Identification of Anti-Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Oxysterol Derivatives In Vitro

The development of effective antiviral drugs targeting the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is urgently needed to combat the coronavirus disease 2019 (COVID-19). We have previously studied the use of semi-synthetic derivatives of oxysterols, oxidized derivatives of cholesterol as drug candidates for the inhibition of cancer, fibrosis, and bone regeneration. In this study, we screened a panel of naturally occurring and semi-synthetic oxysterols for anti-SARS-CoV-2 activity using a cell culture infection assay. We show that the natural oxysterols, 7-ketocholesterol, 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, and 27-hydroxycholesterol, substantially inhibited SARS-CoV-2 propagation in cultured cells. Among semi-synthetic oxysterols, Oxy210 and Oxy232 displayed more robust anti-SARS-CoV-2 activities, reducing viral replication more than 90% at 10 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), based on the dose-dependent curve for antiviral activity in our cell-based assay. Mechanistic studies suggest that Oxy210 reduced replication of SARS-CoV-2 by disrupting the formation of double-membrane vesicles (DMVs); intracellular membrane compartments associated with viral replication. Our study warrants further evaluation of Oxy210 and Oxy232 as a safe and reliable oral medication, which could help protect vulnerable populations with increased risk of developing COVID-19.     

Production of scFv-Fc fusion protein using genetically manipulated quails

The use of transgenic avian species as a transgenic bioreactor for the production of recombinant proteins has been proposed. In recent years, although various procedures for generating transgenic chickens have been reported, the expression of a useful protein at a commercially feasible level has rarely been attained. In this study, we injected a concentrated retroviral vector into quail embryos to generate genetically manipulated quails that produce recombinant proteins. We found that transgene expression in the whole body at a high level was observed for viral injection into the heart of the developing embryos after a 48-h incubation. For the practical production of a useful protein, a retroviral vector encoding an anti-prion scFv-Fc gene under the control of the beta-actin promoter was injected into quail embryos. The quails that hatched stably produced scFv-Fc at a high level in their serum and egg white. The production of scFv-Fc was maintained throughout the breeding period. scFv-Fc purified from the egg white retained the antigen-binding activity. This system exhibited the potential of transgenic quails for the commercial production of recombinant proteins.     

Observation of Si pattern sidewall using inclination atomic force microscope for evaluation of line edge roughness

Inclination atomic force microscope (AFM) imaging has been studied on the possibility to observe a pattern sidewall in contact mode or digital probing (step-in) mode for a line edge roughness (LER) or line width roughness (LWR). Analysis of the AFM tip bending and slipping indicates that it is serious problem to measure and control very fine patterns within an error of less than 1 nm in contact of the tip on the steep slop of the pattern, and it is very important directly to observe the sidewall at inclination angle. In experiments using pyramidal tip and steep Si pattern with about 90 degrees slop, it has demonstrated that the inclination angle is 35-40 degrees for faithful observation of the sidewall. We have observed the etched strip lines on the sidewall with a width of about 100 nm and a depth of about 6.4 nm. We have demonstrated that the inclination AFM is very useful for evaluation of the LER or LWR.     

Study on a wire-type Joule Thomson microcooler with a concentric heat exchanger

This study examines the performance of a wire-type Joule Thomson microcooler utilizing a flexible concentric counterflow heat exchanger. Three gases: C₂H₄, CO₂ and N₂ were used separately for trials conducted at inlet pressures ranging from 0.5 MPa to 5 MPa with C₂H₄ having the best performance. During unloaded tests at an inlet pressure of 2.0 MPa, C₂H₄ obtained a minimum temperature of 225 K while CO₂ obtained a minimum temperature of 232 K. Using CO₂ the microcooler was able to maintain a temperature of 273 K at 100 mW heat input and 2 MPa inlet pressure. An inlet pressure of 3 MPa allowed a 550 mW heat input at 273 K. Theoretical performance calculations were conducted and compared to experimental results revealing considerable reduction of microcooler performance due to the presence of heat in-leak. Results have displayed that the JT coefficient of the coolant gas is a more dominant factor than heat transfer properties in determining the performance of the coolant. Due to the microscale of the device, relevant scaling effects were evaluated, particularly entrance effects, surface roughness and axial conduction.     

Sensing mechanism of SnO2 gas sensors

Studies have been made of the gas sensing properties of both steady and unsteady state SnO₂ thin film gas sensors in contact with CH₄ and H₂ in air from 400 to 500° C. The results suggest a new sensing mechanism model for SnO₂ semiconductor flammable gas sensors. This model is based on the following points: (i) Sensor conductivity is determined by the concentration of carrier electrons. (ii) Carrier concentration is controlled by surface unsaturated oxygen adsorption site concentration which is decided by the balance between oxygen adsorption and the surface reaction between oxygen adsorbate and flammable gases. (iii) The activation energy of the reaction is changed by the Fermi energy change for any change in sensor conductivity. This model explains all experimental results.     

用超高真空扫描隧道显微镜UHV-STM研究多晶铌和单晶铌的表面结构

作者使用超高真空扫描隧道显微镜UHV-STM和表面成分分析仪器俄歇谱仪(Auger El e ctron Spectroscopy (AES))研究了多晶铌和Nb(001).实验中采用净化样品的主要方法是离子轰击和高温加热.经过重结晶后,在多晶铌和Nb(001)表面形成了特征性的表面超结构 .在多晶铌表面,作者观测到了(110)和(100)面,在(100)面上形成的是(n×1)超结构,而在(110)面上形成的是0.28nm×0.40 nm的周期性超结构.在Nb(001)表面作者观测到 C(2×2) 的典型结构.AES实验表明,不纯物"氧"仍然以氧化物的形式存在于单晶和多晶铌样品中.基于这些实验结果,结合铌的微观晶格结构,作者给出了所观测到的超结构的合理的解释,并对有些结构提出了原子排列模型.     

Polarized Raman spectra of doubly oriented poly(vinyl alcohol)

Polarized Raman spectra of doubly oriented samples of atactic poly(vinyl alcohol) have been measured. The great usefulness of such polarized spectra has been clarified for the vibrational analysis. The normal coordinate treatments of syndiotactic and isotactic poly(vinyl alcohol) chain models gave good agreement between the observed and calculated frequencies.     

Thickness Dependence of Critical Current of Superfluid 3He Film

We have measured the critical current J _c , which is defined as the onset of dissipative flow, for a thickness range from 0.3 to 4 μm using inter-digitated capacitors. In the thickness dependence of J _c , two distinct dissipation regimes were observed. The crossover occurred at a thickness of ∼1 μm.     

Direct Determination of the Stereoisomeric Composition of Callosobruchusic Acid,the Copulation Release Pheromone of the Azuki Bean Weevil, <Emphasis Type="Italic">Callosobruchus chinensis</Emphasis> L., by the 2D-Ohrui-Akasaka Method

The stereoisomeric composition of the copulation release pheromone of the azuki bean weevil, Callosobruchus chinensis L., was determined to be R:S = 3.3–3.4:1 by the 2D-Ohrui–Akasaka method.     

Heat transfer enhancement with an inclined semicylindrical turbulence promoter—The relationship between optimum clearance and film thickness

Heat transfer enhancement in a rectangular duct with a semicylindrical turbulence promoter was experimentally studied for a high Prandtl number fluid. The measurements of mass transfer coefficient and wall shear stress as well as flow visualization were performed in order to investigate how the performance of a heat transfer enhancement promoter is influenced by its inclination angle and by the clearance between the promoter and the wall surface. When the inclination angle is 0°, the variation of performance with clearance is closely related to the extent of heat transfer enhancement in the region of slipping flow. In this case, the clearance exhibiting the maximum performance is almost equal to the film thickness for a smooth duct without a promoter. As the inclination angle increases, what influences the variation of performance with clearance gradually shifts to the extent of heat transfer enhancement in the region of circulating and reattaching flows, and the clearance exhibiting the maximum performance decreases. There is no remarkable difference in the maximum performance between inclination angles examined here. It is, however, desirable to set the inclination angle to 30°, since the distribution of the local mass transfer coefficient for this angle is less curved than those for other angles. © 1998 Scripta Technica. Heat Trans Jpn Res, 26(5): 332–344, 1997