Immune signatures underlying post-acute COVID-19 lung sequelae

Severe coronavirus disease 2019 (COVID-19) pneumonia survivors often exhibit long-term pulmonary sequelae, but the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high-dimensional characterization of the pathophysiological and immune traits of aged COVID-19 convalescents, and correlated the local and systemic immune profiles with pulmonary function and lung imaging. We found that chronic lung impairment was accompanied by persistent respiratory immune alterations. We showed that functional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific memory T and B cells were enriched at the site of infection compared with those of blood. Detailed evaluation of the lung immune compartment revealed that dysregulated respiratory CD8+ T cell responses were associated with the impaired lung function after acute COVID-19. Single-cell transcriptomic analysis identified the potential pathogenic subsets of respiratory CD8+ T cells contributing to persistent tissue conditions after COVID-19. Our results have revealed pathophysiological and immune traits that may support the development of lung sequelae after SARS-CoV-2 pneumonia in older individuals, with implications for the treatment of chronic COVID-19 symptoms

Enhancement of Temperature Blending in Convective Heat Transfer by Motionless Inserts With Variable Segment Length

Stationary spiral inserts can effectively enhance heat transfer and temperature blending in the heat convection systems. In this paper, the impact of the segment length on the performance of a stationary insert is studied for flow Re numbers from ~80 to ~7900 through numerical simulation of heat transfer in streams of cold and hot gases flowing across it. The segment length to width ratio is from 1.11 to 2.33. The temperature of the studied gas is from 300 K to 1300 K. It is shown that the insert with variable segment length is more effective in temperature blending for two compressible streams compared with an insert with constant segment length, especially for low-Re-number turbulent flows

FEDSM2006-98070 A NUMERICAL STUDY OF TURBULENT FLOW IN HELICAL STATIC MIXERS

ABSTRACT Many processing applications call for the addition of small quantities of chemicals to working fluid. Hence, fluid mixing plays a critical role in the success or failure of these processes. An optimal combination of turbulent dispersion down to eddies of the Kolmogoroff scale and molecular diffusion would yield fast mixing on a molecular scale which in turn favors the desired reactions. Helical static mixers can be used for those applications. The range of practical flow Reynolds numbers for these mixers in industry is usually from very small (Re ~ 0) to moderate values (Re ~ 5000). In this study, a helical static mixer is investigated numerically using Lagrangian methods to characterize mixer performance under turbulent flow regime conditions. A numerical simulation of turbulent flows in helical static mixers is employed. The model solves the three-dimensional, Reynolds-averaged Navier-Stokes equations, closed with the Spalart-Allmaras turbulence model, using a second-orderaccurate finite-volume numerical method. Numerical simulations are carried out for a six-element mixer, and the computed results are analyzed to elucidate the complex, threedimensional features of the flow. Using a variety of predictive tools, mixing results are obtained and the performance of static mixer under turbulent flow condition is studied

Estimation of Boundary Conditions in the Presence of Unknown Moving Boundary Caused by Ablation

Ablative materials can sustain very high temperatures in which surface thermochemical processes are significant enough to cause surface recession. Existence of moving boundary over a wide range of temperatures, temperature-dependent thermophysical properties of ablators, and no prior knowledge about the location of the moving surface augment the difficulty for predicting the exposed heat flux at the receding surface of ablators. In this paper, the conjugate gradient method is proposed to estimate the unknown surface recession and time-varying net surface heat flux for these kinds of problems. The first order Tikhonov regularization is employed to stabilize the inverse solution. Considering the complicated phenomena that are taking place, it is shown via simulated experiment that unknown quantities can be obtained with reasonable accuracy using this method despite existing noises in the measurement data

The aquaporin-4 water channel as a potential drug target in neurological disorders

IntroductionAquaporin-4 (AQP4) is a water transporting protein expressed at the plasma membrane of astrocytes throughout the central nervous system (CNS). Analysis of AQP4 knockout mice has suggested its broad involvement in brain water balance, neuroexcitation, glial scarring, neuroinflammation, and even neurodegenerative and neuropsychiatric disorders. Broad clinical utility of AQP4 modulators has been speculated. Area covered: This review covers the biology of AQP4, evidence for its roles in normal CNS function and neurological disorders, and progress in AQP4 drug discovery. Expert opinion: Critical examination of available data reduces the lengthy potential applications list to AQP4 inhibitors for early therapy of ischemic stroke and perhaps for reduction of glial scarring following CNS injury. Major challenges in identification and clinical development of AQP4 inhibitors include the apparent poor druggability of AQPs, the many homologous AQP isoforms with broad tissue distribution and functions, technical issues with water transport assays, predicted undesired CNS and non-CNS actions, and the need for high blood-brain barrier permeation. To date, despite considerable effort, validated small-molecule AQP4 inhibitors have not been advanced. However, a biologic ('aquaporumab') is in development for neuromyelitis optica, an autoimmune inflammatory demyelinating disease where CNS pathology is initiated by binding of anti-AQP4 autoantibodies to astrocyte AQP4