The BridgeDb framework: standardized access to gene, protein and metabolite identifier mapping services

BACKGROUND: Many complementary solutions are available for the identifier mapping problem. This creates an opportunity for bioinformatics tool developers. Tools can be made to flexibly support multiple mapping services or mapping services could be combined to get broader coverage. This approach requires an interface layer between tools and mapping services. RESULTS: Here we present BridgeDb, a software framework for gene, protein and metabolite identifier mapping. This framework provides a standardized interface layer through which bioinformatics tools can be connected to different identifier mapping services. This approach makes it easier for tool developers to support identifier mapping. Mapping services can be combined or merged to support multi-omics experiments or to integrate custom microarray annotations. BridgeDb provides its own ready-to-go mapping services, both in webservice and local database forms. However, the framework is intended for customization and adaptation to any identifier mapping service. BridgeDb has already been integrated into several bioinformatics applications. CONCLUSION: By uncoupling bioinformatics tools from mapping services, BridgeDb improves capability and flexibility of those tools. All described software is open source and available at http://www.bridgedb.org

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Self-reported health status and access to health services in a sample of prisoners in Italy

<p>Abstract</p> <p>Background</p> <p>Self-reported health status in underserved population of prisoners has not been extensively explored. The purposes of this cross-sectional study were to assess self-reported health, quality of life, and access to health services in a sample of male prisoners of Italy.</p> <p>Methods</p> <p>A total of 908 prisoners received a self-administered anonymous questionnaire pertaining on demographic and detention characteristics, self-reported health status and quality of life, access to health services, lifestyles, and participation to preventive, social, and rehabilitation programs. A total of 650 prisoners agreed to participate in the study and returned the questionnaire.</p> <p>Results</p> <p>Respectively, 31.6% and 43.5% of prisoners reported a poor perceived health status and a poor quality of life, and 60% admitted that their health was worsened or greatly worsened during the prison stay. Older age, lower education, psychiatric disorders, self-reported health problems on prison entry, and suicide attempts within prison were significantly associated with a perceived worse health status. At the time of the questionnaire delivery, 30% of the prisoners self-reported a health problem present on prison entry and 82% present at the time of the survey. Most frequently reported health problems included dental health problems, arthritis or joint pain, eye problems, gastrointestinal diseases, emotional problems, and high blood pressure. On average, prisoners encountered general practitioners six times during the previous year, and the frequency of medical encounters was significantly associated with older age, sentenced prisoners, psychiatric disorders, and self-reported health problems on prison entry.</p> <p>Conclusions</p> <p>The findings suggest that prisoners have a perceived poor health status, specific care needs and health promotion programs are seldom offered. Programs for correction of risk behaviour and prevention of long-term effects of incarceration on prisoners' health are strongly needed.</p

Contested Collective Intelligence: rationale, technologies, and a human-machine annotation study

We propose the concept of Contested Collective Intelligence (CCI) as a distinctive subset of the broader Collective Intelligence design space. CCI is relevant to the many organizational contexts in which it is important to work with contested knowledge, for instance, due to different intellectual traditions, competing organizational objectives, information overload or ambiguous environmental signals. The CCI challenge is to design sociotechnical infrastructures to augment such organizational capability. Since documents are often the starting points for contested discourse, and discourse markers provide a powerful cue to the presence of claims, contrasting ideas and argumentation, discourse and rhetoric provide an annotation focus in our approach to CCI. Research in sensemaking, computer-supported discourse and rhetorical text analysis motivate a conceptual framework for the combined human and machine annotation of texts with this specific focus. This conception is explored through two tools: a social-semantic web application for human annotation and knowledge mapping (Cohere), plus the discourse analysis component in a textual analysis software tool (Xerox Incremental Parser: XIP). As a step towards an integrated platform, we report a case study in which a document corpus underwent independent human and machine analysis, providing quantitative and qualitative insight into their respective contributions. A promising finding is that significant contributions were signalled by authors via explicit rhetorical moves, which both human analysts and XIP could readily identify. Since working with contested knowledge is at the heart of CCI, the evidence that automatic detection of contrasting ideas in texts is possible through rhetorical discourse analysis is progress towards the effective use of automatic discourse analysis in the CCI framework

Origins of Spatial Working Memory Deficits in Schizophrenia: An Event-Related fMRI and Near-Infrared Spectroscopy Study

Abnormal prefrontal functioning plays a central role in the working memory (WM) deficits of schizophrenic patients, but the nature of the relationship between WM and prefrontal activation remains undetermined. Using two functional neuroimaging methods, we investigated the neural correlates of remembering and forgetting in schizophrenic and healthy participants. We focused on the brain activation during WM maintenance phase with event-related functional magnetic resonance imaging (fMRI). We also examined oxygenated hemoglobin changes in relation to memory performance with the near-infrared spectroscopy (NIRS) using the same spatial WM task. Distinct types of correct and error trials were segregated for analysis. fMRI data indicated that prefrontal activation was increased during WM maintenance on correct trials in both schizophrenic and healthy subjects. However, a significant difference was observed in the functional asymmetry of frontal activation pattern. Healthy subjects showed increased activation in the right frontal, temporal and cingulate regions. Schizophrenic patients showed greater activation compared with control subjects in left frontal, temporal and parietal regions as well as in right frontal regions. We also observed increased ‘false memory’ errors in schizophrenic patients, associated with increased prefrontal activation and resembling the activation pattern observed on the correct trials. NIRS data replicated the fMRI results. Thus, increased frontal activity was correlated with the accuracy of WM in both healthy control and schizophrenic participants. The major difference between the two groups concerned functional asymmetry; healthy subjects recruited right frontal regions during spatial WM maintenance whereas schizophrenic subjects recruited a wider network in both hemispheres to achieve the same level of memory performance. Increased “false memory” errors and accompanying bilateral prefrontal activation in schizophrenia suggest that the etiology of memory errors must be considered when comparing group performances. Finally, the concordance of fMRI and NIRS data supports NIRS as an alternative functional neuroimaging method for psychiatric research

Community Reentry: Perceptions of People with Substance Use Problems Returning Home from New York City Jails

Each year about 100,000 people return to New York City communities from municipal jails. Although about four-fifths report drug or alcohol problems, few have received any formal drug treatment while in jail. Researchers and practitioners have identified a number of policies related to corrections, income, housing, and drug treatment that may be harmful to the successful reintegration of people leaving jail. In order to explore the challenges to successful community reentry, six focus groups and one in-depth interview were conducted with 37 men and women who had been released from jail or prison in the last 12 months. Participants were asked to describe their experiences prior to and immediately following release from jail. Findings suggest that many people leaving jail are not prepared for release and, upon release, face a myriad of obstacles to becoming healthy, productive members of their communities. We discuss the implications of these findings for programs and policies that promote community reintegration of individuals returning from correctional facilities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40303/2/Van Olphen_Community Reentry - Perceptions of People_2006.pd

Smoking patterns and stimulus control in intermittent and daily smokers

Intermittent smokers (ITS) - who smoke less than daily - comprise an increasing proportion of adult smokers. Their smoking patterns challenge theoretical models of smoking motivation, which emphasize regular and frequent smoking to maintain nicotine levels and avoid withdrawal, but yet have gone largely unexamined. We characterized smoking patterns among 212 ITS (smoking 4-27 days per month) compared to 194 daily smokers (DS; smoking 5-30 cigarettes daily) who monitored situational antecedents of smoking using ecological momentary assessment. Subjects recorded each cigarette on an electronic diary, and situational variables were assessed in a random subset (n = 21,539 smoking episodes); parallel assessments were obtained by beeping subjects at random when they were not smoking (n = 26,930 non-smoking occasions). Compared to DS, ITS' smoking was more strongly associated with being away from home, being in a bar, drinking alcohol, socializing, being with friends and acquaintances, and when others were smoking. Mood had only modest effects in either group. DS' and ITS' smoking were substantially and equally suppressed by smoking restrictions, although ITS more often cited self-imposed restrictions. ITS' smoking was consistently more associated with environmental cues and contexts, especially those associated with positive or "indulgent" smoking situations. Stimulus control may be an important influence in maintaining smoking and making quitting difficult among ITS. © 2014 Shiffman et al

Alternative Splicing in the Differentiation of Human Embryonic Stem Cells into Cardiac Precursors

The role of alternative splicing in self-renewal, pluripotency and tissue lineage specification of human embryonic stem cells (hESCs) is largely unknown. To better define these regulatory cues, we modified the H9 hESC line to allow selection of pluripotent hESCs by neomycin resistance and cardiac progenitors by puromycin resistance. Exon-level microarray expression data from undifferentiated hESCs and cardiac and neural precursors were used to identify splice isoforms with cardiac-restricted or common cardiac/neural differentiation expression patterns. Splice events for these groups corresponded to the pathways of cytoskeletal remodeling, RNA splicing, muscle specification, and cell cycle checkpoint control as well as genes with serine/threonine kinase and helicase activity. Using a new program named AltAnalyze (http://www.AltAnalyze.org), we identified novel changes in protein domain and microRNA binding site architecture that were predicted to affect protein function and expression. These included an enrichment of splice isoforms that oppose cell-cycle arrest in hESCs and that promote calcium signaling and cardiac development in cardiac precursors. By combining genome-wide predictions of alternative splicing with new functional annotations, our data suggest potential mechanisms that may influence lineage commitment and hESC maintenance at the level of specific splice isoforms and microRNA regulation

Increased peri-ductal collagen micro-organization may contribute to raised mammographic density

BACKGROUND: High mammographic density is a therapeutically modifiable risk factor for breast cancer. Although mammographic density is correlated with the relative abundance of collagen-rich fibroglandular tissue, the causative mechanisms, associated structural remodelling and mechanical consequences remain poorly defined. In this study we have developed a new collaborative bedside-to-bench workflow to determine the relationship between mammographic density, collagen abundance and alignment, tissue stiffness and the expression of extracellular matrix organising proteins. METHODS: Mammographic density was assessed in 22 post-menopausal women (aged 54–66 y). A radiologist and a pathologist identified and excised regions of elevated non-cancerous X-ray density prior to laboratory characterization. Collagen abundance was determined by both Masson’s trichrome and Picrosirius red staining (which enhances collagen birefringence when viewed under polarised light). The structural specificity of these collagen visualisation methods was determined by comparing the relative birefringence and ultrastructure (visualised by atomic force microscopy) of unaligned collagen I fibrils in reconstituted gels with the highly aligned collagen fibrils in rat tail tendon. Localised collagen fibril organisation and stiffness was also evaluated in tissue sections by atomic force microscopy/spectroscopy and the abundance of key extracellular proteins was assessed using mass spectrometry. RESULTS: Mammographic density was positively correlated with the abundance of aligned periductal fibrils rather than with the abundance of amorphous collagen. Compared with matched tissue resected from the breasts of low mammographic density patients, the highly birefringent tissue in mammographically dense breasts was both significantly stiffer and characterised by large (>80 μm long) fibrillar collagen bundles. Subsequent proteomic analyses not only confirmed the absence of collagen fibrosis in high mammographic density tissue, but additionally identified the up-regulation of periostin and collagen XVI (regulators of collagen fibril structure and architecture) as potential mediators of localised mechanical stiffness. CONCLUSIONS: These preliminary data suggest that remodelling, and hence stiffening, of the existing stromal collagen microarchitecture promotes high mammographic density within the breast. In turn, this aberrant mechanical environment may trigger neoplasia-associated mechanotransduction pathways within the epithelial cell population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0664-2) contains supplementary material, which is available to authorized users