In-solution Y-chromosome capture-enrichment on ancient DNA libraries.

As most ancient biological samples have low levels of endogenous DNA, it is advantageous to enrich for specific genomic regions prior to sequencing. One approach-in-solution capture-enrichment-retrieves sequences of interest and reduces the fraction of microbial DNA. In this work, we implement a capture-enrichment approach targeting informative regions of the Y chromosome in six human archaeological remains excavated in the Caribbean and dated between 200 and 3000 years BP. We compare the recovery rate of Y-chromosome capture (YCC) alone, whole-genome capture followed by YCC (WGC + YCC) versus non-enriched (pre-capture) libraries. The six samples show different levels of initial endogenous content, with very low (< 0.05%, 4 samples) or low (0.1-1.54%, 2 samples) percentages of sequenced reads mapping to the human genome. We recover 12-9549 times more targeted unique Y-chromosome sequences after capture, where 0.0-6.2% (WGC + YCC) and 0.0-23.5% (YCC) of the sequence reads were on-target, compared to 0.0-0.00003% pre-capture. In samples with endogenous DNA content greater than 0.1%, we found that WGC followed by YCC (WGC + YCC) yields lower enrichment due to the loss of complexity in consecutive capture experiments, whereas in samples with lower endogenous content, the libraries' initial low complexity leads to minor proportions of Y-chromosome reads. Finally, increasing recovery of informative sites enabled us to assign Y-chromosome haplogroups to some of the archeological remains and gain insights about their paternal lineages and origins. We present to our knowledge the first in-solution capture-enrichment method targeting the human Y-chromosome in aDNA sequencing libraries. YCC and WGC + YCC enrichments lead to an increase in the amount of Y-DNA sequences, as compared to libraries not enriched for the Y-chromosome. Our probe design effectively recovers regions of the Y-chromosome bearing phylogenetically informative sites, allowing us to identify paternal lineages with less sequencing than needed for pre-capture libraries. Finally, we recommend considering the endogenous content in the experimental design and avoiding consecutive rounds of capture, as clonality increases considerably with each round

Commercial Aircraft-Cabin Egress: The Current State of Simulation Model Development and the Need for Future Research

There has been increasing interest in developing simulation models capable of analyzing commer cial aircraft-cabin egress under both non-life- threatening and life-threatening scenarios. At issue is the ability to accurately simulate human behavior within non-toxic environments, as well as the debilitating effects that toxic environments (e.g., fire and smoke) have on human-decision making. A set of criteria has been identified by the Federal Aviation Administration for developing simulation models capable of analyzing commer cial aircraft-cabin egress. These criteria are used to (a) compare the capabilities and limitations of four aircraft-evacuation models in existence to day, (b) identify the issues that need to be ad dressed when developing these types of models, and (c) propose a new paradigm for developing aircraft-cabin egress models.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The UKIDSS Galactic Plane Survey

'The definitive version is available at www.blackwell-synergy.com .' Copyright Blackwell Publishing DOI: 10.1111/j.1365-2966.2008.13924.xThe UKIDSS Galactic Plane Survey (GPS) is one of the five near-infrared Public Legacy Surveys that are being undertaken by the UKIDSS consortium, using the Wide Field Camera on the United Kingdom Infrared TelescopePeer reviewe

Cellular Array Morphology During Directional Solidification

Cellular array morphology has been examined in the shallow cell, deep cell, and cell-to-dendrite transition regime in Pb-2.2 wt pct Sb and Al-4.1 wt pct Cu alloy single-crystal samples that were directionally solidified along [100]. Statistical analysis of the cellular spacing distribution on transverse sections has been carried out using minimum spanning tree (MST), Voronoi polygons, radial distribution factor, and fast Fourier transform (FFT) techniques. The frequency distribution of the number of nearest neighbors and the MST parameters suggest that the arrangement of cells may be visualized as a hexagonal tessellation with superimposed 50 pct random noise. However, the power spectrum of the Fourier transform of the cell centers shows a diffused single-ring pattern that does not agree with the power spectrum from the hexagonal tessellation having a 50 pct superimposed random (uniformly distributed or Gaussian) noise. The radial distribution factor obtained from the cells is similar to that of liquids. An overall steady-state distribution in terms of the mean primary spacing is achieved after directional solidification of about three mushy-zone lengths. However, the process of nearest-neighbor interaction continues throughout directional solidification, as indicated by about 14 pct of the cells undergoing submerging in the shallow cell regime or by an increasing first and second nearest-neighbor ordering along the growth direction for the cells at the cell-to-dendrite transition. The nature of cell distribution in the Al-Cu alloy appears to be the same as that in the Pb-Sb. The ratio between the upper and lower limits of the primary spacing, as defined by the largest and the smallest 10 pct of the population, respectively, is constant: 1.43 +/- 0.11. It does not depend upon the solidification processing conditions

Long non-coding RNAs defining major subtypes of B cell precursor acute lymphoblastic leukemia

BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as a novel class of RNA due to its diverse mechanism in cancer development and progression. However, the role and expression pattern of lncRNAs in molecular subtypes of B cell acute lymphoblastic leukemia (BCP-ALL) have not yet been investigated. Here, we assess to what extent lncRNA expression and DNA methylation is driving the progression of relapsed BCP-ALL subtypes and we determine if the expression and DNA methylation profile of lncRNAs correlates with established BCP-ALL subtypes. METHODS: We performed RNA sequencing and DNA methylation (Illumina Infinium microarray) of 40 diagnosis and 42 relapse samples from 45 BCP-ALL patients in a German cohort and quantified lncRNA expression. Unsupervised clustering was applied to ascertain and confirm that the lncRNA-based classification of the BCP-ALL molecular subtypes is present in both our cohort and an independent validation cohort of 47 patients. A differential expression and differential methylation analysis was applied to determine the subtype-specific, relapse-specific, and differentially methylated lncRNAs. Potential functions of subtype-specific lncRNAs were determined by using co-expression-based analysis on nearby (cis) and distally (trans) located protein-coding genes. RESULTS: Using an integrative Bioinformatics analysis, we developed a comprehensive catalog of 1235 aberrantly dysregulated BCP-ALL subtype-specific and 942 relapse-specific lncRNAs and the methylation profile of three subtypes of BCP-ALL. The 1235 subtype-specific lncRNA signature represented a similar classification of the molecular subtypes of BCP-ALL in the independent validation cohort. We identified a strong correlation between the DUX4-specific lncRNAs and genes involved in the activation of TGF-β and Hippo signaling pathways. Similarly, Ph-like-specific lncRNAs were correlated with genes involved in the activation of PI3K-AKT, mTOR, and JAK-STAT signaling pathways. Interestingly, the relapse-specific lncRNAs correlated with the activation of metabolic and signaling pathways. Finally, we found 23 promoter methylated lncRNAs epigenetically facilitating their expression levels. CONCLUSION: Here, we describe a set of subtype-specific and relapse-specific lncRNAs from three major BCP-ALL subtypes and define their potential functions and epigenetic regulation. The subtype-specific lncRNAs are reproducible and can effectively stratify BCP-ALL subtypes. Our data uncover the diverse mechanism of action of lncRNAs in BCP-ALL subtypes defining which lncRNAs are involved in the pathogenesis of disease and are relevant for the stratification of BCP-ALL subtypes