Microwave observations of spinning dust emission in NGC6946

We report new cm-wave measurements at five frequencies between 15 and 18GHz of the continuum emission from the reportedly anomalous "region 4" of the nearby galaxy NGC6946. We find that the emission in this frequency range is significantly in excess of that measured at 8.5GHz, but has a spectrum from 15-18GHz consistent with optically thin free-free emission from a compact HII region. In combination with previously published data we fit four emission models containing different continuum components using the Bayesian spectrum analysis package radiospec. These fits show that, in combination with data at other frequencies, a model with a spinning dust component is slightly preferred to those that possess better-established emission mechanisms.Comment: submitted MNRA

Supporting knowledge transfer in web-based managed IT support

Purpose &ndash; The purpose of this paper is to highlight the importance and complexities of the knowledge transfer process in the provision of effective managed after-sales IT support, when the web is used for service delivery.Design/methodology/approach &ndash; The paper features an interpretive case study of a multinational Managed Service Provider (MSP) and a focus group of representatives from five comparable MSPs.Findings &ndash; The paper finds that MSPs that use web-based channels for the provision of after-sales IT support services need to address a range of important social and organisational issues in order to realise cost and efficiency-based benefits.Research limitations/implications &ndash; The paper provides a four stage processual model of knowledge transfer in the provision of web-based managed after-sales IT support services. The barriers and enablers of knowledge transfer at each stage are identified. The paper adopts a MSP perspective and suggests that further research from the customer perspective is required.Practical implications &ndash; The paper highlights some important social and organisational enablers and barriers, which will guide MSPs when providing managed after-sales IT support using webbased channels.Originality/value &ndash; The paper provides the first staged model of inter-organisational knowledge transfer in a complex multi-organisational and multi-channel web-based context.<br /

Translating lung function genome-wide association study (GWAS) findings: new insights for lung biology

Chronic respiratory diseases are a major cause of worldwide mortality and morbidity. Although hereditary severe deficiency of α1 antitrypsin (A1AD) has been established to cause emphysema, A1AD accounts for only ∼1% of Chronic Obstructive Pulmonary Disease (COPD) cases. Genome-wide association studies (GWAS) have been successful at detecting multiple loci harboring variants predicting the variation in lung function measures and risk of COPD. However, GWAS are incapable of distinguishing causal from noncausal variants. Several approaches can be used for functional translation of genetic findings. These approaches have the scope to identify underlying alleles and pathways that are important in lung function and COPD. Computational methods aim at effective functional variant prediction by combining experimentally generated regulatory information with associated region of the human genome. Classically, GWAS association follow-up concentrated on manipulation of a single gene. However association data has identified genetic variants in >50 loci predicting disease risk or lung function. Therefore there is a clear precedent for experiments that interrogate multiple candidate genes in parallel, which is now possible with genome editing technology. Gene expression profiling can be used for effective discovery of biological pathways underpinning gene function. This information may be used for informed decisions about cellular assays post genetic manipulation. Investigating respiratory phenotypes in human lung tissue and specific gene knockout mice is a valuable in vivo approach that can complement in vitro work. Herein, we review state-of-the-art in silico, in vivo, and in vitro approaches that may be used to accelerate functional translation of genetic findings

Genome-wide analyses identify common variants associated with macular telangiectasia type 2

Idiopathic juxtafoveal retinal telangiectasis type 2 (macular telangiectasia type 2; MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS) with 476 cases and 1,733 controls of European ancestry. Genome-wide significant associations (P < 5 × 10−8) were identified at three independent loci (rs73171800 at 5q14.3, P = 7.74 × 10−17; rs715 at 2q34, P = 9.97 × 10−14; rs477992 at 1p12, P = 2.60 × 10−12) and then replicated (P < 0.01) in an independent cohort of 172 cases and 1,134 controls. The 5q14.3 locus is known to associate with variation in retinal vascular diameter, and the 2q34 and 1p12 loci have been implicated in the glycine/serine metabolic pathway. We subsequently found significant differences in blood serum levels of glycine (P = 4.04 × 10−6) and serine (P = 2.48 × 10−4) between MacTel cases and controls

The genome of the sea urchin Strongylocentrotus purpuratus

We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes

Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.

To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted next-generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss-of-function [LoF] variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling is clinically relevant as 28% of all UK families with dependent children are single parent households. In conclusion, to diagnose patients with ID in the absence of parental DNA, we recommend investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes. This will provide 11% additional diagnostic yield beyond the 10%-15% yield from array CGH alone.Action Medical Research (SP4640); the Birth Defect Foundation (RG45448); the Cambridge National Institute for Health Research Biomedical Research Centre (RG64219); the NIHR Rare Diseases BioResource (RBAG163); Wellcome Trust award WT091310; The Cell lines and DNA bank of Rett Syndrome, X-linked mental retardation and other genetic diseases (member of the Telethon Network of Genetic Biobanks (project no. GTB12001); the Genetic Origins of Congenital Heart Disease Study (GO-CHD)- funded by British Heart Foundation (BHF)This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/humu.2290

New constraints on the Polarization of Anomalous Microwave Emission in nearby molecular clouds

Anomalous Microwave Emission (AME) has been previously studied in two well-known molecular clouds and is thought to be due to electric dipole radiation from small spinning dust grains. It is important to measure the polarization properties of this radiation both for component separation in future cosmic microwave background experiments and also to constrain dust models. We have searched for linearly polarized radio emission associated with the $\rho$ Ophiuchi and Perseus molecular clouds using {\it WMAP} 7-year data. We found no significant polarization within an aperture of $2^{\circ}$ diameter. The upper limits on the fractional polarization of spinning dust in the $\rho$ Ophiuchi cloud are 1.7%, 1.6% and 2.6% (at 95% confidence level) at K-, Ka- and Q-bands, respectively. In the Perseus cloud we derived upper limits of 1.4%, 1.9% and 4.7%, at K-, Ka- and Q-bands, respectively; these are similar to those found by L\'opez-Caraballo et al. If AME at high Galactic latitudes has a similarly low level of polarization, this will simplify component separation for CMB polarization measurements. We can also rule out single domain magnetic dipole radiation as the dominant emission mechanism for the 20-40 GHz. The polarization levels are consistent with spinning dust models.Comment: Accepted in MNRAS as a letter - added extra sentence. 5 pages, 2 figures, 1 tabl

Cross-Vendor Test-Retest Validation of Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) for Evaluating Glymphatic System Function

The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method was proposed to evaluate glymphatic system (GS) function. However, few studies have validated its reliability and reproducibility. Fifty participants' DTI data from the MarkVCID consortium were included in this study. Two pipelines by using DSI studio and FSL software were developed for data processing and ALPS index calculation. The ALPS index was obtained by the average of bilateral ALPS index and was used for testing the cross-vendor, inter-rater and test-retest reliability by using R studio software. The ALPS index demonstrated favorable inter-scanner reproducibility (ICC=0.77 to 0.95, P&lt; 0.001), inter-rater reliability (ICC=0.96 to 1, P&lt; 0.001) and test-retest repeatability (ICC=0.89 to 0.95, P&lt; 0.001), offering a potential biomarker for in vivo evaluation of GS function

Synergies between centralized and federated approaches to data quality: a report from the national COVID cohort collaborative

OBJECTIVE: In response to COVID-19, the informatics community united to aggregate as much clinical data as possible to characterize this new disease and reduce its impact through collaborative analytics. The National COVID Cohort Collaborative (N3C) is now the largest publicly available HIPAA limited dataset in US history with over 6.4 million patients and is a testament to a partnership of over 100 organizations. MATERIALS AND METHODS: We developed a pipeline for ingesting, harmonizing, and centralizing data from 56 contributing data partners using 4 federated Common Data Models. N3C data quality (DQ) review involves both automated and manual procedures. In the process, several DQ heuristics were discovered in our centralized context, both within the pipeline and during downstream project-based analysis. Feedback to the sites led to many local and centralized DQ improvements. RESULTS: Beyond well-recognized DQ findings, we discovered 15 heuristics relating to source Common Data Model conformance, demographics, COVID tests, conditions, encounters, measurements, observations, coding completeness, and fitness for use. Of 56 sites, 37 sites (66%) demonstrated issues through these heuristics. These 37 sites demonstrated improvement after receiving feedback. DISCUSSION: We encountered site-to-site differences in DQ which would have been challenging to discover using federated checks alone. We have demonstrated that centralized DQ benchmarking reveals unique opportunities for DQ improvement that will support improved research analytics locally and in aggregate. CONCLUSION: By combining rapid, continual assessment of DQ with a large volume of multisite data, it is possible to support more nuanced scientific questions with the scale and rigor that they require

Proteomics: Clinical and research applications in respiratory diseases

The proteome is the study of the protein content of a definable component of an organism in biology. However, the tissue‐specific expression of proteins and the varied post‐translational modifications, splice variants and protein–protein complexes that may form, make the study of protein a challenging yet vital tool in answering many of the unanswered questions in medicine and biology to date. Indeed, the spatial, temporal and functional composition of proteins in the human body has proven difficult to elucidate for many years. Given the effect of microRNA and epigenetic regulation on silencing and enhancing gene transcription, the study of protein arguably provides more accurate information on homeostasis and perturbation in health and disease. There have been significant advances in the field of proteomics in recent years, with new technologies and platforms available to the research community. In this review, we briefly discuss some of these new technologies and developments in the context of respiratory disease. We also discuss the types of data science approaches to analyses and interpretation of the large volumes of data generated in proteomic studies. We discuss the application of these technologies with regard to respiratory disease and highlight the potential for proteomics in generating major advances in the understanding of respiratory pathophysiology into the future.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146450/1/resp13383_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146450/2/resp13383.pd