scholarly journals The Up state of the SARS-COV-2 Spike homotrimer favors an increased virulence for new variants

2021 ◽  
Author(s):  
Carolina Corrêa Giron ◽  
Aatto Laaksonen ◽  
Fernando Luís Barroso da Silva
Keyword(s):  
Free Energy ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Angiotensin Converting Enzyme 2 ◽  
Constant Ph ◽  
Therapeutic Molecules ◽  
Improved Stability ◽  
History Of ◽  
The Stability ◽  
The One

AbstractThe COVID-19 pandemic has spread widely worldwide. However, as soon as the vaccines were released – the only scientifically verified and efficient therapeutic option thus far – a few mutations combined into variants of SARS-CoV-2 that are more transmissible and virulent emerged raising doubts about their efficiency. Therefore, this work aims to explain possible molecular mechanisms responsible for the increased transmissibility and the increased rate of hospitalizations related to the new variants. A combination of theoretical methods was employed. Constant-pH Monte Carlo simulations were carried out to quantify the stability of several spike trimeric structures at different conformational states and the free energy of interactions between the receptor binding domain (RBD) and Angiotensin Converting Enzyme 2 (ACE2) for the most worrying variants. Electrostatic epitopes were mapped using the PROCEEDpKa method. These analyses showed that the increased virulence is more likely to be due to the improved stability to the S trimer in the opened state (the one in which the virus can interact with the cellular receptor ACE2) than due to alterations in the complexation RBD-ACE2, once the increased observed in the free energy values is small. Conversely, the South African variant (B.1.351), when compared with the wild type SARS-CoV-2, is much more stable in the opened state (either with one or two RBDs in the up position) than in the closed state (with the three RBDs in the down position). Such results contribute to the understanding of the natural history of disease and also to indicate possible strategies to both develop new therapeutic molecules and to adjust the vaccine doses for a higher production of B cells antibodies.Graphical Abstract

scholarly journals Up State of the SARS-COV-2 Spike Homotrimer Favors an Increased Virulence for New Variants

2021 ◽  
Vol 3 ◽  
Author(s):  
Carolina Corrêa Giron ◽  
Aatto Laaksonen ◽  
Fernando Luís Barroso da Silva
Keyword(s):  
Free Energy ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Constant Ph ◽  
Cell Antibody ◽  
Therapeutic Molecules ◽  
Improved Stability ◽  
History Of ◽  
The Difference ◽  
The Stability

The COVID-19 pandemic has spread worldwide. However, as soon as the first vaccines—the only scientifically verified and efficient therapeutic option thus far—were released, mutations combined into variants of SARS-CoV-2 that are more transmissible and virulent emerged, raising doubts about their efficiency. This study aims to explain possible molecular mechanisms responsible for the increased transmissibility and the increased rate of hospitalizations related to the new variants. A combination of theoretical methods was employed. Constant-pH Monte Carlo simulations were carried out to quantify the stability of several spike trimeric structures at different conformational states and the free energy of interactions between the receptor-binding domain (RBD) and angiotensin-converting enzyme II (ACE2) for the most worrying variants. Electrostatic epitopes were mapped using the PROCEEDpKa method. These analyses showed that the increased virulence is more likely to be due to the improved stability to the S trimer in the opened state, in which the virus can interact with the cellular receptor, ACE2, rather than due to alterations in the complexation RBD-ACE2, since the difference observed in the free energy values was small (although more attractive in general). Conversely, the South African/Beta variant (B.1.351), compared with the SARS-CoV-2 wild type (wt), is much more stable in the opened state with one or two RBDs in the up position than in the closed state with three RBDs in the down position favoring the infection. Such results contribute to understanding the natural history of disease and indicate possible strategies for developing new therapeutic molecules and adjusting the vaccine doses for higher B-cell antibody production.

scholarly journals Plant-Distribution from the Standpoint of an Idealist

1919 ◽  
Vol 44 (299) ◽  
pp. 439-472 ◽  
Author(s):  
H. B. Guppy
Keyword(s):  
Statistical Treatment ◽  
Plant Distribution ◽  
The North ◽  
The Family ◽  
Family Types ◽  
History Of ◽  
The Subject ◽  
The Stability ◽  
The One ◽  
The Tropics

SUMMARY From a consideration of the problems of plant-distribution, the writer is led to regard the history of the Angiosperms as resolving itself into two principal eras:— The era that witnessed the rise of the great families, a period of relatively uniform conditions.The era that witnessed the differentiation of these family types in response to the differentiation of the climatic and other conditions. It is argued that conclusions drawn from the prevailing influences now in operation could only be applied to the differentiation of the ancient family types–that is to say, to the second era in plant-history. It is not possible, so it is held, to apply a theory based on the present to an age of other things, other ways, and other conditions. Only the hypothesis that finds its guide to the past in the abnormalities of the present can be of service to us in the interpretation of times so different. The subject is introduced by a reference to two papers, contributed to the ‘Journal of the Linnean Society,’ which have an important bearing on the subject, the one by Bentham on the Compositæ, the other by Huxley on the Gentians. Then follows a statement of the differentiation hypothesis which involves the differentiation of primitive world-ranging types in response to the progressive differentiation of their originally uniform conditions. Allusion is then made to the dilemma into which all theorists fall when they come to handle the larger groups, the very persistence of which in our own age depends on the stability of their essential characters. If stable now, why so unstable then? We are thus forced to the conclusion that in the distant era that witnessed the deployment of the Angiosperms instability prevailed. It was an age of mutations, free and unchecked, and an age of uniformity of conditions, the mutability decreasing and the modifications becoming more and more fixed with progressive differentiation of conditions, an explanation suggested by a perusal of the accounts by Dr. Willis of his prolonged investigation on the Podostemaceæ. The distribution of families is then treated statistically; and it is shown that whilst they largely ignore the cleavage of the land into two great masses diverging from the north, they respond in a marked degree to the differentiation of the climatic zones. Behind their disregard for the present arrangement of continents and oceans lies the story of the first era, and behind their ready response to climatic differentiation lies the story of the second era. In the circumstance that the response made to the bi-cleavage of the land-mass is absent or small with the larger groups and becomes greater and greater as we go down the differentiating scale until it attains its maximum in the species, is recognised the contrast of conditions between the pre-differentiation era and the era when differentiation reigned supreme. It is held that there is a method here disclosed that could only arise by the family differentiating into the tribes, the tribe into the genera, and the genus into the species, since the opposite method of commencing with the species would produce chaos. The paper ends with the application of the statistical treatment to the larger groups behind the families, and it is shown that whilst the Dicotyledons display a much greater tendency to detachment from the tropics than the Monocotyledons, the Sympetalæ stand foremost in this respect amongst all the groups of the Dicotyledons. It may be added that there is a large amount of material in the ten tables which from considerations of space could not be discussed. These data have therefore to tell their own story

scholarly journals Optimizing the landslide-prone slope stabilization

Vestnik MGSU ◽  
2019 ◽  
pp. 1258-1271
Author(s):  
Stanislav V. Solsky ◽  
Sofya A. Bykovskaya
Keyword(s):  
Practical Experience ◽  
Optimal Choice ◽  
Value Engineering ◽  
Industrial Complex ◽  
Slope Stabilization ◽  
Normative Documents ◽  
History Of ◽  
Numerical Simulation Methods ◽  
The Stability ◽  
The One

Introduction. Nowadays, the study of landslide processes is one of the most intensive aspects of construction and maintenance of industrial and civil buildings and installations. The landslides violate the stability of foundations and entire complexes of installations, so the assessment of the stability of the slopes is the most important task before starting the construction. Currently, there is a large number of landslide classifications, which characterize the conditions of their formation, the history of geological development, their age, and structure. Normative documentation gives three ways of slope slump control: preventive, restricting, and liquidation ones. However, this source does not give systematic validity of the engineering solutions. The study sets the following tasks: to develop an algorithm for the optimal choice of rational slope strengthening in landslide construction conditions and to test it with a specific example. Materials and methods. The study analyzed the publications on theoretical and practical experience in dealing with landslides as well as normative documents. Numerical simulation methods were used to calculate the slope stability when testing the algorithm. Results. Using the introduced classification, the study presented an algorithm that makes it possible to choose a rational way of slope strengthening under landslide construction conditions. The concept of the algorithm allows step-by-step approximating parameters of a landslide-prone slope model to the real conditions, on the one hand, and selecting the most reasonable anti-landslide measures, on the other hand. The developed algorithm was tested on the territory of a large industrial complex situated on river overflood plain fringes. By applying the value engineering comparison of several slope stabilization variants, the research has taken the most optimal one of them for realization. Conclusions. The study developed the author’s classification and algorithm for the selection of optimal design solutions to stabilize landslide-prone slopes or slants. Successful approbation of the algorithm confirmed its practical applicability. The algorithm allows choosing the most effective complex for protection against landslides.

Lexical Parallels in Smolensk and Vitebsk Dialects (Non-Derived Vocabulary)

2020 ◽  
pp. 42-56
Author(s):  
Ekaterina Lunkova
Keyword(s):  
Cultural Heritage ◽  
The Other ◽  
Lexical Meaning ◽  
Specific Subject ◽  
Close Interaction ◽  
Historical Processes ◽  
History Of ◽  
The Common ◽  
The Stability ◽  
The One

Close interaction of Smolensk dialects with borderline Vitebsk and Mogilev ones is caused, on the one hand, by the common historical processes of the region, on the other hand, it is determined by the similarity of the cultural heritage of the Russian-Belarusian borderland. Throughout the Russian-Belarusian border, which runs through the territory of Smolensk region, there are a number of lexical formations that are a part of the existing language continuum that is of great interest to researchers from the standpoint of studying the existing dialect systems in synchrony and diachrony. It is expedient to oppose the existing dialect systems to the Russian and Belarusian standard languages in order to exclude possible facts of coincidence with a codified form from the description of the dialect language material. The found nouns with specific subject semantics are considered as lexical correspondences, i.e. regardless of the history of distribution or these units borrowing, from the standpoint of their synchronous existence in particular dialect systems. All dialect lexical correspondences can be divided into three groups, taking into account the similarity or degree of lexical meaning divergence. These groups are equivalent in different accounts and they correlate to each other on this criterion. This fact lets the study speaks in favor of the stability of the lexical meaning of non-derived nouns with specific subject semantics so that these nouns exist as lexical parallels in Smolensk and Vitebsk dialects.

Use of a Lyophilized Reference Plasma to Compare Coagulation Test Procedures

1975 ◽  
Vol 34 (02) ◽  
pp. 426-444 ◽  
Author(s):  
J Kahan ◽  
I Nohén
Keyword(s):  
Oral Anticoagulant Therapy ◽  
Repeated Measurements ◽  
Test Procedures ◽  
Coagulation Activity ◽  
Close Relationship ◽  
Measured Activity ◽  
Test Materials ◽  
The Difference ◽  
The Stability ◽  
The One

SummaryIn 4 collaborative trials, involving a varying number of hospital laboratories in the Stockholm area, the coagulation activity of different test materials was estimated with the one-stage prothrombin tests routinely used in the laboratories, viz. Normotest, Simplastin-A and Thrombotest. The test materials included different batches of a lyophilized reference plasma, deep-frozen specimens of diluted and undiluted normal plasmas, and fresh and deep-frozen specimens from patients on long-term oral anticoagulant therapy.Although a close relationship was found between different methods, Simplastin-A gave consistently lower values than Normotest, the difference being proportional to the estimated activity. The discrepancy was of about the same magnitude on all the test materials, and was probably due to a divergence between the manufacturers’ procedures used to set “normal percentage activity”, as well as to a varying ratio of measured activity to plasma concentration. The extent of discrepancy may vary with the batch-to-batch variation of thromboplastin reagents.The close agreement between results obtained on different test materials suggests that the investigated reference plasma could be used to calibrate the examined thromboplastin reagents, and to compare the degree of hypocoagulability estimated by the examined PIVKA-insensitive thromboplastin reagents.The assigned coagulation activity of different batches of the reference plasma agreed closely with experimentally obtained values. The stability of supplied batches was satisfactory as judged from the reproducibility of repeated measurements. The variability of test procedures was approximately the same on different test materials.

Misreading Egypt

2018 ◽  
Author(s):  
Jesse Schotter
Keyword(s):  
New Media ◽  
Narrative Form ◽  
Experimental Film ◽  
Tower Of Babel ◽  
Avant Garde ◽  
Sergei Eisenstein ◽  
History Of ◽  
The One ◽  
The Relationship ◽  
Modern Technologies

The first chapter of Hieroglyphic Modernisms exposes the complex history of Western misconceptions of Egyptian writing from antiquity to the present. Hieroglyphs bridge the gap between modern technologies and the ancient past, looking forward to the rise of new media and backward to the dispersal of languages in the mythical moment of the Tower of Babel. The contradictory ways in which hieroglyphs were interpreted in the West come to shape the differing ways that modernist writers and filmmakers understood the relationship between writing, film, and other new media. On the one hand, poets like Ezra Pound and film theorists like Vachel Lindsay and Sergei Eisenstein use the visual languages of China and of Egypt as a more primal or direct alternative to written words. But Freud, Proust, and the later Eisenstein conversely emphasize the phonetic qualities of Egyptian writing, its similarity to alphabetical scripts. The chapter concludes by arguing that even avant-garde invocations of hieroglyphics depend on narrative form through an examination of Hollis Frampton’s experimental film Zorns Lemma.

Theodor W. Adorno

2018 ◽  
Author(s):  
Colby Dickinson
Keyword(s):  
The Other ◽  
History Of Thought ◽  
History Of ◽  
The One

In his somewhat controversial book Remnants of Auschwitz, Agamben makes brief reference to Theodor Adorno’s apparently contradictory remarks on perceptions of death post-Auschwitz, positions that Adorno had taken concerning Nazi genocidal actions that had seemed also to reflect something horribly errant in the history of thought itself. There was within such murderous acts, he had claimed, a particular degradation of death itself, a perpetration of our humanity bound in some way to affect our perception of reason itself. The contradictions regarding Auschwitz that Agamben senses to be latent within Adorno’s remarks involve the intuition ‘on the one hand, of having realized the unconditional triumph of death against life; on the other, of having degraded and debased death. Neither of these charges – perhaps like every charge, which is always a genuinely legal gesture – succeed in exhausting Auschwitz’s offense, in defining its case in point’ (RA 81). And this is the stance that Agamben wishes to hammer home quite emphatically vis-à-vis Adorno’s limitations, ones that, I would only add, seem to linger within Agamben’s own formulations in ways that he has still not come to reckon with entirely: ‘This oscillation’, he affirms, ‘betrays reason’s incapacity to identify the specific crime of Auschwitz with certainty’ (RA 81).

Sea Urchins and Circuses: The Modernist Natural Histories of Jean Painlevé and Alexander Calder

2018 ◽  
Vol 13 (2) ◽  
pp. 187-211
Author(s):  
Patricia E. Chu
Keyword(s):  
New Media ◽  
Sea Urchins ◽  
Life Sciences ◽  
Three Dimensional ◽  
Machine Age ◽  
Avant Garde ◽  
History Of ◽  
And Performance ◽  
The One ◽  
Natural Historian

The Paris avant-garde milieu from which both Cirque Calder/Calder's Circus and Painlevé’s early films emerged was a cultural intersection of art and the twentieth-century life sciences. In turning to the style of current scientific journals, the Paris surrealists can be understood as engaging the (life) sciences not simply as a provider of normative categories of materiality to be dismissed, but as a companion in apprehending the “reality” of a world beneath the surface just as real as the one visible to the naked eye. I will focus in this essay on two modernist practices in new media in the context of the history of the life sciences: Jean Painlevé’s (1902–1989) science films and Alexander Calder's (1898–1976) work in three-dimensional moving art and performance—the Circus. In analyzing Painlevé’s work, I discuss it as exemplary of a moment when life sciences and avant-garde technical methods and philosophies created each other rather than being classified as separate categories of epistemological work. In moving from Painlevé’s films to Alexander Calder's Circus, Painlevé’s cinematography remains at the forefront; I use his film of one of Calder's performances of the Circus, a collaboration the men had taken two decades to complete. Painlevé’s depiction allows us to see the elements of Calder's work that mark it as akin to Painlevé’s own interest in a modern experimental organicism as central to the so-called machine-age. Calder's work can be understood as similarly developing an avant-garde practice along the line between the bestiary of the natural historian and the bestiary of the modern life scientist.

NURTURING OF CHILDREN THROUGH DRAMA AND THEATRE: THE CASE OF INTWASA KOBULAWAYO PERFORMANCES

2016 ◽  
Vol 13 (2) ◽  
pp. 86-99
Author(s):  
Vimbai Moreblessing Matiza
Keyword(s):  
Political Development ◽  
Children And Youth ◽  
Main Task ◽  
Growing Up ◽  
Theatrical Performances ◽  
History Of ◽  
The One

Dramatic and theatrical performances have a long history of being used as tools to enhance development in children and youth. In pre-colonial times there were some forms of drama and theatre used by different communities in the socialisation of children. It is in the same vein that this article, through the Intwasa koBulawayo performances, seeks to evaluate how drama and theatre are used to nurture children and youth into different developmental facets of their lives. The only difference which this article will take into cognisance is that the performances are done in a different environment, which is not the one used in the pre-colonial times. Although these performances were like this, the most important factor is the idea that children and youth are socialised through these performances. It is also against this backdrop that children and youth are growing up in a globalised environment, hence the performances should accommodate people from all walks of life and teach them relevant issues pertaining to life as they live it now. Thus the main task of the article is to spell out the role of drama and theatre in the nurturing of children and youth through socio economic and political development in Intwasa koBulawayo festivals.

Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Molecular Design ◽  
Binding Free Energy ◽  
Transmembrane Protein ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Rational Molecular Design ◽  
Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

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