Miracle-dz/UniFAR-FTUs huggingface dataset:
Population-based structural variation discovery with Hydra-Multi

Summary: Current strategies for SNP and INDEL discovery incorporate sequence alignments from multiple individuals to maximize sensitivity and specificity. It is widely accepted that this approach also improves structural variant (SV) detection. However, multisample SV analysis has been stymied by the fundamental difficulties of SV calling, e.g. library insert size variability, SV alignment signal integration and detecting long-range genomic rearrangements involving disjoint loci. Extant tools suffer from poor scalability, which limits the number of genomes that can be co-analyzed and complicates analysis workflows. We have developed an approach that enables multisample SV analysis in hundreds to thousands of human genomes using commodity hardware. Here, we describe Hydra-Multi and measure its accuracy, speed and scalability using publicly available datasets provided by The 1000 Genomes Project and by The Cancer Genome Atlas (TCGA). Availability and implementation: Hydra-Multi is written in C++ and is freely available at https://github.com/arq5x/Hydra. Contact: aaronquinlan@gmail.com or ihall@genome.wustl. edu Supplementary information: Supplementary data are available at Bioinformatics online.
A Data Similarity-Based Strategy for Meta-analysis of Transcriptional Profiles in Cancer

Background Robust transcriptional signatures in cancer can be identified by data similarity-driven meta-analysis of gene expression profiles. An unbiased data integration and interrogation strategy has not previously been available. Methods and Findings We implemented and performed a large meta-analysis of breast cancer gene expression profiles from 223 datasets containing 10,581 human breast cancer samples using a novel data similarity-based approach (iterative EXALT). Cancer gene expression signatures extracted from individual datasets were clustered by data similarity and consolidated into a meta-signature with a recurrent and concordant gene expression pattern. A retrospective survival analysis was performed to evaluate the predictive power of a novel meta-signature deduced from transcriptional profiling studies of human breast cancer. Validation cohorts consisting of 6,011 breast cancer patients from 21 different breast cancer datasets and 1,110 patients with other malignancies (lung and prostate cancer) were used to test the robustness of our findings. During the iterative EXALT analysis, 633 signatures were grouped by their data similarity and formed 121 signature clusters. From the 121 signature clusters, we identified a unique meta-signature (BRmet50) based on a cluster of 11 signatures sharing a phenotype related to highly aggressive breast cancer. In patients with breast cancer, there was a significant association between BRmet50 and disease outcome, and the prognostic power of BRmet50 was independent of common clinical and pathologic covariates. Furthermore, the prognostic value of BRmet50 was not specific to breast cancer, as it also predicted survival in prostate and lung cancers. Conclusions We have established and implemented a novel data similarity-driven meta-analysis strategy. Using this approach, we identified a transcriptional meta-signature (BRmet50) in breast cancer, and the prognostic performance of BRmet50 was robust and applicable across a wide range of cancer-patient populations.
Desiccation and Mortality Dynamics in Seedlings of Different European Beech (Fagus sylvatica L.) Populations under Extreme Drought Conditions

European beech (Fagus sylvatica L., hereafter beech), one of the major native tree species in Europe, is known to be drought sensitive. Thus, the identification of critical thresholds of drought impact intensity and duration are of high interest for assessing the adaptive potential of European beech to climate change in its native range. In a common garden experiment with one-year-old seedlings originating from central and marginal origins in six European countries (Denmark, Germany, France, Romania, Bosnia-Herzegovina, and Spain), we applied extreme drought stress and observed desiccation and mortality processes among the different populations and related them to plant water status (predawn water potential, ΨPD) and soil hydraulic traits. For the lethal drought assessment, we used a critical threshold of soil water availability that is reached when 50% mortality in seedling populations occurs (LD50SWA). We found significant population differences in LD50SWA (10.5–17.8%), and mortality dynamics that suggest a genetic difference in drought resistance between populations. The LD50SWA values correlate significantly with the mean growing season precipitation at population origins, but not with the geographic margins of beech range. Thus, beech range marginality may be more due to climatic conditions than to geographic range. The outcome of this study suggests the genetic variation has a major influence on the varying adaptive potential of the investigated populations.
An analysis of the energetic reward offered by field bean (Vicia faba) flowers: Nectar, pollen, and operative force

Abstract Global consumption of crops with a yield that is dependent on animal pollinators is growing, with greater areas planted each year. However, the floral traits that influence pollinator visitation are not usually the focus of breeding programmes, and therefore, it is likely that yield improvements may be made by optimizing floral traits to enhance pollinator visitation rates. We investigated the variation present in the floral reward of the bee‐pollinated crop Vicia faba (field bean). We examined the genetic potential for breeding flowers with a greater reward into current commercial varieties and used bee behavioral experiments to gain insight into the optimal nectar concentration to maximize bee preference. There was a large range of variation in the amount of pollen and nectar reward of flowers in the genotypes investigated. Bee behavioral experiments using nectar sugar concentrations found in V. faba lines suggest that Bombus terrestris prefers 55% w/w sugar solution over 40% w/w, but has no preference between 55% w/w and 68% w/w sugar solution. We provide a first indication of the force required to open V. faba flowers. Our results provide a valuable starting point toward breeding for varieties with optimized floral reward. Field studies are now needed to verify whether the genetic potential for breeding more rewarding flowers can translate into higher yield and yield stability.
Catecholamines and preconditioning: studies of contraction and function in isolated rat hearts.

The aims of this study were to determine whether 1) like ischemic preconditioning, transient exposure to norepinephrine before ischemia exacerbates contracture during ischemia and 2) protection afforded by norepinephrine is stereospecific (receptor mediated). Isolated perfused rat hearts were randomized into five groups ( n = 6/group): 1) ischemic preconditioning (3 min of ischemia + 3 min of reperfusion + 5 min of ischemia + 5 min of reperfusion), 2) untreated control, 3) vehicle control (ascorbic acid), 4) substitution of preconditioning ischemia by perfusion with d-norepinephrine, and 5) substitution of preconditioning ischemia by perfusion with l-norepinephrine. This was followed by 40 min of zero-flow ischemia and 50 min of reperfusion. Ischemic preconditioning and l-norepinephrine exacerbated contracture (time to 50% contracture = 9.2 ± 1.1 and 9.0 ± 1.1 vs. 13.3 ± 0.3, 12.4 ± 0.5, and 13.2 ± 0.4 min for untreated control, vehicle control, and d-norepinephrine, respectively, P < 0.05). Postischemic left ventricular developed pressure was poor in untreated control (23.0 ± 2.2%), vehicle control (26.9 ± 2.3%), and d-norepinephrine (19.8 ± 2.8%) groups but good in preconditioned (52.4 ± 5.1%) and l-norepinephrine (52.5 ± 1.1%) groups ( P < 0.05). Thus norepinephrine preconditioning, like ischemic preconditioning, causes a paradoxical exacerbation of contracture coupled with enhanced postischemic recovery; both effects are stereospecific.
Localization of a candidate surfactant convertase to type II cells, macrophages, and surfactant subfractions.

Pulmonary surfactant exists in the alveolus in several distinct subtypes that differ in their morphology, composition, and surface activity. Experiments by others have implicated a serine hydrolase in the production of the inactive small vesicular subtype of surfactant (N. J. Gross and R. M. Schultz. Biochim. Biophys. Acta 1044: 222-230, 1990). Our laboratory recently identified this enzyme in the rat as the serine carboxylesterase ES-2 [F. Barr, H. Clark, and S. Hawgood. Am. J. Physiol. 274 ( Lung Cell. Mol. Physiol. 18): L404-L410, 1998]. In the present study, we determined the cellular sites of expression of ES-2 in rat lung using a digoxygenin-labeled ES-2 riboprobe. ES-2 mRNA was localized to type II cells and alveolar macrophages but not to Clara cells. Using a specific ES-2 antibody, we determined the protein distribution of ES-2 in the lung by immunohistochemistry, and it was found to be consistent with the sites of mRNA expression. Most of the ES-2 in rat bronchoalveolar lavage is in the surfactant-depleted supernatant, but ES-2 was also consistently localized to the small vesicular surfactant subfraction presumed to form as a consequence of conversion activity. These results are consistent with a role for endogenous lung ES-2 in surfactant metabolism.
Growth Dynamics of Patient-Provider Internet Communication: Trend Analysis Using the Health Information National Trends Survey (2003 to 2013)

Background Communication is key in chronic disease management, and the internet has altered the manner in which patients and providers can exchange information. Adoption of secure messaging differs among patients due to the digital divide that keeps some populations from having effective access to online resources. Objective This study aimed to examine the current state of online patient-provider communication, exploring trends over time in the use of online patient-provider communication tools. Methods A 3-part analytic process was used to study the following: (1) reanalysis, (2) close replication across years, and (3) trend analysis extension. During the reanalysis stage, the publicly available Health Information National Trends Survey (HINTS) 1 and 2 data were used with the goal of identifying the precise analytic methodology used in a prior study, published in 2007. The original analysis was extended to add 3 additional data years (ie, 2008, 2011, and 2013) using the original analytical approach with the purpose of identifying trends over time. Multivariate logistic regression was used to analyze pooled data across all years, with year as an added predictor, in addition to a model for each individual data year. Results The odds of internet users to communicate online with health care providers was significantly and increasingly higher year-over-year, starting in 2003 (2005: odds ratio [OR] 1.31, 95% CI 1.03-1.68; 2008: OR 2.14, 95% CI 1.76-2.59; 2011: OR 2.92, 95% CI 2.33-3.66; and 2013: OR 5.77; 95% CI 4.62-7.20). Statistically significant socio-economic factors found to be associated with internet users communicating online with providers included age, having health insurance, having a history of cancer, and living in an urban area of residence. Conclusions The proportion of internet users communicating online with their health care providers has significantly increased since 2003. Although these trends are encouraging, access challenges still exist for some groups, potentially giving rise to a new set of health disparities related to communication.
Effect of estrogen on aortic function in postmenopausal women.

We hypothesized that estrogen may alter aortic elastic properties. The aortic pressure-diameter relation was obtained in 20 postmenopausal women, 10 without ( group 1) and 10 with ( group 2) proven coronary artery disease, before and after intravenous administration of 10 μg of 17β-estradiol. Instantaneous aortic diameter was measured by an intravascular catheter developed in our institution simultaneously with aortic pressure at the same aortic level with a catheter-tipped micromanometer. At baseline, elastic properties of the aorta were decreased in group 2 compared with group 1. Compared with baseline, aortic distensibility was increased in both groups ( P< 0.01 and P < 0.05 for groups 1 and 2, respectively) after estrogen administration, whereas the pressure-diameter loop was shifted downward along a different hypothetical line of elasticity, suggesting active changes in the aortic elastic properties. Furthermore, a significant reduction in wave reflection was found in both groups ( P < 0.001). This action may contribute to the beneficial effects of estrogen on the cardiovascular system and may have future therapeutic implications in postmenopausal women.
Assessment of the mechanism of juxtacrine activation and adhesion of leukocytes in liver microcirculation.

Leukotriene C4(LTC4), histamine, and other mediators can induce expression of P-selectin and platelet-activating factor (PAF) on venular endothelium to recruit leukocytes in vivo and in vitro via a juxtacrine mechanism of adhesion. The objective of this study was to assess the effect of histamine and LTC4 on the leukocyte recruitment in the liver and to study the components and molecular mechanisms involved in this process. We visualized the hepatic microvasculature using intravital microscopy and we determined that LTC4 (20 nM) but not histamine (0.1, 0.3, or 1 mM) induced leukocyte recruitment in the liver microcirculation. Histamine could induce leukocyte recruitment but only in the presence of an antihistaminase. The LTC4-induced leukocyte recruitment occurred primarily in sinusoids (not venules) and was not inhibitable by three different anti-P-selectin antibodies (5H1, RMP-1, and RB40). Leukocyte recruitment in P-selectin-deficient mice, intercellular adhesion molecule 1 (ICAM-1)-deficient mice, and mice treated with a PAF antagonist was of the same magnitude as in wild-type animals in response to LTC4. Although PAF alone could induce adhesion in both sinusoids and postsinusoidal venules, this chemotactic agent was not involved in LTC4-induced adhesion in the liver. Finally, an overlapping role for P-selectin and ICAM-1 was ruled out as LTC4 induced leukocyte recruitment in P-selectin and ICAM-1 double-deficient mice. These data demonstrate that LTC4 does not activate the known early mechanisms of leukocyte recruitment, including P-selectin, PAF, or ICAM-1 in the hepatic microvasculature.
Persistence and space preemption explain species‐specific founder effects on the organization of marine sessile communities

Abstract Community assembly may not follow predictable successional stages, with a large fraction of the species pool constituted by potential pioneering species and successful founders defined through lottery. In such systems, priority effects may be relevant in the determination of trajectories of developing communities and hence diversity and assemblage structure at later advanced states. In order to assess how different founder species may trigger variable community trajectories and structures, we conducted an experimental study using subtidal sessile assemblages as model. We manipulated the identity of functionally different founders and initial colony size (a proxy of the time lag before the arrival of later species), and followed trajectories. We did not observe any effects of colony size on response variables, suggesting that priority effects take place even when the time lag between the establishment of pioneering species and late colonizers is very short. Late community structure at experimental panels that started either with the colonial ascidian Botrylloides nigrum, or the arborescent bryozoan Bugula neritina, was similar to control panels allowed natural assembling. In spite of high potential for fast space domination, and hence negative priority effects, B. nigrum suffered high mortality and did not persist throughout succession. Bugula neritina provided complex physical microhabitats through conspecific clustering that have enhanced larval settlement of late species arrivals, but no apparent facilitation was observed. Differently, panels founded by the encrusting bryozoan Schizoporella errata led to different and less diverse communities compared to naturally assembled panels, evidencing strong negative priority effects through higher persistence and space preemption. Schizoporella errata founder colonies inhibited further conspecific settlement, which may greatly relax intraspecific competition, allowing resource allocation to colony growth and space domination, thus reducing the chances for the establishment of other species.
Physical Activity Behaviour: An Overview of Current and Emergent Theoretical Practices

Physical activity research has been dominated by traditional cognitive rationale paradigms utilized within other domains. Though this approach to physical activity behavior has greatly enhanced our understanding of the key determinants, it has done little to eradicate the health problems we currently face. In order to achieve lasting change though, multilevel interventions may prove effective. Ecological perspectives have been proposed as an effective approach in combating current physical inactivity levels. Nevertheless, this approach is in its infancy and much has still to be learned. The aim of this paper is to provide an overview of the main behavioral models used within the physical activity domain while proposing the need for further models that will embrace the principles presented by ecological and complexity theories.
Flow regulation of ecNOS and Cu/Zn SOD mRNA expression in porcine coronary arterioles.

The purpose of this study was to test the hypothesis that increased flow through coronary arterioles increases endothelial cell nitric oxide synthase (ecNOS) and Cu/Zn superoxide dismutase (SOD) mRNA expression. Single porcine coronary arterioles (ID 100-160 μm; pressurized) were cannulated, perfused, and exposed to intraluminal flow sufficient to produce maximal flow-induced dilation of coronary arterioles (high flow; 7.52 ± 0.22 μl/min), low flow (0.84 ± 0.05 μl/min), or no flow for 2 or 4 h. Mean shear stress was calculated to be 5.7 ± 1.0 dyn/cm2 for high-flow arterioles and 1.6 ± 1.0 dyn/cm2 for low-flow arterioles. At the end of the treatment period, mRNA was isolated from each vessel, and ecNOS and SOD mRNA expression was assessed using a semiquantitative RT-PCR. All data were standardized by coamplifying ecNOS or SOD with glyceraldehyde-3-phosphate dehydrogenase. The results indicate that ecNOS mRNA expression is increased in arterioles exposed to 2 or 4 h of high flow. In contrast, SOD mRNA expression was increased only after 4 h of high flow. Neither gene is induced by exposure to low flow. On the basis of these data, we concluded that ecNOS and SOD mRNA expression is regulated by flow in porcine coronary arterioles. In addition, we concluded that a threshold level of flow and shear stress must be sustained to elicit the upregulation of ecNOS and SOD mRNA expression.
Aging-dependent depression in the kinetics of force development in rat skinned myocardium.

Normal aging of the rodent heart results in prominent prolongation of the twitch. We tested the hypothesis that increased expression of β-myosin heavy chain (MHC), as occurs in the normal aging process in the rodent heart, contributes to the prolongation of the twitch by depressing the kinetics of cross-bridge interaction. Using 3-, 9-, 21-, and 33-mo-old male Fischer 344 × Brown Norway F1hybrid rats, we examined both the rate of tension development ( k Ca) and unloaded shortening velocity in chemically skinned myocardium. Although k Ca in all four age groups was dependent on the level of Ca2+ activation, both submaximal and maximal k Cawere significantly slower in 9-, 21-, and 33-mo-old rats relative to 3-mo-old rats. Furthermore, unloaded shortening velocity was significantly reduced in 9-, 21-, and 33-mo-old rats compared with 3-mo-old rats. Collectively, these data strongly suggest that the aging-related increase in β-MHC expression results in a progressive slowing of cross-bridge interaction kinetics in skinned myocardium, which most likely contributes to the overall aging-dependent reduction in myocardial functional capacity.
The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression

Invasive infections caused by Streptococcus pneumoniae, a commensal in the nasopharynx, pose significant risk to human health. Limited serotype coverage by the available polysaccharide-based conjugate vaccines coupled with increasing incidence of antibiotic resistance complicates therapeutic strategies. Bacterial physiology and metabolism that allows pathogens to adapt to the host are a promising avenue for the discovery of novel therapeutics. Intracellular polyamine concentrations are tightly regulated by biosynthesis, transport and degradation. We previously reported that deletion of cadA, a gene that encodes for lysine decarboxylase, an enzyme that catalyzes cadaverine synthesis results in an attenuated phenotype. Here, we report the impact of cadA deletion on pneumococcal capsule and protein expression. Our data show that genes for polyamine biosynthesis and transport are downregulated in ∆cadA. Immunoblot assays show reduced capsule in ∆cadA. Reduced capsule synthesis could be due to reduced transcription and availability of precursors for synthesis. The capsule is the predominant virulence factor in pneumococci and is critical for evading opsonophagocytosis and its loss in ∆cadA could explain the reported attenuation in vivo. Results from this study show that capsule synthesis in pneumococci is regulated by polyamine metabolism, which can be targeted for developing novel therapies.
ASTP: Agent-Based Secure and Trustworthy Packet-Forwarding Protocol for eHealth

Security has been recognized as a key issue for the expansion of eHealth application, where highly sensitive patient's medical data are routed through a non-secure wireless network. In this paper, we look into the various security and privacy requirements for the eHealth application and propose an agent-based secure and trustworthy packet-forwarding Protocol (ASTP) considering the neighbor nodes previous and recent activities. ASTP incorporated with proper security tools that enhanced the overall performance of a cooperative multi-hop wireless network used for an eHealth application. The proposed protocol can successfully detects malicious nodes and the information is used and shared to the neighbors to avoid co-operating with them either for data forwarding, aggregation or any other cooperative function. Patient privacy is maintained by using an renewable pseudo-identity. Finally, security analysis and experimental results demonstrate that ASTP improves the average packet delivery ratio and maintains the require security and privacy at the cost of an acceptable communication delay.