Mixture of Species Sampling Models

We introduce mixtures of species sampling sequences (mSSS) and discuss how these sequences are related to various types of Bayesian models. As a particular case, we recover species sampling sequences with general (not necessarily diffuse) base measures. These models include some “spike-and-slab” non-parametric priors recently introduced to provide sparsity. Furthermore, we show how mSSS arise while considering hierarchical species sampling random probabilities (e.g., the hierarchical Dirichlet process). Extending previous results, we prove that mSSS are obtained by assigning the values of an exchangeable sequence to the classes of a latent exchangeable random partition. Using this representation, we give an explicit expression of the Exchangeable Partition Probability Function of the partition generated by an mSSS. Some special cases are discussed in detail—in particular, species sampling sequences with general base measures and a mixture of species sampling sequences with Gibbs-type latent partition. Finally, we give explicit expressions of the predictive distributions of an mSSS.

The Mordovian Family of the Saratov Province of the Late XIX century according to the Data of Agricultural Censuses

Introduction. Second half of the 19th century for the Russian Empire is marked by the intensification of the process of transition from a traditional society to an industrial one. This transformation also affected such a conservative institution as the family. Its characteristic feature is the decrease in the average size of the family and the simplification of its structure. However, the transformation process was uneven, under the influence of regional characteristics, factors of the socio-economic and cultural type. Research Methods. The research was carried out on the basis of a comprehensive statistical analysis of the primary material of the zemstvo agricultural censuses located in the fund of the Provincial Statistical Committee of the State Archives of the Saratov Region. Results. The surviving materials include over 800 Mordovian households. The analysis of them allows us to speak about the predominance of this ethnos at the end of the 19th century a large, undivided family. This can be traced both in the total number of households of this type and in the number of people living in them. In the general base, the most populated households belonged to the Mordovians, the Tatar and Russian were smaller. Discussion and Conclusion. The article attempted to test the hypothesis that the family structure becomes more complex as it grows. It was found that a small family dominated in a group of households of up to 6 people, and a complex family dominated by 7 or more people. The extended type of household was not predominant in any group, occupying an intermediate position.

Ensemble–function relationships to evaluate catalysis in the ketosteroid isomerase oxyanion hole

Following decades of insights from structure–function studies, there is now a need to progress from a static to dynamic view of enzymes. Comparison of prior cryo X-ray structures suggested that deleterious effects from ketosteroid isomerase (KSI) mutants arise from misalignment of the oxyanion hole catalytic residue, Y16. However, multi-conformer models from room temperature X-ray diffraction revealed an ensemble of Y16 conformers indistinguishable from WT for Y32F/Y57F KSI and a distinct, non-native ensemble for Y16 in Y57F KSI. Functional analyses suggested rate effects arise from weakened hydrogen bonding, due to disruption of the Y16/Y57/Y32 hydrogen bond network, and repositioning of the general base. In general, catalytic changes can be deconvoluted into effects on the probability of occupying a state (P-effects) and the reactivity of each state (k-effects). Our results underscore the need for ensemble–function analysis to decipher enzyme function and ultimately manipulate their extraordinary capabilities.

Water as a reactant in the first step of triosephosphate isomerase catalysis

ABSTRACTThe enzyme triosephosphate isomerase (TIM) performs a crucial role in the extraction of energy from glucose, doing so by converting dihydroxyacetone phosphate (DHAP) into glyceraldehyde phosphate, thereby doubling the yield of ATP molecules during glycolysis. The initial step of the mechanism is the seemingly unlikely abstraction of the pro-R methylene hydrogen from C1 by a conserved glutamate (Glu165), an assignment that has been both universally accepted yet a much-studied phenomenon for decades. In this work we introduce an alternative mechanism in which water as a strong general base abstracts the carbon proton acting effectively as hydroxide. We posit that strong electric fields associated with the substrate phosphate promote facile autoionization of water trapped near the phosphate dianion of DHAP and Glu165, an example of substrate assisted catalysis. Classical molecular dynamics simulations assert that the closest water oxygen atom is consistently closer to the pro-R H than the carboxylate oxygen atoms of the accepted base Glu165. Our proposal is further supported by quantum computations that confirm the implausibility of abstraction of the methylene hydrogen by glutamate and the ease with which it is abstracted by hydroxide. The necessity of Glu165 for efficient catalysis is attributed to its crucial involvement in trapping the vital water in an environment of high electric fields which promote ionization far more rapidly than in bulk solvent.

Analysis of knowledge assessment results of civil servants regarding anti-corruption issues

The article presents the program shell developed by the authors to estimate the knowledge of civil servants regarding anti-corruption issues. This development is a part of an information and analysis system, which is aimed not only at automating the analysis of data on knowledge control but it also includes both educational functions and possibilities for automation of the activity of the personnel divisions on the prevention of corruption offenses, formation of maps of corruption risks, observation, study and forecast of deviant corruption-related changes in the conduct of civil servants, assignment of testing, organization of training, etc. Due to the introduction of this program, the personnel divisions will obtain both systemic organization of awareness-raising measures (lectures, seminars) involving servants and the possibility to estimate their psychological condition and the general base of knowledge regarding prohibitions and restrictions in the civil service, practical and theoretical nuances of providing data about income, expenses, assets, liabilities, etc. The authors consider the issues of the introduction of the programs in the state authorities of both federal and regional levels. They point out the need to take into account the peculiarities of the targeted information system of the organization : the compatibility of the development being introduced with the current version of the operating system, as well as the security policy of the targeted system. The study presents the first results of the testing of the software product and includes an assessment of their main factors.

Assessment of enzyme active site positioning and tests of catalytic mechanisms through X-ray–derived conformational ensembles

How enzymes achieve their enormous rate enhancements remains a central question in biology, and our understanding to date has impacted drug development, influenced enzyme design, and deepened our appreciation of evolutionary processes. While enzymes position catalytic and reactant groups in active sites, physics requires that atoms undergo constant motion. Numerous proposals have invoked positioning or motions as central for enzyme function, but a scarcity of experimental data has limited our understanding of positioning and motion, their relative importance, and their changes through the enzyme’s reaction cycle. To examine positioning and motions and test catalytic proposals, we collected “room temperature” X-ray crystallography data for Pseudomonas putida ketosteroid isomerase (KSI), and we obtained conformational ensembles for this and a homologous KSI from multiple PDB crystal structures. Ensemble analyses indicated limited change through KSI’s reaction cycle. Active site positioning was on the 1- to 1.5-Å scale, and was not exceptional compared to noncatalytic groups. The KSI ensembles provided evidence against catalytic proposals invoking oxyanion hole geometric discrimination between the ground state and transition state or highly precise general base positioning. Instead, increasing or decreasing positioning of KSI’s general base reduced catalysis, suggesting optimized Ångstrom-scale conformational heterogeneity that allows KSI to efficiently catalyze multiple reaction steps. Ensemble analyses of surrounding groups for WT and mutant KSIs provided insights into the forces and interactions that allow and limit active-site motions. Most generally, this ensemble perspective extends traditional structure–function relationships, providing the basis for a new era of “ensemble–function” interrogation of enzymes.

Mild Organic Base-Catalyzed Primary Alcohol-Selective Aroylation Reaction Using N-Aroylcarbazoles for Underexplored Prodrugs

<div>We report a highly primary alcohol-selective aroylation reaction using N-aroylcarbazoles (NAroCs). The aroylation</div><div>proceeded smoothly in the presence of DBU, which most likely works as a general base catalyst in the reaction system. The synthetic utility was displayed in the primary alcohol-selective aroylation of complex drug molecules and natural products to their prodrugs. Stoichiometrically generated carbazole, the starting material of NAroCs could be easily recovered. We also established safer multigram and multidecagram scale preparation methods of NAroCs, which are easy-to-handle bench-stable reagents.</div>

Mild Organic Base-Catalyzed Primary Alcohol-Selective Aroylation Reaction Using N-Aroylcarbazoles for Underexplored Prodrugs

<div>We report a highly primary alcohol-selective aroylation reaction using N-aroylcarbazoles (NAroCs). The aroylation</div><div>proceeded smoothly in the presence of DBU, which most likely works as a general base catalyst in the reaction system. The synthetic utility was displayed in the primary alcohol-selective aroylation of complex drug molecules and natural products to their prodrugs. Stoichiometrically generated carbazole, the starting material of NAroCs could be easily recovered. We also established safer multigram and multidecagram scale preparation methods of NAroCs, which are easy-to-handle bench-stable reagents.</div>

A General Base of Power Transformation to Improve the Boundary Effect in Kernel Density without Shoulder Condition

In this paper, a general base of power transformation under the kernel method is suggested and applied in the line transect sampling to estimate abundance. The suggested estimator performs well at the boundary compared to the classical kernel estimator without using the shoulder condition assumption. The transformed estimator show smaller value of mean squared error and absolute bias from the efficiency results obtained using simulation.