HIV Protease and Integrase Empirical Substitution Models of Evolution: Protein-Specific Models Outperform Generalist Models

Diverse phylogenetic methods require a substitution model of evolution that should mimic, as accurately as possible, the real substitution process. At the protein level, empirical substitution models have traditionally been based on a large number of different proteins from particular taxonomic levels. However, these models assume that all of the proteins of a taxonomic level evolve under the same substitution patterns. We believe that this assumption is highly unrealistic and should be relaxed by considering protein-specific substitution models that account for protein-specific selection processes. In order to test this hypothesis, we inferred and evaluated four new empirical substitution models for the protease and integrase of HIV and other viruses. We found that these models more accurately fit, compared with any of the currently available empirical substitution models, the evolutionary process of these proteins. We conclude that evolutionary inferences from protein sequences are more accurate if they are based on protein-specific substitution models rather than taxonomic-specific (generalist) substitution models. We also present four new empirical substitution models of protein evolution that could be useful for phylogenetic inferences of viral protease and integrase.

The normal, the natural, and the harmonic

Use is made of rigorous definitions for the terms normal, natural, and harmonic to reveal a number of unfamiliaraspects about them. The Gaussian distribution is not sufficient to determine who is normal, and fluctuations above or below a natural-growth curve may or may not be natural. A recipe for harmonically sustained natural growthrequires that the overlap during the substitution process must be limited. As a consequence the overall growthprocess must experience good as well as bad "seasons".© 2006 Elsevier Inc. All rights reserved.

The humanitarian alibi: an overview and a redefinition

This paper explores and illustrates the diverse manifestations of the phenomenon of the ‘humanitarian alibi’, drawing upon historical and contemporary cases of violent conflict in order to identify substitutionary phenomena by governments and international actors. It affirms the existence of substitution process where humanitarian aid intervention substitutes for the prevention and resolution of violent conflict and the protection of civilian populations. The paper argues for expanding the humanitarian alibi, however, to take into account how international aid intervention compensates for both the systemic neglect of conflict related crises and for the systemic harm that exacerbates and perpetuates these crises. It also challenges the suggestion that the humanitarian alibi phenomenon is the product of a bygone era, and finds that the use of aid as a substitute for peacemaking can co-exist alongside the use of aid as a direct component of international intervention.

Palladium-catalyzed regio- and enantioselective migratory allylic C(sp3)-H functionalization

Transition metal-catalyzed asymmetric allylic substitution with a suitably pre-stored leaving group in the substrate is widely used in organic synthesis. In contrast, the enantioselective allylic C(sp3)-H functionalization is more straightforward but far less explored. Here we report a catalytic protocol for the long-standing challenging enantioselective allylic C(sp3)-H functionalization. Through palladium hydride-catalyzed chain-walking and allylic substitution, allylic C-H functionalization of a wide range of acyclic nonconjugated dienes is achieved in high yields (up to 93% yield), high enantioselectivities (up to 98:2 er), and with 100% atom efficiency. Exploring the reactivity of substrates with varying pKa values uncovers a reasonable scope of nucleophiles and potential factors controlling the reaction. A set of efficient downstream transformations to enantiopure skeletons showcase the practical value of the methodology. Mechanistic experiments corroborate the PdH-catalyzed asymmetric migratory allylic substitution process.

Modeling SARS-CoV-2 substitution processes: predicting the next variant

We build statistical models to describe the substitution process in the SARS-CoV-2 as a function of explanatory factors describing the sequence, its function, and more. These models serve two different purposes: first, to gain knowledge about the evolutionary biology of the virus; and second, to predict future mutations in the virus, in particular, non-synonymous amino acid substitutions creating new variants. We use tens of thousands of publicly available SARS-CoV-2 sequences and consider tens of thousands of candidate models. Through a careful validation process, we confirm that our chosen models are indeed able to predict new amino acid substitutions: candidates ranked high by our model are eight times more likely to occur than random amino acid changes. We also show that named variants of interest were highly ranked by our models before their appearance, emphasizing the value of our models for identifying likely variants of interest and potentially utilizing this knowledge in vaccine design and other aspects of the ongoing battle against COVID-19.

Sequential Ambiguity Resolution Method for Poorly-Observed GNSS Data

Integer ambiguity resolution is required to obtain precise coordinates for the global navigation satellite system (GNSS). Poorly observed data cause unfixed integer ambiguity and reduce the coordinate accuracy. Previous studies mostly used denoise filters and partial ambiguity resolution algorithms to address this problem. This study proposes a sequential ambiguity resolution method that includes a float solution substitution process and a double-difference (DD) iterative correction equation process. The float solution substitution process updates the initial float solution, while the DD iterative correction equation process is used to eliminate the residual biases. The satellite-selection experiment shows that the float solution substitution process is adequate to obtain a more accurate float solution. The iteration-correction experiment shows that the double-difference iterative correction equation process is feasible with an improvement in the ambiguity success rate from 28.4% to 96.2%. The superiority experiment shows significant improvement in the ambiguity success rate from 36.1% to 83.6% and a better baseline difference from about 0.1 m to 0.04 m. It is proved that the proposed sequential ambiguity resolution method can significantly optimize the results for poorly-observed GNSS data.

Prediction of Sodium Substitution Sites in Octacalcium Phosphate: The Relationships of Ionic Pair Ratios in Reacting Solutions

Octacalcium phosphate (OCP) is widely used in biomaterial fabrication by virtue of its unique crystal structure and low environmental loading. Although various ion and molecule substitution methods into the OCP unit lattice have been introduced, it remains unclear which factors and mechanisms dominate the substitution process. Experimental studies have indicated that Na alkali metal ions are substituted at the P3 PO4 conjugated site in acidic to weakly acidic conditions and the P5 PO4 conjugated site in neutral to weak basic conditions. Ionic species calculation methods have indicated that the pair ratios of Na and HPO42− (NaHPO4−) are small in acidic reacting solutions but large under weakly basic conditions. Consequently, the roles played by NaHPO4− and ionic pair formation processes are thought to dominate ion and molecule substitution into the OCP unit lattice. Such ionic pair formation strongly inhibits dicarboxylic acid substitution into the OCP unit lattice due to the replacement of the Ca ion, which conjugates P5 PO4 as an anchor of dicarboxylic acid.

Vocabulary performance of students with and without difficulties learning to read and write

ABSTRACT Purpose: to compare vocabulary performances and verify the lexical competence of students with and without difficulties learning to read and write. Methods: 93 first-grade students were divided into Group I (50 students without difficulties) and Group II (43 students with difficulties learning to read and write). They were administered the Child Language Test focusing on vocabulary. The analysis considered aspects of usual word designation, non-designation, and substitution process. The data analysis was conducted with the Mann-Whitney test, with a p-value ≤ 0.05. Results: there were significant performances in the comparison between the groups in all the conceptual fields analyzed. There was no significance for either group regarding the conceptual fields of Foods, Furniture and Appliances, Places, and Professions in non-designation; regarding Means of Transportation in substitution processes; regarding Toys and Musical Instruments in both non-designation and substitution processes. Group I had higher means than Group II in usual word designation, and lower ones in non-designation and substitution processes. Conclusion: students with difficulties learning to read and write had greater difficulties in usual word designation, as well as higher error indexes in substitution processes and non-designation, which reveals a deficient vocabulary concerning lexical access in comparison with students without difficulties.

Rapid relaxation NMR measurements to predict rate coefficients in ionic liquid mixtures. An examination of reaction outcome changes in a homologous series of ionic liquids

A series of ionic liquids based on the 1-alkyl-3-methylimidazolium cations were examined as components of the solvent mixture for a bimolecular substitution process. The effects on both the rate coefficient...