Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Finite Element Analysis Of A Cup Deep Drawing Process [estudo Do Processo De Embutimento Profundo De Copo Pelo Metodo Dos Elementos Finitos]

Deep drawing processes have an important role in manufacturing, mainly in the automotive industry. The increasing competition requires that design and manufacture of dies be fast and without errors. New forms to develop the dies have been used. The finite element method has helped engineers to reduce errors during die development. In this paper an elasto-plastic element was used to simulate the cylindrical deep drawing of an ABNT 1006 steel cup. The simulation made possible the determination of the forces, thickness and circumferential strains occurring during the deep drawing process, which were compared to experimental results.212355363(1993) ANSYS User's Manuals, 1. , (Procedures), 2 (Commands), 3 (Elements) and 4 (Theory), Swanson Analysis Systems IncBathe, K.J., (1982) Finite Elements Procedure in Engineering Analysis, , Prentice-Hall, Englewood CliffsBorst, R., Feenstra, P.M., Studies in anisotropic plasticity with reference to the hill criterion (1990) International Journal of Numerical Methods in Engineering, 29, pp. 315-336Bortolussi, R., (1996) Simulação do Processo de Estampagem Profunda de Corpos Cilíndricos Através do Método dos Elementos Finitos, pp. 81-88. , Dissertação de Mestrado, UNICAMP, cap. 5Bresciani, Fo., Button, S.T., Gomes, E., Nery, F.A.C., Zavaglia, C.A.C., (1996) Conformação Plástica dos Metais, p. 127. , E., Ed. UNICAMPChou, C.H., Pan, J., Analysis of sheet metal forming operations by a stress resultant constitutive law (1990) International Journal of Numerical Methods in Engineering, 29, pp. 315-336Cook, R.D., Malkus, D.S., Plesha, M.E., (1989) Concepts and Applications of Finite Element Analysis, , John Willey &ampSons, 3a EdiçãoDarendeliler, H., Altan, T., Analysis of axisymmetric cup drawing in relation to friction (1996) Journal of Materials Processing Technology, 58, pp. 293-301Dieter, G.E., (1984) Workability Testing Techniques, , ASM InternationalGontier, C., About the numerical simulation of the sheet metal stamping process (1994) International Journal of Numerical Methods in Engineering, 37, pp. 669-692Guo, Y.Q., Batoz, J.L., Detraux, J.M., Duroux, P., Finite elements procedures for strain estimations of sheet metal forming parts (1990) International Journal of Numerical Methods in Engineering, 30, pp. 1385-1401Mahdavian, S.M., He, D., Product thickness analysis in pure cup drawing (1995) Journal of Materials Processing Technology, 51, pp. 387-406Keck, P., Wilhelm, M., Lange, K., Application of the finite element method to the simulation of sheet forming processes: Comparison of calculations and experiments (1990) International Journal of Numerical Methods in Engineering, 30, pp. 1415-1430Lee, D., Majlessi, S.A., Vogel, J.H., Process modeling and simulation for sheet metal (1989) Metals Handbook, 14, pp. 911-927. , 9th Edition ASM InternationalOñate, E., Zienkiewicz, O.C., A viscous shell formulation for the analysis of thin sheet metal forming (1983) International Journal of Mechanical Science, 25 (5), pp. 305-335Rowe, G.W., Strugess, C.E.N., Hartley, P., Pillinger, I., (1991) Finite Element Plasticity and Metal Forming Analysis, , Cambridge University Press, 1a EdiçãoSchey, J.A., (1983) Tribology in Metalworking, , ASM InternationalSlater, R.A.C., (1977) Engineering Plasticity, , The Macmillian Pres

Aluminium Extrusion Analysis By The Finite Volume Method

Present work proposes a novel numerical scheme to calculate stress and velocity fields of metal flow in axisymmetric extrusion process in steady state. Extrusion of aluminium is one main metal forming process largely applied in manufacturing bars and products with complex cross section shape. The upper-bound, slab, slip-line methods and more recently the numerical methods such as the Finite Element Method have been commonly applied in aluminium extrusion analysis. However, recently in the academy, the Finite Volume Method has been developed for metal flow analysis: literature suggests that extrusion of metals can be modelled by the flow formulation. Hence, metal flow can be mathematically modelled such us an incompressible non linear viscous fluid, owing to volume constancy and varying viscosity in metal forming. The governing equations were discretized by the Finite Volume Method, using the Explicit MacCormack Method in structured and collocated mesh. The MacCormack Method is commonly used to simulate compressible fluid flow by the finite volume method. However, metal plastic flow and incompressible fluid flow do not present state equations for the evolution of pressure, and therefore, a velocity-pressure coupling method is necessary to obtain a consistent velocity and pressure fields. The SIMPLE Method was applied to attain pressure-velocity coupling. This new numerical scheme was applied to forward hot extrusion process of an aluminium alloy. The metal extrusion velocity fields achieved fast convergence and a good agreement with experimental results. The MacCormack Method applied to metal extrusion produced consistent results without the need of artificial viscosity as employed by the compressible flow simulation approaches. Therefore, present numerical results also 2suggest that MacCormack method together with SIMPLE method can be applied in the solution of metal forming processes in addition to the traditional application for compressible fluid flow.172183Hill, R., (1950) The Mathematical Theory of Plasticity, , Oxford University PressAvitzur, B., (1980) Metal Forming, the Application of Limit Analysis, , Marcel Dekker, N.YJohnson, W., Sowerby, R., Venter, R.D., (1982) Plaine Strain Slip-Line Fields for Metal Deformation Processes, , Pergamon Press, OxfordMellor, P.B., Johnson, W., (1985) Engineering Plasticity, , Van Nostrand ReinholdKobayashi, S., Oh, S., Altan, T., (1989) Metal Forming and the Finite-Element Method, , Oxford University PressValberg, H.S., (2010) Applied Metal Forming: Inclunding FEM Analysis, , edited by Cambridge University Press, London, UKThomsen, E.G., Frisch, J., Stresses and strains in cold-extruding 2S-O aluminum (1955) Trans. ASME., 77, pp. 1343-1353Johnson, W., Kudo, H., (1962) The Mechanics of Metal Extrusion, , edited by Manchester University Press, Manchester, UKGhosh, S., A new finite element description for simulation of metal forming processes (1989) Numerical Methods in Industrial Forming Processes- Numiform, 89, pp. 159-164. , E.G. Thompson, R.D. Wood, O.C. Zienkiewicz and A. Samuelson (Eds), A.A. BalkemaZienkiewicz, O.C., Huang, G.C., Adaptive modelling of transient coupled metal forming processes (1989) Numerical Methods in Industrial Forming Processes- Numiform, 89, pp. 3-10. , E.G. Thompson, R.D. Wood, O.C. Zienkiewicz and A. Samuelson (Eds), A.A. BalkemaAltan, T., Kobayashi, S., A numerical method for estimating the temperature distribution in extrusion through conical die (1968) J. Eng. Ind., 90, pp. 107-118Sellars, C.M., The physical metallurgy of hot working (1980) Hot Working and Forming Processes, pp. 3-15. , C.M. Sellars and G.J. Davies ( Eds), Metals Society, LondonSellars, C.M., Computer modelling of hot-working processes (1985) Mat. Sci. Eng., 1, pp. 325-332Jain, P.C., (1976) Plastic Flow in Solids (Static, Quasistatic and Dynamic Situations including Temperature Effects), , University College of Swansea, Wales, Ph.D. thesisDawson, P.R., Thompson, E.G., Steady-state thermo mechanic finite element analysis of elastoviscoplastic metal forming processes (1977) Numerical Modelling of Manufacturing Processes, pp. 167-182. , ASME, PVP-PB-025Zienkiewicz, O.C., Godbole, P.N., Flow of plastic and viscoplastic solids with special reference to extrusion and forming processes (1974) Int. J. Num. Meth. Engng., 8, pp. 3-16Zienkiewicz, O.C., Jain, P.C., Onate, E., Flow of solids during forming and extrusion: Some aspects of numerical solutions (1978) Int. J. Solids Struct., 14, pp. 15-38Oñate, E., Cervera, M., Zienkiewicz, O.C., A finite-volume format for structural mechanics (1994) Int. J. Num. Meth. Engng., 37, pp. 181-201Demirdzic, I., Martinovic, D., Finite volume method for thermo-elasto-plastic stress analysis (1993) Computer Meth. Applied Mech. and Engng., 109, pp. 331-349Bailey, C., Cross, M., A finite volume procedure to solve elastic solid mechanics problems in three dimensions on an unstructured mesh (1995) Int. J. Num. Meth. Engng., 38, pp. 1757-1776Greenshields, C.J., Weller, H.G., Ivankovic, A., The finite volume method for coupled fluid flow and stress analysis (1999) Comput. Model Simul. Eng., 4, pp. 213-218Wenke, P., Whell, M.A., A finite volume method for solid mechanics incorporating rotational degrees of freedom (2003) Computers and Structures, 81, pp. 321-329Bressan, J.D., Martins, M.M., Vaz Jr., M., Stress evolution and thermal shock computation using the finite volume method (2010) Journal of Thermal Stresses, 33, pp. 533-558Programmer's Guide, , http://www.openfoam.com/docs/Jasak, H., (1996) Error Analysis and Estimation for the Finite Volume Method with Applications to Fluid Flows, , Ph.D. Thesis, Imperial College LondonBasic, H., Demirdzic, I., Muzaferija, S., Finite volume method for simulation of extrusion processes (2005) Int. J. Num. Meth. Engng., 62, pp. 475-494Martins, M.M., Bressan, J.D., Button, S.T., Ivankovic, A., Extrusion process by finite volume method using openfoam software (2010) International Conference on Advances in Material and Processing Technologies - AMPT2010, , F. Chinesta, Y. Chastel, M. El Mansori, (Eds), Paris, American Institute of PhysicsTannehill, J.C., Anderson, D.A., Pletcher, R.H., (1997) Computational Fluid Mechanics and Heat Transfer, , Taylor & Francis, LondonMartins, M.M., Bressan, J.D., Button, S.T., Metal extrusion analysis by finite volume method (2013) XII International Conference on Computational Plasticity Fundamentals and Applications COMPLAS 2013, , In: E. Oñate, D.R.J. Owen, D. Peric and B. Suárez (Eds), BarcelonaHensel, A., Spittel, T., (1978) Kraft- Und Arbeitsbedarf Bildsamer Formgebungsverfahren, , VEBDeutscher Verlag fur Grundstoffindustrie, LeipzigMartínez, H.V., Coupard, D., Girot, F., (2006) J. Mat. Proc. Techn., 173, pp. 252-25

Lead Extrusion Analysis By Finite Volume Method

Computational numerical simulation is nowadays largely applied in the design and analysis of metal forming process. Extrusion of metals is one main forming process largely applied in the manufacturing of metallic products or parts. Historically, the Finite Element Method has been applied for decades in metal extrusion analysis [4]. However, recently in the academy, there is a trend to use Finite Volume Method: literature suggests that metal flow by extrusion can be analyzed by the flow formulation [1, 2]. Thus, metal flow can be modelled such us an incompressible viscous fluid [2]. This hypothesis can be assumed because extrusion process is an isochoric process. The MacCormack Method is commonly used to simulate compressible fluid flow by the finite volume method [3]. However, metal extrusion and incompressible fluid flow do not present state equations for the evolution of pressure, and therefore, a velocity-pressure coupling method is necessary to obtain a consistent velocity and pressure fields [3]. Present work proposes a new numerical scheme to obtain information about metal flow in the extrusion process, in steady state. The governing equations were discretized by Finite Volume Method, using the Explicit MacCormack Method to structured and collocated mesh. The SIMPLE Method was applied to attain pressure-velocity coupling [3]. These new numerical scheme was applied to forward extrusion process of lead. The incompressible metal extrusion velocity fields achieved faster convergence and a good agreement with analytical and experimental results obtained from literature. The MacCormack Method applied for metals produced consistent results without the need of artificial viscosity as employed by the compressible flow simulation approaches. Furthermore, the present numerical results also suggest that MacCormack Method and SIMPLE can be applied in the solution of metal forming processes besides the traditional application for compressible fluid flow.210220Basic, H., Demirdzic, I., Muzaferija, S., Finite volume method for simulation of extrusion processes (2005) Inter. Journ. for Num. Meth. in Eng., 62, pp. 475-494Demirdzic, I., Dzaferovic, E., Ivankovic, A., Finite-volume approach to thermoviscoelasticity (1995) Num. Heat Trans., 47, pp. 213-237Khan, A.S., Huang, S., (1995) Continuum Theory of Plasticity, , New YorkKobayashi, S., Oh, S.I., Altan, T., (1989) Metal Forming and the Finite Element Method, , Oxford UniversityLou, S., Zhao, G., Wang, R., Wu, X., Modeling of aluminum alloy profile extrusion process using finite volume method (2008) Journ. of Mat. Proc. Tech., 206, pp. 481-490Maliska, C.R., (2004) Transferência de Calor E Mecânica Dos Fluidos Computacional, , LCTMalvern, L.E., (1969) Introduction to the Mechanics of a Continuous Medium, , Prentice-HallMartins, P., Rodrigues, J., Tecnologia mecânica: Tecnologia da deformação plásticafundamentos teóricos (2005) Escolar, 1Mielnik, E., (1991) Metalworking Science and Engineering, , McGraw-HillRhie, C.M., Chow, W.L., A numerical study of the turbulent flow past an isolated airfoil with trailing edge separation (1983) Am. Inst. of Aero. and Astron., 21, pp. 1525-1532Tannehill, J.C., Anderson, D.A., Pletcher, R.H., (1997) Computational Fluid Mechanics and Heat Transfer, , Taylor & FrancisValberg, H.S., (2010) Applied Metal Forming: Including FEM Analysis, , Cambridge University PressWilliams, A.J., Croft, T.N., Cross, M., Computational modeling of metal extrusion and forging processes (2002) Journ. of Mat. Proc. Tech., 125-126, pp. 573-582Zdanski, P.S.B., Vaz Jr., M., Inácio, G.R., A finite volume approach to simulation of polymer melt flow in channels (2008) Eng. Comp., 25, pp. 233-250Jasak, H., (1996) Error Analysis and Estimation for the Finite Volume Method with Applications to Fluid Flows, , Thesis (Doutorado) - Department of Mechanical Engineering, Imperial College of Science, Technology and Medicine, Londo

In-vitro corrosion resistance study of hot worked Ti-6Al-7Nb alloy in a isotonic medium

This investigation reports the results of linear polarization of hot upset Ti-6Al-7Nb bar samples. Current-potential curves recorded in Hank’s solution were analyzed by correlating characteristics of passivation and microstructures obtained after processing. Results have shown that it is important to select temperature process and deformation rate as parameters when more noble potential values are required. Low deformation rate facilitates the formation of beta phase that is retained in the structure at room temperature shifting the corrosion potential to more positive values. However, samples hot compressed from 750°C to 1030 °C showed passive layer stability over a wide range of potentials extending from -0.15 V to 1.75 V vs SCE . Furthermore, passive films grown onto the Ti-6Al-7Nb samples surfaces have shown no sign of rupture for the processing conditions selected for this study

Microstructural Simulation Of Friction Stir Welding In Uns S32205 Duplex Stainless Steel

Hot torsion physical simulation was used to reproduce the microstructure of the thermomechanically affected zone (TMAZ) of friction stir welded UNS S32205 duplex stainless steel. Such microstructure reproduction under controlled conditions allows the estimation of the thermomechanical conditions imposed to the material during FSW. The implementation of a LN2 cooling system to the hot torsion unit of a commercial Gleeble 3800® simulator was instrumental to reproduce the temperature profiles measured during actual friction stir welding of duplex stainless steels. As a result, very good microstructural and thermal matching were obtained. Moreover, ferrite volume fraction of the simulated microstructures perfectly matched the actual thermomechanically affected zone. Numerical simulations of the torsion tests are being carried out to determine the actual values of strain and strain rate in each test. Copyright © 2013 ASM International® All rights reserved.297301ASM InternationalGunn, R.N., (2003) Duplex Stainless Steels: Microstructure. Properties and Applications, , Abington Publishing AbingtonMcGuire, M.F., (2008) Stainless Steels for Design Engineers, , ASM International OhioFarnoush, H., Hot deformation characteristics of 2205 duplex stainless steel based on the behavior of constituent phases (2010) Materials and Design, 31, pp. 220-226Han, Y., Investigation on hot deformation behavior of 00Cr23Ni4N duplex stainless steel under medium-high strain rates (2011) Mater Charac, 62, pp. 198-203Momeni, A., Dehghani, K., Hot working behavior of 2205 austenite-ferrite duplex stainless steel characterized by constitutive equations and processing maps (2011) Mater Sci Eng A, 528, pp. 1448-1454Cizek, P., Wynne, B.P., A mechanism of ferrite softening in a duplex stainless steel deformed in hot torsion (1997) Materials Science and Engineering A, 230 (1-2), pp. 88-94. , PII S0921509397000877Evangelista, E., McQueen, H.J., Niewczas, M., Cabibbo, M., Hot workability of 2304 and 2205 duplex stainless steels (2004) Canadian Metallurgical Quarterly, 43 (3), pp. 339-354Saeid, T., Effect of friction stir welding speed on the microstructure and mechanical properties of a duplex stainless steel (2008) Mater Sci Eng A, 496, pp. 262-268Sato, Y.S., Nelson, T.W., Sterling, C.J., Steel, R.J., Pettersson, C.-O., Microstructure and mechanical properties of friction stir welded SAF 2507 super duplex stainless steel (2005) Materials Science and Engineering A, 397 (1-2), pp. 376-384. , DOI 10.1016/j.msea.2005.02.054, PII S0921509305002054Iza-Mendia, A., Pinol-Juez, A., Urcola, J.J., Gutierrez, I., Microstructural and Mechanical Behavior of a Duplex Stainless Steel under Hot Working Conditions (1998) Metallurgical and Materials Transactions A: Physical Metallurgy and Materials Science, 29 (12), pp. 2975-2986Duprez, L., Flow stress and ductility of duplex stainless steel during high-temperature torsion deformation (2002) Metall Mater Trans A, 33, pp. 1931-1938Mishra, R.S., Mahoney, M.W., (2007) Friction Stir Welding and Processing, , ASM International OhioSantos, T.F.A., Microstructure evaluation of UNS S32205 duplex stainless steel friction stir welds Proc 10th Brazilian Stainless Steel Conf, Rio de Janeiro, Brazil, 2010, pp. 16-20Steel, R.J., Sterling, C.J., Friction stir welding of 2205 duplex stainless and 3Cr12 steels Proc 14th ISOPE Conf, Toulon, France, May 2004, pp. 67-72Santos, T.F.A., Correlating microstructure and performance of UNS S32750 and S32760 superduplex stainless steels friction stir welds Proc 21st ISOPE Conf, Maui, Hawaii, USA, June 2011, pp. 534-540Norton, S., (2006) Ferrous Friction Stir Weld Physical Simulation, , a Dissertation, Ohio State UniversitySinfield, M.F., (2007) Advancements in Physical Simulation and Thermal History Acquisition Techniques for Ferrous Alloy Friction Stir Welding, , a Thesis, Ohio State UniversitySinfield, M.F., Physical simulation of friction stir weld microstructure of a high-strength, low alloy steel (HSLA-65) Proc 7th International Friction Stir Welding Symposium, Awaji Island, Japão, May 200

Numerical And Experimental Analysis Of The Microstructural Evolution During Cross Wedge Rolling Of V-ti Microalloyed Steel [análise Numérica E Experimental Da Evolucão Microestrutural Durante A Laminação Transversal Com Cunha De Um Aço Microligado Ao V-ti]

The improvement of manufacturing processes to assure product quality and reduce the amount of raw material and energy is the main objective of many recent researches. Some of them study cross wedge rolling (CWR) as a substitute to hot upsetting in the manufacture of stepped shafts, pins, eccentric shafts and many other mechanical parts. In this process a cylinder is deformed by two wedge tools assembled on plane plates that move tangentially one against the other. The main objective of this work is to study the thermomechanical behaviour of medium carbon steel during hot CWR by means of a numerical analysis. The numerical results will be compared to the microstructure of microalloyed steel samples which were submitted to CWR experimental tests. The results suggested that dynamic recrystallization was present during CWR and that microstructures in the austenitic region were very refined.624495502Danno, A., Tanaka, T., Hot forming of stepped shafts by wedge rolling with three rolls (1984) Journal of Mechanical Working Technology, 9, pp. 21-35Dean, T.A., Fu, X.P., Past developments, current applications and trends in the cross wedge rolling process (1993) International Journal of Machine Tools and Manufacture, 33 (3), pp. 367-400Gentile, F.C., (2004) Estudo Do Processo De Laminação Cruzada Com Cunha (cross Wedge Rolling) Para Fabricação De Eixos Escalonados, , UNICAMP, agosto de, Tese de DoutoradoJonas, J.J., Dynamic recrystallization-scientific curiosity or industrial tool? (1994) Mat. Scie. and Eng., A184, pp. 155-165McQueen, H.J., Jonas, J.J., Recovery and recrystallization during high temperature deformation (1976) Treatise On Materials Science and Technology, 6, pp. 393-493. , In: ARSENAUT, R. J. (ed.), New York: Academic PressQiang, L.I., Lovell, M.R., Slaughter, W., Tagavi, K., (2002) Journal of Materials Processing Technology, pp. 125-126+248-257Regone, W., Jorge Jr., A.M., Balancin, O., (2000) Metodologia Para Determinar Os Tipos De Amaciamentos Que Atuam Em Processos Termomecânicos, , CBECIMAT, 14.São Pedro - SP, 3 a 6 de dezembro deda Silva, M.L.N., Regone, W., Button, S.T., Microstructure and mechanical properties of microalloyed steel forgings manufactured from cross-wedge-rolled preforms (2005) Scripta Materialia, 54, pp. 213-217Weronski, W., Pater, Z., Selection of geometric parametrs of transverse wedge rolling tools (1992) Journal of Materials Processing Technology, 34, pp. 273-28

In-vitro corrosion resistance study of hot worked Ti-6Al-7Nb alloy in a isotonic medium

This investigation reports the results of linear polarization of hot upset Ti-6Al-7Nb bar samples. Current-potential curves recorded in Hank’s solution were analyzed by correlating characteristics of passivation and microstructures obtained after processing. Results have shown that it is important to select temperature process and deformation rate as parameters when more noble potential values are required. Low deformation rate facilitates the formation of beta phase that is retained in the structure at room temperature shifting the corrosion potential to more positive values. However, samples hot compressed from 750°C to 1030 °C showed passive layer stability over a wide range of potentials extending from -0.15 V to 1.75 V vs SCE . Furthermore, passive films grown onto the Ti-6Al-7Nb samples surfaces have shown no sign of rupture for the processing conditions selected for this study.475