ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

A simple model for the semicontinuous heterophase polymerization: Ethyl methacrylate as a case example

A simple but comprehensive model considering homogeneous and micellar nucleation, coagulation, entry of radicals to particles and to micelles and radicals' exit from particles, is presented. The model is validated, in a starved semicontinuous heterophase polymerization of ethyl methacrylate, at three monomer addition rates. The model accurately describes the overall and instantaneous conversion, the average particle density and diameter, and the number and weight average molar masses evolutions over time. It is found that even though the average number of radicals is much smaller than 0.5, the system is not 0-1. An empirical function was used to describe the gel effect. The homogeneous nucleation was the prevailing mechanism for particle formation and large exit rates of radicals were observed. POLYM. ENG. SCI., 60: 223–232, 2019. © 2019 Society of Plastics Engineers     

Hydrogen adsorption studies in micro-size cobalt dots

Hydrogen desorption curves were obtained from a sample composed of a square arrangement of Co dots with average diameter of 4.4 μm, separated by a distance of 11.6 μm. A macroscopic sample of Co dots grown on a 2.5 × 2.5 cm Si substrate was made by standard lithographic techniques and used in these experiments. Thermal programmed desorption (TPD) was performed under ultra-high vacuum conditions. Hydrogen TPD curves were obtained from a 1 × 1 cm Co dots samples displaying a maximum of intensity at 425 K. Hydrogen TPD curve was also obtained from 1 cm× 1 cm samples of Co films and Co foils for comparison. The hydrogen TPD curves have decreasing intensity from the Co foils to the Co dots and finally to the Co films. This indicates that there are more sites for hydrogen adsorption on the Co dots than in the Co films. This is a surprising result because there is approximately 8.7 times less Co atoms exposed in the Co dots that in the Co film sample. A desorption energy of 27 kcal/mol was obtained for the Co dots suggesting that hydrogen is adsorbed on an hcp hollow site of the Co dot crystalline structure.     

The Possibilities of Community OR in a Third World Country

This paper shows a few possibilities for the application of Community OR in a Third World country based on experience in Venezuela. These possibilities are discussed in a framework of the relationship between the state and community organizations. Emphasis lies in showing that Community OR in Venezuela requires a deep critical commitment to emancipation in order to help community organizations develop in a rather hostile environment. Lastly, results in dealing with community organizations in Venezuela using the Interpretive Systemology approach are presented.     

Usefulness of gastric intramucosal pH for monitoring hemodynamic complications in critically ill children

OBJECTIVE: To assess the efficacy of gastric intramucosal pH for the evaluation of tissue perfusion and prediction of hemodynamic complications in critically ill children. DESIGN: Open prospective study without controls. SETTING: Pediatric intensive care unit (ICU) of a tertiary care university pediatric hospital. PATIENTS: Thirty critically ill children (16 boys and 14 girls), age range: 3 months-12 years. MEASUREMENTS AND RESULTS: A tonometry catheter was placed in the stomach of all patients on admission to the pediatric ICU. Simultaneous tonometry and arterial gas measurements were made on admittance and every 6-12 h throughout the study; a total of 202 measurements were made. The catheter was removed after extubation and/or when the patient was hemodynamically stable. Intramucosal pH was calculated using the Henderson-Hasselbalch equation based on the pCO2 of the tonometer and arterial bicarbonate. Intramucosal pH values between 7.30 and 7.45 were considered to be normal. The patient's condition was analyzed using the Pediatric Risk Mortality Score (PRISM). The relations between intramucosal pH and the presence of major hemodynamic complications (cardiopulmonary arrest, shock), minor hemodynamic complications (hypotension, hypovolemia or arrhythmia), death, PRISM score and the duration of the stay in the pediatric ICU were analyzed. Intramucosal pH on admission was 7.48 +/- 0.15 on average (range 7.04-7.68). Five patients (16%) had an intramucosal pH lower than 7.30 on admission; these patients did not have a higher incidence of hemodynamic complications. The 16 patients (53%) who had an intramucosal pH of less than 7.30 at some time during the course of their disease had more hemodynamic complications than the patients who did not have pH lower than 7.30 (p < 0.0001). Every case of cardiopulmonary arrest and shock was related to intramucosal pH of less than 7.30. Patients with major complications (cardiopulmonary arrest and shock) had lower intramucosal pHs than those with minor hemodynamic complications (p = 0.03); similarly, they had low intramucosal pH readings more often than those with minor complications (p = 0.0032). Intramucosal pH values less than 7.30 had a sensitivity of 90% and a specificity of 98% as a predictor of hemodynamic complications. There was no relation between intramucosal pH lower than 7.30 and either PRISM or the duration of the stay in the pediatric ICU. Patients with intramucosal pH less than 7.20 had a higher PRISM than the patients who did not have pH lower than 7.20 (p < 0.05). A patient who died during the study due to cardiopulmonary arrest had prior intramucosal pH measurements of 7.23 and 7.10, and three patients died of late complications after the end of the study. Hemodynamic complications were not detected with arterial pH. Gap pH (arterial pH-intramucosal pH) and standard pH measurements yielded the same results as gastric intramucosal pH. CONCLUSION: Intramucosal pH could provide a useful early indication of hemodynamic complications in critically ill children.     

Differences in color naming and color salience in Vietnamese and English

The accepted model of color naming postulates that 11 “basic” color terms representing 11 common perceptual experiences show increased processing salience due to a theorized linkage between perception, visual neurophysiology, and cognition. We tested this theory, originally proposed by Berlin and Kay in 1969. Experiment 1 tested salience by comparing unconstrained color naming across two languages, English and Vietnamese. Results were compared with previous research by Berlin and Kay, Boynton and Olson, and colleagues. Experiment 2 validated our stimuli by comparing OSA, Munsell, and newly rendered “basic” exemplars using colorimetry and behavioral measures. Our results show that the relationship between the visual and verbal domains is more complex than current theory acknowledges. An interpoint distance model of color‐naming behavior is proposed as an alternative perspective on color‐naming universality and color‐category structure. © 2003 Wiley Periodicals, Inc. Col Res Appl, 28, 113–138, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.10131     

Using memory and fuzzy rules in a co-operative multi-thread strategy for optimization

In this article, we analyze a co-operative multi-thread search-based optimization strategy, where each solver thread represents a different optimization algorithm (or the same one with different settings), and they are all controlled by a centralized co-ordinator. We also propose the use of memory to keep track of both the state of the individual threads and the obtained solutions. Based on this memory, a very simple fuzzy rule base is used to control the system behavior.We also present the results of three computational experiments. The first of these checks the strategy by comparing it with an independent search strategy and a sequential algorithm, and the superiority of the co-operative scheme is confirmed. The second analyzes how definition of the threads affects the quality of the results, and the importance of there being a balanced set between intensification and diversification is corroborated. The third explores the use of memory with two different fuzzy rules, and the results indicate that the best combination is to use memory together with two rules (solver dependent and solver independent ones) (although this combination should not be activated at the beginning of the search in order to avoid premature convergence).     

A survey on approaches to gridification

The Grid shows itself as a globally distributed computing environment, in which hardware and software resources are virtualized to transparently provide applications with vast capabilities. Just like the electrical power grid, the Grid aims at offering a powerful yet easy‐to‐use computing infrastructure to which applications can be easily ‘plugged’ and efficiently executed. Unfortunately, it is still very difficult to Grid‐enable applications, since current tools force users to take into account many details when adapting applications to run on the Grid. In this paper, we survey some of the recent efforts in providing tools for easy gridification of applications and propose several taxonomies to identify approaches followed in the materialization of such tools. We conclude this paper by describing common features among the proposed approaches, and by pointing out open issues and future directions in the research and development of gridification methods. Copyright © 2007 John Wiley & Sons, Ltd.