Aerodynamically-Actuated Radical Shape-Change Concept

Aerodynamically-actuated radical shape change (AARSC) is a novel concept that enables flight vehicles to conduct a mission profile containing radically different flight regimes while possibly mitigating the typical penalties incurred by radical geometric change. Weight penalties are mitigated by utilizing a primary flight control to generate aerodynamic loads that then drive a shape-change actuation. The flight mission profile used to analyze the AARSC concept is that of a transport aircraft that cruises at a lower altitude than typical transports. Based upon a preliminary analysis, substantial fuel savings are realized for mission ranges below 2000 NM by comparison to a state-of-the-art baseline, with an increasing impact as mission range is reduced. The predicted savings are so significant at short-haul ranges that the shape-change concept rivals the fuel-burn performance of turboprop aircraft while completing missions in less time than typical jet aircraft. Lower-altitude cruise has also been sought after in recent years for environmental benefits, however, the performance penalty to conventional aircraft was prohibitive. AARSC may enable the opportunity to realize the environmental benefits of lower-altitude emissions coupled with mission fuel savings. The findings of this study also reveal that the AARSC concept appears to be controllable, turbulence susceptibility is likely not an issue, and the shape change concept appears to be mechanically and aerodynamically feasible

IGF-1 colocalizes with muscle satellite cells following acute exercise in humans

Insulin-like growth factor-1 (IGF-1) regulates stem cell proliferation and differentiation in vitro. The aim of this study was to quantify the change in satellite cell (SC) specific IGF-1 colocalization following exercise. We observed a significant increase (p &lt; 0.05) in the percentage of SC with IGF-1 colocalization from baseline to 72 h after a bout of resistance exercise. This strongly supports a role for IGF-1 in human SC function following exercise. </jats:p

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

In Silico Whole Genome Association Scan for Murine Prepulse Inhibition

Background The complex trait of prepulse inhibition (PPI) is a sensory gating measure related to schizophrenia and can be measured in mice. Large-scale public repositories of inbred mouse strain genotypes and phenotypes such as PPI can be used to detect Quantitative Trait Loci (QTLs) in silico. However, the method has been criticized for issues including insufficient number of strains, not controlling for false discoveries, the complex haplotype structure of inbred mice, and failing to account for genotypic and phenotypic subgroups. Methodology/Principal Findings We have implemented a method that addresses these issues by incorporating phylogenetic analyses, multilevel regression with mixed effects, and false discovery rate (FDR) control. A genome-wide scan for PPI was conducted using over 17,000 single nucleotide polymorphisms (SNPs) in 37 strains phenotyped. Eighty-nine SNPs were significant at a false discovery rate (FDR) of 5%. After accounting for long-range linkage disequilibrium, we found 3 independent QTLs located on murine chromosomes 1 and 13. One of the PPI positives corresponds to a region of human chromosome 6p which includes DTNBP1, a gene implicated in schizophrenia. Another region includes the gene Tsn which alters PPI when knocked out. These genes also appear to have correlated expression with PPI. Conclusions/Significance These results support the usefulness of using an improved in silico mapping method to identify QTLs for complex traits such as PPI which can be then be used for to help identify loci influencing schizophrenia in humans

Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of european ancestry

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P &lt; 1 7 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 7 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 7 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P 64 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer

The Acute Satellite Cell Response and Skeletal Muscle Hypertrophy following Resistance Training

The extent of skeletal muscle hypertrophy in response to resistance training is highly variable in humans. The main objective of this study was to explain the nature of this variability. More specifically, we focused on the myogenic stem cell population, the satellite cell (SC) as a potential mediator of hypertrophy. Twenty-three males (aged 18–35 yrs) participated in 16 wk of progressive, whole body resistance training, resulting in changes of 7.9±1.6% (range of −1.9–24.7%) and 21.0±4.0% (range of −7.0 to 51.7%) in quadriceps volume and myofibre cross-sectional area (CSA), respectively. The SC response to a single bout of resistance exercise (80% 1RM), analyzed via immunofluorescent staining resulted in an expansion of type II fibre associated SC 72 h following exercise (pre: 11.3±0.9; 72 h: 14.8±1.4 SC/type II fibre; p<0.05). Training resulted in an expansion of the SC pool associated with type I (pre: 10.7±1.1; post: 12.1±1.2 SC/type I fibre; p<0.05) and type II fibres (pre: 11.3±0.9; post: 13.0±1.2 SC/type II fibre; p<0.05). Analysis of individual SC responses revealed a correlation between the relative change in type I associated SC 24 to 72 hours following an acute bout of resistance exercise and the percentage increase in quadriceps lean tissue mass assessed by MRI (r2 = 0.566, p = 0.012) and the relative change in type II associated SC following 16 weeks of resistance training and the percentage increase in quadriceps lean tissue mass assessed by MRI (r2 = 0.493, p = 0.027). Our results suggest that the SC response to resistance exercise is related to the extent of muscular hypertrophy induced by training

Time constraints do not limit group size in arboreal guenons but do explain community size and distribution patterns

To understand how species will respond to environmental changes, it is important to know how those changes will affect the ecological stress that animals experience. Time constraints can be used as indicators of ecological stress. Here we test whether time constraints can help us understand group sizes, distribution patterns and community sizes of forest guenons (Cercopithecus/Allochrocebus). Forest guenons typically live in small to medium sized one-male multi-female groups and often live in communities with multiple forest guenon species. We developed a time-budget model using published data on time budgets, diets, body sizes, climate, and group sizes to predict maximum ecologically tolerable group and community sizes of forest guenons across 202 sub-Saharan African locations. The model correctly predicted presence/absence at 83% of these locations. Feeding-foraging time (an indicator of competition) limited group sizes, while resting and moving time constraints shaped guenon biogeography. Predicted group sizes were greater than observed group sizes but comparable to community sizes, suggesting community sizes are set by competition among guenon individuals irrespective of species. We conclude that time constraints and intra-specific competition are unlikely to be the main determinants of relatively small group sizes in forest guenons. Body mass was negatively correlated with moving time, which may give larger bodied species an advantage over smaller bodied species under future conditions when greater fragmentation of forests is likely to lead to increased moving time. Resting time heavily depended on leaf consumption and is likely to increase under future climatic conditions when leaf quality is expected to decrease

Computational Investigation of Separated Flow and Stall Events on Rotating Systems

Computational Investigation of Separated Flow and Stall Events on Rotating Systems Amanda Grubb 240 Pages Directed by Dr. Marilyn Smith Rotorcraft are highly complex, dynamic vehicles with aeromechanics that are conducive to challenging problems. Many problems encountered by rotorcraft are a result of flow separation on the rotor. Increased speed, range, and agility requirements will only exacerbate these effects. Understanding flow separation on the rotor plane and the effects it has on the vehicle is fundamental to solving problems facing the next generation of rotorcraft development. The best approach to fully understand flow separation on the rotor plane is through a combination of experimentation and computational fluid dynamics. This dissertation couples high fidelity CFD with trusted experimental data sets to create a complete picture of rotorcraft flowfields for study. State-of-the-art CFD modeling techniques, many of which have not been addressed recently, are evaluated to identify and quantify their capabilities and limitations. This includes grid refinement approach, numerical approach, turbulence model effectiveness, and aeroelastic coupling bias. Rich flowfield data from CFD, coupled with experimental data, are explored to further understand separated flow on the rotor and its effects on rotorcraft performance. Separated flow is classified by separation mechanism via isolation of blade motion from shed tip vortices. Dominant flowfield vortices are studied to understand their impact on rotor performance using the Biot-Savart Law.Ph.D