scholarly journals Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS CoV-2

2021 ◽  
Author(s):  
Robert Penner
Keyword(s):  
Free Energy ◽  
Vaccine Development ◽  
Structural Data ◽  
Antiviral Resistance ◽  
Medical Sciences ◽  
Viral Mutation ◽  
Novel Method ◽  
Antiviral Targets ◽  
Universal Solutions ◽  
Regulatory Challenges

AbstractNew tools developed by Moderna, BioNTech/Pfizer and Oxford/Astrazeneca provide universal solutions to previously problematic aspects of drug or vaccine delivery, uptake and toxicity, portending new tools across the medical sciences. A novel method is presented based on estimating protein backbone free energy via geometry to predict effective antiviral targets, antigens and vaccine cargoes that are resistant to viral mutation. This method, partly described in earlier work of the author, is reviewed and reformulated here in light of the profusion of recent structural data on the SARS CoV-2 spike glycoprotein and its latest mutations. Scientific and regulatory challenges to nucleic acid therapeutic and vaccine development and deployment are also discussed.

scholarly journals Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2

2021 ◽  
Vol 9 (1) ◽  
pp. 81-89
Author(s):  
Robert Penner
Keyword(s):  
Free Energy ◽  
Vaccine Development ◽  
A Priori ◽  
Structural Data ◽  
Medical Sciences ◽  
Spike Glycoprotein ◽  
Mutagenic Potential ◽  
Viral Mutation ◽  
Novel Method ◽  
Antiviral Targets

Abstract Tools developed by Moderna, BioNTech/Pfizer, and Oxford/Astrazeneca, among others, provide universal solutions to previously problematic aspects of drug or vaccine delivery, uptake and toxicity, portending new tools across the medical sciences. A novel method is presented based on estimating protein backbone free energy via geometry to predict effective antiviral targets, antigens and vaccine cargos that are resistant to viral mutation. This method is reviewed and reformulated in light of the recent proliferation of structural data on the SARS-CoV-2 spike glycoprotein and its mutations in multiple lineages. Key findings include: collections of mutagenic residues reoccur across strains, suggesting cooperative convergent evolution; most mutagenic residues do not participate in backbone hydrogen bonds; metastability of the glyco-protein limits the change of free energy through mutation thereby constraining selective pressure; and there are mRNA or virus-vector cargos targeting low free energy peptides proximal to conserved high free energy peptides providing specific recipes for vaccines with greater specificity than the full-spike approach. These results serve to limit peptides in the spike glycoprotein with high mutagenic potential and thereby provide a priori constraints on viral and attendant vaccine evolution. Scientific and regulatory challenges to nucleic acid therapeutic and vaccine development and deployment are finally discussed.

scholarly journals Use of scaled-particle theory in the assessment of the Ph4As+/Ph4B− assumption for single ions

1979 ◽  
Vol 57 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Michael H. Abraham ◽  
Asadollah Nasehzadeh
Keyword(s):  
Free Energy ◽  
Recent Work ◽  
Scaled Particle Theory ◽  
Cavity Formation ◽  
Energy Term ◽  
Free Energies ◽  
Particle Theory ◽  
Novel Method ◽  
Energy Of Interaction ◽  
Solvent Molecules

A novel method for the assessment of the Ph4As+/Ph4B− assumption for free energies of transfer of single ions has recently been suggested by Treiner, and used by him to deduce that the assumption is not valid for transfers between water, propylene carbonate, sulpholane, dimethylsulphoxide, N-methyl-2-pyrrolidone, and perhaps also dimethylformamide. The basis of the method is the estimation of the free energy of cavity formation by scaled-particle theory, together with the hypothesis that the free energy of interaction of Ph4As+ (or Ph4B−) with solvent molecules is the same in all solvents, ΔGt0(int) = 0. It is shown in the present paper that (a) whether or not the Ph4As+/Ph4B− assumption applies to transfer to a given solvent depends on which other solvent is taken as the reference solvent in Treiner's method, (b) the calculation of the cavity free energy term by scaled-particle theory and by the theory of Sinanoglu – Reisse – Moura Ramos (SRMR) yields values so different that the method cannot be considered reliable, (c) the calculation of cavity enthalpies and entropies for Ph4As+ or Ph4B− by scaled-particle theory yields results that are chemically not reasonable, (d) the hypothesis that ΔGt0(int) = 0 conflicts with SRMR theory, and (e) the conclusions reached by Treiner are not in accord with recent work that in general supports the Ph4As+/Ph4B− assumption for solvents that are rejected by Treiner.

scholarly journals Exploiting NoSQL Graph Databases and in Memory Architectures for Extracting Graph Structural Data Summaries

2017 ◽  
Vol 25 (01) ◽  
pp. 81-109 ◽  
Author(s):  
Arnaud Castelltort ◽  
Anne Laurent
Keyword(s):  
Relational Databases ◽  
Structural Data ◽  
Scientific Data ◽  
Graph Database ◽  
Graph Databases ◽  
Fuzzy Operators ◽  
Data Volume ◽  
Novel Method ◽  
Memory Architectures ◽  
Data Summaries

NoSQL graph databases have been introduced in recent years for dealing with large collections of graph-based data. Scientific data and social networks are among the best examples of the dramatic increase of the use of such structures. NoSQL repositories allow the management of large amounts of data in order to store and query them. Such data are not structured with a predefined schema as relational databases could be. They are rather composed by nodes and relationships of a certain type. For instance, a node can represent a Person and a relationship Friendship. Retrieving the structure of the graph database is thus of great help to users, for example when they must know how to query the data or to identify relevant data sources for recommender systems. For this reason, this paper introduces methods to retrieve structural summaries. Such structural summaries are extracted at different levels of information from the NoSQL graph database. The expression of the mining queries is facilitated by the use of two frame-works: Fuzzy4S allowing to define fuzzy operators and operations with Scala; Cypherf allowing the use of fuzzy operators and operations in the declarative queries over NoSQL graph databases. We show that extracting such summaries can be impossible with the NoSQL query engines because of the data volume and the complexity of the task of automatic knowledge extraction. A novel method based on in memory architectures is thus introduced. This paper provides the definitions of the summaries with the methods to automatically extract them from NoSQL graph databases only and with the help of in-memory architectures. The benefit of our proposition is demonstrated by experimental results.

scholarly journals Термодинамическая модель зародышеобразования кристаллов n-терфенила с анизотропией поверхностной энергии на межфазной границе жидкость-воздух

2019 ◽  
Vol 61 (12) ◽  
pp. 2432
Author(s):  
В.А. Постников ◽  
А.А. Кулишов ◽  
А.А. Островская ◽  
А.С. Степко ◽  
П.В. Лебедев-Степанов
Keyword(s):  
Free Energy ◽  
Crystal Growth ◽  
Surface Energy ◽  
Force Field ◽  
Structural Data ◽  
Field Method ◽  
Experimental Information ◽  
Growth From Solutions ◽  
Atomic Force ◽  
Air Interface

An analysis of the change in the Gibbs free energy ∆G upon the formation of a flat nucleus of a p-terphenyl crystal at the liquid – air interface is presented, taking into account the anisotropy of the surface energy of the faces. The surface energy values of the p-terphenyl crystal faces were calculated by the atomic force field method OPLS, based on structural data. Experimental information on crystal growth from solutions and their surface properties was used to analyze the model.

scholarly journals TULIP: A Five-Star Table and List - From Machine-Readable to Machine-Understandable Systems

2020 ◽  
Author(s):  
Julthep Nandakwang ◽  
Prabhas Chongstitvatana
Keyword(s):  
Semantic Web ◽  
Open Data ◽  
Structural Data ◽  
Complete Information ◽  
Research Area ◽  
Original Form ◽  
New Information ◽  
Tremendous Amount ◽  
Novel Method ◽  
Machine Readable

Currently, Linked Data is increasing at a rapid rate as the growth of the Web. Aside from new information that has been created exclusively as Semantic Web-ready, part of them comes from the transformation of existing structural data to be in the form of five-star open data. However, there are still many legacy data in structured and semi-structured form, for example, tables and lists, which are the principal format for human-readable, waiting for transformation. In this chapter, we discuss attempts in the research area to transform table and list data to make them machine-readable in various formats. Furthermore, our research proposes a novel method for transforming tables and lists into RDF format while maintaining their essential configurations thoroughly. And, it is possible to recreate their original form back informatively. We introduce a system named TULIP which embodied this conversion method as a tool for the future development of the Semantic Web. Our method is more flexible compared to other works. The TULIP data model contains complete information of the source; hence it can be projected into different views. This tool can be used to create a tremendous amount of data for the machine to be used at a broader scale.

Statistical Thermodynamics Enthalpy, Free Energy, Entropy, and Heat Capacity of Some Hexafluorides of Octahedral Symmetry

1971 ◽  
Vol 26 (10) ◽  
pp. 1658-1666 ◽  
Author(s):  
G. Nagarajan ◽  
Donald C. Brinkley
Keyword(s):  
Heat Capacity ◽  
Free Energy ◽  
Infrared Absorption ◽  
Infrared Absorption Spectrum ◽  
Point Group ◽  
Structural Data ◽  
Octahedral Symmetry ◽  
Symmetry Point Group ◽  
Rigid Rotator ◽  
Energy Entropy

Abstract A detailed analysis of the molecular structural data and infrared absorption and Raman spectra of the hexafluoride of sulfur, selenium, tellurium, molybdenum, technetium, ruthium, rhodium, tungsten, thenium, osmium, iridium, platinum, uranium, neptunium, and plutonium has been made. These molecules, having the greatest number of symmetry elements of all existing molecules, possess an octahedral symmetry with the symmetry point group Oh. They give rise to six fundamental frequencies of which three are allowed in the Raman spectrum, two are allowed in the infrared absorption spectrum, and one is inactive. The inactive mode in normally determined from the overtones and combinations. On the basis of a rigid rotator and harmonic oscillator model, enthalpy, free energy, entropy, and heat capacity for temperatures from 200 °K to 2000 °K have been computed for these molecules. The results are briefly discussed and compared with available experimental data.

scholarly journals Breadth of Human Immunodeficiency Virus-Specific Neutralizing Activity in Sera: Clustering Analysis and Association with Clinical Variables

2009 ◽  
Vol 84 (3) ◽  
pp. 1631-1636 ◽  
Author(s):  
Nicole A. Doria-Rose ◽  
Rachel M. Klein ◽  
Marcus G. Daniels ◽  
Sijy O'Dell ◽  
Martha Nason ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Clustering Analysis ◽  
Vaccine Development ◽  
Elite Controllers ◽  
Immunodeficiency Virus ◽  
History Of ◽  
Novel Method ◽  
Route Of Exposure ◽  
Hiv 1

ABSTRACT Induction of antibodies that neutralize a broad range of human immunodeficiency virus type 1 (HIV-1) isolates is a major goal of vaccine development. To study natural examples of broad neutralization, we analyzed sera from 103 HIV-1-infected subjects. Among progressor patients, 20% of sera neutralized more than 75% of a panel of 20 diverse viral isolates. Little activity was observed in sera from long-term nonprogressors (elite controllers). Breadth of neutralization was correlated with viral load, but not with CD4 count, history of past antiretroviral use, age, gender, race/ethnicity, or route of exposure. Clustering analysis of sera by a novel method identified a statistically robust subgrouping of sera that demonstrated broad and potent neutralization activity.

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