Synthesis of acyclic nucleoside analogues by one-step Vorbrüggen glyco-sylation of 1,2,4-triazolo[1,5-a]pyrimidine-7-ones

New analogues of acyclovir have been prepared by reacting 1,2,4 -triazolo[1,5-a]pyrimidin-7-ones 1а-i and (2-acetoxyethoxy)methyl acetate 2 in the presence of trimethylsilyl trifluoromethanesulfonate as a catalyst. The interaction between the compounds 1а-е and 2 has led to a mixture of N3 and N4 isomers. In contrast, the reaction of compounds 1g-i and 2 proceeded selectively to form N3 isomers. In the case of compounds 1a-c the predominant product is the one with the acyclic moiety in azine ring (N4 isomer). Interaction between 1d-f and 2 has led to mixtures comprising mainly N3 isomer. It has been found that the ratio of glycosylation products 1 and 2 are thermodynamically controlled. The structure of the obtained compounds has been proved by 1Н, 13С, two-dimensional 1Н-13С NMR spectroscopy and X-ray analysis

Quasi-stationary States of Dust Flows Under Poynting-Robertson Drag: New Analytical and Numerical Solutions

The effect of solar or stellar radiation on dust particles' trajectories (the Poynting-Robertson drag) has been studied by a number of authors and applied to interplanetary dust dynamics in numerical computations. Meanwhile some important features of dust flows can be studied analytically by implementing our novel hydrodynamical approach to use the continuity equation written in the particle's orbital elements as coordinates (Gor'kavyi, Ozernoy, & Mather 1997). By employing this approach and integrating the continuity equation, we are able to find two integrals of motion when the Poynting-Robertson drag dominates the dissipative forces in the dust flow. These integrals of motion enable us to explore basic characteristics of dust flows from any sources in the Solar system (such as asteroids, comets, Kuiper belt, etc.) or in another planetary system. In particular, we have reproduced the classical solution $n(r)\propto r^{-1}$ that approximately represents the overall distribution of dust in the Solar system. We have also investigated various factors that could be responsible for the deviations of the power law index in $n(r)\propto r^{\delta}$ from $\delta=-1$, including the influences of the orbital characteristics of dust sources, the evaporation of dust particles, as well as mixtures of dust particles of both asteroidal and cometary origin. We have calculated the masses and number densities of asteroidal and cometary components of the zodiacal cloud at different distances from the Sun.Comment: Accepted for publication in ApJ, v. 488, Oct. 10, 1997; 22 pages, Latex, 12 Postscript figure

Spin-spin coupling constants 13C-15N and 1H-15N in the investigation of azido-tetrazole tautomerism in a series of 2-azidopyrimidines

A new method was developed for the investigation of an azido-tetrazole equilibrium based on using a complex analysis of 13C-15N and 1H-15N spin-spin coupling constants. The use of this approach became possible due to the selective inclusion of 15N isotopes into the structures of 2-azidopyrimidines and their cyclic analogs tetrazolo[1,5-a]pyrimidines. © 2013 Springer Science+Business Media New York

Long-range 1H-15N J couplings providing a method for direct studies of the structure and azide-tetrazole equilibrium in a series of azido-1,2,4-triazines and azidopyrimidines

The selectively 15N labeled azido-1,2,4-triazine 2*A and azidopyrimidine 4*A were synthesized by treating hydrazinoazines with 15N-labeled nitrous acid. The synthesized compounds were studied by 1H, 13C, and 15N NMR spectroscopy in DMSO, TFA, and DMSO/TFA solutions, where the azide-tetrazole equilibrium could lead to the formation of two tetrazoles (T, T′) and one azide (A) isomer for each compound. The incorporation of the 15N label led to the appearance of long-range 1H-15N coupling constants (JHN), which can be measured easily by using amplitude-modulated 1D 1H spin-echo experiments with selective inversion of the 15N nuclei. The observed JHN patterns enable the unambiguous determination of the mode of fusion between the azole and azine rings in the two groups of tetrazole isomers (2*T′, 4*T′ and 2*T, 4*T), even for minor isoforms with a low concentration in solution. However, the azide isomers (2*A and 4*A) are characterized by the absence of detectable J HN coupling. The analysis of the JHN couplings in 15N-labeled compounds provides a simple and efficient method for direct NMR studies of the azide-tetrazole equilibrium in solution. © 2013 American Chemical Society

STUDING THE PRECONDITIONS OF ESTABLISHING THE LEGISLATION OF RUSSIA IN THE FIELD OF RENEWABLE ENERGY

The initial stage of development of the legal framework affecting the area of renewable energy discusses in details in this paper. The author analyzes the prerequisites of becoming law in the direction of non-traditional and renewable energy. The legislative documents, which were adopted prior to the amendment of November 4, 2007 the Federal Law "On Electric Power Industry" were studied in details, and we presented, how the legislative documents could affect the development of legislation in this area.В работе подробно рассмотрен первоначальный этап развития законодательной базы, затрагивающей область применения возобновляемых источников энергии. Автором были проанализированы предпосылки становления законодательства в направлении нетрадиционной и возобновляемой энергетики. В данной работе подробно изучены законодательные документы, которые были приняты в период до внесения поправок 4 ноября 2007 года в Федеральный закон «Об электроэнергетике» и представлено, как законодательные документы могли повлиять на развитие законодательства в рассматриваемой сфере

Covariance and Time Regained in Canonical General Relativity

Canonical vacuum gravity is expressed in generally-covariant form in order that spacetime diffeomorphisms be represented within its equal-time phase space. In accordance with the principle of general covariance, the time mapping {\T}: {\yman} \to {\rman} and the space mapping {\X}: {\yman} \to {\xman} that define the Dirac-ADM foliation are incorporated into the framework of the Hilbert variational principle. The resulting canonical action encompasses all individual Dirac-ADM actions, corresponding to different choices of foliating vacuum spacetimes by spacelike hypersurfaces. In this framework, spacetime observables, namely, dynamical variables that are invariant under spacetime diffeomorphisms, are not necessarily invariant under the deformations of the mappings \T and \X, nor are they constants of the motion. Dirac observables form only a subset of spacetime observables that are invariant under the transformations of \T and \X and do not evolve in time. The conventional interpretation of the canonical theory, due to Bergmann and Dirac, can be recovered only by postulating that the transformations of the reference system ({\T},{\X}) have no measurable consequences. If this postulate is not deemed necessary, covariant canonical gravity admits no classical problem of time.Comment: 41 pages, no figure

Renal effects of glucagon-like peptide receptor agonists in patients with type 1 diabetes mellitus

The purpose of our study is to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1R agonists) on early markers of kidney damage in patients with type 1 diabetes mellitus (DM). Materials and methods. The study included 27 patients with type 1 diabetes with normo- (n=16) and microalbuminuria (n=11) on intensive insulin injection regimen with insulin analogs. Patients were divided into two groups: 15 patients continued insulin therapy throughout the follow-up period, 12 patients were given 1.2 mg GLP-1R agonist (Liraglutide) once a day in addition to the insulin therapy for 6 months. HbA1c, lipid profile, classic markers of kidney damage (albuminuria, creatinine, glomerular filtration rate); plazma (neutrophilic gelatinase-associated lipoxalin - NGAL, molecule renal damage of type 1 - KIM-1, cystatin C, osteopontin) and urinary kidney biomarkers (nephrin, podocyne, uromodulin, NGAL, KIM-1, collagen type IV, cystatin C) were evaluated prior and in dynamics at 6 months. Kidney biomarkers levels were assessed by the enzyme-linked immunosorbent assay (ELISA). Results. We observed a significant decrease in the urinary excretion of type IV collagen, cystatin C, increased uromodulin excretion and decrease in the plasma levels of osteopontin, NGAL and cystatin C in the group of combined insulin and GLP-1R agonist therapy. Conclusions. Changes in the level of sensitive kidney biomarkers indicate a possible renoprotective effect of GLP-1R agonist therapy in patients with type 1 diabetes at an early stages of kidney damage

Feсal microbiota transplantation in the format of complex therapy in obesive siblings: clinical case

Obesity and associated metabolic diseases are often accompanied by changes in the gut microbiota leading to metagenome gene diversity decrease. Fecal microbiota transplantation (FMT) is one of the most effective methods for correcting the  intestinal microflora. FMT obtained from healthy donors has been proven to be an effective treatment of infections caused by Clostridium difficile. The use of FMT for correction of metabolic disorders is promising, however, data on its application is limited and has contradictory results. In our work, two patients (siblings) presented with obesity grade II and various types of diabetes mellitus (DM): the older brother (44 years old) with diabetes mellitus type 2 (DM 2), a younger brother (39 years old) with diabetes mellitus type 1 (DM 1). Both patients underwent FMT as part of complex antidiabetic therapy. During the course of treatment, a decrease in body weight was noted in both patients (4–5 kg for the first month of observation, then -1–2 kg per month). One year after FMT, a patient with type 2 diabetes showed a decrease in the severity of insulin resistance (IR), measured by the hyperinsulinemic euglycemic clamp test (initial M-index 2.42 mg/kg*min, after 1 year — 3.83 mg/kg* min) as well as the maintenance of satisfactory carbohydrate metabolism compensation against the diminishing the hypoglycemic therapy. In a patient with DM 1, no significant dynamics of carbohydrate exchange indices, including detected glycated hemoglobin (HbA1c), insulin dose and IR were during the observation period. Metagenomic sequencing of stool samples (n = 20) collected from both patients before and within 1 year after FMT showed no significant changes in the taxonomic profile of the microbiota at the level of microbial families. Metabolomic analysis of the composition of feces showed no directed changes in the composition of metabolites after the FMT procedure, the nature of changes within the samples from each patient during the entire study period was random. Thus, FMT had no effect on the course of DM1, but served as a starting point for weight loss and improvement glucose profile in DM2. However, convincing data confirming a causal correlation between FMT and improvement in the course of T2DM have not been obtained

Antiviral drug Triazavirin, selectively labeled with 2H, 13C, and 15N stable isotopes. Synthesis and properties

[Figure not available: see fulltext.] Isotope-labeled antiviral drug Triazavirin containing 2H, 13C, and 15N atoms in its structure has been synthesized. 13C2H3I and KS13CN served as donors of 13C isotopes. The use of 13С-MeI containing 2H atoms made it possible to additionally incorporate deuterium labels into the structure of the compound. The 15N atoms were incorporated using 15N-enriched sodium nitrite, aminoguanidine carbonate, and ethyl nitroacetate. The resulting 2H3,13C2,15N3-Triazavirin was characterized by NMR spectroscopy. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.This work was supported by the Russian Foundation for Basic Research (grant 20-03-00842) and the Ministry of Science and Higher Education of the Russian Federation (project No. FEUZ-2020-0058 (N687.42B.223/20))