Cerulean: A hybrid assembly using high throughput short and long reads

Genome assembly using high throughput data with short reads, arguably, remains an unresolvable task in repetitive genomes, since when the length of a repeat exceeds the read length, it becomes difficult to unambiguously connect the flanking regions. The emergence of third generation sequencing (Pacific Biosciences) with long reads enables the opportunity to resolve complicated repeats that could not be resolved by the short read data. However, these long reads have high error rate and it is an uphill task to assemble the genome without using additional high quality short reads. Recently, Koren et al. 2012 proposed an approach to use high quality short reads data to correct these long reads and, thus, make the assembly from long reads possible. However, due to the large size of both dataset (short and long reads), error-correction of these long reads requires excessively high computational resources, even on small bacterial genomes. In this work, instead of error correction of long reads, we first assemble the short reads and later map these long reads on the assembly graph to resolve repeats. Contribution: We present a hybrid assembly approach that is both computationally effective and produces high quality assemblies. Our algorithm first operates with a simplified version of the assembly graph consisting only of long contigs and gradually improves the assembly by adding smaller contigs in each iteration. In contrast to the state-of-the-art long reads error correction technique, which requires high computational resources and long running time on a supercomputer even for bacterial genome datasets, our software can produce comparable assembly using only a standard desktop in a short running time.Comment: Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013

Approximate String Matching Using a Bidirectional Index

International audienceWe study strategies of approximate pattern matching that exploit bidirectional text indexes, extending and generalizing ideas of [5]. We introduce a formalism, called search schemes, to specify search strate-gies of this type, then develop a probabilistic measure for the efficiency of a search scheme, prove several combinatorial results on efficient search schemes, and finally, provide experimental computations supporting the superiority of our strategies

Life-history characteristics and climate correlates of dioecious plant species in central southern Australia

First published online: 27 April 2023 OnlinePublContext. The proportion of dioecious species can vary considerably among climates and habitats. However, studies often involve isolated communities or large diverse areas and fail to capture how proportions vary across diverse landscapes. Aims. To identify (1) life-history associations of terrestrial dioecious plant species in central southern Australia, (2) whether proportion of dioecy varies spatially across central southern Australia, and (3) whether proportion of dioecy is correlated with life-history and/or climate factors. Methods. Species growth form, pollination mechanisms and seed-dispersal features were extracted from herbarium databases to determine potential dioecy-linked traits. Distribution data for native terrestrial species in 66 Interim Biogeographical Regionalisation of Australia subregions were extracted from the Australasian Virtual Herbarium to calculate the proportion of total native species richness that are dioecious. Climate data for each subregion were also obtained from Terrestrial Ecology Research Network databases to investigate relationships among climate, life-history traits and dioecy. Key results. Woodiness, abiotic pollination and endozoochory were more prevalent in dioecious than non-dioecious taxa. Proportion of dioecy ranged from 1.7% to 8.5% among subregions and correlated negatively with annual temperature range, January to March rainfall and precipitation seasonality and with average annual daily mean, minimum, maximum and average annual minimum temperature. The highest-ranked models of dioecy incorporated the additive effects of the relative proportion of woody species and either annual temperature ranges, January to March rainfall or average annual daily maximum temperature. Conclusions. Dioecy was associated with woodiness, abiotic pollination and endozoochory, in line with studies of other flora, with the model of stable temperature range and woodiness being the highest-ranked model of dioecy. Implications. Areas with higher proportions of dioecy can be targeted for future investigations into dioecious plant ecology to aid conservation and ecosystem management.J. T. Draper, S. Delean, J. G. Conran, P. Weinstein and B. S. Simpso

Axonal Preservation in Deep Subcortical White Matter Lesions in the Ageing Brain

Cerebral white matters lesions (WML) are seen in 94% of the population aged 64 and over and are associated with cognitive decline and depression. We used immunohistochemistry and stereological methods on post mortem brain samples derived from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) cohort to investigate the axonal density within deep subcortical lesions. There was no significant difference between the lesional and control white matter, therefore, we conclude that there is axonal preservation within these lesions that are characterized by demyelination

Pilot study linking primary care records to Census, cardiovascular hospitalization and mortality data in Scotland: feasibility, utility and potential

Background There are substantial ethnic variations in the risk of cardiovascular disease (CVD)-related hospitalization and mortality in Scotland. We piloted extracting and linking primary care risk factors to Scottish Census and health data, to test the feasibility of further investigating these variations.Methods Data extracted from 10 general practices were linked at individual level to Census and hospitalization/death records. Linkage rates, reasons for non-linkage and completeness of primary care data were examined. CVD relative risks were calculated, adjusting for age, socioeconomic status and primary care-derived risk factors.Results Practice enrolment and data extraction proved challenging. Primary care records for 52 975 (55.2%) people were linked to Census data. Completeness and validity of risk variables were similar across ethnic groups. A total of 48 325 (91.2%) records had a valid smoking status recorded and 2900 (5.5%) people had a primary care record of diabetes. Ethnic-specific adjusted estimates of CVD risk were plausible and consistent with previous work.Conclusions Risk factor data extracted from primary care were of good quality and successfully linked to national Census records. Given further methodological refinement, this method illustrates the potential value of linkage using national primary care datasets to contribute to public health surveillance and research.<br/

Archaeological signatures of landscape and settlement change on the Isle of Harris

Between 2004 and 2011, a programme of archaeological investigation by the University of Birmingham on the Isle of Harris, a distinctive island forming part of the Western Isles of Scotland, has allowed the archaeological remains of this enigmatic place to be further characterised and understood. Despite intensive archaeological interest in the archipelago for a number of decades, the Isle of Harris has been overlooked and only now are we beginning to identify the archaeological resource and make comparisons to the wealth of published data from islands such as the Uists, Barra and Lewis. This paper highlights some generic overall patterns of archaeological signatures on the Isle which has been identified through a range of archaeological methods including field walking, intrusive excavation, aerial reconnaissance, geophysical and topographical survey, and documentary research. Several key case studies will be introduced including upland shieling complexes and mulitperiod settlement sites on the west coast machair systems. The purpose of the paper is not to present a gazetteer of the results of the work to date, but to highlight some of the key findings with a view to demonstrating that the Isle of Harris is directly comparable with the archaeologically rich landscapes of the other islands

Holocene El Niño–Southern Oscillation variability reflected in subtropical Australian precipitation

The La Niña and El Niño phases of the El Niño-Southern Oscillation (ENSO) have major impacts on regional rainfall patterns around the globe, with substantial environmental, societal and economic implications. Long-term perspectives on ENSO behaviour, under changing background conditions, are essential to anticipating how ENSO phases may respond under future climate scenarios. Here, we derive a 7700-year, quantitative precipitation record using carbon isotope ratios from a single species of leaf preserved in lake sediments from subtropical eastern Australia. We find a generally wet (more La Niña-like) mid-Holocene that shifted towards drier and more variable climates after 3200 cal. yr BP, primarily driven by increasing frequency and strength of the El Niño phase. Climate model simulations implicate a progressive orbitally-driven weakening of the Pacific Walker Circulation as contributing to this change. At centennial scales, high rainfall characterised the Little Ice Age (~1450–1850 CE) in subtropical eastern Australia, contrasting with oceanic proxies that suggest El Niño-like conditions prevail during this period. Our data provide a new western Pacific perspective on Holocene ENSO variability and highlight the need to address ENSO reconstruction with a geographically diverse network of sites to characterise how both ENSO, and its impacts, vary in a changing climate

Discursive constructions of language and identity: parents' competing perspectives in London Turkish complementary schools

In this paper, I draw on interview data to explore parents' constructions of language and identity in two London Turkish complementary schools. I examine parents' evaluative talk about standard Turkish, Cypriot-Turkish and other regional varieties of Turkish, the cultural values they attach to them and images of personhood these invoke. I demonstrate how parents brought up in Turkey and Cyprus tend to privilege standard Turkish and acknowledge the crucial role Turkish complementary schools play as one of the key vehicles for its spread and promotion. Some parents, however, especially those politically active in promoting Cypriot-Turkish language, culture and history to the British-born generation, voice an alternative discourse where Cypriot-Turkish is intimately linked to their sense of self. Moreover, I investigate parents' perspectives of their children and of their own Turkish language competence in the case of parents brought up in the UK. I illustrate how their Turkish and their children's are compared against a ‘native’ speaker norm firmly located in the countries of origin. The parents' accounts show how different self- and other-ascriptions of proficiency in Turkish are linked to claims of or lack of ‘Turkishness’, largely shaped by their migration histories and narratives, personal and professional transnational experiences

Long-term efficacy and safety of dupilumab in adolescents with moderate-to-severe atopic dermatitis : results through week 52 from a phase III open-label extension trial (LIBERTY AD PED-OLE)

Background For adolescent patients (aged ≥ 12 to < 18 years) with uncontrolled moderate-to-severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo, with an acceptable safety profile. However, long-term data on the approved dose regimens of dupilumab in adolescents with AD are lacking. Objectives This open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in adolescents with moderate-to-severe AD who had participated in dupilumab parent trials. Methods Patients enrolled under the original study protocol received subcutaneous dupilumab according to a weight-based regimen (2 or 4 mg/kg every week). Following protocol amendment, patients were switched to subcutaneous dupilumab 300 mg every 4 weeks (q4w) irrespective of weight, and newly enrolled patients were started on dupilumab 300 mg q4w. Patients with an inadequate clinical response (Investigator’s Global Assessment [IGA] score of 0/1 was not reached) to the q4w regimen could be uptitrated to the approved dupilumab dose regimens of 200 or 300 mg every 2 weeks (body weight < 60 or ≥ 60 kg, respectively). Patients whose IGA score of 0/1 was maintained continuously for a 12-week period after week 40 were discontinued from dupilumab, monitored for relapse, and re-initiated on dupilumab if required. Results Data for 294 patients (mean age 14.7 years) were analyzed, 102 (34.7%) of whom had completed the 52-week visit at the database lock. The dupilumab long-term safety profile was comparable to that seen in adults and consistent with the known safety profile. Most treatment-emergent adverse events were mild/moderate. By week 52, 42.7% of patients had an IGA score of 0/1 (clear/almost clear), and 93.1%, 81.2%, and 56.4%, respectively, had at least a 50%, 75%, or 90% improvement in Eczema Area and Severity Index (EASI). Most (70.9%) patients required uptitration to the approved dupilumab dose regimen. The proportions of uptitrated patients with an IGA score of 0/1 or 75% improvement in EASI increased over time, reaching 35.7% and 51.9%, respectively, 48 weeks after the first uptitration visit. By week 52, 29.4% of patients had clear/almost clear skin sustained for 12 weeks and had stopped medication; 56.7% relapsed and were subsequently re-initiated on treatment, with a mean time to re-initiation of 17.5 (± standard deviation 17.3) weeks. Conclusions Consistent with results seen with short-term treatment, long-term treatment with dupilumab showed an acceptable safety profile while providing incremental clinical benefit with continued treatment over time. The high proportion of patients who needed uptitration because of inadequate response to q4w dosing supports the q2w dose regimen as optimal for this age group. Finally, the majority of patients who stopped medication after having clear/almost clear skin sustained over 12 weeks experienced disease recurrence, suggesting the need for continued dupilumab dosing to maintain efficacy. Trial Registration ClinicalTrials.gov Identifiers: NCT02612454, NCT02407756, NCT03054428, and NCT03050151

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix