Miracle-dz/UniFAR-FTUs huggingface dataset:
Anterior Cingulate Cortex Instigates Adaptive Switches in Choice by Integrating Immediate and Delayed Components of Value in Ventromedial Prefrontal Cortex

Actions can lead to an immediate reward or punishment and a complex set of delayed outcomes. Adaptive choice necessitates the brain track and integrate both of these potential consequences. Here, we designed a sequential task whereby the decision to exploit or forego an available offer was contingent on comparing immediate value and a state-dependent future cost of expending a limited resource. Crucially, the dynamics of the task demanded frequent switches in policy based on an online computation of changing delayed consequences. We found that human subjects choose on the basis of a near-optimal integration of immediate reward and delayed consequences, with the latter computed in a prefrontal network. Within this network, anterior cingulate cortex (ACC) was dynamically coupled to ventromedial prefrontal cortex (vmPFC) when adaptive switches in choice were required. Our results suggest a choice architecture whereby interactions between ACC and vmPFC underpin an integration of immediate and delayed components of value to support flexible policy switching that accommodates the potential delayed consequences of an action.
Increased Vascular Smooth Muscle Contractility in TRPC6−/− Mice

ABSTRACT Among the TRPC subfamily of TRP (classical transient receptor potential) channels, TRPC3, -6, and -7 are gated by signal transduction pathways that activate C-type phospholipases as well as by direct exposure to diacylglycerols. Since TRPC6 is highly expressed in pulmonary and vascular smooth muscle cells, it represents a likely molecular candidate for receptor-operated cation entry. To define the physiological role of TRPC6, we have developed a TRPC6-deficient mouse model. These mice showed an elevated blood pressure and enhanced agonist-induced contractility of isolated aortic rings as well as cerebral arteries. Smooth muscle cells of TRPC6-deficient mice have higher basal cation entry, increased TRPC-carried cation currents, and more depolarized membrane potentials. This higher basal cation entry, however, was completely abolished by the expression of a TRPC3-specific small interference RNA in primary TRPC6 − / − smooth muscle cells. Along these lines, the expression of TRPC3 in wild-type cells resulted in increased basal activity, while TRPC6 expression in TRPC6 −/− smooth muscle cells reduced basal cation influx. These findings imply that constitutively active TRPC3-type channels, which are up-regulated in TRPC6-deficient smooth muscle cells, are not able to functionally replace TRPC6. Thus, TRPC6 has distinct nonredundant roles in the control of vascular smooth muscle tone.
Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma.

Background/Aim Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions) and serum concentration with clinical and histopathological parameters in melanoma patients. Methods The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI). The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of survivin+cells (9 ± 7 vs 19 ± 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase, without signs of lympho-hematological disease spreading, with the highest number of mitoses and the smallest Clark index. Conclusion Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Survivin determination in tumor tissue is of great significance in estimation of DFI.
Is a “critical” area studies possible?

At a time when nearly every topic seems to be labeled “critical” in geography, this essay asks why the discipline has lacked a clear commitment to advancing a “critical area studies” agenda. The term “critical” can take many meanings but, I argue, it has generally been an important way to “other” geography’s past, including the encyclopedism of old-fashioned regional studies. With roots in the late 1980s, the idea of joining critical theory and area studies was initially challenged by questions of representation, which are inherent in area studies scholarship. Placing power at the center of their studies, and highly conscious of their own positionality, critical geographers have lacked a coherent approach to the political and ethical issues of representation. Another difficulty lies with critical geography’s general skepticism about engaging the “policy community”, which, especially in the US, tends to be imagined as an uncritical “other”. Given the discipline’s cyclical anxieties about policy relevance that typically surface when funding programs are subject to cuts, this has largely resulted in US geographers speaking past these audiences. With respect to both of these othering practices, I suggest that a critical area studies project would benefit from a more positive framing, stressing “deep listening” in empirically informed work, and actively imagining what a critical policy community might look like.
Fragment-Based Flexible Ligand Docking by Evolutionary Optimization

Abstract A new computational approach for the efficient docking of flexible ligands in a rigid protein is presented. It exploits the binding modes of functional groups determined by an exhaustive search with solvation. The search in ligand conformational space is performed by a genetic algorithm whose scoring function approximates steric effects and intermolecular hydrogen bonds. Ligand conformations generated by the genetic algorithm are docked in the protein binding site by optimizing the fit of their fragments to optimal positions of chemically related functional groups. We show that the use of optimal binding modes of molecular fragments allows to dock known inhibitors with about ten rotatable bonds in the active site of the uncomplexed and complexed conformations of thrombin and HIV-1 protease.
Longitudinal study of perceived negative impact in African American and Caucasian mothers of children with autism spectrum disorder

The purpose of this study was to examine the stability of mothers’ perceptions of the negative impact of having a child with ASD in a sample of African American and Caucasian families as their children transitioned to early adolescence. Participants were mothers and children participating in an ongoing longitudinal study of children referred for diagnosis of ASD at age two. Analyses included data from two time points, when child participants were approximately 9 and 14 years old. Linear mixed model analyses were used to examine the relationship between the primary outcome variable, mothers’ perceived negative impact across time, and hypothesized predictors. Negative impact increased significantly from late childhood to into adolescence. However, African American mothers with lower education reported significantly lower levels of perceived negative impact at both time points. Findings show that for some families, the transition to adolescence is a period in which mothers experience increased amounts of negative impact and highlight the importance of examining the influence of socioeconomic variables. Furthermore, data suggest that there may be cultural differences mediating the relationship between maternal education, ethnicity, and perceived negative impact. Implications for the importance of including families from varying levels of socioeconomic status in ASD research are discussed.
Transcriptomes of Eight Arabidopsis thaliana Accessions Reveal Core Conserved, Genotype- and Organ-Specific Responses to Flooding Stress1[OPEN]

Eight Arabidopsis accessions highlight early transcriptional and posttranscriptional responses to starvation and flooding stress. Climate change has increased the frequency and severity of flooding events, with significant negative impact on agricultural productivity. These events often submerge plant aerial organs and roots, limiting growth and survival due to a severe reduction in light reactions and gas exchange necessary for photosynthesis and respiration, respectively. To distinguish molecular responses to the compound stress imposed by submergence, we investigated transcriptomic adjustments to darkness in air and under submerged conditions using eight Arabidopsis (Arabidopsis thaliana) accessions differing significantly in sensitivity to submergence. Evaluation of root and rosette transcriptomes revealed an early transcriptional and posttranscriptional response signature that was conserved primarily across genotypes, although flooding susceptibility-associated and genotype-specific responses also were uncovered. Posttranscriptional regulation encompassed darkness- and submergence-induced alternative splicing of transcripts from pathways involved in the alternative mobilization of energy reserves. The organ-specific transcriptome adjustments reflected the distinct physiological status of roots and shoots. Root-specific transcriptome changes included marked up-regulation of chloroplast-encoded photosynthesis and redox-related genes, whereas those of the rosette were related to the regulation of development and growth processes. We identified a novel set of tolerance genes, recognized mainly by quantitative differences. These included a transcriptome signature of more pronounced gluconeogenesis in tolerant accessions, a response that included stress-induced alternative splicing. This study provides organ-specific molecular resolution of genetic variation in submergence responses involving interactions between darkness and low-oxygen constraints of flooding stress and demonstrates that early transcriptome plasticity, including alternative splicing, is associated with the ability to cope with a compound environmental stress.
Genetic Diversity among Yersinia enterocolitica Isolated from Chicken and Fish in and around Coimbatore City, India

Abstract Background Yersinia enterocolitica is rapidly emerging worldwide as an enteric pathogen and has become a major cause of diarrhea even in developed countries. The aim of this study was to characterize and genetic diversity analysis among Y. enterocolitica strains isolated from fish and chicken sources. Methods From 44 strains, 55% (24 strains) found to be positive for Y. enterocolitica by colony morphology, biochemical tests and 16S rRNA. We investigate the diversity of Y. enterocolitica by hemolytic activity, antimicrobial resistance, RAPD, ERIC and REP-PCRs PCR, profiling of outermembrane proteins and lipopolysaccarides. Results Forty one percent of the strains were found to be the producers of haemolysin at 37 °C but not at 28 °C. All the isolates were exhibiting multi-drug resistance and found sensitive to chloramphenicol, and resistant to ciprofloxacin and amoxicillin. Eight, eleven and twelve different genotypic patterns were observed in RAPD, ERIC and REP-PCRs respectively. Five isolates have produced high molecular weight protein (HMWP) with a molecular weight of 150 — 220 kDa. Mostly LPS produce identical profiles, 22 strains have produced smooth LPS, while 2 strains have produced the rough LPS pattern. Conclusion Genotyping tools strongly confirm the co-existence wide genetic diversity among the strains tested. By using any or the combination of these molecular tools, epidemiological investigation on Y. enterocolitica could be elucidated effectively. These results showed that the REP-PCR is more informative and discriminative than other for analysis of Y. enterocolitica diversity.
Treatment of Spasticity with Tizanidine in Multiple Sclerosis

ABSTRACT: Spasticity is a frequent and often disabling symptom in MS patients. Current drugs used as antispastic agents include Dantrolene Sodium, Baclofen and Diazepam. Tizanidine (5-chloro-4-(2imidazolin-2 yl amino) -2, 1, 3-benzothialdiazole) is a new antispasticity agent that has purported central action. A double blind placebo controlled trial was performed to study the efficacy of this drug in MS patients. Sixty-six patients entered an eight week therapeutic trial and fifty-nine completed the trial. Patients were assessed at 0, 2, 3 and 8 weeks of therapy for clinical effects. Electrophysiologic tests were performed at 0 and 8 weeks. A statistically significant benefit was noted in spastic muscle groups in the legs with concomitant significant reduction in hyperactive stretch reflexes and ankle clonus. Side effects most frequently cited included dry mouth and drowsiness. Two patients developed elevated liver function test that decreased with cessation of therapy. Other clinical details, side effects and electrophysiologic data will be presented. Tizanidine appears to reduce clinical spasticity and hyperreflexia in MS patients although no change in functional status was detected. Tizanidine may well serve as an alternate antispastic agent, alone or in combination with other agents.
Recombination in the Human Pseudoautosomal Region PAR1

The pseudoautosomal region (PAR) is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome.
Impacts of the Hutan Kamasyarakatan Social Forestry Program in the Sumberjaya Watershed, West Lampung District of Sumatra, Indonesia

"This paper investigates the impacts of a social forestry program in Indonesia, Hutan Kamasyarakatan (HKm), based on analysis of a survey of 640 HKm and comparable non-HKm plots in the Sumberjaya watershed of southern Sumatra, and of the households operating those plots. The HKm program provides groups of farmers with secure-tenure permits to continue farming on state Protection Forest land and in exchange for protecting remaining natural forestland, planting multistrata agroforests, and using recommended soil and water conservation (SWC) measures on their coffee plantations. Using farmers' perceptions, econometric techniques, and propensity score matching, we investigated the impacts of the HKm program on perceived land tenure security, land purchase prices, farmers' investments in tree planting and SWC measures, and plot-level profits. A significant fraction of HKm group members are not aware of the program or fully aware of its requirements. Although farmers who are aware of the program perceive its strong effects on tenure security and land values, we found insignificant impacts on the actual purchase prices of plots. Nevertheless, our survey revealed that the HKm program has contributed to increased planting of timber and multipurpose trees. We did not find significant impacts on investments in SWC measures or on soil fertility management practices. HKm has had mixed impacts on profits, with timber trees reducing profitability because timber harvesting is not allowed and multipurpose nontimber trees contributing to increased profits. The policy implications of these findings are also discussed in the paper. " from Author's Abstract
Bystander Responses to Risk for Rape Perpetrated by a Friend, Acquaintance, or Stranger

ABSTRACT This study explored bystander responses to risk for an alcohol-facilitated rape perpetrated by a friend, acquaintance, or stranger. Undergraduates (N = 331) were randomly assigned to read 1 of 3 scenarios in which an apparently sober male friend, acquaintance, or stranger leads an intoxicated woman into a bedroom. Participants completed self-report measures of intent to directly intervene and barriers to intervention. Compared to men, women reported greater intent to help the potential victim and fewer barriers to intervention. Participant gender moderated the effect of the bystander’s relationship with the potential perpetrator on intent to confront and responsibility to intervene. Men reported more confrontation and more responsibility to intervene when perpetrators were identified as either friends or acquaintances than strangers. In contrast, women reported more confrontation when perpetrators were identified as friends than either strangers or acquaintances. Bystander education programs that address specific barriers to intervening with strangers and acquaintances could promote more frequent bystander behavior.
Changes in Disability Levels Among Older Adults Experiencing Adverse Events in Postacute Rehabilitation Care

Abstract This study aimed to assess the relationship between adverse events (AEs) and changes in the levels of disability from admission to discharge during inpatient rehabilitation programs. A prospective cohort study was conducted among a cohort of inpatients (216 older adults) admitted to a rehabilitation unit. The occurrences of any AE were reported. The level of disability regarding mobility activities was estimated using the disability qualifiers from the International Classification of Functioning, Disability, and Health. Changes in the levels of disability between admission and discharge were assessed. Baseline-measured covariates were also selected. Regarding all 4 disability levels (“no limitation,” “mild,” “moderate,” “severe,” and “complete disability”), a total of 159 participants experienced an improvement at discharge (126 participants progressed 1 level, whereas 33 improved 2 disability levels), 56 made no change, and no participants experienced a decline. The occurrence of fall-related events and the diagnostic group (musculoskeletal system) are specific predictive factors of change in the level of disability. The odds of undergoing a change in any disability level between admission and discharge decreases by 68% (1–0.32) when patients experience fall-related events (odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.11–0.97, P = 0.041) and increases for individuals with musculoskeletal conditions (OR = 3.91, 95% CI = 1.34–11.38, P = 0.012). Our findings suggest that increased efforts to prevent the occurrence of these AEs, together with early interventions suited to the diagnosis of the affected system, may have a positive influence on the improvement of disability. Further studies should evaluate disability over time after discharge to obtain a better sense of how transient or permanent the associated disability may be.
Rubella metapopulation dynamics and importance of spatial coupling to the risk of congenital rubella syndrome in Peru

Rubella is generally a mild childhood disease, but infection during early pregnancy may cause spontaneous abortion or congenital rubella syndrome (CRS), which may entail a variety of birth defects. Consequently, understanding the age-structured dynamics of this infection has considerable public health value. Vaccination short of the threshold for local elimination of transmission will increase the average age of infection. Accordingly, the classic concern for this infection is the potential for vaccination to increase incidence in individuals of childbearing age. A neglected aspect of rubella dynamics is how age incidence patterns may be moulded by the spatial dynamics inherent to epidemic metapopulations. Here, we use a uniquely detailed dataset from Peru to explore the implications of this for the burden of CRS. Our results show that the risk of CRS may be particularly severe in small remote regions, a prediction at odds with expectations in the endemic situation, and with implications for the outcome of vaccination. This outcome results directly from the metapopulation context: specifically, extinction–re-colonization dynamics are crucial because they allow for significant leakage of susceptible individuals into the older age classes during inter-epidemic periods with the potential to increase CRS risk by as much as fivefold.
An interval join optimized for modern hardware

We develop an algorithm for efficiently joining relations on interval-based attributes with overlap predicates, which, for example, are commonly found in temporal databases. Using a new data structure and a lazy evaluation technique, we are able to achieve impressive performance gains by optimizing memory accesses exploiting features of modern CPU architectures. In an experimental evaluation with real-world datasets our algorithm is able to outperform the state-of-the-art by an order of magnitude.