Particle Spectra and Mass Composition in the Ultra-High Energy Region in the Framework of the Galactic Origin of Cosmic Rays

The possibility for a self-consistent description of all the basic features of the observed cosmic ray spectra and primary composition variations in the energy range of $10^{15}\div 10^{20}$ eV within the Galactic origin scenario is examined. We assume the existence of Galactic sources that accelerate particles up to $\sim 3\cdot 10^{18}Z$ eV and take into account a highly inhomogeneous (fractal-like) distribution of matter and magnetic fields in the Galaxy that leads to extremely large free paths of particles ("L\'{e}vy flights"), along with an overwhelming contribution to the cosmic ray fluxes observed above $\sim 10^{18}$ eV from particles reaching the Solar System without scattering. Our scenario was refined on the basis of recent experimental results on primary mass composition. Model predictions, which could be verified with the improved high-precision measurements in the nearest future are discussed.Comment: 5 pages, 2 figures, 19th International Symposium on Very High Energy Cosmic Ray Interactions (22-27 August 2016). Moscow, Russia. P.N. Lebedev Physical Institute of the Russian Academy of Sciences (LPI RAS

Anatomical and physiological aspects of the HIV infection pathogenesis in animal models

Understanding the entire pathogenesis of HIV infection, from penetration at the gates of infection to the induction of severe immunodeficiency, is an essential tool for the development of new treatment methods. Less than 40 years of research into the mechanisms of HIV infection that lead to the development of acquired immunodeficiency syndrome have accumulated a huge amount of information, but HIV's own unique variability identifies new whitespaces. Despite the constant improvement of the protocols of antiretroviral therapy and the success of its use, it has not yet been possible to stop the spread of HIV infection. The development of new protocols and the testing of new groups of antiretroviral drugs is possible, first of all, due to the improvement of animal models of the HIV infection pathogenesis. Their relevance, undoubtedly increases, but still depends on specific research tasks, since none of the in vivo models can comprehensively simulate the mechanism of the infection pathology in humans which leads to multi-organ damage. The aim of the review was to provide up-to-date information on known animal models of HIV infection, focusing on the method of their infection and anatomical, physiological and pathological features

Microstructure and mechanical properties of heat-resistant 12 % Cr ferritic-martensitic steel EK-181 after thermomechanical treatment

The effect of high-temperature thermomechanical treatment (TMT) with the deformation in the austenitic region on the features of microstructure, phase transformations and mechanical properties of low-activation 12% Cr ferritic-martensitic steel EK-181 is investigated. It is established, that directly after thermomechanical treatment (without tempering) the sizes and density of V(CN) particles are comparable with those after a traditional heat treatment (air quenching and tempering at 720°C, 3 h), where these particles are formed only during tempering. It causes the increasing of the yield strength of the steel up to ≈1450 MPa at room temperature and up to ≈430 MPa at the test temperature T = 650°C. The potential of microstructure modification by this treatment aimed at improving heat resistance of steel is discussed

Accumulated experience and future prospects of <i>in vivo</i> hepatitis B virus research

Nowadays, an estimated more than 300 million people live with hepatitis B virus (HBV) infection globally. One of the main goals of the World Health Organization (WHO) is to eliminate viral hepatitis by the year 2030. The study of the pathogenic and immunologic properties of HBV, as well as therapeutic substances and treatment regimens, is significantly complicated by the insufficient number of susceptible biological test subjects (animal models) and the lack of zoonotic reservoirs of the virus. In this regard, researching the properties of HBV and related hepadnaviruses provides invaluable material for understanding the biology of the pathogen and the developing methods of prevention and control of this chronic infectious disease, leading to severe hepatopathies (cirrhosis and hepatocellular carcinoma). Furthermore, prolonged HBV viremia leads to depletion of the immune system, reducing resistance against pathogens of other infections, especially those with a chronic course and socially determined spread. The aim of this research is to evaluate existing animal models of HBV infection in the context of pathogenesis, immunologic and pathomorphological features. For the first time, the hypothesis of the possible use of certain models for the research of HBV-associated socially significant infections is considered from the point of view of the development of pathomorphological features. To complete this review, we analyzed the information about the features of HBV infection models in vivo, published over the last 25 years in open sources (Web of Science, PubMed, Scopus, ScienceDirect, Springer). The main criteria for literature selection were the type of infecting agent, the observed immunologic features of the course of the infectious process and the availability of a description of the pathomorphological features in model organisms

On inconsistency of experimental data on primary nuclei spectra with sea level muon intensity measurements

For the first time a complete set of the most recent direct data on primary cosmic ray spectra is used as input into calculations of muon flux at sea level in wide energy range $E_\mu=1-3\cdot10^5$ GeV. Computations have been performed with the CORSIKA/QGSJET and CORSIKA/VENUS codes. The comparison of the obtained muon intensity with the data of muon experiments shows, that measurements of primary nuclei spectra conform to sea level muon data only up to several tens of GeV and result in essential deficit of muons at higher energies. As it follows from our examination, uncertainties in muon flux measurements and in the description of nuclear cascades development are not suitable to explain this contradiction, and the only remaining factor, leading to this situation, is underestimation of primary light nuclei fluxes. We have considered systematic effects, that may distort the results of the primary cosmic ray measurements with the application of the emulsion chambers. We suggest, that re-examination of these measurements is required with the employment of different hadronic interaction models. Also, in our point of view, it is necessary to perform estimates of possible influence of the fact, that sizable fraction of events, identified as protons, actually are antiprotons. Study of these cosmic ray component begins to attract much attention, but today nothing definite is known for the energies $>40$ GeV. In any case, to realize whether the mentioned, or some other reasons are the sources of disagreement of the data on primaries with the data on muons, the indicated effects should be thoroughly analyzed

Sequence analysis of the non-coding control region of John Cunningham virus isolates from patients with multiple sclerosis treated with natalizumab

Introduction. The John Cunningham virus (JCPyV) causes a fatal demyelinating disease of the central nervous system known as progressive multifocal leukoencephalopathy (PML). In healthy people, the JCPyV non-coding control region (NCCR) is not rearranged, while NCCRs in immunocompromised patients are characterized by frequent rearrangements and can be associated with PML development. Therefore, patients treated with natalizumab, which decreases the migration of leukocytes and monocytes through the blood-brain barrier to inflammatory foci, are at increased risk of developing PML. The purpose of the study was to analyze NCCR sequences of JCPyV isolates from patients with multiple sclerosis (MS) treated with natalizumab. Materials and methods. A total of 26 blood plasma samples and 8 cerebrospinal fluid samples were analyzed using nested PCR to study the JCPyV NCCR structure in Russian MS patients treated with natalizumab. The NCCRs present in the samples were cloned and sequenced by Sanger sequencing. All the JCPyV NCCR sequences were compared with the archetype sequence and mapped. The NCCR sequences were also examined for presence of putative transcription factor binding sites. Results. A total of 48 NCCR sequences were found. The analysis showed that up to 55% of NCCRs were identified as rearranged NCCRs, while the other were archetype-like NCCRs. All the sequences can be divided into 6 types with one dominant rearrangement pattern. This rearranged NCCR was also found in a patient with the confirmed PML diagnosis and a poor prognosis. All the rearranged NCCRs were characterized by the presence of additional transcription factor binding sites. Conclusion. The study has helped identify previously unknown NCCR patterns typical of MS patients treated with natalizumab in Russia, thus confirming the need for the further research on NCCR rearrangements in MS patients undergoing natalizumab treatment to gain better understanding of the origin of neurovirulent JCPyV variants