes. An R package, scripts and data are available:https://github.com/wwylab/DeMixT/.
The uptake of attractant and flavour enhanced baits by foxes (Vulpes vulpes) in rural England
Authors: Smith G.C. , Woods J.A.
Published: June 2017

Over a 15 month period the removal rates of different attractant and flavour enhanced baits, by foxes, was investigated at permanent and single use sites. All baits were composed of mechanically recovered chicken meat (MRM) and were treated with one of four additives (an attractant or flavour); untreated baits were used as experimental controls. The addition of synthetic ferment egg (SFE) increased bait removal compared with untreated and valeric acid (VA) treated bait. However, the addition of beef flavour or honey flavour to bait did not increase bait removal rates compared to untreated bait.

There was limited evidence of learning (by foxes and other species responsible for removing the bait) at one of the permanent study sites but no evidence of such behaviour at the other site. There was no evidence of consistent seasonal differences in bait removal rates.

It was concluded that the use of attractants may increase bait removal rate in areas where bait removal rate is low; but where bait removal rate is high (in most rural areas of Britain) the addition of attractants or flavours offers little advantage.
PinAPL-Py: A comprehensive web-application for the analysis of CRISPR/Cas9 screens
Authors: Spahn Philipp N. , Bath Tyler , Weiss Ryan J. , Kim Jihoon , Esko Jeffrey D. , Lewis Nathan E. , Harismendy Olivier
Published: June 2017

Background

Large-scale genetic screens using CRISPR/Cas9 technology have emerged as a major tool for functional genomics. With its increased popularity, experimental biologists frequently acquire large sequencing datasets for which they often do not have an easy analysis option. While a few bioinformatic tools have been developed for this purpose, their utility is still hindered either due to limited functionality or the requirement of bioinformatic expertise.

Results

To make sequencing data analysis of CRISPR/Cas9 screens more accessible to a wide range of scientists, we developed a Platform-independent Analysis of Pooled Screens using Python (PinAPL-Py), which is operated as an intuitive web-service. PinAPL-Py implements state-of-the-art tools and statistical models, assembled in a comprehensive workflow covering sequence quality control, automated sgRNA sequence extraction, alignment, sgRNA enrichment/depletion analysis and gene ranking. The workflow is set up to use a variety of popular sgRNA libraries as well as custom libraries that can be easily uploaded. Various analysis options are offered, suitable to analyze a large variety of CRISPR/Cas9 screening experiments. Analysis output includes ranked lists of sgRNAs and genes, and publication-ready plots.

Conclusions

PinAPL-Py helps to advance genome-wide screening efforts by combining comprehensive functionality with user-friendly implementation. PinAPL-Py is freely accessible athttp://pinapl-py.ucsd.eduwith instructions, documentation and test datasets. The source code is available athttps://github.com/LewisLabUCSD/PinAPL-Py
TCGAbiolinksGUI: A graphical user interface to analyze GDC cancer molecular and clinical data
Authors: Silva Tiago C , Colaprico Antonio , Olsen Catharina , Bontempi Gianluca , Ceccarelli Michele , Berman Benjamin P , Noushmehr Houtan
Published: June 2017

Background:

The GDC (Genomic Data Commons) data portal provides users with data from cancer genomics studies. Recently, we developed the R/Bioconductor TCGAbiolinks package, which allows users to search, download and prepare cancer genomics data for integrative data analysis. The use of this package requires users to have advanced knowledge of R thus limiting the number of users.

Results:

To overcome this obstacle and improve the accessibility of the package by a wider range of users, we developedTCGAbiolinksGUIthat uses shiny graphical user interface (GUI) available through the R/Bioconductor package.

Conclusion:

The TCGAbiolinksGUI package is freely available within the Bioconductor project athttp://bioconductor.org/packages/TCGAbiolinksGUI/. Links to the GitHub repository, a demo version of the tool, a docker image and PDF/video tutorials are available athttp://bit.do/TCGAbiolinksDocs.
Independent contributions of noradrenaline to behavioural flexibility and motivation
Authors: Jahn Caroline , Gilardeau Sophie , Varazzani Chiara , Blain Bastien , Sallet Jerome , Walton Mark , Bouret Sebastien
Published: June 2017

Among neuromodulatory systems, the noradrenergic system remains one of the least understood. Several theories have pointed out its implication in behavioural flexibility and more recently in motivation, with a strong role in effort processing. Here, we designed a sequential cost/benefit decision task to test the causal role of noradrenaline in these two functions. We manipulated noradrenaline using clonidine, an alpha-2 noradrenergic receptor agonist, which reduces central noradrenaline levels. Clonidine had two distinct effects: it decreased choice volatility (without affecting the cost/benefit trade off) and reduced force production. Because the effects were independent, they cannot be accounted for by a non-specific effect on arousal. Altogether, these results support the global implication of noradrenaline in facing challenging situations in two complementary ways: by modulating behavioural volatility, which would facilitate adaptation depending on the lability of the environment, and by modulating the mobilization of resources to face immediate challenges.
Highly parallel genome variant engineering with CRISPR/Cas9 in eukaryotic cells
Authors: Sadhu Meru J. , Bloom Joshua S. , Day Laura , Siegel Jake J. , Kosuri Sriram , Kruglyak Leonid
Published: June 2017

Direct measurement of functional effects of DNA sequence variants throughout a genome is a major challenge. We developed a method that uses CRISPR/Cas9 to engineer many specific variants of interest in parallel in the budding yeastSaccharomyces cerevisiae, and to screen them for functional effects. We used the method to examine the functional consequences of premature termination codons (PTCs) at different locations within all annotated essential genes in yeast. We found that most PTCs were highly deleterious unless they occurred close to the C-terminal end and did not interrupt an annotated protein domain. Surprisingly, we discovered that some putatively essential genes are dispensable, while others have large dispensable regions. This approach can be used to profile the effects of large classes of variants in a high-throughput manner.
Competition in the savanna: models of species assemblages in Kruger National Park, South Africa
Authors: Ryan Sadie J. , Ladau Joshua
Published: June 2017

We examined hypotheses of spatial association arising from direct or indirect competitive interactions, using thirteen years of gridded mammal census data from Kruger National Park, South Africa. As interactions occur at different scales, we explored the data at 1, 5, 10, and 15 km2. We proposed four hypotheses structuring the mammal community: H1. direct competition between carnivores and herbivores; H2-4: indirect competition produced by each of three types of herbivore diet specialization: H2. ruminants and non-ruminants, H3. grazers and browsers, and H4. a four-way division of small and large grazers and browsers. We used the software CoOccur to implement a robus test for evidence of our hypotheses against null models of community assemblage. At 5, 10, and 15km2scales, the results supported a competition mechanism in the majority of years for hypotheses H1, H3, and H4, and facilitation in H2. At the finest spatial scale (1km2), we saw evidence for a mixture of competitive, neutral and facilitative process. These results suggest strong, large-scale effects of interspecific interactions on distributions of African megafauna, which may not operate at a more local (1km2) scale, underscoring the importance of scale and mechanism in the guild structure of communities.
Chimeric CRISPR guides enhance Cas9 target specificity
Authors: Jakimo Noah , Chatterjee Pranam , Jacobson Joseph M
Published: June 2017

Oligonucleotide-guided nucleases (OGNs) have enabled rapid advances in precision genome engineering. Though much effort has gone into characterizing and mitigating mismatch tolerance for the most widely adopted OGN, Streptococcus pyogenes Cas9 (SpCas9), potential off-target interactions may still limit applications where on-target specificity is critical. Here we present a new axis to control mismatch sensitivity along the recognition-conferring spacer sequence of SpCas9’s guide RNA (gRNA). We introduce mismatch-evading loweredthermostability guides (melt-guides) and exhibit how nucleotide-type substitutions in the spacer can reduce cleavage of sequences mismatched by as few as a single base pair. Cotransfecting melt-guides into human cell culture with an exonuclease involved in DNA repair, we observe indel formation on a standard genomic target at approximately 70% the rate of canonical gRNA and undetectable on off-target data.
A Negative Feedback Regulates The Flow Of Signal Through Akt/mTORC1/S6K1 Pathway
Authors: Dutta Poulami , Devaraj Vimalathithan , Bose Biplab
Published: June 2017

Abstract

Several growth factors, cytokines, hormones activate PI3K/Akt pathway. Akt is a key node in this pathway and activates different downstream paths. One such path is Akt/mTORC1/S6K1 that controls protein synthesis, cell survival, and proliferation. Here we show that a negative feedback controls activation of S6K1 through this pathway. Due to this negative feedback, a sustained phospho-Akt signal generates a transient pulse of phospho-S6K1. We have created a mathematical model for this circuit. Analysis of this model shows that the negative feedback acts as a filter and preferentially allows a signal, with sharp and faster rise of phospho-Akt, to induce pronounced activation of S6K1. It blocks an input with a fast oscillation of phospho-Akt to flow through this path. We show that this negative feedback leads to differential activation of S6K1 by Insulin and Insulin-like Growth Factor 1. Such differential effect may explain the difference in the mitogenic effect of these two molecules.
Robust Averaging Protects Decisions from Noise in Neural Computations
Authors: Li Vickie , Castañón Santiago Herce , Solomon Joshua A , Vandormael Hildward , Summerfield Christopher
Published: June 2017

An ideal observer will give equivalent weight to sources of information that are equally reliable. However, when averaging visual information, human observers tend to downweight or discount features that are relatively outlying or deviant (‘robust averaging’). Why humans adopt an integration policy that discards important decision information remains unknown. Here, observers were asked to judge the average tilt in a circular array of high-contrast gratings, relative to an orientation boundary defined by a central reference grating. Observers showed robust averaging of orientation, but the extent to which they did so was a positive predictor of their overall performance. Using computational simulations, we show that although robust averaging is suboptimal for a perfect integrator, it paradoxically enhances performance in the presence of “late” noise, i.e. which corrupts decisions during integration. In other words, robust decision strategies increase the brain’s resilience to noise arising in neural computations during decision-making.

Author Summary

Humans often make decisions by averaging information from multiple sources. When all the sources are equally reliable, they should all have equivalent impact (or weight) on the decisions of an “ideal” observer, i.e. one with perfect memory. However, recent experiments have suggested that humans give unequal weight to sources that are deviant or unusual, a phenomenon called “robust averaging”. Here, we use computer simulations to try to understand why humans do this. Our simulations show that under the assumption that information processing is limited by a source of internal uncertainty that we call “late” noise, robust averaging actually leads to improved performance. Using behavioural testing, we replicate the finding of robust averaging in a cohort of healthy humans, and show that those participants that engage in robust averaging perform better on the task. This study thus provides new information about the limitations on human decision-making.
Integrating long-range connectivity information into de Bruijn graphs
Authors: Turner Isaac , Garimella Kiran V , Iqbal Zamin , McVean Gil
Published: June 2017

Motivation

The de Bruijn graph is a simple and efficient data structure that is used in many areas of sequence analysis including genome assembly, read error correction and variant calling. The data structure has a single parameterk, is straightforward to implement and is tractable for large genomes with high sequencing depth. It also enables representation of multiple samples simultaneously to facilitate comparison. However, unlike the string graph, a de Bruijn graph does not retain long range information that is inherent in the read data. For this reason, applications that rely on de Bruijn graphs can produce sub-optimal results given their input.

Results

We present a novel assembly graph data structure: theLinked de Bruijn Graph (LdBG). Constructed by adding annotations on top of a de Bruijn graph, it stores long range connectivity information through the graph. We show that with error-free data it is possible to losslessly store and recover sequence from a Linked de Bruijn graph. With assembly simulations we demonstrate that the LdBG data structure outperforms both the de Bruijn graph and the String Graph Assembler (SGA). Finally we apply the LdBG toKlebsiella pneumoniaeshort read data to make large (12 kbp) variant calls, which we validate using PacBio sequencing data, and to characterise the genomic context of drug-resistance genes.

Availability

Linked de Bruijn Graphs and associated algorithms are implemented as part of McCortex, available under the MIT license athttps://github.com/mcvean/mccortex.

Contact

turner.isaac@gmail.com.
A DNA Contact Map for the MouseRunx1Gene Identifies Novel Hematopoietic Enhancers
Authors: Marsman Judith , Thomas Amarni , Osato Motomi , O’Sullivan Justin M. , Horsfield Julia A.
Published: June 2017

The transcription factor Runx1 is essential for definitive hematopoiesis, and theRUNX1gene is frequently translocated or mutated in leukemia.Runx1is transcribed from two promoters, P1 and P2, to give rise to different protein isoforms. Although the expression of Runx1 must be tightly regulated for normal blood development, the mechanisms that regulateRunx1isoform expression during hematopoiesis remain poorly understood. Gene regulatory elements located in non-coding DNA are likely to be important forRunx1transcription. Here we use circular chromosome conformation capture sequencing to identify DNA interactions with the P1 and P2 promoters ofRunx1, and the previously identified +24 enhancer, in the mouse multipotent hematopoietic progenitor cell line HPC-7. The active promoter, P1, interacts with nine non-coding regions that are occupied by transcription factors within a 1 Mb topologically associated domain. Eight of nine regions function as blood-specific enhancers in zebrafish. Interestingly, the +24 enhancer interacted with multiple distant regions on chromosome 16, indicating it may regulate the expression of additional genes. TheRunx1DNA contact map identifies connections with multiple novel hematopoietic enhancers that are likely to be involved in regulatingRunx1expression in hematopoietic progenitor cells.
Metabolomics and biochemical approaches link salicylic acid biosynthesis to cyanogenesis in peach plants
Authors: Pedro Diaz-Vivancos , Agustina Bernal-Vicente , Daniel Cantabella , Cesar Petri , Antonio Hernández José
Published: June 2017

Highlight

Mandelonitrile, and hence cyanogenic glycosides turnover, is involved in salicylic acid (SA) biosynthesis in peach plants under control and stress conditions. A third pathway for SA synthesis in peach is proposed.

Despite the long-established importance of salicylic acid (SA) in plant stress responses and other biological processes, its biosynthetic pathway has not been fully characterized. The proposed SA synthesis originates from chorismate by two distinct pathways: isochorismate and penhylalanine (Phe) ammonia-lyase (PAL) pathways. Cyanogenesis is the process related to the release of hydrogen cyanide from endogenous cyanogenic glycosides (CNglcs), and it has been linked to plant plasticity improvement. To date, however, no relationship has been suggested between both pathways. In this work, by metabolomics and biochemical approaches (including [13C]-labelled compounds), we provide evidences showing that CNglcs turnover is involved, at least in part, in SA biosynthesis in peach plants under control and stress conditions.

The main CNglcs in peach are prunasin and amygdalin, with mandelonitrile (MD), synthesized from Phe, controlling their turnover. In peach plants MD is at the hub of the suggested new SA biosynthetic pathway and CNglcs turnover, regulating both the amygdalin and SA biosynthesis. MD-treated peach plants displayed increased SA levels via benzoic acid (SA precursor). In addition, MD also provides partial protection againstPlum pox virusinfection in peach seedlings. Thus, we proposed a third pathway, alternative to the PAL pathway, for SA synthesis in peach plants.
WebMeV: a Cloud Platform for Analyzing and Visualizing Cancer Genomic Data
Authors: Wang Yaoyu E. , Kuznetsov Lev , Partensky Antony , Farid Jalil , Quackenbush John
Published: June 2017

Although large, complex genomic data sets are increasingly easy to generate, and the number of publicly available data sets in cancer and other diseases is rapidly growing, the lack of intuitive, easy to use analysis tools has remained a barrier to the effective use of such data. WebMeV (https://mev.tm4.org) is an open-source, web-based tool that gives users access to sophisticated tools for analysis of RNA-Seq and other data in an interface designed to democratize data access. WebMeV combines cloud-based technologies with a simple user interface to allow users to access large public data sets such as that from The Cancer Genome Atlas (TCGA) or to upload their own. The interface allows users to visualize data and to apply advanced data mining analysis methods to explore the data and draw biologically meaningful conclusions. We provide an overview of WebMeV and demonstrate two simple use cases that illustrate the value of putting data analysis in the hands of those looking to explore the underlying biology of the systems being studied.
Polarization effects and the calibration of a donut beam axial optical tweezers for single-molecule force spectroscopy
Authors: Pollari Russell , Milstein Joshua
Published: June 2017

Advances in light shaping techniques are leading to new tools for optical trapping and micromanipulation. For example, optical tweezers made from Laguerre-Gaussian or donut beams display an increased axial trap strength and can impart angular momentum to rotate a specimen. However, their application to precision, biophysical measurements remains limited as their are a number of challenges to applying this tool to optical force spectroscopy. One notable complication, not present when trapping with a Gaussian beam, is that the polarization of the trap light can significantly affect the tweezers’ strength as well as the precise location of the trap. In this article, we provide a practical implementation of a donut beam optical tweezers for applying axial forces. We show how to precisely calibrate the height of the optical trap above the coverslip surface while accounting for focal shifts in the trap position that arise due to radiation pressure, mismatches in the index of refraction, and polarization induced intensity variations.
eGARD: Extracting associations between genomic anomalies and drug responses from text
Authors: Mahmood A. S. M. Ashique , Rao Shruti , McGarvey Peter , Wu Cathy , Madhavan Subha , Vijay-Shanker K.
Published: June 2017

Tumor molecular profiling plays an integral role in identifying genomic anomalies which may help in personalizing cancer treatments, improving patient outcomes and minimizing risks associated with different therapies. However, critical information regarding the evidence of clinical utility of such anomalies is largely buried in biomedical literature. It is becoming prohibitive for biocurators, clinical researchers and oncologists to keep up with the rapidly growing volume and breadth of information, especially those that describe therapeutic implications of biomarkers and therefore relevant for treatment selection. In an effort to improve and speed up the process of manually reviewing and extracting relevant information from literature, we have developed a natural language processing (NLP)-based text mining (TM) system called eGARD (extracting Genomic Anomalies association with Response to Drugs). This system relies on the syntactic nature of sentences coupled with various textual features to extract relations between genomic anomalies and drug response from MEDLINE abstracts. Our system achieved high precision, recall and F-measure of up to 0.95, 0.86 and 0.90, respectively, on annotated evaluation datasets created in-house and obtained externally from PharmGKB. Additionally, the system extracted information that helps determine the confidence level of extraction to support prioritization of curation. Such a system will enable clinical researchers to explore the use of published markers to stratify patients upfront for ‘best-fit’ therapies and readily generate hypotheses for new clinical trials.
Saccharomyces cerevisiaeas a Platform for Assessing Sphingolipid Lipid Kinase Inhibitors
Authors: Kharel Yugesh , Agah Sayeh , Huang Tao , Mendelson Anna J. , Eletu Oluwafunmilayo T. , Barkey-Bircann Peter , Gesualdi James , Smith Jeffrey S. , Santos Webster L. , Lynch Kevin R.
Published: June 2017

Successful medicinal chemistry campaigns to discover and optimize sphingosine kinase inhibitors require a robust assay for screening chemical libraries and for determining rank order potencies. Existing assays for these enzymes are laborious, expensive and/or low throughput. The toxicity of excessive levels of phosphorylated sphingoid bases for the budding yeast,Saccharomyces cerevisiae, affords an assay wherein inhibitors added to the culture media rescue growth in a dose-dependent fashion. Herein, we describe our adaptation of a simple, inexpensive, and high throughput assay for assessing inhibitors of sphingosine kinase types 1 and 2 as well as ceramide kinase and for testing enzymatic activity of sphingosine kinase type 2 mutants. The assay was validated using recombinant enzymes and generally agrees with rank order of potencies of existing inhibitors.
A novel tubular hydrogen-bond pattern in a new diazaphosphole oxide: a combination of X-ray crystallography and theoretical study of hydrogen bonds
Authors: Sabbaghi Fahimeh , Pourayoubi Mehrdad , Farhadipour Abolghasem , Ghorbanian Nazila , Andreev Pavel V.
Published: June 2017

In the structure of 2-(4-chloroanilino)-1,3,2λ4-diazaphosphol-2-one, C12H11ClN3OP, each molecule is connected with four neighbouring molecules through (N—H)2...O hydrogen bonds. These hydrogen bonds form a tubular arrangement along the [001] direction built from R
3
3(12) and R
4
3(14) hydrogen-bond ring motifs, combined with a C(4) chain motif. The hole constructed in the tubular architecture includes a 12-atom arrangement (three P, three N, three O and three H atoms) belonging to three adjacent molecules hydrogen bonded to each other. One of the N—H groups of the diazaphosphole ring, not co-operating in classical hydrogen bonding, takes part in an N—H...π interaction. This interaction occurs within the tubular array and does not change the dimension of the hydrogen-bond pattern. The energies of the N—H...O and N—H...π hydrogen bonds were studied by NBO (natural bond orbital) analysis, using the experimental hydrogen-bonded cluster of molecules as the input file for the chemical calculations. In the 1H NMR experiment, the nitrogen-bound proton of the diazaphosphole ring has a high value of 17.2 Hz for the 2
J
H–P coupling constant.
Investigation of turbulent flow through microchannels consisting of different micropost arrangements
Authors: Kharati-Koopaee Masoud , Rezaee Mahsa
Published: June 2017

Purpose

The purpose of the current research is to study the turbulent flow through microchannels having a micropost in aligned and staggered arrangements.

Design/methodology/approach

Numerical calculations are performed on the basis of the finite volume approach, which is based on the SIMPLEC algorithm. In this work, the slip velocity, flow velocity distribution and friction factor for the two micropost patterns are examined at friction Reynolds numbers of Reτ = 395 and 590, relative module widths of Wm = 0.1 and 1 and cavity fraction range of Fc = 0.1 to 0.9.

Findings

Results reveal that for the two micropost patterns, as the friction Reynolds number, relative module width or cavity fraction increases, the slip velocity increases and friction factor decreases. It is found that the aligned micropost configuration leads to higher slip velocity and lower friction factor. Numerical findings indicate that the existence of the continuous cavity surface along the flow direction could be a significant criterion to realize if the velocity distribution deviates from that of the smooth channel. It is also shown that the turbulent flows are capable of producing more drag reduction than the laminar ones.

Originality/value

Previous studies have shown that microchannels consisting of a micropost pattern in aligned and staggered arrangements could be viewed as a promising alternative in the microscale flows for the heat removal purposes. Therefore, understanding the fluid flow through microchannels consisting of these configurations (which is a prerequisite to better understand thermal performance of such microchannels) is a significant issue, which is the subject of the present work.
A numerical investigation of transient MHD free convective flow of a nanofluid over a moving semi-infinite vertical cylinder
Authors: Rajesh V. , Chamkha A.J. , Sridevi Ch. , Al-Mudhaf A.F.
Published: June 2017

Purpose

The purpose of this paper is to study numerically the influence of a magnetic field on the transient free convective boundary layer flow of a nanofluid over a moving semi-infinite vertical cylinder with heat transfer

Design/methodology/approach

The problem is governed by the coupled non-linear partial differential equations with appropriate boundary conditions. The fluid is a water-based nanofluid containing nanoparticles of copper. The Brinkman model for dynamic viscosity and Maxwell–Garnett model for thermal conductivity are used. The governing boundary layer equations are written according to The Tiwari–Das nanofluid model. A robust, well-tested, implicit finite difference method of Crank–Nicolson type, which is unconditionally stable and convergent, is used to find the numerical solutions of the problem. The velocity and temperature profiles are studied for significant physical parameters such as the magnetic parameter, nanoparticles volume fraction and the thermal Grashof number Gr. The local skin-friction coefficient and the Nusselt number are also analysed and presented graphically.

Findings

The present computations have shown that an increase in the values of either magnetic parameter M or nanoparticle volume fraction decreases the local skin-friction coefficient, whereas the opposite effect is observed for thermal Grashof number Gr. The local Nusselt number increases with a rise in Gr and ϕ values. But an increase in M reduces the local Nusselt number.

Originality/value

This paper is relatively original and presents numerical investigation of transient two-dimensional laminar boundary layer free convective flow of a nanofluid over a moving semi-infinite vertical cylinder in the presence of an applied magnetic field. The present study is of immediate application to all those processes which are highly affected by heat enhancement concept and a magnetic field. Further the present study is relevant to nanofluid materials processing, chemical engineering coating operations exploiting nanomaterials and others.
Explicit dynamic analysis of sheet metal forming processes using linear prismatic and hexahedral solid-shell elements
Authors: Wang Peng , Chalal Hocine , Abed-Meraim Farid
Published: June 2017

Purpose

The purpose of this paper is to propose two linear solid-shell finite elements, a six-node prismatic element denoted SHB6-EXP and an eight-node hexahedral element denoted SHB8PS-EXP, for the three-dimensional modeling of thin structures in the context of explicit dynamic analysis.

Design/methodology/approach

These two linear solid-shell elements are formulated based on a purely three-dimensional (3D) approach, with displacements as the only degrees of freedom. To prevent various locking phenomena, a reduced-integration scheme is used along with the assumed-strain method. The resulting formulations are computationally efficient, as only a single layer of elements with an arbitrary number of through-thickness integration points is required to model 3D thin structures.

Findings

Via the VUEL user-element subroutines, the performance of these elements is assessed through a set of selective and representative dynamic elastoplastic benchmark tests, impact-type problems and deep drawing processes involving complex non-linear loading paths, anisotropic plasticity and double-sided contact. The obtained numerical results demonstrate good performance of the SHB-EXP elements in the modeling of 3D thin structures, with only a single element layer and few integration points in the thickness direction.

Originality/value

The extension of the SHB-EXP solid-shell formulations to large-strain anisotropic plasticity enlarges their application range to a wide variety of dynamic elastoplastic problems and sheet metal forming simulations. All simulation results reveal that the numerical strategy adopted in this paper can efficiently prevent the various locking phenomena that commonly occur in the 3D modeling of thin structural problems.
Partially coupled extended stochastic gradient algorithm for nonlinear multivariable output error moving average systems
Authors: Wang Xuehai , Ding Feng
Published: June 2017

Purpose

The purpose of this paper is to study the parameter estimation problem of nonlinear multivariable output error moving average systems.

Design/methodology/approach

A partially coupled extended stochastic gradient algorithm is presented for nonlinear multivariable systems by using the decomposition technique.

Findings

The proposed algorithm can realize the coupled computation of the parameter estimates between subsystems.

Originality/value

This paper develops a coupled parameter estimation algorithm for nonlinear multivariable systems and directly estimates the system parameters without over-parameterization.
Degenerate-scale problem of the boundary integral equation method/boundary element method for the bending plate analysis
Authors: Chen Jeng-Tzong , Kuo Shyh-Rong , Chang Yu-Lung , Kao Shing-Kai
Published: June 2017

Purpose

The purpose of this paper is to detect the degenerate scale of a 2D bending plate analytically and numerically.

Design/methodology/approach

To avoid the time-consuming scheme, the influence matrix of the boundary element method (BEM) is reformulated to an eigenproblem of the 4 by 4 matrix by using the scaling transform instead of the direct-searching scheme to find degenerate scales. Analytical degenerate scales are derived from the boundary integral equation (BIE) by using the degenerate kernel only for the circular case. Numerical results of the direct-searching scheme and the eigen system for the arbitrary shape are also considered.

Findings

Results using three methods, namely, analytical derivation, the direct-searching scheme and the 4 by 4 eigen system, are also given for the circular case and arbitrary shapes. Finally, addition of a constant for the kernel function makes original eigenvalues (2 real roots and 2 complex roots) of the 4 by 4 matrix to be all real. This indicates that a degenerate scale depends on the kernel function.

Originality/value

The analytical derivation for the degenerate scale of a 2D bending plate in the BIE is first studied by using the degenerate kernel. Through the reformed eigenproblem of a 4 by 4 matrix, the numerical solution for the plate of an arbitrary shape can be used in the plate analysis using the BEM.
Aspect ratio effects in Rayleigh–Bénard convection of Herschel–Bulkley fluids
Authors: Aghighi Mohammad Saeid , Ammar Amine
Published: June 2017

Purpose

The purpose of this paper is to analyze two-dimensional steady-state Rayleigh–Bénard convection within rectangular enclosures in different aspect ratios filled with yield stress fluids obeying the Herschel–Bulkley model.

Design/methodology/approach

In this study, a numerical method based on the finite element has been developed for analyzing two-dimensional natural convection of a Herschel–Bulkley fluid. The effects of Bingham number Bn and power law index n on heat and momentum transport have been investigated for a nominal Rayleigh number range (5 × 103 < Ra < 105), three different aspect ratios (ratio of enclosure length:height AR = 1, 2, 3) and a single representative value of nominal Prandtl number (Pr = 10).

Findings

Results show that the mean Nusselt number Nu¯ increases with increasing Rayleigh number due to strengthening of convective transport. However, with the same nominal value of Ra, the values of Nu¯ for shear thinning fluids n < 1 are greater than shear thickening fluids n > 1. The values of Nu¯ decrease with Bingham number and for large values of Bn, Nu¯ rapidly approaches unity, which indicates that heat transfer takes place principally by thermal conduction. The effects of aspect ratios have also been investigated and results show that Nu¯ increases with increasing AR due to stronger convection effects.

Originality/value

This paper presents a numerical study of Rayleigh–Bérnard flows involving Herschel–Bulkley fluids for a wide range of Rayleigh numbers, Bingham numbers and power law index based on finite element method. The effects of aspect ratio on flow and heat transfer of Herschel–Bulkley fluids are also studied.
Design strategies for multi-objective optimization of aerodynamic surfaces
Authors: Amrit Anand , Leifsson Leifur , Koziel Slawomir
Published: June 2017

Purpose

This paper aims to investigates several design strategies to solve multi-objective aerodynamic optimization problems using high-fidelity simulations. The purpose is to find strategies which reduce the overall optimization time while still maintaining accuracy at the high-fidelity level.

Design/methodology/approach

Design strategies are proposed that use an algorithmic framework composed of search space reduction, fast surrogate models constructed using a combination of physics-based surrogates and kriging and global refinement of the Pareto front with co-kriging. The strategies either search the full or reduced design space with a low-fidelity model or a physics-based surrogate.

Findings

Numerical investigations of airfoil shapes in two-dimensional transonic flow are used to characterize and compare the strategies. The results show that searching a reduced design space produces the same Pareto front as when searching the full space. Moreover, as the reduced space is two orders of magnitude smaller (volume-wise), the number of required samples to setup the surrogates can be reduced by an order of magnitude. Consequently, the computational time is reduced from over three days to less than half a day.

Originality/value

The proposed design strategies are novel and holistic. The strategies render multi-objective design of aerodynamic surfaces using high-fidelity simulation data in moderately sized search spaces computationally tractable.
Software tool for simulation of vehicle – road interaction
Authors: Duarte Francisco , Ferreira Adelino , Fael Paulo
Published: June 2017

Purpose

This paper aims to deal with the development of a software tool to simulate and study vehicle – road interaction (VRI) to quantify the forces induced and energy released from vehicles to the road pavement, in different vehicle motion scenarios, and the energy absorbed by the road surface, speed reducers or a specific energy harvester surface or device. The software tool also enables users to quantify the energetic efficiency of the process.

Design/methodology/approach

Existing software tools were analysed and its limitations were identified in terms of performing energetic analysis on the interaction between the vehicle and the road pavement elements, such as speed reducers or energy harvest devices. The software tool presented in this paper intends to overcome those limitations and precisely quantify the energy transfer.

Findings

Different vehicle models and VRI models were evaluated, allowing to conclude about each model precision: bicycle car model has a 60 per cent higher precision when compared with quarter-car model, and contact patch analysis model has a 67 per cent higher precision than single force analysis model. Also, a technical study was performed for different equipment surface shapes and displacements, concluding that these variables have a great influence on the energy released by the vehicle and on the energy harvested by the equipment surface.

Originality/value

The developed software tool allows to study VRI with a higher precision than existing tools, especially when energetic analyses are performed and when speed reduction or energy harvesting devices are applied on the pavement.