Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study.

BACKGROUND There is controversy regarding the association of the angiotensin-converting enzyme deletion-insertion (ACE D/I) polymorphism with systemic hypertension and with blood pressure. We investigated these relations in a large population-based sample of men and women by using association and linkage analyses. METHODS AND RESULTS The study sample consisted of 3095 participants in the Framingham Heart Study. Blood pressure measurements were obtained at regular examinations. The ACE D/I polymorphism was identified by using a polymerase chain reaction assay. In logistic regression analysis, the adjusted odds ratios for hypertension among men for the DD and DI genotypes were 1.59 (95% confidence interval [CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively, versus II (chi2 P=.02). In women, adjusted odds ratios for the DD and DI genotypes were 1.00 (95% CI, 0.70 to 1.44) and 0.78 (95% CI, 0.56 to 1.09), respectively (P=.14). In linear regression analysis, there was an association of the ACE DD genotype with increased diastolic blood pressure in men (age-adjusted P=.03, multivariate-adjusted P=.14) but not women. Quantitative trait linkage analyses in 1044 pairs of siblings, by using both ACE D/I and a nearby microsatellite polymorphism of the human growth hormone gene, supported a role of the ACE locus in influencing blood pressure in men but not in women. CONCLUSIONS In our large, population-based sample, there is evidence for association and genetic linkage of the ACE locus with hypertension and with diastolic blood pressure in men but not women. Our data support the hypothesis that ACE, or a nearby gene, is a sex-specific candidate gene for hypertension. Confirmatory studies in other large population-based samples are warranted.
Activation of ZAP-70 through Specific Dephosphorylation at the Inhibitory Tyr-292 by the Low Molecular Weight Phosphotyrosine Phosphatase (LMPTP)*

The ZAP-70 protein-tyrosine kinase plays a central role in signaling from the T cell antigen receptor. Recruitment and activation of ZAP-70 are transient and are terminated by phosphorylation of negative regulatory tyrosine residues and dephosphorylation of positively acting sites. We report that the low molecular weight protein-tyrosine phosphatase (LMPTP) specifically dephosphorylates the negative regulatory Tyr-292 of ZAP-70, thereby counteracting inactivation of ZAP-70. Expression of low levels of LMPTP resulted in increased ZAP-70 phosphorylation, presumably at the activating Tyr-493 and other sites, increased kinase activity, and augmented downstream signaling to the mitogen-activated protein kinase pathway. The ZAP-70 Y292F mutant was not affected by LMPTP. Our results indicate that LMPTP, like CD45, dephosphorylates a negative regulatory tyrosine site in a protein-tyrosine kinase and thereby strengthens T cell receptor signaling.
Open Borders? Immigration in Open Source Projects

Open source software is built by teams of volunteers. Each project has a core team of developers, who have the authority to commit changes to the repository; this team is the elite, committed foundation of the project, selected through a meritocratic process from a larger number of people who participate on the mailing list. Most projects carefully regulate admission of outsiders to full developer privileges; some projects even have formal descriptions of this process. Understanding the factors that influence the "who, how and when" of this process is critical, both for the sustainability of FLOSS projects, and for outside stakeholders who want to gain entry and succeed. In this paper we mount a quantitative case study of the process by which people join FLOSS projects, using data mined from the Apache Web server, Postgres, and Python. We develop a theory of open source project joining, and evaluate this theory based on our data.
Vulnerability of shallow subarctic lakes to evaporate and desiccate when snowmelt runoff is low

Snowmelt is a crucial source of water for many shallow subarctic lakes, but climate models predict that snowfall will decrease in some regions, with profound ecological consequences. Here we use lake water isotope data across gradients of terrestrial vegetation cover (open tundra to closed forest) and topographic relief to identify lakes that are vulnerable to desiccation under conditions of low snowmelt runoff in two subarctic landscapes—Old Crow Flats, Yukon, and Hudson Bay Lowlands, Manitoba (Canada). Lakes located in low‐relief, open tundra catchments in both landscapes displayed a systematic, positive offset between directly measured lake water δ18O over multiple sampling campaigns and lake water δ18O inferred from cellulose in recently deposited surface sediments. We attribute this offset to a strong evaporative 18O‐enrichment response to lower‐than‐average snowmelt runoff in recent years. Notably, some lakes underwent near‐complete desiccation during midsummer 2010 following a winter of very low snowfall. Based on the paleolimnological record of one such lake, the extremely dry conditions in 2010 may be unprecedented in the past ~200 years. Findings fuel concerns that a decrease in snowmelt runoff will lead to widespread desiccation of shallow lakes in these landscapes.
Dynamical measure and field theory models free of the cosmological constant problem

Summary of abstract Field theory models including gauge theories with SSB are presented where the energy density of the true vacuum state (TVS) is zero without fine tuning. The above models are constructed in the gravitational theory where a measure of integration \Phi in the action is not necessarily \sqrt{-g} but it is determined dynamically through additional degrees of freedom. The ratio \Phi/\sqrt{-g} is a scalar field which can be solved in terms of the matter degrees of freedom due to the existence of a constraint. We study a few explicit field theory models where it is possible to combine the solution of the cosmological constant problem with: 1) possibility for inflationary scenario for the early universe; 2) spontaneously broken gauge unified theories (including fermions). The models are free from the well known problem of the usual scalar-tensor theories in what is concerned with the classical GR tests. The only difference of the field equations in the Einstein frame from the canonical equations of the selfconsistent system of Einstein's gravity and matter fields, is the appearance of the effective scalar field potential which vanishes in TVS without fine tuning.
Key Role for the Epsilon Isoform of Protein Kinase C in Painful Alcoholic Neuropathy in the Rat

Chronic alcohol consumption produces a painful peripheral neuropathy for which there is no reliably successful therapy, attributable to, in great part, a lack of understanding of the underlying mechanisms. We tested the hypothesis that neuropathic pain associated with chronic alcohol consumption is a result of abnormal peripheral nociceptor function. In rats maintained on a diet to simulate chronic alcohol consumption in humans, mechanical hyperalgesia was present by the fourth week and maximal at 10 weeks. Thermal hyperalgesia and mechanical allodynia were also present. Mechanical threshold of C-fibers in ethanol fed rats was lowered, and the number of action potentials during sustained stimulation increased. The hyperalgesia was acutely attenuated by intradermal injection of nonselective protein kinase C (PKC) or selective PKCε inhibitors injected at the site of nociceptive testing. Western immunoblot analysis indicated a higher level of PKCε in dorsal root ganglia from alcohol-fed rats, supporting a role for enhanced PKCε second-messenger signaling in nociceptors contributing to alcohol-induced hyperalgesia.
Speeding Up Chemical Database Searches Using a Proximity Filter Based on the Logical Exclusive OR

In many large chemoinformatics database systems, molecules are represented by long binary fingerprint vectors whose components record the presence or absence in the molecular graphs of particular functional groups or combinatorial features, such as labeled paths or labeled trees. To speed up database searches, we propose to store with each fingerprint a small header vector containing primarily the result of applying the logical exclusive OR (XOR) operator to the fingerprint vector after modulo wrapping to a smaller number of bits, such as 128 bits. From the XOR headers of two molecules, tight bounds on the intersection and union of their fingerprint vectors can be rapidly obtained, yielding tight bounds on derived similarity measures, such as the Tanimoto measure. During a database search, every time these bounds are unfavorable, the corresponding molecule can be rapidly discarded with no need for further inspection. We derive probabilistic models that allow us to estimate precisely the behavior of the XOR headers and the level of pruning under different conditions in terms of similarity threshold and fingerprint density. These theoretical results are corroborated by experimental results on a large set of molecules. For a Tanimoto threshold of 0.5 (respectively 0.9), this approach requires searching less than 50% (respectively 10%) of the database, leading to typical search speedups of 2 to 3 times over the previous state-of-the-art.
Effect of preconditioning ischemia on reperfusion arrhythmias after coronary artery occlusion and reperfusion in the rat.

Severe arrhythmias occur predictably on reperfusion after 5 minutes of coronary occlusion in the rat. There is little data available on whether ischemic preconditioning (PC) of hearts can reduce the incidence of such arrhythmias. The effect of PC (three cycles of 2 minutes of coronary occlusion and 5 minutes of reperfusion) on development of arrhythmias after a subsequent 5-minute coronary artery occlusion and reperfusion was studied. Rats (n = 16 each group) underwent 5-minute occlusion and reperfusion alone or preceded by PC; arrhythmias were monitored during ischemia and for 10 minutes of reperfusion, and biopsies were taken for creatine phosphate and adenosine triphosphate in ischemic and nonischemic zones of the left ventricle. PC reduced the incidence of ventricular tachycardia (VT) during occlusion (81% control versus 13% PC, p less than 0.001). On subsequent reperfusion, ventricular fibrillation (VF) developed in zero PC animals versus 13 (81%) of controls (p less than 0.001), and irreversible VF in zero of PC versus seven (44%) of controls (p = 0.007). VT occurred in four (25%) of PC versus all (100%) of controls (p less than 0.001). PC reduced mean duration of VT plus VF from 320 +/- 54 to 5 +/- 1 seconds (p less than 0.001) and delayed arrhythmia onset from 8 +/- 2 to 85 +/- 35 seconds after reperfusion. There was no difference in creatine phosphate levels in the ischemic zone at the end of reperfusion in PC animals compared with controls without irreversible VF (16.2 +/- 4.1 versus 15.5 +/- 3.9 nmol/mg protein, p = NS). (ABSTRACT TRUNCATED AT 250 WORDS)
Transitivity, flexibility, conjunctive representations, and the hippocampus. I. An empirical analysis

After training on a set of four ordered, simultaneous, odor discrimination problems (A+B−, B+C−, C+D−, D+E), intact rats display transitivity: When tested on the novel combination BD, they choose B. Rats with damage to the hippocampus, however, do not show transitivity (Dusek and Eichenbaum, 1997. Proc Natl Acad Sci U S A 94:7109–7114). These results have been interpreted as support for the idea that the hippocampus is a relational memory storage system that enables the subject to make comparisons among representations of the individual problems and choose based on inferential logic. We provide evidence for a simpler explanation. Specifically, subjects make their choices based on the absolute excitatory value of the individual stimuli. This value determines the ability of that stimulus to attract a response. This conclusion emerged because after training on a five‐problem set (A+B−, B+C−, C+D−, D+E−, E+F−) rats preferred B when tested with BE, but not when tested with BD. The implication of these results for how to conceptualize the role of the hippocampus in transitive‐like phenomena is discussed. Hippocampus 2003;13:334–340. © 2003 Wiley‐Liss, Inc.
SURNAME AND CONSANGUINEOUS MARRIAGES IN JAPAN

A survey of consanguineous marriages in Japan was conducted on 1 September 1983, by questionnaires. The total number of couples surveyed was 9225. They were chosen from six widely different areas and the inbreeding coefficients from isonymy and pedigrees were estimated for each area. Random inbreeding remained constant with the marriage year whereas total (F) and non-random (Fn) inbreeding from isonymy and inbreeding from pedigrees (α) decreased with the marriage year in each area. Estimates of genetic microdifferentiation from surnames were obtained; estimates of the reduced variance indicated low microdifferentiation (0·000014-0·000081) in five areas and a higher value in Fukue City (0·0004). The ratio of FST (the average within-group a priori kinship) to α-value ranged from 0·42 in Kawanishi City to 3·9 in Minobu-Cho.
An EM-Based Forward-Backward Kalman Filter for the Estimation of Time-Variant Channels in OFDM

Orthogonal frequency division multiplexing (OFDM) combines the advantages of high achievable rates and relatively easy implementation. However, for proper recovery of the input, the OFDM receiver needs accurate channel information. In this paper, we propose an expectation-maximization algorithm for joint channel and data recovery in fast fading environments. The algorithm makes a collective use of the data and channel constraints inherent in the communication problem. This comes in contrast to other works which have employed these constraints selectively. The data constraints include pilots, the cyclic prefix, and the finite alphabet restriction, while the channel constraints include sparsity, finite delay spread, and the statistical properties of the channel (frequency and time correlation). The algorithm boils down to a forward-backward Kalman filter. We also suggest a suboptimal modification that is able to track the channel and recover the data with no latency. Simulations show the favorable behavior of both algorithms compared to other channel estimation techniques.
Effective Five Directional Partial Derivatives-Based Image Smoothing and a Parallel Structure Design

Image smoothing has been used for image segmentation, image reconstruction, object classification, and 3D content generation. Several smoothing approaches have been used at the pre-processing step to retain the critical edge, while removing noise and small details. However, they have limited performance, especially in removing small details and smoothing discrete regions. Therefore, to provide fast and accurate smoothing, we propose an effective scheme that uses a weighted combination of the gradient, Laplacian, and diagonal derivatives of a smoothed image. In addition, to reduce computational complexity, we designed and implemented a parallel processing structure for the proposed scheme on a graphics processing unit (GPU). For an objective evaluation of the smoothing performance, the images were linearly quantized into several layers to generate experimental images, and the quantized images were smoothed using several methods for reconstructing the smoothly changed shape and intensity of the original image. Experimental results showed that the proposed scheme has higher objective scores and better successful smoothing performance than similar schemes, while preserving and removing critical and trivial details, respectively. For computational complexity, the proposed smoothing scheme running on a GPU provided 18 and 16 times lower complexity than the proposed smoothing scheme running on a CPU and the L0-based smoothing scheme, respectively. In addition, a simple noise reduction test was conducted to show the characteristics of the proposed approach; it reported that the presented algorithm outperforms the state-of-the art algorithms by more than 5.4 dB. Therefore, we believe that the proposed scheme can be a useful tool for efficient image smoothing.
ISEV position paper: extracellular vesicle RNA analysis and bioinformatics

Extracellular vesicles (EVs) are the collective term for the various vesicles that are released by cells into the extracellular space. Such vesicles include exosomes and microvesicles, which vary by their size and/or protein and genetic cargo. With the discovery that EVs contain genetic material in the form of RNA (evRNA) has come the increased interest in these vesicles for their potential use as sources of disease biomarkers and potential therapeutic agents. Rapid developments in the availability of deep sequencing technologies have enabled the study of EV-related RNA in detail. In October 2012, the International Society for Extracellular Vesicles (ISEV) held a workshop on “evRNA analysis and bioinformatics. ” Here, we report the conclusions of one of the roundtable discussions where we discussed evRNA analysis technologies and provide some guidelines to researchers in the field to consider when performing such analysis.
Effects of Serotonin 2C Receptor Agonists on the Behavioral and Neurochemical Effects of Cocaine in Squirrel Monkeys

Accumulating evidence indicates that the serotonin system modulates the behavioral and neurochemical effects of cocaine, but the receptor subtypes mediating these effects remain unknown. Recent studies have demonstrated that pharmacological activation of the serotonin 2C receptor (5-HT2CR) attenuates the behavioral and neurochemical effects of cocaine in rodents, but such compounds have not been systematically evaluated in nonhuman primates. The present experiments sought to determine the impact of pretreatment with the preferential 5-HT2CR agonist m-chlorophenylpiperazine (mCPP) and the selective 5-HT2CR agonist Ro 60-0175 [(α-S)-6-chloro-5-fluoro-α-methyl-1H-indole-1-ethanamine fumarate] on the behavioral and neurochemical effects of cocaine in squirrel monkeys. In subjects trained to lever-press according to a 300-s fixed-interval schedule of stimulus termination, pretreatment with either 5-HT2CR agonist dose-dependently and insurmountably attenuated the behavioral stimulant effects of cocaine. In subjects trained to self-administer cocaine, both compounds dose-dependently and insurmountably attenuated cocaine-induced reinstatement of previously extinguished responding in an antagonist-reversible manner, and the selective agonist Ro 60-0175 also attenuated the reinforcing effects of cocaine during ongoing cocaine self-administration. It is noteworthy that the selective agonist Ro 60-0175 exhibited behavioral specificity because it did not significantly alter nondrug-maintained responding. Finally, in vivo microdialysis studies revealed that pretreatment with Ro 60-0175 caused a reduction of cocaine-induced dopamine increases within the nucleus accumbens, but not the caudate nucleus. These results suggest that 5-HT2CR agonists functionally antagonize the behavioral effects of cocaine in nonhuman primates, possibly via a selective modulation of cocaine-induced dopamine increases within the mesolimbic dopamine system and may therefore represent a novel class of pharmacotherapeutics for the treatment of cocaine abuse.
Improvement of the Specificity of an Enzyme-Linked Immunosorbent Assay for Diagnosis of Paracoccidioidomycosis

ABSTRACT In an attempt to improve the specificity of an enzyme-linked immunosorbent assay (ELISA) for the diagnosis of paracoccidioidomycosis (PCM), sera from patients with PCM were tested using various approaches, such as sodium metaperiodate antigen (gp43) treatment, a serum absorption process with Candida albicans or Histoplasma capsulatum antigens, and dilution of serum in galactose, the main common epitope among pathogenic fungi. The maximum specificity found in this ELISA was 84%. All of these procedures proved inefficient for eliminating all cross-reacting antibodies and obtaining an ELISA specific for PCM diagnosis.
Reading Consumer Reviews to Confirm My Expectations: The Accelerated Impact of Confirmation under Extreme Review Tones

This study examines how the initially perceived product value affects a consumer’s purchase intention after he/she reads various tones of online reviews. It proposes that the associations among the initially perceived product value, the level of confirmation made by reading reviews and final purchase intention would differ across review tones that; 1) when the tone is extreme, the impact of confirmation will be stronger than when the tone is moderate and 2) when the tone is favorable, the impact of initially perceived product value will be stronger than when the tone is critical. The survey was conducted to 276 online shopping mall users in Korea and most of hypotheses were supported. This study emphasizes that the impact of online review should be discussed together with the level of expectation that a customer had before reading online reviews, because the customers have to go through searching and screening processes before reading online reviews.
Infarct Volume is a Major Determiner of Post-Stroke Immune Cell Function and Susceptibility to Infection

Background and Purpose— Acute ischemic stroke in humans is associated with profound alterations in the immune system. Hallmarks of this stroke-induced immunodepression syndrome are: lymphocytopenia, impairment of T helper cell and monocyte function. We studied which stroke-specific factors predict these immunologic alterations and subsequent infections. Methods— Leukocyte/lymphocyte subsets were assessed serially by white blood cell count and fluorescence-activated cell sorter analysis in ischemic stroke patients (n=50) at baseline, day 1, and day 4 after stroke onset and compared to an age-matched control group (n=40). Concomitantly, monocytic human leukocyte antigen-DR expression and the in vitro function of blood monocytes measured by the production of tumor necrosis factor-&agr; upon stimulation with lipopolysaccharide were assessed. Associations of these immunologic parameters with stroke specific factors (National Institutes of Health Stroke Scale, infarct size) were explored. Multivariable logistic regression analysis was applied to identify early predictors for poststroke respiratory and urinary tract infections. Results— Infarct volume was the main factor associated with lymphocytopenia on day 1 and day 4 poststroke. Particularly, blood natural killer cell counts were reduced after stroke. Monocyte counts increased after ischemia paralleled by a profound deactivation predominantly after extensive infarcts. Reduced T helper cell counts, monocytic human leukocyte antigen-DR expression, and monocytic in vitro production of tumor necrosis factor-&agr; were associated with infections in univariate analyses. However, only stroke volume prevailed as independent early predictor for respiratory infections (OR 1.03; CI 1.01 to 1.04). Conclusions— Infarct volume determines the extent of lymphocytopenia, monocyte dysfunction, and is a main predictor for subsequent infections.