Thermal Performance of Orion Active Thermal Control System With Seven-Panel Reduced-Curvature Radiator

The active thermal control system (ATCS) of the crew exploration vehicle (Orion) uses radiator panels with fluid loops as the primary system to reject heat from spacecraft. The Lockheed Martin (LM) baseline Orion ATCS uses eight-panel radiator coated with silver Teflon coating (STC) for International Space Station (ISS) missions, and uses seven-panel radiator coated with AZ 93 white paint for lunar missions. As an option to increase the radiator area with minimal impact on other component locations and interfaces, the reduced-curvature (RC) radiator concept was introduced and investigated here for the thermal perspective. Each RC radiator panel has 15 percent more area than each Lockheed Martin (LM) baseline radiator panel. The objective was to determine if the RC seven-panel radiator concept could be used in the ATCS for both ISS and lunar missions. Three radiator configurations the LM baseline, an RC seven-panel radiator with STC, and an RC seven-panel radiator with AZ 93 coating were considered in the ATCS for ISS missions. Two radiator configurations the LM baseline and an RC seven-panel radiator with AZ 93 coating were considered in the ATCS for lunar missions. A Simulink/MATLAB model of the ATCS was used to compute the ATCS performance. Some major hot phases on the thermal timeline were selected because of concern about the large amount of water sublimated for thermal topping. It was concluded that an ATCS with an RC seven-panel radiator could be used for both ISS and lunar missions, but with two different coatings STC for ISS missions and AZ 93 for lunar missions to provide performance similar to or better than that of the LM baseline ATCS

Orion Service Module Reaction Control System Plume Impingement Analysis Using PLIMP/RAMP2

The Orion Crew Exploration Vehicle Service Module Reaction Control System engine plume impingement was computed using the plume impingement program (PLIMP). PLIMP uses the plume solution from RAMP2, which is the refined version of the reacting and multiphase program (RAMP) code. The heating rate and pressure (force and moment) on surfaces or components of the Service Module were computed. The RAMP2 solution of the flow field inside the engine and the plume was compared with those computed using GASP, a computational fluid dynamics code, showing reasonable agreement. The computed heating rate and pressure using PLIMP were compared with the Reaction Control System plume model (RPM) solution and the plume impingement dynamics (PIDYN) solution. RPM uses the GASP-based plume solution, whereas PIDYN uses the SCARF plume solution. Three sets of the heating rate and pressure solutions agree well. Further thermal analysis on the avionic ring of the Service Module showed that thermal protection is necessary because of significant heating from the plume

Orion Service Module Reaction Control System Plume Impingement Analysis Using PLIMP/RAMP2

The Orion Crew Exploration Vehicle Service Module Reaction Control System engine plume impingement was computed using the plume impingement program (PLIMP). PLIMP uses the plume solution from RAMP2, which is the refined version of the reacting and multiphase program (RAMP) code. The heating rate and pressure (force and moment) on surfaces or components of the Service Module were computed. The RAMP2 solution of the flow field inside the engine and the plume was compared with those computed using GASP, a computational fluid dynamics code, showing reasonable agreement. The computed heating rate and pressure using PLIMP were compared with the Reaction Control System plume model (RPM) solution and the plume impingement dynamics (PIDYN) solution. RPM uses the GASP-based plume solution, whereas PIDYN uses the SCARF plume solution. Three sets of the heating rate and pressure solutions agree well. Further thermal analysis on the avionic ring of the Service Module was performed using MSC Patran/Pthermal. The obtained temperature results showed that thermal protection is necessary because of significant heating from the plume

Mast Cells Are Required for Full Expression of Allergen/SEB-Induced Skin Inflammation

Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. We recently described an animal model in which repeated epicutaneous applications of a house dust mite extract and Staphylococcal enterotoxin B induced eczematous skin lesions. In this study we showed that global gene expression patterns are very similar between human AD skin and allergen/staphylococcal enterotoxin B–induced mouse skin lesions, particularly in the expression of genes related to epidermal growth/differentiation, skin barrier, lipid/energy metabolism, immune response, or extracellular matrix. In this model, mast cells and T cells, but not B cells or eosinophils, were shown to be required for the full expression of dermatitis, as revealed by reduced skin inflammation and reduced serum IgE levels in mice lacking mast cells or T cells (TCRβ−/- or Rag1−/-). The clinical severity of dermatitis correlated with the numbers of mast cells, but not eosinophils. Consistent with the idea that T helper type 2 (Th2) cells play a predominant role in allergic diseases, the receptor for the Th2-promoting cytokine thymic stromal lymphopoietin and the high-affinity IgE receptor, FcεRI, were required to attain maximal clinical scores. Therefore, this clinically relevant model provides mechanistic insights into the pathogenic mechanism of human AD

Liver imaging : it is time to adopt standardized terminology

Liver imaging plays a vital role in the management of patients at risk for hepatocellular carcinoma (HCC); however, progress in the field is challenged by nonuniform and inconsistent terminology in the published literature. The Steering Committee of the American College of Radiology (ACR)’s Liver Imaging Reporting And Data System (LI-RADS), in conjunction with the LI-RADS Lexicon Writing Group and the LI-RADS International Working Group, present this consensus document to establish a single universal liver imaging lexicon. The lexicon is intended for use in research, education, and clinical care of patients at risk for HCC (i.e., the LI-RADS population) and in the general population (i.e., even when LI-RADS algorithms are not applicable). We anticipate that the universal adoption of this lexicon will provide research, educational, and clinical benefits

LI-RADS: A Conceptual and Historical Review from Its Beginning to Its Recent Integration into AASLD Clinical Practice Guidance

The Liver Imaging Reporting and Data System (LI-RADS®) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting, and data collection of liver observations in individuals at high risk for hepatocellular carcinoma (HCC). LI-RADS is supported and endorsed by the American College of Radiology (ACR). Upon its initial release in 2011, LI-RADS applied only to liver observations identified at CT or MRI. It has since been refined and expanded over multiple updates to now also address ultrasound-based surveillance, contrast-enhanced ultrasound for HCC diagnosis, and CT/MRI for assessing treatment response after locoregional therapy. The LI-RADS 2018 version was integrated into the HCC diagnosis, staging, and management practice guidance of the American Association for the Study of Liver Diseases (AASLD). This article reviews the major LI-RADS updates since its 2011 inception and provides an overview of the currently published LI-RADS algorithms

WNT activates the AAK1 kinase to promote clathrin-mediated endocytosis of LRP6 and establish a negative feedback loop

beta-Catenin-dependent WNT signal transduction governs development, tissue homeostasis, and a vast array of human diseases. Signal propagation through a WNT-Frizzled/LRP receptor complex requires proteins necessary for clathrin-mediated endocytosis (CME). Paradoxically, CME also negatively regulates WNT signaling through internalization and degradation of the receptor complex. Here, using a gain-of-function screen of the human kinome, we report that the AP2 associated kinase 1 (AAK1), a known CME enhancer, inhibits WNT signaling. Reciprocally, AAK1 genetic silencing or its pharmacological inhibition using a potent and selective inhibitor activates WNT signaling. Mechanistically, we show that AAK1 promotes clearance of LRP6 from the plasma membrane to suppress the WNT pathway. Time-course experiments support a transcription-uncoupled, WNT-driven negative feedback loop; prolonged WNT treatment drives AAK1-dependent phosphorylation of AP2M1, clathrin-coated pit maturation, and endocytosis of LRP6. We propose that, following WNT receptor activation, increased AAK1 function and CME limits WNT signaling longevity2617993FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2013/50724-5; 2016/17469-0M.B.M. acknowledges support from the NIH (RO1-CA187799 and U24-DK116204-01). M.J.A. received financial support from NIH T32 Predoctoral Training Grants in Pharmacology (T32-GM007040-43 and T32-GM007040-42), an Initiative for Maximizing Student Diversity Grant (R25-GM055336-16), and the NIH National Cancer Institute (NCI) NRSA Predoctoral Fellowship to Promote Diversity in Health-Related Research (F31CA228289). M.P.W. received support from the Lymphoma Research Foundation (337444) and the NIH (T32-CA009156-35). Y.N. was supported by grants-in-aid from the Japan Society for the Promotion of Science (JSPS) (15KK0356 and 16K11493). T.T. was supported by the Howard Hughes Medical Institute Gilliam Fellowship for Advanced Study. M.V.G. was supported by Cancer Research UK (grants C7379/A15291 and C7379/A24639 to Mariann Bienz). The UNC Flow Cytometry Core Facility is supported in part by Cancer Center Core Support Grant P30 CA016086 to the UNC Lineberger Comprehensive Cancer Center, and research reported in this publication was supported by the Center for AIDS Research (award number 5P30AI050410), and the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The Structural Genomics Consortium (SGC) is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, the Canada Foundation for Innovation, the Eshelman Institute for Innovation, Genome Canada, the Innovative Medicines Initiative (European Union [EU]/European Federation of Pharmaceutical Industries and Associations [EFPIA]) (ULTRA-DD grant no. 115766), Janssen, Merck & Company, Merck KGaA, Novartis Pharma AG, the Ontario Ministry of Economic Development and Innovation, Pfizer, the São Paulo Research Foundation (FAPESP) (2013/50724-5), Takeda, and the Wellcome Trust (106169/ZZ14/Z). R.R.R. received financial support from FAPESP (2016/17469-0). We would also like to thank Claire Strain-Damerell and Pavel Savitsky for cloning various mutants of AAK1 and BMP2K proteins that were used in the crystallization trials. Additionally, we thank Dr. Sean Conner for providing the AAK1 plasmids, Dr. Stephane Angers for kindly providing the HEK293T DVL TKO cells, and Dr. Mariann Bienz for providing comments and feedback. We would like to thank members of the Major laboratory for their feedback and expertise regarding experimental design and project directio

Representational predicaments at three Hong Kong sites

Representational predicaments arise when a job incumbent believes that attributions and images assumed by dominant authorities unfavourably ignore, or disproportionately and unfavourably emphasize, aspects of the incumbent\u27s own work and social identity. This is likely to happen when the incumbent does not have a close relationship with a dominant authority, and when power asymmetries give the former relatively little control over which aspects of their work and social identity are made visible or invisible to the latter. We draw on critical incident interviews from three organizations to illustrate a typology of six types of representational predicament: invasive spotlighting, idiosyncratic spotlighting, embedded background work, paradoxical social visibility, standardization of work processes, and standardization of work outputs. We analyse responses to representational predicaments according to whether they entailed exit, voice, loyalty, or neglect. Incumbents tended to respond with loyalty if they felt able and willing to accommodate their work behaviour and/or social identity to the dominant representations, and if there were sufficient compensatory factors, such as intrinsic rewards from the work or solidarity with colleagues. Exit or neglect appeared to reflect the belief that it was impossible to accommodate. Power asymmetries appeared to deter voice. Individual employees with a close and cordial working relationship with a member of a dominant authority group, or who were relationally networked to one, appeared not to experience representational predicaments