Gambling taxation in today’s Russia : principles, practices and actual figures

The article is devoted to today's situation and prospects for the development of gambling taxation in the country. The gambling industry is continually developed. Currently, this type of entrepreneurial activities can be found almost throughout the Russian Federation. But the problem of gambling industry is associated, to a large extent, with the fact that it is rather difficult to control the income and expense of bookmakers, owners of casinos and slot machines. Insufficient transparency of gambling industry leads to new restrictions or prohibitions by the state, instead of implementing an effective taxation system. As the objects for the study, the authors selected the main elements of the tax on gambling. In this article the dynamics of the number of taxpayers, subjects of taxation and amount of budget income by taxing the gambling industry over time is analysed. As a result of the study the problems of gambling taxation are defined and their possible solutions are proposed.peer-reviewe

Parabolic resonances and instabilities in near-integrable two degrees of freedom Hamiltonian flows

When an integrable two-degrees-of-freedom Hamiltonian system possessing a circle of parabolic fixed points is perturbed, a parabolic resonance occurs. It is proved that its occurrence is generic for one parameter families (co-dimension one phenomenon) of near-integrable, t.d.o. systems. Numerical experiments indicate that the motion near a parabolic resonance exhibits new type of chaotic behavior which includes instabilities in some directions and long trapping times in others. Moreover, in a degenerate case, near a {\it flat parabolic resonance}, large scale instabilities appear. A model arising from an atmospherical study is shown to exhibit flat parabolic resonance. This supplies a simple mechanism for the transport of particles with {\it small} (i.e. atmospherically relevant) initial velocities from the vicinity of the equator to high latitudes. A modification of the model which allows the development of atmospherical jets unfolds the degeneracy, yet traces of the flat instabilities are clearly observed

Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison

We performed a comparative cytogenomic analysis of cultured and uncultured uterine leiomyoma (UL) samples. The experimental approach included karyotyping, aCGH, verification of the detected chromosomal abnormalities by metaphase and interphase FISH, MED12 mutation analysis and telomere measurement by Q-FISH. An abnormal karyotype was detected in 12 out of 32 cultured UL samples. In five karyotypically abnormal ULs, MED12 mutations were found. The chromosomal abnormalities in ULs were present mostly by complex rearrangements, including chromothripsis. In both karyotypically normal and abnormal ULs, telomeres were ~40% shorter than in the corresponding myometrium, being possibly prerequisite to chromosomal rearrangements. The uncultured samples of six karyotypically abnormal ULs were checked for the detected chromosomal abnormalities through interphase FISH with individually designed DNA probe sets. All chromosomal abnormalities detected in cultured ULs were found in corresponding uncultured samples. In all tumors, clonal spectra were present by the karyotypically abnormal cell clone/clones which coexisted with karyotypically normal ones, suggesting that chromosomal abnormalities acted as drivers, rather than triggers, of the neoplastic process. In vitro propagation did not cause any changes in the spectrum of the cell clones, but altered their ratio compared to uncultured sample. The alterations were unique for every UL. Compared to its uncultured counterpart, the frequency of chromosomally abnormal cells in the cultured sample was higher in some ULs and lower in others. To summarize, ULs are characterized by both inter- and intratumor genetic heterogeneity. Regardless of its MED12 status, a tumor may be comprised of clones with and without chromosomal abnormalities. In contrast to the clonal spectrum, which is unique and constant for each UL, the clonal frequency demonstrates up or down shifts under in vitro conditions, most probably determined by the unequal ability of cells with different genetic aberrations to exist outside the body

Предикторы отмены генно-инженерных биологических препаратов ввиду развития нежелательных явлений у пациентов с ревматоидным артритом

Currently, a large number of highly effective biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are used for the treatment of rheumatoid arthritis (RA). However, in addition to effectiveness, it is necessary to evaluate the risk of adverse events (AEs) when using them.Objective: to determine the predictors of bDMARDs and tsDMARDs discontinuation due to AEs in patients with RA.Patients and methods. The study included 661 patients with RA who took bDMARDs and tsDMARDs. The search for predictors of targeted therapy discontinuation due to AEs was carried out in two stages. At the first stage, using the Kaplan-Meier method, we selected indicators that showed the greatest significant single-factor relationship with the duration of retention on therapy. At the second stage, significant independent indicators were obtained by iterative selection of variables within the multivariate proportional risk model according to Cox.Results and discussion. The presence of rheumatoid nodules (p<0.001), high doses of glucocorticoids (GC; p<0.001), low doses of methotrexate (MT; p=0.009) are significant independent factors for increasing the risk of drugs discontinuation due to the development of AEs. The type of bDMARDs/tsDMARD used also significantly correlated with the risk of discontinuation of therapy due to AEs. A relatively high risk of treatment discontinuation was observed with infliximab (IFN) and certolizumab pegol (CZP). Cancellation of IFN was associated with the occurrence of infusion reactions and infectious complications, and CZP was associated with infectious complications.Conclusion. An increase in the dose of MT and decrease in the use of GCs can help prevent the development of AEs leading to the abolition of biologics and tsDMARDs. Significant differences were found between bDMARDs in terms of the risk of their cancellation due to AEs.В настоящее время для лечения ревматоидного артрита (РА) используется большое число генно-инженерных биологических (ГИБП) и таргетных синтетических базисных противовоспалительных препаратов (тсБПВП), которые обладают высокой эффективностью. Однако, помимо эффективности, необходимо оценивать риск возникновения нежелательных явлений (НЯ) при их использовании.Цель исследования — определить предикторы отмены ГИБП и тсБПВП из-за НЯ у пациентов с РА.Пациенты и методы. В исследование включен 661 пациент с РА, принимавший ГИБП и тсБПВП. Поиск предикторов отмены таргетной терапии ввиду НЯ проводился в два этапа. На первом этапе с помощью метода Каплана—Майера были отобраны показатели, которые демонстрировали наибольшую значимую однофакторную связь с длительностью удержания на терапии. На втором этапе значимые независимые показатели были получены путем пошагового отбора переменных в рамках многофакторной модели пропорционального риска по Коксу.Результаты и обсуждение. Наличие ревматоидных узелков (p<0,001), высокие дозы глюкокортикоидов (ГК; p<0,001), низкие дозы метотрексата (МТ; p=0,009) являются значимыми независимыми факторами увеличения риска отмены препаратов из-за развития НЯ. Используемый ГИБП/тсБПВП также значимо коррелировал с риском отмены терапии из-за НЯ. Относительно высокий риск прекращения лечения был отмечен у инфликсимаба (ИНФ) и цертолизумаба пэгола (ЦЗП). Отмена ИНФ была связана с возникновением инфузионных реакций и инфекционных осложнений, а ЦЗП — с инфекционными осложнениями.Заключение. Увеличение дозы МТ, уменьшение использования ГКмогут способствовать предотвращению развития НЯ, приводящих к отмене ГИБП и тсБПВП. Выявлены существенные различия между ГИБП в отношении риска их отмены вследствие НЯ

Democracy, protest and public sphere in Russia after the 2011–2012 anti-government protests: digital media at stake

The 2011–2012 Russian protest mobilisations were largely enabled by the rise of social networks. Social and technological advancements paired to pave the way for the ‘biggest protests since the fall of USSR’. Ubiquitous and uncensored social media facilitated the networking and mobilisation for this protest activity: Liberal masses were able to share and discuss their grievances, unite and coordinate online for the offline protest. The digitally savvy protest public developed to confront the government, which appeared to be astonished by the scale of protest. Those mobilisations marked an important gap between the government’s conception of the society and the real state of resistance. This article studies three main hypotheses regarding the potential of the protest movement in Russia. The hypotheses were drawn from recent sociological, political and media studies on Russian resistance. Current research aims to contribute to the debate from the digital media perspective. It therefore evaluates three main assumptions: Digital media have the potential to empower, dependent upon the relevant political, social and economic factors; digital media isolates protest publics and therefore may be more useful for the government than the resistance; and recent censorship of digital media communication signals a tightening of both formal and informal restrictions against opposition and protest politics. This article uses theoretical and factual evidence on the limitations of democracy and the public sphere and conceptualises the government’s management of resistance in Russia during and after the 2011–2012 protests. It studies how the hybrid political regime in Russia balances restrictions on freedom of speech with strengthened state propaganda and how it mediates media oppression and invites self-censorship. Finally, it examines how the state communication watchdog has recently focused its attention at the digital realm. This move confirms the importance of the online protest communication for the Russian political environment. Yet the state’s acknowledgement of digital political resistance may lead to further oppression and curbing of this emerging component of Russian politics

Ubiquitous [Na+]i/[K+]i-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca2+i-Independent Excitation-Transcription Coupling

Stimulus-dependent elevation of intracellular Ca2+ ([Ca2+]i) affects the expression of numerous genes – a phenomenon known as excitation-transcription coupling. Recently, we found that increases in [Na+]i trigger c-Fos expression via a novel Ca2+i-independent pathway. In the present study, we identified ubiquitous and tissue-specific [Na+]i/[K+]i-sensitive transcriptomes by comparative analysis of differentially expressed genes in vascular smooth muscle cells from rat aorta (RVSMC), the human adenocarcinoma cell line HeLa, and human umbilical vein endothelial cells (HUVEC). To augment [Na+]i and reduce [K+]i, cells were treated for 3 hrs with the Na+,K+-ATPase inhibitor ouabain or placed for the same time in the K+-free medium. Employing Affymetrix-based technology, we detected changes in expression levels of 684, 737 and 1839 transcripts in HeLa, HUVEC and RVSMC, respectively, that were highly correlated between two treatments (p<0.0001; R2>0.62). Among these Na+i/K+i-sensitive genes, 80 transcripts were common for all three types of cells. To establish if changes in gene expression are dependent on increases in [Ca2+]i, we performed identical experiments in Ca2+-free media supplemented with extracellular and intracellular Ca2+ chelators. Surprisingly, this procedure elevated rather than decreased the number of ubiquitous and cell-type specific Na+i/K+i-sensitive genes. Among the ubiquitous Na+i/K+i-sensitive genes whose expression was regulated independently of the presence of Ca2+ chelators by more than 3-fold, we discovered several transcription factors (Fos, Jun, Hes1, Nfkbia), interleukin-6, protein phosphatase 1 regulatory subunit, dual specificity phosphatase (Dusp8), prostaglandin-endoperoxide synthase 2, cyclin L1, whereas expression of metallopeptidase Adamts1, adrenomedulin, Dups1, Dusp10 and Dusp16 was detected exclusively in Ca2+-depleted cells. Overall, our findings indicate that Ca2+i-independent mechanisms of excitation-transcription coupling are involved in transcriptomic alterations triggered by elevation of the [Na+]i/[K+]i ratio. There results likely have profound implications for normal and pathological regulation of mammalian cells, including sustained excitation of neuronal cells, intensive exercise and ischemia-triggered disorders

Topographical and Biological Evidence Revealed FTY720-Mediated Anergy-Polarization of Mouse Bone Marrow-Derived Dendritic Cells In Vitro

Abnormal inflammations are central therapeutic targets in numerous infectious and autoimmune diseases. Dendritic cells (DCs) are involved in these inflammations, serving as both antigen presenters and proinflammatory cytokine providers. As an immuno-suppressor applied to the therapies of multiple sclerosis and allograft transplantation, fingolimod (FTY720) was shown to affect DC migration and its crosstalk with T cells. We posit FTY720 can induce an anergy-polarized phenotype switch on DCs in vitro, especially upon endotoxic activation. A lipopolysaccharide (LPS)-induced mouse bone marrow-derived dendritic cell (BMDC) activation model was employed to test FTY720-induced phenotypic changes on immature and mature DCs. Specifically, methods for morphology, nanostructure, cytokine production, phagocytosis, endocytosis and specific antigen presentation studies were used. FTY720 induced significant alterations of surface markers, as well as decline of shape indices, cell volume, surface roughness in LPS-activated mature BMDCs. These phenotypic, morphological and topographical changes were accompanied by FTY720-mediated down-regulation of proinflammatory cytokines, including IL-6, TNF-α, IL-12 and MCP-1. Together with suppressed nitric oxide (NO) production and CCR7 transcription in FTY720-treated BMDCs with or without LPS activation, an inhibitory mechanism of NO and cytokine reciprocal activation was suggested. This implication was supported by the impaired phagocytotic, endocytotic and specific antigen presentation abilities observed in the FTY720-treated BMDCs. In conclusion, we demonstrated FTY720 can induce anergy-polarization in both immature and LPS-activated mature BMDCs. A possible mechanism is FTY720-mediated reciprocal suppression on the intrinsic activation pathway and cytokine production with endpoint exhibitions on phagocytosis, endocytosis, antigen presentation as well as cellular morphology and topography

OPTIMIZATION OF THE MOLECULAR DIAGNOSIS OF ALLERGIC DISEASES THROUGH THE USE OF CCD-BLOCKERS

Background. The development of methodological approaches aimed to overcome non-specific reactions caused by the presence of antibodies to CCD, in order to assign a rational molecular diagnosis is relevant and economically reasonable. Goal. Optimization of the tactics of serological examination of patients with multiple reactions to allergens. Material and Methods. 2197 patients were examined for IgE antibodies to plant and household respiratory allergens, of these 84 patients with multiple reactions were retested on blots similar to those used during the initial examination after the absorption of serum by CCD-blocker. After that 33 patients underwent component-resolved diagnosis for birch and timothy grass allergens. Results. The prognostic value of the absence of IgE antibodies blocking by CCD blocker reached 91.9%, meaning that a constant reaction class after blocking the serum with a probability of 91.9% did not require molecular diagnostics. The predictive value of the complete disappearance of the marker after blocking was 86.2%, so antibodies to recombinant allergens could be detected only in 13.8% patients. Conclusion. The use of CCD-blocker in patients with polysensitization allows eliminating false positive reactions and optimizing the subsequent prescription of adequate molecular diagnostics

Iron-Phosphate Ceramics for Solidification of Mixed Low-Level Waste

A method of immobilizing mixed low-level waste is provided which uses low cost materials and has a relatively long hardening period. The method includes: forming a mixture of iron oxide powders having ratios, in mass %, of FeO: Fe{sub 2}O{sub 3}: Fe{sub 3}O{sub 4} equal to 25-40: 40-10: 35-50, or weighing a definite amount of magnitite powder. Metallurgical cinder can also be used as the source of iron oxides. A solution of the orthophosphoric acid, or a solution of the orthophosphoric acid and ferric oxide, is formed and a powder phase of low-level waste and the mixture of iron oxide powders or cinder (or magnetite powder) is also formed. The acid solution is mixed with the powder phase to form a slurry with the ratio of components (mass %) of waste: iron oxide powders or magnitite: acid solution = 30-60: 15-10: 55-30. The slurry is blended to form a homogeneous mixture which is cured at room temperature to form the final product