Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses.

Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that loci on chromosomes 8, 11, and 18 influence susceptibility to S. aureus sepsis in A/J mice. We then used two candidate gene selection strategies to identify genes on these three chromosomes associated with S. aureus susceptibility, and targeted genes identified by both gene selection strategies. First, we used whole genome transcription profiling to identify 191 (56 on chr. 8, 100 on chr. 11, and 35 on chr. 18) genes on our three chromosomes of interest that are differentially expressed between S. aureus-infected A/J and C57BL/6J. Second, we identified two significant quantitative trait loci (QTL) for survival post-infection on chr. 18 using N(2) backcross mice (F(1) [C18A]xC57BL/6J). Ten genes on chr. 18 (March3, Cep120, Chmp1b, Dcp2, Dtwd2, Isoc1, Lman1, Spire1, Tnfaip8, and Seh1l) mapped to the two significant QTL regions and were also identified by the expression array selection strategy. Using real-time PCR, 6 of these 10 genes (Chmp1b, Dtwd2, Isoc1, Lman1, Tnfaip8, and Seh1l) showed significantly different expression levels between S. aureus-infected A/J and C57BL/6J. For two (Tnfaip8 and Seh1l) of these 6 genes, siRNA-mediated knockdown of gene expression in S. aureus-challenged RAW264.7 macrophages induced significant changes in the cytokine response (IL-1 beta and GM-CSF) compared to negative controls. These cytokine response changes were consistent with those seen in S. aureus-challenged peritoneal macrophages from CSS 18 mice (which contain A/J chromosome 18 but are otherwise C57BL/6J), but not C57BL/6J mice. These findings suggest that two genes, Tnfaip8 and Seh1l, may contribute to susceptibility to S. aureus in A/J mice, and represent promising candidates for human genetic susceptibility studies.

Use of 16S ribosomal RNA gene analyses to characterize the bacterial signature associated with poor oral health in West Virginia.

BACKGROUND: West Virginia has the worst oral health in the United States, but the reasons for this are unclear. This pilot study explored the etiology of this disparity using culture-independent analyses to identify bacterial species associated with oral disease. METHODS: Bacteria in subgingival plaque samples from twelve participants in two independent West Virginia dental-related studies were characterized using 16S rRNA gene sequencing and Human Oral Microbe Identification Microarray (HOMIM) analysis. Unifrac analysis was used to characterize phylogenetic differences between bacterial communities obtained from plaque of participants with low or high oral disease, which was further evaluated using clustering and Principal Coordinate Analysis. RESULTS: Statistically different bacterial signatures (P<0.001) were identified in subgingival plaque of individuals with low or high oral disease in West Virginia based on 16S rRNA gene sequencing. Low disease contained a high frequency of Veillonella and Streptococcus, with a moderate number of Capnocytophaga. High disease exhibited substantially increased bacterial diversity and included a large proportion of Clostridiales cluster bacteria (Selenomonas, Eubacterium, Dialister). Phylogenetic trees constructed using 16S rRNA gene sequencing revealed that Clostridiales were repeated colonizers in plaque associated with high oral disease, providing evidence that the oral environment is somehow influencing the bacterial signature linked to disease. CONCLUSIONS: Culture-independent analyses identified an atypical bacterial signature associated with high oral disease in West Virginians and provided evidence that the oral environment influenced this signature. Both findings provide insight into the etiology of the oral disparity in West Virginia.

CMIP5 climate model analyses: Climate extremes in the United States

Given the increases in spatial resolution and other improvements in climate modeling capabilities over the last decade since the CMIP3 simulations were completed, CMIP5 provides a unique opportunity to assess scientific understanding of climate variability and change over a range of historical and future conditions. With participation from over 20 modeling groups and more than 40 global models, CMIP5 represents the latest and most ambitious coordinated international climate model intercomparison exercise to date. Observations dating back to 1900 show that the temperatures in the twenty-first century have the largest spatial extent of record breaking and much above normal mean monthly maximum and minimum temperatures. The 20-yr return value of the annual maximum or minimum daily temperature is one measure of changes in rare temperature extremes.

Rhyme and Reason: Analyses of Dual Retrieval Cues

If and only if each single cue uniquely defines its target, a independence model based on fragment theory can predict the strength of a combined dual cue from the strengths of its single cue components. If the single cues do not each uniquely define their target, no single monotonic function can predict the strength of the dual cue from its components; rather, what matters is the number of possible targets. The probability of generating a target word was .19 for rhyme cues, .14 for category cues, and .97 for rhyme-plus-category dual cues. Moreover, some pairs of cues had probabilities of producing their targets of .03 when used individually and 1.00 when used together, whereas other pairs had moderate probabilities individually and together. The results, which are interpreted in terms of multiple constraints limiting the number of responses, show why rhymes, which play a minimal role in laboratory studies of memory, are common in real-world mnemonics.

Comparative analyses of seven algorithms for copy number variant identification from single nucleotide polymorphism arrays.

Determination of copy number variants (CNVs) inferred in genome wide single nucleotide polymorphism arrays has shown increasing utility in genetic variant disease associations. Several CNV detection methods are available, but differences in CNV call thresholds and characteristics exist. We evaluated the relative performance of seven methods: circular binary segmentation, CNVFinder, cnvPartition, gain and loss of DNA, Nexus algorithms, PennCNV and QuantiSNP. Tested data included real and simulated Illumina HumHap 550 data from the Singapore cohort study of the risk factors for Myopia (SCORM) and simulated data from Affymetrix 6.0 and platform-independent distributions. The normalized singleton ratio (NSR) is proposed as a metric for parameter optimization before enacting full analysis. We used 10 SCORM samples for optimizing parameter settings for each method and then evaluated method performance at optimal parameters using 100 SCORM samples. The statistical power, false positive rates, and receiver operating characteristic (ROC) curve residuals were evaluated by simulation studies. Optimal parameters, as determined by NSR and ROC curve residuals, were consistent across datasets. QuantiSNP outperformed other methods based on ROC curve residuals over most datasets. Nexus Rank and SNPRank have low specificity and high power. Nexus Rank calls oversized CNVs. PennCNV detects one of the fewest numbers of CNVs.

Comparative analyses of clinical and environmental populations of Cryptococcus neoformans in Botswana.

Cryptococcus neoformans var. grubii (Cng) is the most common cause of fungal meningitis, and its prevalence is highest in sub-Saharan Africa. Patients become infected by inhaling airborne spores or desiccated yeast cells from the environment, where the fungus thrives in avian droppings, trees and soil. To investigate the prevalence and population structure of Cng in southern Africa, we analysed isolates from 77 environmental samples and 64 patients. We detected significant genetic diversity among isolates and strong evidence of geographic structure at the local level. High proportions of isolates with the rare MATa allele were observed in both clinical and environmental isolates; however, the mating-type alleles were unevenly distributed among different subpopulations. Nearly equal proportions of the MATa and MATα mating types were observed among all clinical isolates and in one environmental subpopulation from the eastern part of Botswana. As previously reported, there was evidence of both clonality and recombination in different geographic areas. These results provide a foundation for subsequent genomewide association studies to identify genes and genotypes linked to pathogenicity in humans.

Phylogenomic analyses data of the avian phylogenomics project.

BACKGROUND: Determining the evolutionary relationships among the major lineages of extant birds has been one of the biggest challenges in systematic biology. To address this challenge, we assembled or collected the genomes of 48 avian species spanning most orders of birds, including all Neognathae and two of the five Palaeognathae orders. We used these genomes to construct a genome-scale avian phylogenetic tree and perform comparative genomic analyses. FINDINGS: Here we present the datasets associated with the phylogenomic analyses, which include sequence alignment files consisting of nucleotides, amino acids, indels, and transposable elements, as well as tree files containing gene trees and species trees. Inferring an accurate phylogeny required generating: 1) A well annotated data set across species based on genome synteny; 2) Alignments with unaligned or incorrectly overaligned sequences filtered out; and 3) Diverse data sets, including genes and their inferred trees, indels, and transposable elements. Our total evidence nucleotide tree (TENT) data set (consisting of exons, introns, and UCEs) gave what we consider our most reliable species tree when using the concatenation-based ExaML algorithm or when using statistical binning with the coalescence-based MP-EST algorithm (which we refer to as MP-EST*). Other data sets, such as the coding sequence of some exons, revealed other properties of genome evolution, namely convergence. CONCLUSIONS: The Avian Phylogenomics Project is the largest vertebrate phylogenomics project to date that we are aware of. The sequence, alignment, and tree data are expected to accelerate analyses in phylogenomics and other related areas.

Response to Comment on "Whole-genome analyses resolve early branches in the tree of life of modern birds".

Mitchell et al. argue that divergence-time estimates for our avian phylogeny were too young because of an "inappropriate" maximum age constraint for the most recent common ancestor of modern birds and that, as a result, most modern bird orders diverged before the Cretaceous-Paleogene mass extinction event 66 million years ago instead of after. However, their interpretations of the fossil record and timetrees are incorrect.

A computational study of the characteristics of aircraft post-crash fires

Full-scale furnished cabin fires have been studied experimentally for the purpose of characterising the post-crash cabin fire environment by the US Federal Aviation Administration for many years. In this paper the Computational Fluid Dynamics fire field model SMARTFIRE is used to simulate one of these fires conducted in the C-133 test facility in order to provide further validation of the computational approach and the SMARTFIRE software. The experiment involves exposing the interior cabin materials to an external fuel fire, opening only one exit at the far end of the cabin (the same side as the rupture) for ventilation, and noting the subsequent spread of the external fire to the cabin interior and the onset of flashover at approximately 210 seconds. Through this analysis, the software is shown to be in good agreement with the experimental data, producing reasonable agreement with the fire dynamics prior to flashover and producing a reasonable prediction of the flashover time i.e. 225 seconds. The paper then proceeds to utilize the model to examine the impact on flashover time of the extent of cabin furnishings and cabin ventilation provided by available exits

Analysis of the structural characteristics of an intermediate rail vehicle and their effect on vehicle crash performance

In the current paper, the authors present an analysis of the structural characteristics of an intermediate rail vehicle and their effects on crash performance of the vehicle. Theirs is a simulation based analysis involving four stages. First, the crashworthiness of the vehicle is assessed by simulating an impact of the vehicle with a rigid wall. Second, the structural characteristics of the vehicle are analysed based on the structural behaviour during this impact and then the structure is modified. Third, the modified vehicle is tested again in the same impact scenario with a rigid wall. Finally, the modified vehicle is subjected to a modelled head-on impact which mirrors the real-life impact interface between two intermediate vehicles in a train impact. The emphasis of the current study is on the structural characteristics of the intermediate vehicle and the differences compared to an impact of a leading vehicle. The study shows that, similar to a leading vehicle, bending, or jackknifing is a main form of failure in this conventionally designed intermediate vehicle. It has also been found that the location of the door openings creates a major difference in the behaviour of an intermediate vehicle. It causes instability of the vehicle in the door area and leads to high stresses at the joint of the end beam with the solebar and shear stresses at the joint of the inner pillar with the cantrail. Apart from this, the shapes of the vehicle ends and impact interfaces are also different and have an effect on the crash performance of the vehicles. The simulation results allow the identification of the structural characteristics and show the effectiveness of relevant modifications. The conclusions have general relevance for the crashworthiness of rail vehicle design

Predicting the likely impact of aircraft post crash fire on aircraft evacuation using fire and evacuation simulation

The SMARTFIRE Computational Fluid Dynamics (CFD) fire field model has successfully reproduced the observed characteristics including measured temperatures, species concentrations and time to flashover for a post-crash fire experiment conducted by the FAA within their C-133 cabin test facility. In this test only one exit was open in order to provide ventilation for the developing cabin fire. In real post-crash fires, many exits are likely to be open as passangers attempt to evacuate. In this paper, the likely impacts on evacuation of a post-crash fire in which various exiting combinations are available are investigated. The fire scenario, investigated using the SMARTFIRE software, is based on the C-133 experiment but with a fully furnished cabin and with four different exit availability options. The fire data is imported into the airEXODUS evacuation simulation software and the resulting evacuations examined. The combined fire and evacuation analysis reveals that even though the aircraft configuration is predicted to comfortably satisfy the evacuation certification requirement, when fire is included, a number of casualties result, even from the certification compliant exit configuration.

Comparison of crash dynamics of articulated and non-articulated trains

This paper presents a comparison of impact dynamic performance between articulated trains and non-articulated trains. This is carried out by investigation of the characteristics of the two trains types and analysis of their effects on impact dynamics. The analysis shows that the differences in bogie support positions on the carbody and coupling devices lead to differences in several structural and compositional characteristics. These characteristics result in different impact responses for the two types of train and are directly related to their impact stablity. Articulated trains have stiff connection and integral performance in collisions but with less capability for absorbing impact energy between carriages, whereas non-articulated trains show loose connection and scattered performance in collisions but with more options for energy absorber installation between carriages.