Advanced propfan analysis for the family of commuter airplanes

Advanced propfans were selected to be used throughout the family of commuters. These propulsion systems offer a 25 to 28 percent fuel savings over comparably sized turbofans operating in the 1990s. A brief study of the propulsion systems available for the family of commuters is provided and the selection of the advanced turboprops justified. The propeller and engine designs and performance are discussed. The integration of these designs are examined. Also addressed is the noise considerations and constraints due to propfan installation

Presentation of structural component designs for the family of commuter airplanes

The purpose is to present the implementation of structural commonality in the family of commuter airplanes. One of the main goals is implementation of structural commonality to as high a degree as possible. The structural layouts of those parts of the airplanes in which commonality is possible with all members of the family will be presented. The following airplane sections, which are common on all of the airplanes in the family, will be presented: common nose cone design; common wing torque box design; and common tail cone design. A proposed production and manufacturing breakdown is described. The advantages and disadvantages of implementing structural commonality and recommendations for further work will be discussed

Presentation of flight control design and handling quality commonality by separate surface stability augmentation for the family of commuter airplanes

The methodology and results for a flight control design and implementation for common handling qualities by Separate Surface Stability Augmentation (SSSA) for the family of commuter airplanes are contained. The open and closed loop dynamics and the design results of augmenting for common handling qualities are presented. The physical and technology requirements are presented for implementing the SSSA system. The conclusion of this report and recommendations for changes or improvement are discussed

Is habitat fragmentation good for biodiversity?

Habitat loss is a primary threat to biodiversity across the planet, yet contentious debate has ensued on the importance of habitat fragmentation ‘per se’ (i.e., altered spatial configuration of habitat for a given amount of habitat loss). Based on a review of landscape-scale investigations, Fahrig (2017; Ecological responses to habitat fragmentation per se. Annual Review of Ecology, Evolution, and Systematics 48:1-23) reports that biodiversity responses to habitat fragmentation ‘per se’ are more often positive rather than negative and concludes that the widespread belief in negative fragmentation effects is a ‘zombie idea’. We show that Fahrig's conclusions are drawn from a narrow and potentially biased subset of available evidence, which ignore much of the observational, experimental and theoretical evidence for negative effects of altered habitat configuration. We therefore argue that Fahrig's conclusions should be interpreted cautiously as they could be misconstrued by policy makers and managers, and we provide six arguments why they should not be applied in conservation decision-making. Reconciling the scientific disagreement, and informing conservation more effectively, will require research that goes beyond statistical and correlative approaches. This includes a more prudent use of data and conceptual models that appropriately partition direct vs indirect influences of habitat loss and altered spatial configuration, and more clearly discriminate the mechanisms underpinning any changes. Incorporating these issues will deliver greater mechanistic understanding and more predictive power to address the conservation issues arising from habitat loss and fragmentation

Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health.

The association between altered gut microbiota, intestinal permeability, inflammation and cardiometabolic diseases is becoming increasingly clear but remains poorly understood1,2. Indoleamine 2,3-dioxygenase is an enzyme induced in many types of immune cells, including macrophages in response to inflammatory stimuli, and catalyzes the degradation of tryptophan along the kynurenine pathway. Indoleamine 2,3-dioxygenase activity is better known for its suppression of effector T cell immunity and its activation of regulatory T cells3,4. However, high indoleamine 2,3-dioxygenase activity predicts worse cardiovascular outcome5-9 and may promote atherosclerosis and vascular inflammation6, suggesting a more complex role in chronic inflammatory settings. Indoleamine 2,3-dioxygenase activity is also increased in obesity10-13, yet its role in metabolic disease is still unexplored. Here, we show that obesity is associated with an increase of intestinal indoleamine 2,3-dioxygenase activity, which shifts tryptophan metabolism from indole derivative and interleukin-22 production toward kynurenine production. Indoleamine 2,3-dioxygenase deletion or inhibition improves insulin sensitivity, preserves the gut mucosal barrier, decreases endotoxemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. These beneficial effects are due to rewiring of tryptophan metabolism toward a microbiota-dependent production of interleukin-22 and are abrogated after treatment with a neutralizing anti-interleukin-22 antibody. In summary, we identify an unexpected function of indoleamine 2,3-dioxygenase in the fine tuning of intestinal tryptophan metabolism with major consequences on microbiota-dependent control of metabolic disease, which suggests indoleamine 2,3-dioxygenase as a potential therapeutic target

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Retention of progenitor cell phenotype in otospheres from guinea pig and mouse cochlea

Abstract\ud \ud Background\ud Culturing otospheres from dissociated organ of Corti is an appropriate starting point aiming at the development of cell therapy for hair cell loss. Although guinea pigs have been widely used as an excellent experimental model for studying the biology of the inner ear, the mouse cochlea has been more suitable for yielding otospheres in vitro. The aim of this study was to compare conditions and outcomes of otosphere suspension cultures from dissociated organ of Corti of either mouse or guinea pig at postnatal day three (P3), and to evaluate the guinea pig as a potential cochlea donor for preclinical cell therapy.\ud \ud \ud Methods\ud Organs of Corti were surgically isolated from P3 guinea pig or mouse cochlea, dissociated and cultivated under non-adherent conditions. Cultures were maintained in serum-free DMEM:F12 medium, supplemented with epidermal growth factor (EGF) plus either basic fibroblast growth factor (bFGF) or transforming growth factor alpha (TGFα). Immunofluorescence assays were conducted for phenotype characterization.\ud \ud \ud Results\ud The TGFα group presented a number of spheres significantly higher than the bFGF group. Although mouse cultures yielded more cells per sphere than guinea pig cultures, sox2 and nestin distributed similarly in otosphere cells from both organisms. We present evidence that otospheres retain properties of inner ear progenitor cells such as self-renewal, proliferation, and differentiation into hair cells or supporting cells.\ud \ud \ud Conclusions\ud Dissociated guinea pig cochlea produced otospheres in vitro, expressing sox2 and nestin similarly to mouse otospheres. Our data is supporting evidence for the presence of inner ear progenitor cells in the postnatal guinea pig. However, there is limited viability for these cells in neonatal guinea pig cochlea when compared to the differentiation potential observed for the mouse organ of Corti at the same developmental stage