ANALYSIS OF FRACTION CONTENTS IN ROCK SCRATCH TESTS FOR ESTIMATING THE ANGLE OF INTERNAL FRICTION FOR THE SEDIMENTARY COVER OF THE KOVYKTA FIELD

The article describes the possibility of using the granulometric analysis of rock cuttings formed in controlled core scratching tests to estimate the angle of internal friction.The study object is the Kovykta gas-condensate field (GCF) that occupies a wide area in the southeastern part of the Irkutsk amphitheater of the Siberian platform. This uniquely complex geological structure holds significant reserves of hydrocarbons. Its sedimentary cover is composed of the Vendian – lower Paleozoic and partly Riphean formations. Their total thickness exceeds 6000 m, as estimated from the new seismic survey data [Vakhromeev et al., 2019].The sedimentary cover of the Kovykta GCF has been studied by surface and borehole geophysical techniques, remote sensing and geostructural methods, in combination with the tectonophysical approach [Seminsky et al., 2018] based on drilling data, including standard and special core sampling data

Lack of association between genetic markers on chromosome 16q22-Q24 and type 1 diabetes in Russian affected families

Aim To evaluate whether the T1D susceptibility locus on chromosome 16q contributes to the genetic susceptibility to T1D in Russian patients. Method Thirteen microsatellite markers, spanning a 47-centimorgan genomic region on 16q22-q24 were evaluated for linkage to T1D in 98 Russian multiplex families. Multipoint logarithm of odds (LOD) ratio (MLS) and nonparametric LOD (NPL) values were computed for each marker, using GENEHUNTER 2.1 software. Four microsatellites (D16S422, D16S504, D16S3037, and D16S3098) and 6 biallelic markers in 2 positional candidate genes, ICSBP1 and NQO1, were additionally tested for association with T1D in 114 simplex families, using transmission disequilibrium test (TDT). Results A peak of linkage (MLS = 1.35, NPL = 0.91) was shown for marker D16S750, but this was not significant (P = 0.18). The subsequent linkage analysis in the subset of 46 multiplex families carrying a common risk HLA-DR4 haplotype increased peak MLS and NPL values to 1.77 and 1.22, respectively, but showed no significant linkage (P = 0.11) to T1D in the 16q22-q24 genomic region. TDT analysis failed to find significant association between these markers and disease, even after the conditioning for the predisposing HLA-DR4 haplotype. Conclusion Our results did not support the evidence for the susceptibility locus to T1D on chromosome 16q22-24 in the Russian family data set. The lack of association could reflect genetic heterogeneity of type 1 diabetes in diverse ethnic groups

Competing ideologies of Russia's civil society

Many analysts and public opinion makers in the West conflate the notions of Russia’s non-systemic liberal opposition and the country’s civil society. Indeed, despite garnering the support of a minority of Russia’s population, non-systemic liberal opposition represents a well-organized civic group with a clearly articulated agenda and the ability to take action. Yet, does Russia’s civil society end there? A closer look at the country’s politics shows that Russia has a substantial conservative-traditionalist faction that has also developed agenda for action and formulated opinions. This group is anti-liberal rather than illiberal ideologically and pro-strong state/pro a geopolitically independent Russia rather than pro-Kremlin politically. The interaction between liberal and conservative civic groups represents the battle of meanings, ideas, and ethics, and ultimately determines the future trajectory of Russia’s evolution. Thus, the analysis of Russia’s civil society must represent a rather more nuanced picture than a mere study of the liberal non-systemic opposition. This article will examine the complexity of Russia’s civil society scene with reference to the interplay between the liberal opposition and conservative majority factions. The paper will argue that such complexity stems from ideological value pluralism that falls far beyond the boundaries of the liberal consensus, often skewing our understanding of political practice in Russia

GENETIC POLYMORPHISM OF INFLAMMATORY FACTORS IS ASSOCIATED WITH THROMBOEMBOLIC COMPLICATIONS OF ATRIAL FIBRILLATION

Aim. To reveal the association of hereditary specifics of inflammatory factors with the adverse risk in atrial fibrillation (AF).Material and methods. Totally 258 patients studied (68,5±0,67 y. o.) with nonvalvular AF, recording the events as ischemic stroke, myocardial infarction, venous and arterial thromboembolism. Mean follow-up was 455±11,71 days.Results. Factors that are independently associated with ischemic stroke development in patients not receiving anticoagulants (n=101), were the allele C of polymorphic marker rs2228145(А/С) of gene IL-6 receptor (OR 13,25 CI 1,57112,18, р=0,018), age ?75 y. o. (OR 1,1, CI 1,008-1,2, р=0,032) and EF LV (OR 0,97 CI 0,94-0,99 р=0,027), with a “thrombotic endpoint” development — DM (OR 4,3 CI 1,46-12,45 р=0,008), EF LV (OR 0,96 CI 0,94-0,98, р<0,0001) and carriage of allele C of polymorphic marker rs2228145(А/С) of receptor to IL-6 gene (OR 4,03 CI 1,0715,26, р=0,04). There was no association with adverse outcomes in genes IL-6 polymorphisms as (G(-174)C and G(-572)C), ИЛ-10 (C(-819)T), ФНО (G(-238)A, G(-308)A and ФНО? rs180630). In those receiving adequate anticoagulant therapy (n=157) there was no significant association of IL-6 receptor gene polymorphism with adverse outcomes.Conclusion. Therefore, the carriage of allele C of polymorphic marker rs2228145(А/С) of the IL-6 receptor gene might be an independent risk marker for adverse outcome in non-valvular AF, potentially, being a selection tool for those patients not having enough high risk according to common scores

A structured telephone-delivered intervention to reduce problem alcohol use (Ready2Change): study protocol for a parallel group randomised controlled trial

Background: Current population surveys suggest around 20% of Australians meet diagnostic criteria for an alcohol use disorder. However, only a minority seek professional help due to individual and structural barriers, such as low health literacy, stigma, geography, service operating hours and wait lists. Telephone-delivered interventions are readily accessible and ideally placed to overcome these barriers. We will conduct a randomised controlled trial (RCT) to examine the efficacy of a standalone, structured telephone-delivered intervention to reduce alcohol consumption, problem severity and related psychological distress among individuals with problem alcohol use. Methods/design: This is a single site, parallel group, two-arm superiority RCT. We will recruit 344 participants from across Australia with problem alcohol use. After completing a baseline assessment, participants will be randomly allocated to receive either the Ready2Change (R2C) intervention (n = 172, four to six sessions of structured telephone-delivered intervention, R2C self-help resource, guidelines for alcohol consumption and stress management pamphlets) or the control condition (n = 172, four phone check-ins < 5 min, guidelines for alcohol consumption and stress management pamphlets). Telephone follow-up assessments will occur at 4-6 weeks, 3 months, 6 months and 12 months post-baseline. The primary outcome is the Alcohol Use Disorders Identification Test (AUDIT) score administered at 3 months post-baseline. Secondary outcomes include change in AUDIT score (6 and 12 months post-baseline), change in number of past-month heavy drinking days, psychological distress, health and wellbeing, quality of life, client treatment evaluation and cost effectiveness. Discussion: This study will be one of the first RCTs conducted internationally to examine the impact of a standalone, structured telephone-delivered intervention to address problem alcohol use and associated psychological morbidity. The proposed intervention is expected to contribute to the health and wellbeing of individuals who are otherwise unlikely to seek treatment through mainstream service models, to reduce the burden on specialist services and primary care providers and to provide an accessible and proportionate response, with resulting cost savings for the health system and broader community. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12618000828224. Pre-registered on 16 May 2018

Development and characterization of a novel C-terminal inhibitor of Hsp90 in androgen dependent and independent prostate cancer cells

Background: The molecular chaperone, heat shock protein 90 (Hsp90) has been shown to be overexpressed in a number of cancers, including prostate cancer, making it an important target for drug discovery. Unfortunately, results with N-terminal inhibitors from initial clinical trials have been disappointing, as toxicity and resistance resulting from induction of the heat shock response (HSR) has led to both scheduling and administration concerns. Therefore, Hsp90 inhibitors that do not induce the heat shock response represent a promising new direction for the treatment of prostate cancer. Herein, the development of a C-terminal Hsp90 inhibitor, KU174, is described, which demonstrates anti-cancer activity in prostate cancer cells in the absence of a HSR and describe a novel approach to characterize Hsp90 inhibition in cancer cells.Methods: PC3-MM2 and LNCaP-LN3 cells were used in both direct and indirect in vitro Hsp90 inhibition assays (DARTS, Surface Plasmon Resonance, co-immunoprecipitation, luciferase, Western blot, anti-proliferative, cytotoxicity and size exclusion chromatography) to characterize the effects of KU174 in prostate cancer cells. Pilot in vivo efficacy studies were also conducted with KU174 in PC3-MM2 xenograft studies.Results: KU174 exhibits robust anti-proliferative and cytotoxic activity along with client protein degradation and disruption of Hsp90 native complexes without induction of a HSR. Furthermore, KU174 demonstrates direct binding to the Hsp90 protein and Hsp90 complexes in cancer cells. In addition, in pilot in-vivo proof-of-concept studies KU174 demonstrates efficacy at 75 mg/kg in a PC3-MM2 rat tumor model.Conclusions: Overall, these findings suggest C-terminal Hsp90 inhibitors have potential as therapeutic agents for the treatment of prostate cancer.Peer reviewedBiochemistry and Molecular Biolog

UN Convention on the Law of the Sea of 1982 and International Seabed Authority: the United States’ Position

It has been more than 30 years from the date when the UN Convention on the Law of the Sea of 1982 was adopted and almost 10 years from its entry into force and still there is a number of unresolved issues, related inter alia to the adoption of the regime under this Convention by other states for the purposes of its universal application and unification. USA is one of the group of countries which have not still ratified or otherwise recognized Convention’s binding force for thyself. In fact, there have been a lot of discussions in the United States regarding the advantages and disadvantages of ratifying the Convention. This article is dedicated to studying the approaches of the United States to the ratification, analyses of the argument of both lawyers and politicians for or against the international legal regime introduced by the Convention, namely the legal regime of the sea-bed area beyond the state jurisdiction. The chosen aspect is of interest, taking account the steadfast attention to the legal regime of the sea-bed resources beyond the state jurisdiction from the leading industrialized and developed countries which are in the permanent search for the new source of energy and the further development of the economies

Regulations on Prospecting and Exploration of the Polymetallic Nodules in the International Seabed Area

The article addresses one of the key documents regarding the activity of the states on prospecting, exploration and exploitation of the mineral resources of the International seabed area – the Regulations on prospecting, exploration and exploitation of the polymetallic nodules in the International seabed area. The mentioned Regulations were the first to develop the provisions of the United Nations Convention on the Law of the Sea of 1982, set forth a legal framework for the states’ activity in the area, and also serve as a basis for adoption of the similar regulations on ferromanganese nodules and cobalt-rich crusts by the international seabed authority in future. For the purposes of clarity and readers’ convenience the narration of the article resembles the structure of the regulations with the concurrent analysis of the most important issues being given at the same time