We describe Bioconductor infrastructure for representing and computing on annotated genomic ranges and integrating genomic data with the statistical computing features of R and its extensions. At the ...core of the infrastructure are three packages: IRanges, GenomicRanges, and GenomicFeatures. These packages provide scalable data structures for representing annotated ranges on the genome, with special support for transcript structures, read alignments and coverage vectors. Computational facilities include efficient algorithms for overlap and nearest neighbor detection, coverage calculation and other range operations. This infrastructure directly supports more than 80 other Bioconductor packages, including those for sequence analysis, differential expression analysis and visualization.
Recent research on economic sanctions has produced significant advances in our theoretical and empirical understanding of the causes and effects of these phenomena. Our theoretical understanding, ...which has been guided by empirical findings, has reached the point where existing datasets are no longer adequate to test important hypotheses. This article presents a recently updated version of the Threat and Imposition of Economic Sanctions dataset. This version of the data extends the temporal domain, corrects errors, updates cases that were ongoing as of the last release, and includes a few additional variables. We describe the dataset, paying special attention to the key differences in the new version, and we present descriptive statistics for some of the key variables, highlighting differences across versions. Since the major change in the dataset was to more than double the time period covered, we also present some simple statistics showing trends in sanctions use over time.
Infection and inflammation are associated with downregulation of hepatic and extrahepatic cytochrome P450s as well as other drug‐metabolizing enzymes and transporters. We review the genesis of ...inflammatory reactions and discuss the relevance of the inflammation‐related regulation of cytochrome P450 enzymes to clinical drug–disease and drug–drug interactions. An understanding of the enzyme specificity and mechanisms of regulation will allow us to make better decisions about adjusting drug dosage regimens when a patient's inflammatory status changes.
Clinical Pharmacology & Therapeutics (2009); 85, 4, 434–438 doi:10.1038/clpt.2008.302
Social animals detect the affective states of conspecifics and utilize this information to orchestrate social interactions. In a social affective preference text in which experimental adult male rats ...could interact with either naive or stressed conspecifics, the experimental rats either approached or avoided the stressed conspecific, depending upon the age of the conspecific. Specifically, experimental rats approached stressed juveniles but avoided stressed adults. Inhibition of insular cortex, which is implicated in social cognition, and blockade of insular oxytocin receptors disrupted the social affective behaviors. Oxytocin application increased intrinsic excitability and synaptic efficacy in acute insular cortex slices, and insular oxytocin administration recapitulated the behaviors observed toward stressed conspecifics. Network analysis of c-Fos immunoreactivity in 29 regions identified functional connectivity between insular cortex, prefrontal cortex, amygdala and the social decision-making network. These results implicate insular cortex as a key component in the circuit underlying age-dependent social responses to stressed conspecifics.
evolutionary basis of human social learning Morgan, T. J. H; Rendell, L. E; Ehn, M ...
Proceedings of the Royal Society. B, Biological sciences,
02/2012, Letnik:
279, Številka:
1729
Journal Article
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Humans are characterized by an extreme dependence on culturally transmitted information. Such dependence requires the complex integration of social and asocial information to generate effective ...learning and decision making. Recent formal theory predicts that natural selection should favour adaptive learning strategies, but relevant empirical work is scarce and rarely examines multiple strategies or tasks. We tested nine hypotheses derived from theoretical models, running a series of experiments investigating factors affecting when and how humans use social information, and whether such behaviour is adaptive, across several computer-based tasks. The number of demonstrators, consensus among demonstrators, confidence of subjects, task difficulty, number of sessions, cost of asocial learning, subject performance and demonstrator performance all influenced subjects' use of social information, and did so adaptively. Our analysis provides strong support for the hypothesis that human social learning is regulated by adaptive learning rules.
Hominin reliance on Oldowan stone tools-which appear from 2.5 mya and are believed to have been socially transmitted-has been hypothesized to have led to the evolution of teaching and language. Here ...we present an experiment investigating the efficacy of transmission of Oldowan tool-making skills along chains of adult human participants (N=184) using five different transmission mechanisms. Across six measures, transmission improves with teaching, and particularly with language, but not with imitation or emulation. Our results support the hypothesis that hominin reliance on stone tool-making generated selection for teaching and language, and imply that (i) low-fidelity social transmission, such as imitation/emulation, may have contributed to the ~700,000 year stasis of the Oldowan technocomplex, and (ii) teaching or proto-language may have been pre-requisites for the appearance of Acheulean technology. This work supports a gradual evolution of language, with simple symbolic communication preceding behavioural modernity by hundreds of thousands of years.
Recent increases in renewable power generation challenge the operation of the power grid: generation rates fluctuate in time and are not synchronized with power demand fluctuations. Demand response ...(DR) consists of adjusting user electricity demand to match available power supply. Chemical plants are appealing candidates for DR programs; they offer large, concentrated loads that can be modulated via production scheduling. Price‐based DR is a common means of engaging industrial entities; its benefits increase significantly when a longer (typically, a few days) scheduling time horizon is considered. DR production scheduling comes with its own challenges, related to uncertainty in future (i.e., forecast) electricity prices and product demand. In this work, we provide a framework for DR production scheduling under uncertainty based on a chance‐constrained formulation that also accounts for the dynamics of the production facility. The ideas are illustrated with an air separation unit case study.
Environmental DNA (eDNA) techniques have only recently been applied in the marine environment to detect the presence of marine species. Species-specific primers and probes were designed to detect the ...eDNA of the endangered Maugean skate (Zearaja maugeana) from as little as 1 L of water collected at depth (10-15 m) in Macquarie Harbour (MH), Tasmania. The identity of the eDNA was confirmed as Z. maugeana by sequencing the qPCR products and aligning these with the target sequence for a 100% match. This result has validated the use of this eDNA technique for detecting a rare species, Z. maugeana, in the wild. Being able to investigate the presence, and possibly the abundance, of Z. maugeana in MH and Bathurst harbour (BH), would be addressing a conservation imperative for the endangered Z. maugeana. For future application of this technique in the field, the rate of decay was determined for Z. maugeana eDNA under ambient dissolved oxygen (DO) levels (55% saturation) and lower DO (20% saturation) levels, revealing that the eDNA can be detected for 4 and 16 hours respectively, after which eDNA concentration drops below the detection threshold of the assay. With the rate of decay being influenced by starting eDNA concentrations, it is recommended that samples be filtered as soon as possible after collection to minimize further loss of eDNA prior to and during sample processing.
Accurate diagnosis and subsequent treatment of latent tuberculosis infection (LTBI) is essential for TB elimination. However, the absence of a gold standard test for diagnosing LTBI makes assessment ...of the true prevalence of LTBI and the accuracy of diagnostic tests challenging. Bayesian latent class models can be used to make inferences about disease prevalence and the sensitivity and specificity of diagnostic tests using data on the concordance between tests. We performed the largest meta-analysis to date aiming to evaluate the performance of tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) for LTBI diagnosis in various patient populations using Bayesian latent class modelling.
Systematic search of PubMeb, Embase and African Index Medicus was conducted without date and language restrictions on September 11, 2017 to identify studies that compared the performance of TST and IGRAs for LTBI diagnosis. Two IGRA methods were considered: QuantiFERON-TB Gold In Tube (QFT-GIT) and T-SPOT.TB. Studies were included if they reported 2x2 agreement data between TST and QFT-GIT or T-SPOT.TB. A Bayesian latent class model was developed to estimate the sensitivity and specificity of TST and IGRAs in various populations, including immune-competent adults, immune-compromised adults and children. A TST cut-off value of 10 mm was used for immune-competent subjects and 5 mm for immune-compromised individuals.
A total of 157 studies were included in the analysis. In immune-competent adults, the sensitivity of TST and QFT-GIT were estimated to be 84% (95% credible interval CrI 82-85%) and 52% (50-53%), respectively. The specificity of QFT-GIT was 97% (96-97%) in non-BCG-vaccinated and 93% (92-94%) in BCG-vaccinated immune-competent adults. The estimated figures for TST were 100% (99-100%) and 79% (76-82%), respectively. T-SPOT.TB has comparable specificity (97% for both tests) and better sensitivity (68% versus 52%) than QFT-GIT in immune-competent adults. In immune-compromised adults, both TST and QFT-GIT display low sensitivity but high specificity. QFT-GIT and TST are equally specific (98% for both tests) in non-BCG-vaccinated children; however, QFT-GIT is more specific than TST (98% versus 82%) in BCG-vaccinated group. TST is more sensitive than QFT-GIT (82% versus 73%) in children.
This study is the first to assess the utility of TST and IGRAs for LTBI diagnosis in different population groups using all available data with Bayesian latent class modelling. Our results challenge the current beliefs about the performance of LTBI screening tests, and have important implications for LTBI screening policy and practice. We estimated that the performance of IGRAs is not as reliable as previously measured in the general population. However, IGRAs are not or minimally affected by BCG and should be the preferred tests in this setting. Adoption of IGRAs in settings where BCG is widely administered will allow for a more accurate identification and treatment of LTBI.
Spliceosomal introns are ubiquitous non-coding RNAs that are typically destined for rapid debranching and degradation. Here we describe 34 excised introns in Saccharomyces cerevisiae that-despite ...being rapidly degraded in log-phase growth-accumulate as linear RNAs under either saturated-growth conditions or other stresses that cause prolonged inhibition of TORC1, which is a key integrator of growth signalling. Introns that become stabilized remain associated with components of the spliceosome and differ from other spliceosomal introns in having a short distance between their lariat branch point and 3' splice site, which is necessary and sufficient for their stabilization. Deletion of these unusual introns is disadvantageous in saturated conditions and causes aberrantly high growth rates in yeast that are chronically challenged with the TORC1 inhibitor rapamycin. The reintroduction of native or engineered stable introns suppresses this aberrant rapamycin response. Thus, excised introns function within the TOR growth-signalling network of S. cerevisiae and, more generally, excised spliceosomal introns can have biological functions.
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