Nuclear Receptor Signaling Atlas (): hyperlinking the nuclear receptor signaling community

The nuclear receptor signaling (NRS) field has generated a substantial body of information on nuclear receptors, their ligands and coregulators, with the ultimate goal of constructing coherent models of the biological and clinical significance of these molecules. As a component of the Nuclear Receptor Signaling Atlas (NURSA)—the development of a functional atlas of nuclear receptor biology—the NURSA Bioinformatics Resource is developing a strategy to organize and integrate legacy and future information on these molecules in a single web-based resource (). This entails parallel efforts of (i) developing an appropriate software framework for handling datasets from NURSA laboratories and (ii) designing strategies for the curation and presentation of public data relevant to NRS. To illustrate our approach, we have described here in detail the development of a web-based interface for the NURSA quantitative PCR nuclear receptor expression dataset, incorporating bioinformatics analysis which provides novel perspectives on functional relationships between these molecules. We anticipate that the free and open access of the community to a platform for data mining and hypothesis generation strategies will be a significant contribution to the progress of research in this field

School violence, school differences and school discourses

This article highlights one strand of a study which investigated the concept of the violenceresilient school. In six inner-city secondary schools, data on violent incidents in school and violent crime in the neighbourhood were gathered, and compared with school practices to minimise violence, accessed through interviews. Some degree of association between the patterns of behaviour and school practices was found: schools with a wider range of wellconnected practices seemed to have less difficult behaviour. Interviews also showed that the different schools had different organisational discourses for construing school violence, its possible causes and the possible solutions. Differences in practices are best understood in connection with differences in these discourses. Some of the features of school discourses are outlined, including their range, their core metaphor and their silences. We suggest that organisational discourse is an important concept in explaining school effects and school differences, and that improvement attempts could have clearer regard to this concept

Genetic Evidence on the Origins of Indian Caste Populations

This is the published version, also available here: http://www.dx.doi.org/10.1101/gr.173301.The origins and affinities of the ∼1 billion people living on the subcontinent of India have long been contested. This is owing, in part, to the many different waves of immigrants that have influenced the genetic structure of India. In the most recent of these waves, Indo-European-speaking people from West Eurasia entered India from the Northwest and diffused throughout the subcontinent. They purportedly admixed with or displaced indigenous Dravidic-speaking populations. Subsequently they may have established the Hindu caste system and placed themselves primarily in castes of higher rank. To explore the impact of West Eurasians on contemporary Indian caste populations, we compared mtDNA (400 bp of hypervariable region 1 and 14 restriction site polymorphisms) and Y-chromosome (20 biallelic polymorphisms and 5 short tandem repeats) variation in ∼265 males from eight castes of different rank to ∼750 Africans, Asians, Europeans, and other Indians. For maternally inherited mtDNA, each caste is most similar to Asians. However, 20%–30% of Indian mtDNA haplotypes belong to West Eurasian haplogroups, and the frequency of these haplotypes is proportional to caste rank, the highest frequency of West Eurasian haplotypes being found in the upper castes. In contrast, for paternally inherited Y-chromosome variation each caste is more similar to Europeans than to Asians. Moreover, the affinity to Europeans is proportionate to caste rank, the upper castes being most similar to Europeans, particularly East Europeans. These findings are consistent with greater West Eurasian male admixture with castes of higher rank. Nevertheless, the mitochondrial genome and the Y chromosome each represents only a single haploid locus and is more susceptible to large stochastic variation, bottlenecks, and selective sweeps. Thus, to increase the power of our analysis, we assayed 40 independent, biparentally inherited autosomal loci (1 LINE-1 and 39 Alu elements) in all of the caste and continental populations (∼600 individuals). Analysis of these data demonstrated that the upper castes have a higher affinity to Europeans than to Asians, and the upper castes are significantly more similar to Europeans than are the lower castes. Collectively, all five datasets show a trend toward upper castes being more similar to Europeans, whereas lower castes are more similar to Asians. We conclude that Indian castes are most likely to be of proto-Asian origin with West Eurasian admixture resulting in rank-related and sex-specific differences in the genetic affinities of castes to Asians and Europeans

St. Louis Area Earthquake Hazards Mapping Project: Seismic and Liquefaction Hazard Maps

We present probabilistic and deterministic seismic and liquefaction hazard maps for the densely populated St. Louis metropolitan area that account for the expected effects of surficial geology on earthquake ground shaking. Hazard calculations were based on a map grid of 0.005°, or about every 500 m, and are thus higher in resolution than any earlier studies. To estimate ground motions at the surface of the model (e.g., site amplification), we used a new detailed near-surface shear-wave velocity model in a 1D equivalent- linear response analysis. When compared with the 2014 U.S. Geological Survey (USGS) National Seismic Hazard Model, which uses a uniform firm-rock-site condition, the new probabilistic seismic-hazard estimates document much more variability. Hazard levels for upland sites (consisting of bedrock and weathered bedrock overlain by loess-covered till and drift deposits), show up to twice the ground-motion values for peak ground acceleration (PGA), and similar ground-motion values for 1.0 s spectral acceleration (SA). Probabilistic ground-motion levels for lowland alluvial floodplain sites (generally the 20-40-m-thick modern Mississippi and Missouri River floodplain deposits overlying bedrock) exhibit up to twice the ground-motion levels for PGA, and up to three times the ground-motion levels for 1.0 s SA. Liquefaction probability curves were developed from available standard penetration test data assuming typical lowland and upland water table levels. A simplified liquefaction hazard map was created from the 5%-in-50-year probabilistic ground-shaking model. The liquefaction hazard ranges from low (\u3c40% of area expected to liquefy) in the uplands to severe (\u3e60% of area expected to liquefy) in the lowlands. Because many transportation routes, power and gas transmission lines, and population centers exist in or on the highly susceptible lowland alluvium, these areas in the St. Louis region are at significant potential risk from seismically induced liquefaction and associated ground deformation

An Anti-HIV-1 V3 Loop Antibody Fully Protects Cross-Clade and Elicits T-Cell Immunity in Macaques Mucosally Challenged with an R5 Clade C SHIV

Neutralizing antibodies have been shown to protect macaques against SHIV challenge. However, genetically diverse HIV-1 clades have evolved, and a key question left unanswered is whether neutralizing antibodies can confer cross-clade protection in vivo. The novel human monoclonal antibody HGN194 was isolated from an individual infected with an HIV-1 clade AG recombinant circulating recombinant form (CRF). HGN194 targets an epitope in the third hypervariable loop (V3) of HIV-1 gp120 and neutralizes a range of relatively neutralization-sensitive and resistant viruses. We evaluated the potential of HGN194 to protect infant rhesus monkeys against a SHIV encoding a primary CCR5-tropic HIV-1 clade C envelope. After high-dose mucosal challenge, all untreated controls became highly viremic while all HGN194-treated animals (50 mg/kg) were completely protected. When HGN194 was given at 1 mg/kg, one out of two monkeys remained aviremic, whereas the other had delayed, lower peak viremia. Interestingly, all protected monkeys given high-dose HGN194 developed Gag-specific proliferative responses of both CD4+ and CD8+ T cells. To test whether generation of the latter involved cryptic infection, we ablated CD8+ cells after HGN194 clearance. No viremia was detected in any protected monkeys, thus ruling out virus reservoirs. Thus, induction of CD8 T-cell immunity may have resulted from transient “Hit and Run” infection or cross priming via Ag-Ab-mediated cross-presentation. Together, our data identified the HGN194 epitope as protective and provide proof-of-concept that this anti-V3 loop mAb can prevent infection with sterilizing immunity after challenge with virus of a different clade, implying that V3 is a potential vaccine target

The 6dF Galaxy Survey: bulk flows on 50-70 h

We measure the bulk flow of the local Universe using the 6dF Galaxy Survey peculiar velocity sample (6dFGSv), the largest and most homogeneous peculiar velocity sample to date. 6dFGSv is a Fundamental Plane sample of ∼104 peculiar velocities covering the whole Southern hemisphere for galactic latitude |b| > 10°, out to redshift z = 0.0537. We apply the ‘minimum variance’ bulk flow weighting method, which allows us to make a robust measurement of the bulk flow on scales of 50 and 70 h−1 Mpc. We investigate and correct for potential bias due to the lognormal velocity uncertainties, and verify our method by constructing Λ cold dark matter (ΛCDM) 6dFGSv mock catalogues incorporating the survey selection function. For a hemisphere of radius 50 h−1 Mpc we find a bulk flow amplitude of U = 248 ± 58 km s−1 in the direction (l, b) = (318° ± 20°, 40° ± 13°), and for 70 h−1 Mpc we find U = 243 ± 58 km s−1, in the same direction. Our measurement gives us a constraint on σ8 of 1.01+1.07−0.58. Our results are in agreement with other recent measurements of the direction of the bulk flow, and our measured amplitude is consistent with a ΛCDM prediction

Introductory programming: a systematic literature review

As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming. This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research

VaTEST III : validation of 8 potential super-earths from TESS data

Funding: The ULiege’s contribution to SPECULOOS has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) (grant Agreement n◦ 336480/SPECULOOS). This research is in part funded by the European Union’s Horizon 2020 research and innovation programme (grants agreements n◦ 803193/BEBOP), and from the Science and Technology Facilities Council (STFC; grant n◦ ST/S00193X/1, and ST/W000385/1).NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61 +0.09−0.10 R ⊕ ), TOI-771b (1.42 +0.11−0.09 R ⊕ ), TOI-871b (1.66 +0.11−0.11 R ⊕ ), TOI-1467b (1.83 +0.16−0.15 R ⊕ ), TOI-1739b (1.69 +0.10−0.08 R ⊕ ), TOI-2068b (1.82 +0.16−0.15 R ⊕ ), TOI-4559b (1.42 +0.13−0.11 R ⊕ ), and TOI-5799b (1.62 +0.19−0.13 R ⊕ ). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.Peer reviewe

Systematic voiding programme in adults with urinary incontinence following acute stroke: the ICONS-II RCT

Background: Urinary incontinence affects around half of stroke survivors in the acute phase, and it often presents as a new problem after stroke or, if pre-existing, worsens significantly, adding to the disability and helplessness caused by neurological deficits. New management programmes after stroke are needed to address urinary incontinence early and effectively. Objective: The Identifying Continence OptioNs after Stroke (ICONS)-II trial aimed to evaluate the clinical effectiveness and cost-effectiveness of a systematic voiding programme for urinary incontinence after stroke in hospital. Design: This was a pragmatic, multicentre, individual-patient-randomised (1 : 1), parallel-group trial with an internal pilot. Setting: Eighteen NHS stroke services with stroke units took part. Participants: Participants were adult men and women with acute stroke and urinary incontinence, including those with cognitive impairment. Intervention: Participants were randomised to the intervention, a systematic voiding programme, or to usual care. The systematic voiding programme comprised assessment, behavioural interventions (bladder training or prompted voiding) and review. The assessment included evaluation of the need for and possible removal of an indwelling urinary catheter. The intervention began within 24 hours of recruitment and continued until discharge from the stroke unit. Main outcome measures: The primary outcome measure was severity of urinary incontinence (measured using the International Consultation on Incontinence Questionnaire) at 3 months post randomisation. Secondary outcome measures were taken at 3 and 6 months after randomisation and on discharge from the stroke unit. They included severity of urinary incontinence (at discharge and at 6 months), urinary symptoms, number of urinary tract infections, number of days indwelling urinary catheter was in situ, functional independence, quality of life, falls, mortality rate and costs. The trial statistician remained blinded until clinical effectiveness analysis was complete. Results: The planned sample size was 1024 participants, with 512 allocated to each of the intervention and the usual-care groups. The internal pilot did not meet the target for recruitment and was extended to March 2020, with changes made to address low recruitment. The trial was paused in March 2020 because of COVID-19, and was later stopped, at which point 157 participants had been randomised (intervention, n = 79; usual care, n = 78). There were major issues with attrition, with 45% of the primary outcome data missing: 56% of the intervention group data and 35% of the usual-care group data. In terms of the primary outcome, patients allocated to the intervention group had a lower score for severity of urinary incontinence (higher scores indicate greater severity in urinary incontinence) than those allocated to the usual-care group, with means (standard deviations) of 8.1 (7.4) and 9.1 (7.8), respectively. Limitations: The trial was unable to recruit sufficient participants and had very high attrition, which resulted in seriously underpowered results. Conclusions: The internal pilot did not meet its target for recruitment and, despite recruitment subsequently being more promising, it was concluded that the trial was not feasible owing to the combined problems of poor recruitment, poor retention and COVID-19. The intervention group had a slightly lower score for severity of urinary incontinence at 3 months post randomisation, but this result should be interpreted with caution. Future work: Further studies to assess the effectiveness of an intervention starting in or continuing into the community are required

The Y-Chromosome Tree Bursts into Leaf: 13,000 High-Confidence SNPs Covering the Majority of Known Clades

Many studies of human populations have used the male-specific region of the Y chromosome (MSY) as a marker, but MSY sequence variants have traditionally been subject to ascertainment bias. Also, dating of haplogroups has relied on Y-specific short tandem repeats (STRs), involving problems of mutation rate choice, and possible long-term mutation saturation. Next-generation sequencing can ascertain single nucleotide polymorphisms (SNPs) in an unbiased way, leading to phylogenies in which branch-lengths are proportional to time, and allowing the times-to-most-recent-common-ancestor (TMRCAs) of nodes to be estimated directly. Here we describe the sequencing of 3.7 Mb of MSY in each of 448 human males at a mean coverage of 51x, yielding 13,261 high-confidence SNPs, 65.9% of which are previously unreported. The resulting phylogeny covers the majority of the known clades, provides date estimates of nodes, and constitutes a robust evolutionary framework for analyzing the history of other classes of mutation. Different clades within the tree show subtle but significant differences in branch lengths to the root. We also apply a set of 23 Y-STRs to the same samples, allowing SNP- and STR-based diversity and TMRCA estimates to be systematically compared. Ongoing purifying selection is suggested by our analysis of the phylogenetic distribution of nonsynonymous variants in 15 MSY single-copy genes