Study of the single body yawed-wing aircraft concept

Areas relating to the development and improvement of the single-fuselage, yawed-wing transonic transport concept were investigated. These included: (1) developing an alternate configuration with a simplified engine installation;(2) determining a structural design speed placard that would allow the engine-airframe match for optimum airplane performance; and (3) conducting an aeroelastic stability and control analysis of the yawed-wing configuration with a flexible wing. A two-engine, single-fuselage, yawed-wing configuration was developed that achieved the Mach 1.2 design mission at 5560 km (3000 nmi) and payload of 18,140 kg (40,000 lb) with a gross weight of 217,700 kg (480,000 lb). This airplane was slightly heavier than the aft-integrated four-engine configuration that had been developed in a previous study. A modified structural design speed placard, which was determined, resulted in a 6% to 8% reduction in the gross weight of the yawed-wing configurations. The dynamic stability characteristics of the single-fuselage yawed-wing configuration were found to be very dependent on the magnitude of the pitch/roll coupling, the static longitudinal stability, and the dihedral effect

Development of the Coordination Dimension of Relational Capabilities: Comparison between For- Profit and Non-profit Technology Transfer Partnerships

In order to ensure the success of a technology transfer partnership for-profit or non-profit, it is necessary to understand which relational capabilities (RC) to explore. This article analyses which factors can assist in the development of the coordination dimension of RC, in cooperation with the development of non-profit and profit-oriented technologies, highlighting their similarities and differences. The method used was multi-case qualitative research, studying two groups (group N and group P), each with 5 entities. The main differences highlighted is the increase of social credibility for the group N and the knowledge dissemination of the partners and the processes improvement for the group P. Within this research, it was possible to deepen the model of Alves (2015), regarding the inclusion of factors that can help the development of RC Management dimensions. Understanding capabilities development in each alliance is the implication of the study

Modelling Technical and Biological Effects in scRNA-seq data with Scalable GPLVMs

Single-cell RNA-seq datasets are growing in size and complexity, enabling the study of cellular composition changes in various biological/clinical contexts. Scalable dimensionality reduction techniques are in need to disentangle biological variation in them, while accounting for technical and biological confounders. In this work, we extend a popular approach for probabilistic non-linear dimensionality reduction, the Gaussian process latent variable model, to scale to massive single-cell datasets while explicitly accounting for technical and biological confounders. The key idea is to use an augmented kernel which preserves the factorisability of the lower bound allowing for fast stochastic variational inference. We demonstrate its ability to reconstruct latent signatures of innate immunity recovered in Kumasaka et al. (2021) with 9x lower training time. We further analyze a COVID dataset and demonstrate across a cohort of 130 individuals, that this framework enables data integration while capturing interpretable signatures of infection. Specifically, we explore COVID severity as a latent dimension to refine patient stratification and capture disease-specific gene expression.Comment: Machine Learning and Computational Biology Symposium (Oral), 202

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Visual Analytics for Epidemiologists: Understanding the Interactions Between Age, Time, and Disease with Multi-Panel Graphs

Visual analytics, a technique aiding data analysis and decision making, is a novel tool that allows for a better understanding of the context of complex systems. Public health professionals can greatly benefit from this technique since context is integral in disease monitoring and biosurveillance. We propose a graphical tool that can reveal the distribution of an outcome by time and age simultaneously.We introduce and demonstrate multi-panel (MP) graphs applied in four different settings: U.S. national influenza-associated and salmonellosis-associated hospitalizations among the older adult population (≥65 years old), 1991-2004; confirmed salmonellosis cases reported to the Massachusetts Department of Public Health for the general population, 2004-2005; and asthma-associated hospital visits for children aged 0-18 at Milwaukee Children's Hospital of Wisconsin, 1997-2006. We illustrate trends and anomalies that otherwise would be obscured by traditional visualization techniques such as case pyramids and time-series plots.MP graphs can weave together two vital dynamics--temporality and demographics--that play important roles in the distribution and spread of diseases, making these graphs a powerful tool for public health and disease biosurveillance efforts

Cells of the human intestinal tract mapped across space and time.

Funder: Medical Research CouncilThe cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease

Cells of the human intestinal tract mapped across space and time

Acknowledgements We acknowledge support from the Wellcome Sanger Cytometry Core Facility, Cellular Genetics Informatics team, Cellular Generation and Phenotyping (CGaP) and Core DNA Pipelines. This work was financially supported by the Wellcome Trust (W1T20694, S.A.T.; 203151/Z/16/Z, R. A. Barker.); the European Research Council (646794, ThDefine, S.A.T.); an MRC New Investigator Research Grant (MR/T001917/1, M.Z.); and a project grant from the Great Ormond Street Hospital Children’s Charity, Sparks (V4519, M.Z.). The human embryonic and fetal material was provided by the Joint MRC/Wellcome (MR/R006237/1) Human Developmental Biology Resource (https://www.hdbr.org/). K.R.J. holds a Non-Stipendiary Junior Research Fellowship from Christ’s College, University of Cambridge. M.R.C. is supported by a Medical Research Council Human Cell Atlas Research Grant (MR/S035842/1) and a Wellcome Trust Investigator Award (220268/Z/20/Z). H.W.K. is funded by a Sir Henry Wellcome Fellowship (213555/Z/18/Z). A.F. is funded by a Wellcome PhD Studentship (102163/B/13/Z). K.T.M. is funded by an award from the Chan Zuckerberg Initiative. H.H.U. is supported by the Oxford Biomedical Research Centre (BRC) and the The Leona M. and Harry B. Helmsley Charitable Trust. We thank A. Chakravarti and S. Chatterjee for their contribution to the analysis of the enteric nervous system. We also thank R. Lindeboom and C. Talavera-Lopez for support with epithelium and Visium analysis, respectively; C. Tudor, T. Li and O. Tarkowska for image processing and infrastructure support; A. Wilbrey-Clark and T. Porter for support with Visium library preparation; A. Ross and J. Park for access to and handling of fetal tissue; A. Hunter for assistance in protocol development; D. Fitzpatrick for discussion on developmental intestinal disorders; and J. Eliasova for the graphical images. We thank the tissue donors and their families, and the Cambridge Biorepository for Translational Medicine and Human Developmental Biology Resource, for access to human tissue. This publication is part of the Human Cell Atlas: https://www.humancellatlas.org/publications.Peer reviewedPublisher PD

Promoter-anchored chromatin interactions predicted from genetic analysis of epigenomic data

Promoter-anchored chromatin interactions (PAIs) play a pivotal role in transcriptional regulation. Current high-throughput technologies for detecting PAIs, such as promoter capture Hi-C, are not scalable to large cohorts. Here, we present an analytical approach that uses summary-level data from cohort-based DNA methylation (DNAm) quantitative trait locus (mQTL) studies to predict PAIs. Using mQTL data from human peripheral blood ([Formula: see text]), we predict 34,797 PAIs which show strong overlap with the chromatin contacts identified by previous experimental assays. The promoter-interacting DNAm sites are enriched in enhancers or near expression QTLs. Genes whose promoters are involved in PAIs are more actively expressed, and gene pairs with promoter-promoter interactions are enriched for co-expression. Integration of the predicted PAIs with GWAS data highlight interactions among 601 DNAm sites associated with 15 complex traits. This study demonstrates the use of mQTL data to predict PAIs and provides insights into the role of PAIs in complex trait variation

Low CD4/CD8 T-Cell Ratio Associated with Inflammatory Arthropathy in Human T-Cell Leukemia Virus Type I Tax Transgenic Mice

Human T-cell leukemia virus type I (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATL) as well as inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A transgenic mouse that expresses HTLV-1 Tax also develops T-cell leukemia/lymphoma and an inflammatory arthropathy that resembles rheumatoid arthritis. The aim of this study was to identify the primary T-cell subsets involved in the development of arthropathy in Tax transgenic mice. mRNA was strong in the spleen and joints of arthropathic mice, with a 40-fold increase compared with healthy transgenic mice.Our findings reveal that Tax transgenic mice develop rheumatoid-like arthritis with proliferating synovial cells in the joints; however, the proportion of different splenic T-cell subsets in these mice was completely different from other commonly used animal models of rheumatoid arthritis. The crucial T-cell subsets in arthropathic Tax transgenic mice appear to resemble those in HAM/TSP patients rather than those in rheumatoid arthritis patients