Miracle-dz/UniFAR-FTUs huggingface dataset:
Variation in Transcription Factor Binding Among Humans

Like Father, Like Mother, Like Child Transcriptional regulation is mediated by chromatin structure, which may affect the binding of transcription factors, but the extent of how individual-to-individual genetic variation affects such regulation is not well understood. Kasowski et al. (p. 232, published online 18 March) investigated the binding of two transcription factors across the genomes of human individuals and one chimpanzee. Transcription factor binding was associated with genomic features such as nucleotide variation, insertions and deletions, and copy number variation. Thus, genomic sequence variation affects transcription factor binding and may explain expression difference among individuals. McDaniell et al. (p. 235, published online 18 March) provide a genome-wide catalog of variation in chromatin and transcription factor binding in two parent-child trios of European and African ancestry. Up to 10% of active chromatin binding sites were specific to a set of individuals and were often inherited. Furthermore, variation in active chromatin sites showed heritable allele-specific correlation with variation in gene expression. Transcription factor binding sites vary among individuals and are correlated with differences in expression. Differences in gene expression may play a major role in speciation and phenotypic diversity. We examined genome-wide differences in transcription factor (TF) binding in several humans and a single chimpanzee by using chromatin immunoprecipitation followed by sequencing. The binding sites of RNA polymerase II (PolII) and a key regulator of immune responses, nuclear factor κB (p65), were mapped in 10 lymphoblastoid cell lines, and 25 and 7.5% of the respective binding regions were found to differ between individuals. Binding differences were frequently associated with single-nucleotide polymorphisms and genomic structural variants, and these differences were often correlated with differences in gene expression, suggesting functional consequences of binding variation. Furthermore, comparing PolII binding between humans and chimpanzee suggests extensive divergence in TF binding. Our results indicate that many differences in individuals and species occur at the level of TF binding, and they provide insight into the genetic events responsible for these differences.
Identification of Hematopoietic Stem Cell Engraftment Genes in Gene Therapy Studies

Hematopoietic stem cell (HSC) therapy using replication-incompetent retroviral vectors is a promising approach to provide life-long correction for genetic defects. HSC gene therapy clinical studies have resulted in functional cures for several diseases, but in some studies clonal expansion or leukemia has occurred. This is due to the dyregulation of endogenous host gene expression from vector provirus insertional mutagenesis. Insertional mutagenesis screens using replicating retroviruses have been used extensively to identify genes that influence oncogenesis. However, retroviral mutagenesis screens can also be used to determine the role of genes in biological processes such as stem cell engraftment. The aim of this review is to describe the potential for vector insertion site data from gene therapy studies to provide novel insights into mechanisms of HSC engraftment. In HSC gene therapy studies dysregulation of host genes by replication-incompetent vector proviruses may lead to enrichment of repopulating clones with vector integrants near genes that influence engraftment. Thus, data from HSC gene therapy studies can be used to identify novel candidate engraftment genes. As HSC gene therapy use continues to expand, the vector insertion site data collected will be of great interest to help identify novel engraftment genes and may ultimately lead to new therapies to improve engraftment.
Mechanism of Ion Permeation in Skeletal Muscle Chloride Channels

Voltage-gated Cl− channels belonging to the ClC family exhibit unique properties of ion permeation and gating. We functionally probed the conduction pathway of a recombinant human skeletal muscle Cl− channel (hClC-1) expressed both in Xenopus oocytes and in a mammalian cell line by investigating block by extracellular or intracellular I− and related anions. Extracellular and intracellular I− exert blocking actions on hClC-1 currents that are both concentration and voltage dependent. Similar actions were observed for a variety of other halide (Br−) and polyatomic (SCN−, NO3 −, CH3SO3 −) anions. In addition, I− block is accompanied by gating alterations that differ depending on which side of the membrane the blocker is applied. External I− causes a shift in the voltage-dependent probability that channels exist in three definable kinetic states (fast deactivating, slow deactivating, nondeactivating), while internal I− slows deactivation. These different effects on gating properties can be used to distinguish two functional ion binding sites within the hClC-1 pore. We determined K D values for I− block in three distinct kinetic states and found that binding of I− to hClC-1 is modulated by the gating state of the channel. Furthermore, estimates of electrical distance for I− binding suggest that conformational changes affecting the two ion binding sites occur during gating transitions. These results have implications for understanding mechanisms of ion selectivity in hClC-1, and for defining the intimate relationship between gating and permeation in ClC channels.
Abyssal connections of Antarctic Bottom Water in a Southern Ocean State Estimate

Antarctic Bottom Water (AABW) is formed in a few locations around the Antarctic continent, each source with distinct temperature and salinity. After formation, the different AABW varieties cross the Southern Ocean and flow into the subtropical abyssal basins. It is shown here, using the analysis of Lagrangian trajectories within the Southern Ocean State Estimate (SOSE) model, that the pathways of the different sources of AABW have to a large extent amalgamated into one pathway by the time it reaches 31°S in the deep subtropical basins. The Antarctic Circumpolar Current appears to play an important role in the amalgamation, as 70% of the AABW completes at least one circumpolar loop before reaching the subtropical basins. This amalgamation of AABW pathways suggests that on decadal to centennial time scales, changes to properties and formation rates in any of the AABW source regions will be conveyed to all three subtropical abyssal basins.
Cross-Layer Packet Retry Limit Adaptation for Video Transport Over Wireless LANs

Video transport over wireless networks requires retransmissions to successfully deliver video data to a receiver in case of packet loss, leading to increased delay time for the data to arrive at the receiver. Delay constraint is one of the most important requirements in real-time applications. A video packet arriving later than the presentation time will become useless for the client. In this paper, we propose a cross-layer content-aware retry limit adaptation scheme for video streaming over IEEE 802.11 wireless LANs. Video packets of different importance are unequally protected with different retry limits at the media access control (MAC) layer. The error propagation effect of each packet is estimated to guide the determination of its retry limit. More retry numbers are allocated to packets of higher loss impact to achieve unequal error protection. Our scheme also analyzes the backoff time for each retry and then takes into account the estimated backoff time for retransmission scheduling. Experimental results show that the proposed adaptation scheme can effectively mitigate the error propagation due to packet loss and assure the on-time arrival of packets for presentation, so as to improve video quality significantly.
Assessment of sea ice simulations in the CMIP5 models

Abstract. The historical simulations of sea ice during 1979 to 2005 by the Coupled Model Intercomparison Project Phase 5 (CMIP5) are compared with satellite observations, Global Ice-Ocean Modeling and Assimilation System (GIOMAS) output data and Pan-Arctic Ice Ocean Modeling and Assimilation System (PIOMAS) output data in this study. Forty-nine models, almost all of the CMIP5 climate models and earth system models with historical simulation, are used. For the Antarctic, multi-model ensemble mean (MME) results can give good climatology of sea ice extent (SIE), but the linear trend is incorrect. The linear trend of satellite-observed Antarctic SIE is 1.29 (±0.57) × 105 km2 decade−1; only about 1/7 CMIP5 models show increasing trends, and the linear trend of CMIP5 MME is negative with the value of −3.36 (±0.15) × 105 km2 decade−1. For the Arctic, both climatology and linear trend are better reproduced. Sea ice volume (SIV) is also evaluated in this study, and this is a first attempt to evaluate the SIV in all CMIP5 models. Compared with the GIOMAS and PIOMAS data, the SIV values in both the Antarctic and the Arctic are too small, especially for the Antarctic in spring and winter. The GIOMAS Antarctic SIV in September is 19.1 × 103 km3, while the corresponding Antarctic SIV of CMIP5 MME is 13.0 × 103 km3 (almost 32% less). The Arctic SIV of CMIP5 in April is 27.1 × 103 km3, which is also less than that from PIOMAS SIV (29.5 × 103 km3). This means that the sea ice thickness simulated in CMIP5 is too thin, although the SIE is fairly well simulated.
Expression of UGT1A and UGT2B mRNA in Human Normal Tissues and Various Cell Lines

UDP-glucuronosyltransferases (UGTs) are major phase II drug metabolism enzymes that catalyze the glucuronidation of numerous endogenous and exogenous compounds. UGTs are divided into two families, UGT1 and UGT2, based on evolutionary divergence and homology. Nine UGT1A and seven UGT2B functional isoforms have been identified in humans. Glucuronidation occurs mainly in liver but also in various extrahepatic tissues, possibly affecting the pharmacokinetics. In the present study, we comprehensively determined the expression of all functional UGT1A and UGT2B isoforms in normal human tissues including liver, lung, stomach, small intestine, colon, kidney, bladder, adrenal gland, breast, ovary, uterus, and testis by semiquantitative reverse transcription-polymerase chain reaction. In addition, the expressions of these UGTs mRNA in 15 kinds of human tissue-derived cell lines were also analyzed. Many UGT isoforms were abundantly expressed in the liver, gastrointestinal tract, and kidney, supporting previous studies. Interestingly, we found that all UGTs except UGT2B17 were expressed in bladder. In steroid-related tissues, UGTs were expressed in tissue- and isoform-specific manners. Expression profiles in human tissue-derived cell lines were not necessarily consistent with those in corresponding normal tissues. Different expression profiles were observed in distinct cell lines derived from the same organ. The information presented here will be helpful for understanding the glucuronidation in various tissues and for choosing appropriate cell lines for in vitro studies.
Web proxy cache replacement: do's, don'ts, and expectations

Numerous research efforts have produced a large number of algorithms and mechanisms for web proxy caches. In order to build powerful web proxies and understand their performance, one must be able to appreciate the impact and significance of earlier contributions and how they can be integrated To do this we employ a cache replacement algorithm, 'CSP, which integrates key knowledge from previous work. CSP utilizes the communication Cost to fetch web objects, the objects' Sizes, their Popularifies, an auxiliary cache and a cache admission control algorithm. We study the impact of these components with respect to hit ratio, latency, and bandwidth requirements. Our results show that there are clear performance gains when utilizing the communication cost, the popularity of objects, and the auxiliary cache. In contrast, the size of objects and the admission controller have a negligible performance impact. Our major conclusions going against those in related work are that (i) LRU is preferable to CSP for important parameter values, (ii) accounting for the objects' sizes does not improve latency and/or bandwidth requirements, and (iii) the collaboration of nearby proxies is not very beneficial. Based on these results, we chart the problem solution space, identifying which algorithm is preferable and under which conditions. Finally, we develop a dynamic replacement algorithm that continuously utilizes the best algorithm as the problem-parameter values (e.g., the access distributions) change with time.
Spontaneous Brain Activity in the Default Mode Network Is Sensitive to Different Resting-State Conditions with Limited Cognitive Load

Background Recent functional MRI (fMRI) studies have demonstrated that there is an intrinsically organized default mode network (DMN) in the resting brain, primarily made up of the posterior cingulate cortex (PCC) and the medial prefrontal cortex (MPFC). Several previous studies have found that the DMN is minimally disturbed during different resting-state conditions with limited cognitive demand. However, this conclusion was drawn from the visual inspection of the functional connectivity patterns within the DMN and no statistical comparison was performed. Methodology/Principal Findings Four resting-state fMRI sessions were acquired: 1) eyes-closed (EC) (used to generate the DMN mask); 2) EC; 3) eyes-open with no fixation (EO); and 4) eyes-open with a fixation (EO-F). The 2–4 sessions were counterbalanced across participants (n = 20, 10 males). We examined the statistical differences in both functional connectivity and regional amplitude of low frequency fluctuation (ALFF) within the DMN among the 2–4 resting-state conditions (i.e., EC, EO, and EO-F). Although the connectivity patterns of the DMN were visually similar across these three different conditions, we observed significantly higher functional connectivity and ALFF in both the EO and the EO-F conditions as compared to the EC condition. In addition, the first and second resting EC conditions showed significant differences within the DMN, suggesting an order effect on the DMN activity. Conclusions/Significance Our findings of the higher DMN connectivity and regional spontaneous activities in the resting state with the eyes open suggest that the participants might have more non-specific or non-goal-directed visual information gathering and evaluation, and mind wandering or daydreaming during the resting state with the eyes open as compared to that with the eyes closed, thus providing insights into the understanding of unconstrained mental activity within the DMN. Our results also suggest that it should be cautious when choosing the type of a resting condition and designating the order of the resting condition in multiple scanning sessions in experimental design.
Flooding through the lens of mobile phone activity

Natural disasters affect hundreds of millions of people worldwide every year. Emergency response efforts depend upon the availability of timely information, such as information concerning the movements of affected populations. The analysis of aggregated and anonymized Call Detail Records (CDR) captured from the mobile phone infrastructure provides new possibilities to characterize human behavior during critical events. In this work, we investigate the viability of using CDR data combined with other sources of information to characterize the floods that occurred in Tabasco, Mexico in 2009. An impact map has been reconstructed using Landsat-7 images to identify the floods. Within this frame, the underlying communication activity signals in the CDR data have been analyzed and compared against rainfall levels extracted from data of the NASA-TRMM project. The variations in the number of active phones connected to each cell tower reveal abnormal activity patterns in the most affected locations during and after the floods that could be used as signatures of the floods - both in terms of infrastructure impact assessment and population information awareness. The representativeness of the analysis has been assessed using census data and civil protection records. While a more extensive validation is required, these early results suggest high potential in using cell tower activity information to improve early warning and emergency management mechanisms.
The Role of Deleterious Substitutions in Crop Genomes

Populations continually incur new mutations with fitness effects ranging from lethal to adaptive. While the distribution of fitness effects (DFE) of new mutations is not directly observable, many mutations likely have either no effect on organismal fitness or are deleterious. Historically, it has been hypothesized that a population may carry many mildly deleterious variants as segregating variation, which reduces the mean absolute fitness of the population. Recent advances in sequencing technology and sequence conservation-based metrics for inferring the functional effect of a variant permit examination of the persistence of deleterious variants in populations. The issue of segregating deleterious variation is particularly important for crop improvement, because the demographic history of domestication and breeding allows deleterious variants to persist and reach moderate frequency, potentially reducing crop productivity. In this study, we use exome resequencing of fifteen barley accessions and genome resequencing of eight soybean accessions to investigate the prevalence of deleterious SNPs in the protein-coding regions of the genomes of two crops. We conclude that individual cultivars carry hundreds of deleterious SNPs on average, and that nonsense variants make up a minority of deleterious SNPs. Our approach annotates known phenotype-altering variants as deleterious more frequently than the genome-wide average, suggesting that putatively deleterious variants are likely to affect phenotypic variation. We also report the implementation of a SNP annotation tool (BAD_Mutations) that makes use of a likelihood ratio test based on alignment of all currently publicly available Angiosperm genomes.
Magnesium and cardiovascular system

Hypomagnesemia is common in hospitalized patients, especially in the elderly with coronary artery disease (CAD) and/or those with chronic heart failure. Hypomagnesemia is associated with an increased incidence of diabetes mellitus, metabolic syndrome, mortality rate from CAD and all causes. Magnesium supplementation improves myocardial metabolism, inhibits calcium accumulation and myocardial cell death; it improves vascular tone, peripheral vascular resistance, afterload and cardiac output, reduces cardiac arrhythmias and improves lipid metabolism. Magnesium also reduces vulnerability to oxygen-derived free radicals, improves human endothelial function and inhibits platelet function, including platelet aggregation and adhesion, which potentially gives magnesium physiologic and natural effects similar to adenosine-diphosphate inhibitors such as clopidogrel. The data regarding its use in patients with acute myocardial infarction (AMI) is conflicting. Although some previous, relatively small randomized clinical trials demonstrated a remarkable reduction in mortality when administered to relatively high risk AMI patients, two recently published large-scale randomized clinical trials (the Fourth International Study of Infarct Survival and Magnesium in Coronaries) failed to show any advantage of intravenous magnesium over placebo. Nevertheless, there are theoretical potential benefits of magnesium supplementation as a cardioprotective agent in CAD patients, as well as promising results from previous work in animal and humans. These studies are cost effective, easy to handle and are relatively free of adverse effects, which gives magnesium a role in treating CAD patients, especially high-risk groups such as CAD patients with heart failure, the elderly and hospitalized patients with hypomagnesemia. Furthermore, magnesium therapy is indicated in life-threatening ventricular arrhythmias such as Torsades de Pointes and intractable ventricular tachycardia.
NIHSS Score and Arteriographic Findings in Acute Ischemic Stroke

Background and Purpose— To test the hypothesis that the National Institutes of Health Stroke Scale (NIHSS) score is associated with the findings of arteriography performed within the first hours after ischemic stroke. Methods— We analyzed NIHSS scores on hospital admission and clinical and arteriographic findings of 226 consecutive patients (94 women, 132 men; mean age 62±12 years) who underwent arteriography within 6 hours of symptom onset in carotid stroke and within 12 hours in vertebrobasilar stroke. Results— From stroke onset to hospital admission, 155±97 minutes elapsed, and from stroke onset to arteriography 245±100 minutes elapsed. Median NIHSS was 14 (range 3 to 38), and scores differed depending on the arteriographic findings (P<0.001). NIHSS scores in basilar, internal carotid, and middle cerebral artery M1 and M2 segment occlusions (central occlusions) were higher than in more peripherally located, nonvisible, or absent occlusions. Patients with NIHSS scores ≥10 had positive predictive values (PPVs) to show arterial occlusions in 97% of carotid and 96% of vertebrobasilar strokes. With an NIHSS score of ≥12, PPV to find a central occlusion was 91%. In a multivariate analysis, NIHSS subitems such as “level of consciousness questions,” “gaze,” “motor leg,” and “neglect” were predictors of central occlusions. Conclusions— There is a significant association of NIHSS scores and the presence and location of a vessel occlusion. With an NIHSS score ≥10, a vessel occlusion will likely be seen on arteriography, and with a score ≥12, its location will probably be central.
Neural correlates of cognitive dissonance and choice-induced preference change

According to many modern economic theories, actions simply reflect an individual's preferences, whereas a psychological phenomenon called “cognitive dissonance” claims that actions can also create preference. Cognitive dissonance theory states that after making a difficult choice between two equally preferred items, the act of rejecting a favorite item induces an uncomfortable feeling (cognitive dissonance), which in turn motivates individuals to change their preferences to match their prior decision (i.e., reducing preference for rejected items). Recently, however, Chen and Risen [Chen K, Risen J (2010) J Pers Soc Psychol 99:573–594] pointed out a serious methodological problem, which casts a doubt on the very existence of this choice-induced preference change as studied over the past 50 y. Here, using a proper control condition and two measures of preferences (self-report and brain activity), we found that the mere act of making a choice can change self-report preference as well as its neural representation (i.e., striatum activity), thus providing strong evidence for choice-induced preference change. Furthermore, our data indicate that the anterior cingulate cortex and dorsolateral prefrontal cortex tracked the degree of cognitive dissonance on a trial-by-trial basis. Our findings provide important insights into the neural basis of how actions can alter an individual's preferences.