POLARIMETRIC RESEARCH OF PHARMACEUTICAL SUBSTANCES IN AQUEOUS SOLUTIONS WITH DIFFERENT WATER ISOTOPOLOGUES RATIO

Objective: Methodology development for quality control of optically active pharmaceutical substances based on water isotopologues. Methods: Solutions of L-ascorbic acid, glucose, galactose and valine stereoisomers were prepared using deuterium depleted water (DDW-«light» water, D/H=4 ppm), natural deionized high-ohmic water (BD, D/H=140 ppm), heavy water (99.9% D2O). The optical rotation was observed using an automatic polarimeter Atago POL-1/2. The size distribution of giant heterogeneous clusters (GHC) of water was recorded by low angle laser light scattering (LALLS) method. Results: The infringement of Biot's Law was found for solutions of ascorbic acid, expressed in the absence of a constant value of the specific optical rotation  at a concentration of below 0.1%, depends on the D/H ratio. The inequality was established in absolute values of optical rotation for L-and D-isomers of valine in solutions with different ratios of hydrogen isotopologues. The mutarotation of glucose confirmed the first-order kinetics, and the activation energies were statistically distinguishable for BD and DDW. The mutarotation of the natural galactose D-isomer proceeded with a lower energy consumption compared to the L-isomer. In heavy water, the mutarotation of monosaccharides had different kinetic mechanisms. Polarimetric results correlated with the number and size of GHC, which confirmed the possibility of chiral solvent structures induction by optically active pharmaceutical substances. Conclusion: In the optically active pharmaceutical substances quality control there should be considered the contribution of induced chiral GHC of water to the optical rotation value that depends on the isotopic D/H ratio, the substance nature and the form of its existence at a given pH

Catalog of dessins d'enfants with \le 4 edges

In this work all the dessins d'enfant with no more than 4 edges are listed and their Belyi pairs are computed. In order to enumerate all dessins the technique of matrix model computations was used. The total number of dessins is 134; among them 77 are spherical, 53 of genus 1 and 4 of genus 2. The orders of automorphism groups of all the dessins are also found. Dessins are listed by the number of edges. Dessins with the same number of edges are ordered lexicographically by their lists of 0-valencies. The corresponding matrix model for any list of 0-valencies is given and computed. Complex matrix models for dessins with 1 -- 3 edges are used. For the dessins with 4 edges we use Hermitian matrix model, correlators for which are computed in [1].Comment: 64 pages, 134 figure

Взаимодействие аниона [2-В10Н9О(СН2)4О]− с вторичными аминами

Objectives. One of the most promising methods of treating malignant tumors is 10B-neutron capture therapy. While compounds based on cluster boron anions [BnHn]2− (n = 10, 12) are often used as boron-containing agents due to the very high specific concentration of boron atoms per particle, the use of such compounds is associated with the need to develop new methods for the functionalization of boron clusters associated with the production of boron-containing derivatives containing biologically active functional groups. One of the most convenient methods of modification of [BnHn]2− (n = 10, 12) anions is the interaction of their derivatives containing cyclic oxonium-type substituents with negatively charged or neutral nucleophilic reagents. The disclosure of substituents of this type leads to the formation of closo-borates with functional groups separated from the cluster by an alkoxyl spacer chain. The purpose of this study is to develop methods for the synthesis of derivatives of the closo-decaborate anion [B10H10]2− with pendant nitrogen-containing groups.Methods. The general control of the reactions of the disclosure of cyclic substituents was carried out on the basis of 11B nuclear magnetic resonance (NMR) spectroscopy data. The structure of the obtained derivatives, including the nature of the attached functional groups, was determined using 1H, 13C attached proton test (APT) NMR and infrared (IR) spectroscopy data. The molecular weight of the synthesized compounds was confirmed by electrospray ionization mass-spectrometry (ESI–MS).Results. The interaction of the anion [2-B10H9O(CH2)4O]− with secondary amines (dimethylamine, dipropylamine, diallylamine, dibutylamine, diisobutylamine, morpholine, di-sec-butylamine) in an ethanol environment is investigated. As a result of the reactions, a cyclic substituent is shown to expand with the addition of a nucleophilic reagent. Seven new derivatives of the closodecaborate anion with pendant nitrogen-containing groups have been synthesized.Conclusions. A developed method for obtaining closo-decaborates with ammonium groups separated from the boron cluster by an alkoxyl spacer group is presented. It is shown that the use of amines of various structures does not fundamentally affect the course of the reactions, allowing the composition and structure of the target derivatives to be effectively regulated. The resulting compounds can be involved in further modification reactions due to a reactive pendant group, as well as being suitable for use as effective polydentate ligands. Closo-decaborates with pendant nitrogen-containing groups and their derivatives are of considerable interest in the synthesis of compounds for use in 10B-neutron capture therapy of malignant tumors.Цели. 10B-нейтронозахватная терапия является одним из наиболее перспективных методов лечения злокачественных опухолей. В качестве борсодержащих агентов нередко применяются соединения на основе кластерных анионов бора [BnHn]2− (n = 10, 12), как имеющие очень высокую удельную концентрацию атомов бора в расчете на одну частицу. Однако использование таких соединений связано с необходимостью разработки новых методов функционализации борных кластеров, связанных с получением борсодержащих производных с биологически активными функциональными группами. Одним из наиболее удобных методов модификации анионов [BnHn]2− (n = 10, 12) является взаимодействие их производных, содержащих циклические заместители оксониевого типа, с отрицательно заряженными или нейтральными нуклеофильными реагентами. Раскрытие заместителей данного типа приводит к образованию клозо-боратов с функциональными группами, отделенными от кластера алкоксильной спейсерной цепочкой. Целью настоящего исследования является разработка методов синтеза производных клозо-декаборатного аниона [B10H10]2− с пендантными азотсодержащими группами.Методы. Общий контроль протекания реакций раскрытия циклических заместителей осуществлялся на основании данных 11B спектроскопии ядерного магнитного резонанса (ЯМР). Строение полученных производных, в том числе природу присоединенных функциональных групп определяли на основании данных 1H, 13C ЯМР с тестом на присоединенные протоны (APT) и инфракрасной спектроскопии (ИК). Молекулярную массу синтезированных соединений подтверждали методом масс-спектрометрии с ионизацией электрораспылением (ИЭР-МС).Результаты. Исследовано взаимодействие аниона [2-B10H9O(CH2)4O]− с вторичными аминами (диметиламин, дипропиламин, диаллиламин, дибутиламин, диизобутиламин, морфолин, ди-втор-бутиламин) в среде этанола. Показано, что в результате реакций происходит раскрытие циклического заместителя с присоединением нуклеофильного реагента. Синтезированы семь новых производных клозо-декаборатного аниона с пендантными азотсодержащими группами.Выводы. Разработан новый метод получения клозо-декаборатов с аммониевыми группами, отделенными от борного кластера алкоксильной спейсерной группой. Показано, что применение аминов различного строения принципиально не влияет на ход протекающих реакций и позволяет эффективно регулировать состав и строение целевых производных. Полученные соединения могут быть вовлечены в дальнейшие реакции модификации за счет реакционноспособной пендантной группы, а также могут быть использованы в роли эффективных полидентатных лигандов. Клозо-декабораты с пендантными азотсодержащими группами и их производные представляют значительный интерес в синтезе соединений, перспективных для применения в 10B-нейтронозахватной терапии злокачественных опухолей

Performance of the LHCb muon system

The performance of the LHCb Muon system and its stability across the full 2010 data taking with LHC running at ps = 7 TeV energy is studied. The optimization of the detector setting and the time calibration performed with the first collisions delivered by LHC is described. Particle rates, measured for the wide range of luminosities and beam operation conditions experienced during the run, are compared with the values expected from simulation. The space and time alignment of the detectors, chamber efficiency, time resolution and cluster size are evaluated. The detector performance is found to be as expected from specifications or better. Notably the overall efficiency is well above the design requirementsComment: JINST_015P_1112 201

Performance of the LHCb muon system with cosmic rays

The LHCb Muon system performance is presented using cosmic ray events collected in 2009. These events allowed to test and optimize the detector configuration before the LHC start. The space and time alignment and the measurement of chamber efficiency, time resolution and cluster size are described in detail. The results are in agreement with the expected detector performance.Comment: Submitted to JINST and accepte

Topology of "white" stars in relativistic fragmentation of light nuclei

In the present paper, experimental observations of the multifragmentation processes of light relativistic nuclei carried out by means of emulsions are reviewed. Events of the type of "white" stars in which the dissociation of relativistic nuclei is not accompanied by the production of mesons and the target-nucleus fragments are considered. A distinctive feature of the charge topology in the dissociation of the Ne, Mg, Si, and S nuclei is an almost total suppression of the binary splitting of nuclei to fragments with charges higher than 2. The growth of the nuclear fragmentation degree is revealed in an increase in the multiplicity of singly and doubly charged fragments with decreasing charge of the non-excited part of the fragmenting nucleus. The processes of dissociation of stable Li, Be, B, C, N, and O isotopes to charged fragments were used to study special features of the formation of systems consisting of the lightest $\alpha$, d, and t nuclei. Clustering in form of the $^3$He nucleus can be detected in "white" stars via the dissociation of neutron-deficient Be, B, C, and N isotopes.Comment: 20 pages, 3 figures, 9 tables, conference: Conference on Physics of Fundamental Interactions, Moscow, Russia, 1-5 Mar 2004.(Author's translation

MULTIFACTORIAL ASSESSMENT OF POSTMORTEM LUNG DONOR

The appropriate evaluation and the development of special measures to protect donor lungs are important factors for successful lung transplantation. Aim. To develop and determine the effectiveness of the protocol of morpho- functional assessment of potential lung donor. Methods and results. During the period from May, 2011 to May, 2012, 37 donors with diagnoses of brain death were surveyed. 5 bilateral lung transplantations were performed only in 2 cases donors have been evaluated as «ideal». In the majority of recipients early postoperative period was evaluated as satisfactory. Conclusion. Designed multivariate algorithm of donor with brain death assess- ment, effectively implemented through the selection of donors for lung transplantation with satisfactory results in the early postoperative period. However, compliance with ideal criteria will not allow to effectively provide care for patients with terminal lung disease under conditions of continuous growth of «waiting list»

Murine Gammaherpesvirus-68 Inhibits Antigen Presentation by Dendritic Cells

Dendritic cells (DCs) play a central role in initiating adaptive immunity. Murine gammaherpesvirus-68 (MHV-68), like many persistent viruses, infects DCs during normal host colonization. It therefore provides a means to understanding what host and viral genes contribute to this aspect of pathogenesis. The infected DC phenotype is likely to depend on whether viral gene expression is lytic or latent and whether antigen presentation is maintained. For MHV-68, neither parameter has been well defined. Here we show that MHV-68 infects immature but not mature bone marrow-derived DCs. Infection was predominantly latent and these DCs showed no obvious defect in antigen presentation. Lytically infected DCs were very different. These down-regulated CD86 and MHC class I expression and presented a viral epitope poorly to CD8+ T cells. Antigen presentation improved markedly when the MHV-68 K3 gene was disrupted, indicating that K3 fulfils an important function in infected DCs. MHV-68 infects only a small fraction of the DCs present in lymphoid tissue, so K3 expression is unlikely to compromise significantly global CD8+ T cell priming. Instead it probably helps to maintain lytic gene expression in DCs once CD8+ T cell priming has occurred

A Single CD8+ T Cell Epitope Sets the Long-Term Latent Load of a Murid Herpesvirus

The pathogenesis of persistent viral infections depends critically on long-term viral loads. Yet what determines these loads is largely unknown. Here, we show that a single CD8+ T cell epitope sets the long-term latent load of a lymphotropic gamma-herpesvirus, Murid herpesvirus-4 (MuHV-4). The MuHV-4 M2 latency gene contains an H2-Kd -restricted T cell epitope, and wild-type but not M2− MuHV-4 was limited to very low level persistence in H2d mice. Mutating the epitope anchor residues increased viral loads and re-introducing the epitope reduced them again. Like the Kaposi's sarcoma–associated herpesvirus K1, M2 shows a high frequency of non-synonymous mutations, suggesting that it has been selected for epitope loss. In vivo competition experiments demonstrated directly that epitope presentation has a major impact on viral fitness. Thus, host MHC class I and viral epitope expression interact to set the long-term virus load