Great Debate Research Articles

Molecular docking, molecular dynamics, and in vitro studies reveal the potential of angiotensin II receptor blockers to inhibit the COVID-19 main protease

Drug repurposing is the most rapid and economic way nowadays to rapidly provide effective drugs for our pandemic coronavirus disease 2019 (COVID-19). It was a great debate about ARBs whether to be stopped or continued for patients using them especially at the beginning of the COVID-19 pandemic. In this study, we carried out a virtual screening for almost all members of ARBs (nine) against COVID-19 main protease. Molecular docking as one of the important computational techniques was performed in this work. Interestingly, the tested compounds showed variable binding affinities in the order of N3 inhibitor (10, docked) > Fimasartan (8) > Candesartan (2) > Olmesartan (7) > Azilsartan (9) > Eprosartan (5) > Valsartan (3) > Losartan (1) > Irbesartan (6) > Telmisartan (4). Moreover, Fimasartan (8), Candesartan (2), and Olmesartan (7) were additionally estimated through molecular dynamic simulations monitored via computing the binding free energy using MM-GBSA. The results are promising for rapidly repurposing such drugs (especially, Fimasartan (8) and Candesartan (2)) after further preclinical and clinical studies either alone or in combination with others for the treatment of COVID-19 virus especially known to cause vasodilatation (to prevent blood coagulation) and to reduce inflammation and fibrosis (to prevent pulmonary fibrosis), with well-known safety profiles. In vitro, the virtual findings were consistent with the experimental testing of four representative ARBs. Out of the tested compounds, Olmesartan (7) showed the most promising anti-SARS-CoV-2 activity (IC50 = 1.808 μM, and CC50 = 557.6 μM) with high selectivity index (308.4) against SARS-CoV-2 in Vero E6 cells. This work may clarify and approve not only the safety of ARBs used by a large group of patients worldwide but also their possible effectiveness against the COVID-19 virus either as a prophylactic or treatment option. It intended also to give a clear spot on the structure-activity relationship (SAR) required for the future design of new drugs targeting the newly emerged SARS-CoV-2 protease by medicinal chemists.

Sites of the Aesthetic Self: John Cassian and Christian Ethical Formation by Niki Kasumi Clements

Reviewed by: Sites of the Aesthetic Self: John Cassian and Christian Ethical Formation by Niki Kasumi Clements Jude P. Dougherty CLEMENTS, Niki Kasumi. Sites of the Aesthetic Self: John Cassian and Christian Ethical Formation. Notre Dame, Ind.: University of Notre Dame Press, 2020. xi + 280 pp. Cloth, $65.00 —The book opens with an account of a well-educated young man, John Cassian, and his companion, Germanus, who attempt to establish in Bethlehem a monastic community based on the asceticism of the Egyptian desert model. The middle decades of the fifth century have been described by Robert Markus as the watershed of the great debates in the Latin West about what it means to be and live as a Christian. There is ample evidence to support that judgment as we follow the writing and activity of John Cassian, Augustine, John Chrysostom, Benedict of Nursia, and Pope Innocent I. John Cassian, who lived from 360 to 436, was born in what is now Romania. A contemporary of St. Augustine (354–430), like Augustine he was led to address the issue of self-formation which in one formulation reads as follows: “In orienting oneself toward the proximate goal of purity of heart and the ultimate end of the Kingdom of God, how much is to be attributed to one’s own agency as distinct from the grace of God.” Augustine spoke to the problem in his On Grace and Free Will (426), where he stressed human fallenness and human inability. Cassian in Conferences 15, “On God’s Protection,” was thought to offer a direct response to Augustine despite its antecedent composition. Cassian’s position, which later became known as semi-pelagian, differed from Augustine’s insofar as Cassian feared that the doctrine of Augustine possessed an element of fatalism. “We must take care not to ascribe all merits of the saints to the Lord, so as to leave nothing but what is perverse to human activity. Cassian claimed that the initial step to salvation was within the power of the individual unaided by grace. God created humans with a good will, and when human effort fosters this will, God encourages its growth, and spurs it on to salvation, increasing what he himself had planted and saw arise from individual effort. According to Cassian, human progress in ascetic formation requires adaptation as well as human toil and effort. Cassian notes that divine protection goes “together not with the lazy or careless person, but with the one who labors and toils.” Cassian brought to his early works a knowledge of Egyptian asceticism and of the desert hermits. This is seen in his Institutes of Monastic Life (418) and Conferences of the Fathers (419). A third work, On the Incarnation of the Lord, was written against the heretic Nestorius at the request of Pope Leo I. That book, considered his master work, took him nearly a decade to write and appeared in 490. Without doubt his collected works were to influence the whole of Western monasticism. Benedict in [End Page 383] his Rule made Cassian’s Conferences and Institutes required reading. In the opinion of Niki Kasumi Clements, “Cassian is remarkable as a translator between Eastern and Western Christianities. He bridges geographies, languages, politics, customs and friends.” Notably, he was embraced not only in the West but by Eastern Christianity, as evidenced by the fact that his Latin texts were translated into Greek. Cassian writes about what an ascetic life looks like, materially and performatively, how it feels and is socially transmitted. He emphasizes its positive aspects—not renunciation. In writing about communal practices, he stresses adaptation and accommodation for different geographic sites and times. He recognizes how subjects are directed by desire but need to be confirmed in their ambition through practice. Commissioned by Pope Innocent I to work in southern Gaul, he established near Marseilles two monasteries, one for men and one for women. He founded and became the first abbot of the Abbey St. Victor, where he remained for the rest of his life. His foundation for women was known as the Abbey St. Salvador. Cassian was ordained a deacon by John Chrysostom, Archbishop of Constantinople, around 404 and ordained a priest...

La reconfiguración de la esfera pública en América Latina: un acercamiento analítico desde la ciudadanía subalterna

La democracia se ha constituido en uno de los temas de gran interés y debate para las ciencias sociales, en particular para el campo de la sociología política en América Latina. El trayecto histórico que ha tenido la esfera de lo público se ha convertido en un espacio epistémico encargado de reconfigurar las relaciones sociopolíticas que existen entre la ciudadanía y el Estado en el marco de los procesos endógenos/exógenos que constituyen la democracia en su concepción de lo público. Así pues, el propósito del presente artículo consiste en realizar un breve análisis sobre la discusión de la democracia en el marco del imaginario de los grupos subalternos que ejercen una mirada crítica sobre los procesos hegemónicos fomentados por los grupos dominantes, los cuales instituyen un modelo propio de la democracia moderna/liberal que está en función de un orden político en el plano vertical que genera actores marginados en la región.

Understanding Derrida’s “Structure, Sign, and Play”

Deconstruction, a philosophical post-structural theory derived mainly from the work of the French philosopher Jacques Derrida, has evoked a great controversial debate over the past few decades. Promoting a sophisticated philosophical view of literary criticism, deconstruction has always been a complicated topic to comprehend especially for students and novice researchers in the field of literary criticism. This article review paper attempts to present an explanation of the main notions of the theory by reviewing one of Derrida’s most influencing articles on critical theory: “Structure, Sign, and Play in the Discourse of the Human Sciences”. The article which marked the birth of post-structuralism theory, was first delivered in 1966 at John Hopkins International Colloquium on “The Language of Criticism and the Sciences of Man”. This seminal work of Derrida criticizes structuralism for the great importance given to centralism and binary oppositions for the sake of accessing meaning. It can be claimed that the article sums up his ideas on deconstruction which in fact attacks all notions of center, totality and origin. Deconstruction is perceived as a method of breaking down and analyzing text in an attempt to approach some new interpretations which might be totally different from any other previous ones.

The great population debate

Is the coronavirus pandemic just the latest indication that there are too many of us on the planet? Richard Webb investigates

The influence of classroom seating arrangement on children's cognitive processes in primary school: the role of individual variables.

To date, despite the great debate regarding the best seating arrangement for learning in classrooms, no empirical studies have examined the direct effects of different seating arrangements on children’s cognitive processes. This is particularly important nowadays that the COVID-19 measures include maintaining distance in the classroom. Aim of this study was experimentally investigating the effect of changing the seating arrangement (clusters vs. single desks), on logical reasoning, creativity and theory of mind, in children attending primary school. Furthermore, some individual characteristics (e.g., gender, loneliness, popularity) were analysed as potential moderators. Results on 77 participants showed that, when children were seated in single desks, their score in logical reasoning was globally higher. Furthermore, when seated in single desks, girls showed a better performance in the theory of mind, and lonelier children performed better in theory of mind and creativity. This on field experimental study suggests the importance of considering both the nature of the task and children’s individual characteristics when deciding on a seating arrangement in the classroom.

Sexo entre homens e vulnerabilidade moral: percepções de estudantes de medicina sobre as restrições à doação de sangue

Objetivo: Investigar o conhecimento e opiniões de estudantes de medicina sobre os atuais critérios de doação de sangue, incluindo aqueles relacionados aos homens que fazem sexo com outros homens (HSH), analisando as implicações éticas e morais a partir da luz da bioética. Métodos: Trata-se de um estudo exploratório, descritivo, observacional e com abordagem quantitativa, desenvolvido com a participação de 167 estudantes do curso de medicina de uma universidade pública localizada em Belém/Pará. O questionário foi aplicado através da Plataforma Google Forms, após aprovação em Comitê de Ética em Pesquisa. Resultados: Constatou-se que a maioria dos participantes tinham conhecimento dos critérios de doação de sangue e das restrições aplicadas a HSH. Entretanto, mais de 80% dos participantes concordava que tal restrição era um indicativo da vulnerabilidade moral desses indivíduos, sendo que a maioria não se opunha a receber sangue doado por HSH. Conclusão: Em se tratando da educação médica, os resultados demonstram a importância de um maior debate sobre o tema na formação de futuros profissionais, de modo a problematizar os argumentos usados na adoção de tais critérios.

Urbanização e preservação cultural: caso do Bairro das Chicalas em Luanda

O processo de urbanização em Luanda tem sido pontual, sendo priorizadas as áreas centrais da cidade e negligenciando-se os projetos habitacionais para a população mais pobre. Os planos de requalificação tendem a ser planos com propostas duvidosas, se analisados sob a ótica dos grandes debates urbanísticos que abordam a integração social e o direito à cidade. Prevalecem interesses financeiros e finalidades corporativistas, e não a melhoria da qualidade de vida dos moradores que, frente a realidade latente, não se reconhecem enquanto unidade populacional. O plano de requalificação da Baía de Luanda, na qual Chicala faz parte, envolve destruições de bairros informais em seu entorno. Discute-se aqui as implicações desta reforma urbanística e seus impactos no bairro da Chicala, à luz da segregação territorial, identidade cultural, políticas públicas habitacionais e o habitat. Frente aos impasses de uma gestão territorial conturbada e direcionada, e as ações que reforçam a desigualdade social, sugere-se, aqui, uma reflexão sobre a requalificação e a preservação cultural aplicados a este bairro. O pensamento global aliado às ações locais promovem diálogos com as experiências internacionais que podem contribuir para a gestão do território de modo coerente, tendo em vista a sua unidade cultural e os interesses de seus habitantes.

Novel platform for the multidimensional analysis of magnetic nanoparticles

The success of Magnetic Particle Imaging (MPI) as a clinical imaging modality is inextricably linked to the availability of purpose-build magnetic nanoparticles (MNP). Attempts to develop MNP with tailored properties and predictable MPI-performance are underway and still of great debate. However, it is well-known that the MPI performance is hampered by the size distribution present in MNP systems. The hyphenation of asymmetric flow field-flow fractionation (AF4) with on-line detectors has proven to provide reliable multidimensional information of MNP size distributions in a quasi-closed system without additional preparation steps. We recently introduced a novel combination of AF4 with a magnetic detector. This detector is based on the same physical principle as MPI, called Magnetic Particle Spectroscopy (MPS), which has already proven a straightforward technique for MNP specific quantification and characterization. In this study we demonstrate that the AF4 multidetector approach, including our MPS detector, is feasible to assist the targeted development of MNP with optimized imaging capabilities in MPI by directly measuring the MNP size as well as the indispensable magnetic functionality. Furthermore, the new platform provides important insights into the physics of MNP and can be used for quality control of MNP in biomedical applications.

The classic “Carrot-and-stick approach”: Addressing underutilization of ICD-10 increased data granularity

The classic “Carrot-and-stick approach”: Addressing underutilization of ICD-10 increased data granularity

Statistical properties of turbulent fluctuations associated with electron-only magnetic reconnection

Context. Recent satellite measurements in the turbulent magnetosheath of Earth have given evidence of an unusual reconnection mechanism that is driven exclusively by electrons. This newly observed process was called electron-only reconnection, and its interplay with plasma turbulence is a matter of great debate. Aims. By using 2D-3V hybrid Vlasov–Maxwell simulations of freely decaying plasma turbulence, we study the role of electron-only reconnection in the development of plasma turbulence. In particular, we search for possible differences with respect to the turbulence associated with standard ion-coupled reconnection. Methods. We analyzed the structure functions of the turbulent magnetic field and ion fluid velocity fluctuations to characterize the structure and the intermittency properties of the turbulent energy cascade. Results. We find that the statistical properties of turbulent fluctuations associated with electron-only reconnection are consistent with those of turbulent fluctuations associated with standard ion-coupled reconnection, and no peculiar signature related to electron-only reconnection is found in the turbulence statistics. This result suggests that the turbulent energy cascade in a collisionless magnetized plasma does not depend on the specific mechanism associated with magnetic reconnection. The properties of the dissipation range are discussed as well, and we claim that only electrons contribute to the dissipation of magnetic field energy at sub-ion scales.

Development and Analysis of Combinational Pico-Energy Generation Framework

Alternative energy is extracted via unlimited resources. Appropriate practice of energy assets is a great debate heading these times. It is extremely significant to determine of which resource needs to be employed and for what reason. Number of points just like cleanness, expense, steadiness, effectiveness and so geographical impacts needs to be considered. Because of India getting the world’s 4th leading emitter of Carbon Dioxide, it is vital to figure out what precisely the India's exhausts are presently as well as, just where these may be advancing. Considering India’s early on level of monetary evolution, poor per-capita exhausts and so its significant populace, certainly, there is distinctive probability to get its exhausts to boost. Hence, certainly, there is a requirement of option to lessen this carbon foot printing as per Kyoto protocol. Hence, this paper presents the methodology to lower the carbon foot printing by means of combinational Pico-energy generation.

The Great Debate

Born in New York City only fifteen months apart, the Harlem-raised James Baldwin and the privileged William F. Buckley, Jr. could not have been more different, but they both rose to the height of American intellectual life during the civil rights movement. By the time they met in February 1965 to debate race and the American Dream at the Cambridge Union, Buckley—a founding father of the American conservative movement—was determined to sound the alarm about a man he considered an “eloquent menace.” For his part, Baldwin viewed Buckley as a deluded reactionary whose popularity revealed the sickness of the American soul. The stage was set for an epic confrontation that pitted Baldwin’s call for a moral revolution in race relations against Buckley’s unabashed elitism and implicit commitment to white supremacy. In this article I introduce readers to the story at the heart of my new book about Baldwin and Buckley, The Fire Is Upon Us.

The Debate Over Egg Consumption and Incident Cardiovascular Disease.

There is a great debate regarding the association of cholesterol intake from egg consumption and the incidence of cardiovascular disease (CVD). Most studies show that moderate egg consumption is not associated with a significant increase in CVD, stroke, heart failure, and type 2 diabetes mellitus (T2DM), whereas others dispute this fact and state that there is an association with increased egg consumption, especially if they are consumed with saturated fats. In addition, the recent relaxation of cholesterol intake to greater than 300 mg/d by the American College of Cardiology/American Heart Association Nutritional Guidelines has fueled this debate. In order to get a current perspective on the significance of moderate egg consumption with the primary incidence of CVD, a focused Medline search of the English language literature was conducted between 2010 and March 2020 using the terms, cholesterol intake, egg consumption, coronary artery disease, CVD, and T2DM. Nineteen pertinent articles were retrieved, and these, together with collateral literature, will be discussed in this review article. The analysis of data from the articles retrieved indicated that several studies showed that moderate egg consumption (1 egg/d) is not associated with adverse cardiovascular effects in subjects free of CVD or T2DM, whereas other studies showed a positive association, especially in patients with preexisting CVD or T2DM. Therefore, at present, there is no unanimous agreement on this subject, and the controversy will continue until new confirmatory evidence becomes available.

Assessing the effectiveness of development co‐operation: Method matters

AbstractMotivationThe Great Aid Debate is at an impasse between those who believe aid works and those who do not. The impasse is in part because people are arguing about the answers to different questions and in part because the methods historically used are not fit for purpose. The methods have not helped advance our understanding about how and why aid works.Research questionsAre there better questions and ways of measuring effectiveness that are better suited to developing and testing theories of aid, at a level more useful for policy‐makers in promoting more effective development co‐operation?Approach and methodsThe article reviews the literature on aid effectiveness, development effectiveness and evaluation methods. It focuses on the questions these methods aimed to answer and the methods adopted. The literature broadly covers two questions at the macro level: “Does aid work?” and “How effectively is aid managed?” and a third question at the micro level: “How effective is each aid project?”FindingsA focus on the wrong questions and/or methods at the macro level has been at the expense of explicit aid theory as opposed to development theory. The micro level is too small to be useful in informing policy.A more useful question at a meso level is: “What types of development co‐operation work in which contexts and why?” A trend of systematic reviews which rely on randomized control trials (RCTs) falls into similar traps as historical measures. Theory‐based evaluation approaches are more explanatory as they investigate the mechanisms by which different types of development co‐operation work.Policy implicationsI propose that a meso level of analysis that sits above the level of individual initiatives and draws on the explanatory powers of theory‐based evaluation and mechanisms will yield more useful theories about how different types of development co‐operation work. It will also provide development co‐operation policy‐makers insights into what types of development co‐operation are more likely to work effectively in different contexts, potentially allowing them to make better decisions.

Index to Titles and Authors/Editors of Books Reviewed

Index to Titles and Authors/Editors of Books Reviewed

The immutability of valence and arousal in the foundation of emotion.

Over the past century, great debate has ensued regarding the fundamental properties of emotions. The idea that 2 properties-valence and arousal-are critical for emotion and psychologically irreducible has had substantial staying power in the literature. In the present report, we examine whether a third dimension-reflecting the social properties of emotion-might arise if stimuli high in that dimension (i.e., "theoretically social emotions") were included in the task and, or, if social information was primed. We used a similarity-rating task to evaluate whether a dimension representing the "socialness" of emotion-the extent to which emotions are associated with social contexts-might arise as the result of inclusion of emotion words that are theorized to represent "social emotions." In Study 1, we assessed the dimensional structure of 41 different emotion terms (of which 41% were "social emotions") based on pairwise similarity ratings of a subset of the emotion terms. In Study 2, we tested whether priming social information before and during the similarity rating task would shift the emergent dimensional structure of emotion words. Results of multidimensional scaling across both studies indicated that the structure of emotion is best described by 2 dimensions-valence and arousal-and was not influenced by the priming of social information. Contrary to predictions, evidence did not emerge for a third dimension corresponding to socialness, nor any other property. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Is COVID-19 the end of US hegemony? Public bads, leadership failures and monetary hegemony.

COVID-19 is the most invasive global crisis in the postwar era, jeopardizing all dimensions of human activity. By theorizing COVID-19 as a public bad, I shed light on one of the great debates of the twentieth and twenty-first centuries regarding the relationship between the United States and liberal international order (LIO). Conceptualizing the pandemic as a public bad, I analyze its consequences for US hegemony. Unlike other international public bads and many of the most important public goods that make up the LIO, the COVID-19 public bad not only has some degree of rivalry but can be made partially excludable, transforming it into more of a club good. Domestically, I demonstrate how the failure to effectively manage the COVID-19 public bad has compromised America's ability to secure the health of its citizens and the domestic economy, the very foundations for its international leadership. These failures jeopardize US provision of other global public goods. Internationally, I show how the US has already used the crisis strategically to reinforce its opposition to free international movement while abandoning the primary international institution tasked with fighting the public bad, the World Health Organization (WHO). While the only area where the United States has exercised leadership is in the monetary sphere, I argue this feat is more consequential for maintaining hegemony. However, even monetary hegemony could be at risk if the pandemic continues to be mismanaged.

DO WE STILL NEED TO DEPRIORITIZE THE TRANSFER OF ‘LOW GRADE MOSAIC EMBRYOS’?

The efficiency of PGT-A is currently the subject of great debate for possible embryo wastage associated with the technique. Thus, the establishment of evidence-based guidelines for transferring mosaic embryos has become a priority. In this study, we compared the clinical outcomes of over a hundred embryos diagnosed as low grade (<50%) mosaic with embryos diagnosed as euploid by Next Generation Sequencing (NGS). At the time of transfer, no prioritization of euploid embryos versus low grade mosaic embryos were applied.

The appraisal of body content (ABC) trial: obesity does not significantly impact gamete production in infertile men and women.

As obesity becomes increasingly prevalent, its impact on fertility has been a subject of great debate. Nearly all prior research is retrospective and evaluates obesity utilizing body mass index (BMI), which may overestimate adiposity in individuals with a greater amount of lean muscle and underestimate adiposity in those with less muscle mass. We prospectively evaluated 2013 couples undergoing infertility treatment with in vitro fertilization (IVF). Percent body fat (%BF) was measured by use of a bioelectric impedance analysis (BIA) scale at baseline. BMI was also determined. Ovarian reserve parameters, ovarian response to controlled ovarian hyperstimulation, and semen analyses were measured in correlation with their %BF and BMI. Females classified as obese based on %BF or BMI had lower serum FSH. However, when the analysis was limited to women without PCOS (n = 1706), obesity based on %BF or BMI was associated with lower serum AMH. Female obesity-regardless of a PCOS diagnosis-did not affect number of mature oocytes retrieved. Males who were in obese %BF category were found to have lower TMSC compared with normal weight counterparts (p < 0.05); however, the observed decrease was not significant enough to limit the success of assisted reproductive technologies. These findings suggest that while obesity may affect ovarian reserve in women variably depending on presence of PCOS, it does not affect number of mature oocytes available after COH. Similarly, while a high %BF in males is associated with lower TMSC, the observed difference is unlikely to affect IVF outcomes.