Transcriptional networks specifying homeostatic and inflammatory programs of gene expression in human aortic endothelial cells.

Endothelial cells (ECs) are critical determinants of vascular homeostasis and inflammation, but transcriptional mechanisms specifying their identities and functional states remain poorly understood. Here, we report a genome-wide assessment of regulatory landscapes of primary human aortic endothelial cells (HAECs) under basal and activated conditions, enabling inference of transcription factor networks that direct homeostatic and pro-inflammatory programs. We demonstrate that 43% of detected enhancers are EC-specific and contain SNPs associated to cardiovascular disease and hypertension. We provide evidence that AP1, ETS, and GATA transcription factors play key roles in HAEC transcription by co-binding enhancers associated with EC-specific genes. We further demonstrate that exposure of HAECs to oxidized phospholipids or pro-inflammatory cytokines results in signal-specific alterations in enhancer landscapes and associate with coordinated binding of CEBPD, IRF1, and NFκB. Collectively, these findings identify cis-regulatory elements and corresponding trans-acting factors that contribute to EC identity and their specific responses to pro-inflammatory stimuli

Aerodynamic Simulation of Runback Ice Accretion

This report presents the results of recent investigations into the aerodynamics of simulated runback ice accretion on airfoils. Aerodynamic tests were performed on a full-scale model using a high-fidelity, ice-casting simulation at near-flight Reynolds (Re) number. The ice-casting simulation was attached to the leading edge of a 72-in. (1828.8-mm ) chord NACA 23012 airfoil model. Aerodynamic performance tests were conducted at the ONERA F1 pressurized wind tunnel over a Reynolds number range of 4.7?10(exp 6) to 16.0?10(exp 6) and a Mach (M) number ran ge of 0.10 to 0.28. For Re = 16.0?10(exp 6) and M = 0.20, the simulated runback ice accretion on the airfoil decreased the maximum lift coe fficient from 1.82 to 1.51 and decreased the stalling angle of attack from 18.1deg to 15.0deg. The pitching-moment slope was also increased and the drag coefficient was increased by more than a factor of two. In general, the performance effects were insensitive to Reynolds numb er and Mach number changes over the range tested. Follow-on, subscale aerodynamic tests were conducted on a quarter-scale NACA 23012 model (18-in. (457.2-mm) chord) at Re = 1.8?10(exp 6) and M = 0.18, using low-fidelity, geometrically scaled simulations of the full-scale castin g. It was found that simple, two-dimensional simulations of the upper- and lower-surface runback ridges provided the best representation of the full-scale, high Reynolds number iced-airfoil aerodynamics, whereas higher-fidelity simulations resulted in larger performance degrada tions. The experimental results were used to define a new subclassification of spanwise ridge ice that distinguishes between short and tall ridges. This subclassification is based upon the flow field and resulting aerodynamic characteristics, regardless of the physical size of the ridge and the ice-accretion mechanism

Massive Ice Control on Permafrost Coast Erosion and Sensitivity

High overall rates of permafrost cliff retreat, coupled with spatial variability, have been accompanied by increased uncertainty over future landscape dynamics. We map long‐term (>80 years) retreat of the shoreline and photogrammetrically analyze historic aerial imagery to quantify the processes at a permafrost coast site with massive ground ice. Retreat rates have been relatively constant, but topographic changes show that subsidence is a potentially critical but often ignored component of coastal sensitivity, exceeding landward recession by over three times during the last 24 years. We calibrate novel passive seismic surveys along clear and variable exposures of massive ground ice and then spatially map key subsurface layers. Combining decadal patterns of volumetric change with new ground ice variation maps enables past trends to be interpreted, future volumetric geomorphic behavior to be better constrained, and improves the assessment of permafrost coast sensitivity and the release of carbon‐bearing material

Effective monitoring of permafrost coast erosion: Wide-scale storm impacts on outer islands in the Mackenzie Delta area.

Permafrost coasts are extensive in scale and complex in nature, resulting in particular challenges for understanding how they respond to both long-term shifts in climate and short-term extreme weather events. Taking examples from the Canadian Beaufort Sea coastline characterised by extensive areas of massive ground ice within slump and block failure complexes, we conduct a quantitative analysis of the practical performance of helicopter-based photogrammetry. The results demonstrate that large scale (>1 km2) surface models can be achieved at comparable accuracy to standard UAV surveys, but 36 times faster. Large scale models have greater potential for progressive alignment and contrast issues and so breaking down image sequences into coherent chunks has been found the most effective technique for accurate landscape reconstructions. The approach has subsequently been applied in a responsive acquisition immediately before and after a large storm event and during conditions (wind gusts >50 km hr-1) that would have prohibited UAV data acquisition. Trading lower resolution surface models for large scale coverage and more effective responsive monitoring, the helicopter-based data have been applied to assess storm driven-change across the exposed outer islands of the Mackenzie Delta area for the first time. These data show that the main storm impacts were concentrated on exposed North orientated permafrost cliff sections (particularly low cliffs, >20 m in height) where cliff recession was 43% of annual rates and in places up to 29% of the annual site-wide erosion volume was recorded in this single event. In contrast, the thaw-slump complexes remained relatively unaffected, debris flow fans were generally more resistant to storm erosion than the ice-rich cliffs, perhaps due to the relatively low amounts of precipitation that occurred. Therefore, the variability of permafrost coast erosion rates is controlled by interactions between both the forcing conditions and local response mechanisms. Helicopter-based photogrammetric surveys have the potential to effectively analyse these controls with greater spatial and temporal consistency across more representative scales and resolutions than has previously been achieved, improving the capacity to adequately constrain and ultimately project future Arctic coast sensitivity

Detection of phylogenetically informative polymorphisms in the entire euchromatic portion of human Y chromosome from a Sardinian sample

Background: Next-Generation Sequencing methods have led to a great increase in phylogenetically useful markers within the male specific portion of the Y chromosome, but previous studies have limited themselves to the study of the X-degenerate regions. Methods: DNA was extracted from peripheral blood samples of adult males whose paternal grandfathers were born in Sardinia. The DNA samples were sequenced, genotyped and subsequently analysed for variant calling for approximately 23.1 Mbp of the Y chromosome. A phylogenetic tree was built using Network 4.6 software. Results: From low coverage whole genome sequencing of 1,194 Sardinian males, we extracted 20,155 phylogenetically informative single nucleotide polymorphisms from the whole euchromatic region, including the X-degenerate, X-transposed, and Ampliconic regions, along with variants in other unclassified chromosome intervals and in the readable sequences of the heterochromatic region. Conclusions: The non X-degenerate classes contain a significant portion of the phylogenetic variation of the whole chromosome and their inclusion in the analysis, almost doubling the number of informative polymorphisms, refining the known molecular phylogeny of the human Y chromosome

A Comparison of Y-Chromosome variation in Sardinia and Anatolia is more consistent with cultural rather than demic diffusion of agriculture

Two alternative models have been proposed to explain the spread of agriculture in Europe during the Neolithic period. The demic diffusion model postulates the spreading of farmers from the Middle East along a Southeast to Northeast axis. Conversely, the cultural diffusion model assumes transmission of agricultural techniques without substantial movements of people. Support for the demic model derives largely from the observation of frequency gradients among some genetic variants, in particular haplogroups defined by single nucleotide polymorphisms (SNPs) in the Y-chromosome. A recent network analysis of the R-M269 Y chromosome lineage has purportedly corroborated Neolithic expansion from Anatolia, the site of diffusion of agriculture. However, the data are still controversial and the analyses so far performed are prone to a number of biases. In the present study we show that the addition of a single marker, DYSA7.2, dramatically changes the shape of the R-M269 network into a topology showing a clear Western-Eastern dichotomy not consistent with a radial diffusion of people from the Middle East. We have also assessed other Y-chromosome haplogroups proposed to be markers of the Neolithic diffusion of farmers and compared their intra-lineage variation—defined by short tandem repeats (STRs)—in Anatolia and in Sardinia, the only Western population where these lineages are present at appreciable frequencies and where there is substantial archaeological and genetic evidence of pre-Neolithic human occupation. The data indicate that Sardinia does not contain a subset of the variability present in Anatolia and that the shared variability between these populations is best explained by an earlier, pre-Neolithic dispersal of haplogroups from a common ancestral gene pool. Overall, these results are consistent with the cultural diffusion and do not support the demic model of agriculture diffusion

Variation of the Myelin Oligodendrocyte Glycoprotein gene is not primarily associated with multiple sclerosis in the Sardinian population

Background. Multiple sclerosis (MS) is consistently associated with particular HLA-DRB1-DQB1 haplotypes. However, existing evidence suggests that variation at these loci does not entirely explain association of the HLA region with the disease. The MOG locus is a prime positional and functional candidate for such additional predisposing effects but the analysis is complicated by the strong, albeit labyrinthine pattern of linkage disequilibrium in the region. Here we have assessed the association of MOG variation with MS in the Sardinian population to see if it represents an independent contributor to MS predisposition. Results. After re-sequencing the MOG gene in 21 healthy parents of MS patients we detected 134 variants, 33 of which were novel. A set of 40 informative SNPs was then selected and assessed for disease association together with 1 intragenic microsatellite in an initial data set of 239 MS families. This microsatellite and 11 SNPs were found to be positively associated with MS, using the transmission disequilibrium test, and were followed up in an additional 158 families (total families analysed = 397). While in these 397 families, 8 markers showed significant association with MS, through conditional tests we determined that these MOG variants were not associated with MS independently of the main DRB1-DQB1 disease associations. Conclusion. These results indicate that variation within the MOG gene is not an important independent determinant of MS-inherited risk in the Sardinian population