Dual output variable pitch turbofan actuation system

An improved actuating mechanism was provided for a gas turbine engine incorporating fan blades of the variable pitch variety, the actuator adapted to rotate the individual fan blades within apertures in an associated fan disc. The actuator included means such as a pair of synchronizing ring gears, one on each side of the blade shanks, and adapted to engage pinions disposed thereon. Means were provided to impart rotation to the ring gears in opposite directions to effect rotation of the blade shanks in response to a predetermined input signal. In the event of system failure, a run-away actuator was prevented by an improved braking device which arrests the mechanism

Energy efficient engine: Flight propulsion system preliminary analysis and design

The characteristics of an advanced flight propulsion system (FPS), suitable for introduction in the late 1980's to early 1990's, was more fully defined. It was determined that all goals for efficiency, environmental considerations, and economics could be met or exceeded with the possible exception of NOx emission. In evaluating the FPS, all aspects were considered including component design, performance, weight, initial cost, maintenance cost, engine system integration (including nacelle), and aircraft integration considerations. The current FPS installed specific fuel consumption was reduced 14.2% from that of the CF6-50C reference engine. When integrated into an advanced, subsonic, study transport, the FPS produced a fuel burn savings of 15 to 23% and a direct operating cost reduction of 5 to 12% depending on the mission and study aircraft characteristics relative to the reference engine

xQTL workbench: a scalable web environment for multi-level QTL analysis

Summary: xQTL workbench is a scalable web platform for the mapping of quantitative trait loci (QTLs) at multiple levels: for example gene expression (eQTL), protein abundance (pQTL), metabolite abundance (mQTL) and phenotype (phQTL) data. Popular QTL mapping methods for model organism and human populations are accessible via the web user interface. Large calculations scale easily on to multi-core computers, clusters and Cloud. All data involved can be uploaded and queried online: markers, genotypes, microarrays, NGS, LC-MS, GC-MS, NMR, etc. When new data types come available, xQTL workbench is quickly customized using the Molgenis software generator

Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer

This study identified LIMK2 kinase as a disease-specific target in castration resistant prostate cancer (CRPC) pathogenesis, which is upregulated in response to androgen deprivation therapy, the current standard of treatment for prostate cancer. Surgical castration increases LIMK2 expression in mouse prostates due to increased hypoxia. Similarly, human clinical specimens showed highest LIMK2 levels in CRPC tissues compared to other stages, while minimal LIMK2 was observed in normal prostates. Most notably, inducible knockdown of LIMK2 fully reverses CRPC tumorigenesis in castrated mice, underscoring its potential as a clinical target for CRPC. We also identified TWIST1 as a direct substrate of LIMK2, which uncovered the molecular mechanism of LIMK2-induced malignancy. TWIST1 is strongly associated with CRPC initiation, progression and poor prognosis. LIMK2 increases TWIST1 mRNA levels upon hypoxia; and stabilizes TWIST1 by direct phosphorylation. TWIST1 also stabilizes LIMK2 by inhibiting its ubiquitylation. Phosphorylation-dead TWIST1 acts as dominant negative and fully prevents EMT and tumor formation in vivo, thereby highlighting the significance of LIMK2-TWIST1 signaling axis in CRPC. As LIMK2 null mice are viable, targeting LIMK2 should have minimal collateral toxicity, thereby improving the overall survival of CRPC patients

The point of maximum curvature as a marker for physiological time series

We present a geometric analysis of the model of Stirling. In particular we analyze the curvature of a heart rate time series in response to a step like increment in the exercise intensity. We present solutions for the point of maximum curvature which can be used as a marker of physiological interest. This marker defines the point after which the heart rate no longer continues to rapidly rise and instead follows either a steady state or slow rise. These methods are then applied to find analytic solutions for a mono exponential model which is commonly used in the literature to model the response to a moderate exercise intensity. Numerical solutions are then found for the full model and parameter values presented in Stirling

Acute-Phase CD8 T cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus

The overall CD8 T cell response to human/simian immunodeficiency virus (HIV/SIV) targets a collection of discrete epitope specificities. Some of these epitope-specific CD8 T cells emerge in the weeks and months following infection and rapidly select forsequence variants, whereas other CD8 T cell responses develop during the chronic infection phase and rarely select for sequence variants. In this study, we tested the hypothesis that acute-phase CD8 T cell responses that do not rapidly select for escapevariants are unable to control viral replication in vivo as well as those that do rapidly select for escape variants. We created a derivative of live attenuated SIV (SIVmac239Δnef) in which we ablated five epitopes that elicit early CD8 T cell responses and rapidly accumulate sequence variants in SIVmac239-infected Mauritian cynomolgus macaques (MCMs) that are homozygous for the M3 major histocompatibility complex (MHC) haplotype. This live attenuated SIV variant was called m3KOΔnef. Viremia was significantly higher in M3 homozygous MCMs infected withm3KOΔnef than in either MHC-mismatched MCMs infected with m3KOΔ nef or MCMs infected with SIVmac239Δnef. Three CD8 T cell responses, including two that do not rapidly select for escape variants, predominated during earlym3KOΔnef infection in the M3 homozygous MCMs, but these animals were unable to control viral replication. These re-sults provide evidence that acute-phase CD8 T cell responses that have the potential to rapidly select for escape variants in the early phase ofinfection are needed to establish viral control in vivo

qtl.outbred: Interfacing outbred line cross data with the R/qtl mapping software

<p>Abstract</p> <p>Background</p> <p><b>qtl.outbred </b>is an extendible interface in the statistical environment, R, for combining quantitative trait loci (QTL) mapping tools. It is built as an umbrella package that enables outbred genotype probabilities to be calculated and/or imported into the software package R/<b>qtl</b>.</p> <p>Findings</p> <p>Using <b>qtl.outbred</b>, the genotype probabilities from outbred line cross data can be calculated by interfacing with a new and efficient algorithm developed for analyzing arbitrarily large datasets (included in the package) or imported from other sources such as the web-based tool, GridQTL.</p> <p>Conclusion</p> <p><b>qtl.outbred </b>will improve the speed for calculating probabilities and the ability to analyse large future datasets. This package enables the user to analyse outbred line cross data accurately, but with similar effort than inbred line cross data.</p

Arsenic and high affinity phosphate uptake gene distribution in shallow submarine hydrothermal sediments

The toxicity of arsenic (As) towards life on Earth is apparent in the dense distribution of genes associated with As detoxification across the tree of life. The ability to defend against As is particularly vital for survival in As-rich shallow submarine hydrothermal ecosystems along the Hellenic Volcanic Arc (HVA), where life is exposed to hydrothermal fluids containing up to 3000 times more As than present in seawater. We propose that the removal of dissolved As and phosphorus (P) by sulfide and Fe(III)(oxyhydr)oxide minerals during sediment-seawater interaction, produces nutrient-deficient porewaters containing < 2.0 ppb P. The porewater arsenite-As(III) to arsenate-As(V) ratios, combined with sulfide concentration in the sediment and/or porewater, suggest a hydrothermally-induced seafloor redox gradient. This gradient overlaps with changing high affinity phosphate uptake gene abundance. High affinity phosphate uptake and As cycling genes are depleted in the sulfide-rich settings, relative to the more oxidizing habitats where mainly Fe(III)(oxyhydr)oxides are precipitated. In addition, a habitat-wide low As-respiring and As-oxidizing gene content relative to As resistance gene richness, suggests that As detoxification is prioritized over metabolic As cycling in the sediments. Collectively, the data point to redox control on Fe and S mineralization as a decisive factor in the regulation of high affinity phosphate uptake and As cycling gene content in shallow submarine hydrothermal ecosystems along the HVA

An SNP-Based Linkage Map for Zebrafish Reveals Sex Determination Loci

A surprising diversity of mechanisms controls sex determination of vertebrate organisms, even among closely related species. Both genetic and temperature-dependent systems of sex determination have been described in teleost fish. In the common zebrafish model organism, heteromorphic sex chromosomes are not observed, and the potential role of a genetic component of sex determination remains largely unknown. Here we report a genome-wide linkage study of sex determination in zebrafish using a novel SNP genetic map. We identified loci on zebrafish chromosomes 5 (LOD score 7.9) and 16 (LOD score 9.3) governing sex determination as a complex trait, rather than as an XY or ZW genetic system. Each of these loci contains a prominent candidate gene with a conserved role in sex determination across additional species that suggest potential mechanisms of sex determination in zebrafish. The chromosome 5 locus harbors dmrt1, a key gene in sex determination from fruit flies to humans; mutation of the human DMRT1 ortholog is a cause of complete sex reversal of XY individuals. The chromosome 16 locus harbors cyp21a2; mutation of the human CYP21A2 ortholog is one of the more common causes of pseudohermaphroditism. Mutation detection at each of these candidate genes within the zebrafish cross identified hypomorphic variants on the female-associated allele of each locus. The two loci together accounted for 16% of variance of the trait. Interacting environmental cues are likely to be an additional important component of sex determination in zebrafish