GeTallele: A Method for Analysis of DNA and RNA Allele Frequency Distributions

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: The data analyzed in this study is subject to the following licenses/restrictions: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Requests to access these datasets should be directed to [email protected] allele frequencies (VAF) are an important measure of genetic variation that can be estimated at single-nucleotide variant (SNV) sites. RNA and DNA VAFs are used as indicators of a wide-range of biological traits, including tumor purity and ploidy changes, allele-specific expression and gene-dosage transcriptional response. Here we present a novel methodology to assess gene and chromosomal allele asymmetries and to aid in identifying genomic alterations in RNA and DNA datasets. Our approach is based on analysis of the VAF distributions in chromosomal segments (continuous multi-SNV genomic regions). In each segment we estimate variant probability, a parameter of a random process that can generate synthetic VAF samples that closely resemble the observed data. We show that variant probability is a biologically interpretable quantitative descriptor of the VAF distribution in chromosomal segments which is consistent with other approaches. To this end, we apply the proposed methodology on data from 72 samples obtained from patients with breast invasive carcinoma (BRCA) from The Cancer Genome Atlas (TCGA). We compare DNA and RNA VAF distributions from matched RNA and whole exome sequencing (WES) datasets and find that both genomic signals give very similar segmentation and estimated variant probability profiles. We also find a correlation between variant probability with copy number alterations (CNA). Finally, to demonstrate a practical application of variant probabilities, we use them to estimate tumor purity. Tumor purity estimates based on variant probabilities demonstrate good concordance with other approaches (Pearson's correlation between 0.44 and 0.76). Our evaluation suggests that variant probabilities can serve as a dependable descriptor of VAF distribution, further enabling the statistical comparison of matched DNA and RNA datasets. Finally, they provide conceptual and mechanistic insights into relations between structure of VAF distributions and genetic events. The methodology is implemented in a Matlab toolbox that provides a suite of functions for analysis, statistical assessment and visualization of Genome and Transcriptome allele frequencies distributions. GeTallele is available at: https://github.com/SlowinskiPiotr/GeTalleleMcCormick Genomic and Proteomic Center (MGPC)George Washington UniversityWellcome TrustEngineering and Physical Sciences Research Council (EPSRC

Optimal estimation for global ground-level fine particulate matter concentrations

We develop an optimal estimation (OE) algorithm based on top-of-atmosphere reflectances observed by the MODIS satellite instrument to retrieve near-surface fine particulatematter (PM2.5). The GEOS-Chem chemical transport model is used to provide prior information for the Aerosol Optical Depth (AOD) retrieval and to relate total column AOD to PM2.5. We adjust the shape of the GEOS-Chem relative vertical extinction profiles by comparison with lidar retrievals from the CALIOP satellite instrument. Surface reflectance relationships used in the OE algorithm are indexed by land type. Error quantities needed for this OE algorithm are inferred by comparison with AOD observations taken by a worldwide network of sun photometers (AERONET) and extended globally based upon aerosol speciation and cross correlation for simulated values, and upon land type for observational values. Significant agreement in PM2.5 is found over North America for 2005 (slope = 0.89; r = 0.82; 1-σ error = 1 μg/m3 + 27%), with improved coverage and correlation relative to previous work for the same region and time period, although certain subregions, such as the San Joaquin Valley of California are better represented by previous estimates. Independently derived error estimates of the OE PM2.5 values at in situ locations over North America (of ±(2.5 μg/m3 + 31%) and Europe of ±(3.5 μg/m3 + 30%) are corroborated by comparison with in situ observations, although globally (error estimates of (3.0 μg/m3 + 35%), may be underestimated. Global population-weighted PM2.5 at 50% relative humidity is estimated as 27.8 μg/m3 at 0.1° × 0.1° resolution

Dissipation of vibration in rough contact

The relationship which links the normal vibration occurring during the sliding of rough surfaces and the nominal contact area is investigated. Two regimes are found. In the first one, the vibrational level does not depend on the contact area, while in the second one, it is propor- tional to the contact area. A theoretical model is proposed. It is based on the assumption that the vibrational level results from a competition between two processes of vibration damping, the internal damping of the material and the contact damping occurring at the interface

Three Novel Pigmentation Mutants Generated by Genome-Wide Random ENU Mutagenesis in the Mouse

Three mutant mice with pigmentation phenotypes were recovered from a genomewide random mouse chemical mutagenesis study. White toes (Whto; MGI:1861986), Belly spot and white toes (Bswt; MGI:2152776) and Dark footpads 2 (Dfp2; MGI:1861991) were identified following visual inspection of progeny from a male exposed to the point mutagen ethylnitrosourea (ENU). In order to rapidly localize the causative mutations, genome-wide linkage scans were performed on pooled DNA samples from backcross animals for each mutant line. Whto was mapped to proximal mouse chromosome (Mmu) 7 between Cen (the centromere) and D7Mit112 (8.0 cM from the centromere), Bswt was mapped to centric Mmul between D1Mit214 (32.1 cM) and D1Mit480 (32.8 cM) and Dfp2 was mapped to proximalMmu4 between Cen and D4Mit18 (5.2 cM). Whto, Bswt and Dfp2 may provide novel starting points in furthering the elucidation of genetic and biochemical pathways relevant to pigmentation and associated biological processes

Impregnation of Bombax ceiba and Bombax insigne wood with a N-methylol melamine compound

Methylated N-methylol melamine (NMM) is known for its ability to enhance physico-mechanical properties, anti-fungal ability, and hydrophobicity and was therefore used to impregnate two less used and non-durable wood species from Myanmar, Bombax ceiba and Bombax insigne. Solution uptake, weight percent gain and nitrogen content were increased by increasing melamine concentrations with B. ceiba always achieving higher values compared with B. insigne. According to the leaching results, a higher degree of condensation after curing as well as a better crosslinking of NMM could be obtained at higher temperatures. However, both curing temperatures used (90 and 120 A degrees C) resulted in almost the same amount of nitrogen fixed in the cell wall. UV microspectrophotometry confirmed the penetration of the NMM into different morphological regions of wood tissues, which was again supported by the analysis of point measurement spectra of treated and untreated specimens

Models of peer support to remediate post-intensive care syndrome: A report developed by the SCCM Thrive International Peer Support Collaborative

Objective: Patients and caregivers can experience a range of physical, psychological, and cognitive problems following critical care discharge. The use of peer support has been proposed as an innovative support mechanism. Design: We sought to identify technical, safety and procedural aspects of existing operational models of peer support, among the Society of Critical Care Medicine Thrive Peer Support Collaborative. We also sought to categorize key distinctions between these models and elucidate barriers and facilitators to implementation. Subjects: 17 Thrive sites from the USA, UK, and Australia were represented by a range of healthcare professionals. Interventions: Via an iterative process of in-person and email/conference calls, members of the Collaborative, defined the key areas on which peer support models could be defined and compared; collected detailed self-reports from all sites; reviewed the information and identified clusters of models. Barriers and challenges to implementation of peer support models were also documented. Results: Within the Thrive Collaborative, six general models of peer support were identified: Community based, Psychologist-led outpatient, Models based within ICU follow-up clinics, Online, Groups based within ICU and Peer mentor models. The most common barriers to implementation were: recruitment to groups, personnel input and training: sustainability and funding, risk management and measuring success. Conclusion: A number of different models of peer support are currently being developed to help patients and families recover and grow in the post-critical care setting