Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at −8.3 kcal/mol, followed by Zn and Ca at −8.0 kcal/mol, and Fe and Mg at −7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn–Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.     

Chemorheology and Kinetics of High-Performance Polyurethane Binders Based on HMDI

Aliphatic diisocyanates, such as 1,6-hexamethylene diisocyanate (HMDI), are preferred curing agents for the formation of polyurethanes (PUs) in applications where resistance to abrasion or degradation by ultraviolet light takes precedence. Aside from the final properties, the curing agent plays a key role in the bulk manufacturing of such materials, and it mainly affects the polymerization kinetics and their rheology. The copolymerization of HMDI and a metallo-prepolymer derivative from hydroxyl-terminated polybutadiene (HTPB) is studied under isothermal conditions (50–80 °C). This study is carried out by means of an indirect method, using both rotational viscometry and dynamic rheometry. At the beginning of the process, the viscosity growth fit well to a first-order kinetic model. Afterward, the reactive system passes through gelation, from which only rheology is allowed for the investigation of the entire polymerization process. This transition is analyzed in depth together with predictions from percolation theory. The conversion degree is determined from rheological measurements, and then an autocatalytic kinetic model is applied to describe the overall process. Finally, an isoconversional method allows the evolution of activation energy to be studied. This analysis merits attention for the development of high-performance binders that are of great interest in aerospace propulsion technology.     

Visualization of Flow Patterns in Closed Loop Flat Plate Pulsating Heat Pipe Acting as Hybrid Thermosyphons under Various Gravity Levels

A particular flat plate pulsating heat pipe (FPPHP), filled with FC72, is tested during the 62^th and 64^th ESA parabolic flight campaigns under vertical orientation. The FPPHP is made of a thin copper plate, in which a curved channel disposed with 11 U-turns is milled and closed on the top face by a transparent borosilicate plate. The particular characteristics is that the equivalent hydraulic diameter of the square channel (2.5 × 2.5 mm²) is above the working fluid capillary diameter on ground, inducing a stratification of the liquid/vapor phases under ground and hyper-gravity conditions, whatever the orientation. The energy transfer mode in such conditions is represented either by pure pool boiling inside the channels almost completely filled by the liquid phase or by an annular flow pattern inside the channels mostly filled by the refrigerant vapor. Instead, during the microgravity phases, the fluid regime naturally turns into a slug-plug flow pattern. During the transition from 1.8 g to 0 g a rapid dry-out may occur in some of the channels, followed by a similarly fast reaction of liquid plugs moving towards the evaporator from the condenser zone. Such stop-and-start motion events continue during the whole microgravity period, leading to strong temperature oscillations, but also to a still acceptable thermal performance of the device.     

Candida tropicalis biofilm formation and expression levels of the CTRG ALS-like genes in sessile cells

Candida tropicalis is an emergent pathogen with a high rate of mortality associated with it; however, less is known about its pathogenic capacity. Biofilm formation (BF) has important clinical repercussions, and it begins with adherence to a substrate. The adherence capacity depends principally on the cell surface hydrophobicity (CSH) and, at a later stage, on specific adherence due to adhesins. The ALS family in C. tropicalis, implicated in adhesion and BF, is represented in several CTRG genes. In this study, we determined the biofilm-forming ability, the primary adherence, and the CSH of C. tropicalis, including six isolates from blood and seven from urine cultures. We also compared the expression of four CTRG ALS-like genes (CTRG_01028, CTRG_02293, CTRG_03786, and CTRG_03797) in sessile versus planktonic cells, selected for their possible contribution to BF. All the C. tropicalis strains were biofilm producers, related to its filamentation capacity; all the strains displayed a high adherence ability correlated to the CSH, and all the strains expressed the CTRG genes in both types of growth. Urine isolates present, although not significantly, higher CSH, adherence, and biofilm formation than blood isolates. This study reveals that three CTRG ALS-like genes—except CTRG_03797—were more upregulated in biofilm cells, although with a considerable variation in expression across the strains studied and between the CTRG genes. C. tropicalis present a high biofilm capacity, and the overexpression of several CTRG ALS-like genes in the sessile cells suggests a role by the course of the biofilm formation.     

A method for determining the optimal districting in urban emergency services

In this paper a method is suggested for dealing with one of the main allocation problems often appearing in urban emergency services, that of districting.A mathematical model is developed in terms of constrained optimization with binary variables.An algorithm, derived from Balas' filter-method, which seems to be quite efficient for this class of problems, has been utilized.The objective function, considered here, is the overall travel time in the region under consideration.The optimal travel time, in the case of the Rome fire service, turns out to be meaningfully lower than that derived from the actual situation. At the end is indicated a way of applying the method to the assignment of response areas to the different stations as a function of the current state of the system.     

Programs for two-sided printed circuit board design

A set of programs for the computer-aided design of two-sided PCB's uses a routing algorithm based on artificial intelligence techniques. The data input is translated and checked. The programs also supply a component map as well as the routing solution draft distinguishing the pins, via holes and each side of the board.     

Shelf-life of tortilla extended with fungal amylases

Corn (maize), the main source of starch and calories in the Mexican diet, is consumed mainly as tortillas , which have a short shelf-life. A fungal α-amylase blend (10μU g⁻¹) was added during hydration of maize flour to produce masa , and modified the starch during tortilla cooking up to the denaturating temperature. Control and treated tortillas , fresh and staled by storage at −12°C and by freeze-thaw cycles, were compared for amounts of retrograded starch, flexibility, rheological properties and by preference ranking by a panel of 75 judges. Results showed significant improvements in delayed staling and, by implication, extended shelf-life. The process was regarded as financially viable on a commercial scale.     

Low-cost Position and Force Measurement System for Payload Transport Using UAVs

Machine Intelligence Research - In recent years, multiple applications have emerged in the area of payload transport using unmanned aerial vehicles (UAVs). This has attracted considerable interest...     

Autonomic resource contention‐aware scheduling

The complexity of computing systems introduces a few issues and challenges such as poor performance and high energy consumption. In this paper, we first define and model resource contention metric for high performance computing workloads as a performance metric in scheduling algorithms and systems at the highest level of resource management stack to address the main issues in computing systems. Second, we propose a novel autonomic resource contention‐aware scheduling approach architected on various layers of the resource management stack. We establish the relationship between distributed resource management layers in order to optimize resource contention metric. The simulation results confirm the novelty of our approach.Copyright © 2013 John Wiley & Sons, Ltd.