Mechanisms of Producing Primordial Black Holes and Their Evolution

Primordial black holes have become a highly intriguing and captivating field of study in cosmology due to their potential theoretical and observational significance. This review delves into a variety of mechanisms that could give rise to PBHs and explores various methods for examining their evolution through mass accretion

In Vitro and in Silico Liver Models: Current Trends, Challenges and Opportunities

Most common drug development failures originate from either bioavailability problems, or unexpected toxic effects. The culprit is often the liver, which is responsible for biotransformation of a majority of xenobiotics. Liver may be modeled using liver on a chip devices, which may include established cell lines, primary human cells, and stem cell-derived hepatocyte-like cells. The choice of biological material along with its processing and maintenance greatly influence both the device performance and the resultant toxicity predictions. Impediments to the development of liver on a chip technology include the problems with standardization of cells, limitations imposed by culturing and the necessity to develop more complicated fluidic contours. Fortunately, recent breakthroughs in the development of cell-based reporters, including ones with fluorescent label, permits monitoring of the behavior of the cells embed into the liver on a chip devices. Finally, a set of computational approaches has been developed to model both particular toxic response and the homeostasis of human liver as a whole; these approaches pave a way to enhance the in silico stage of assessment for a potential toxicity

Clusters of primordial black holes

The Primordial Black Holes (PBHs) are gradually involved into consideration as the phenomenon having reliable basis. We discuss here the possibility of their agglomeration into clusters that may have several prominent observable features. The clusters can form due to closed domain walls appearance in the natural and the hybrid inflation with subsequent evolution and gravitational collapse. Early dustlike stages of dominance of heavy metastable dissipative particles, at which star-like objects are formed, can also naturally lead to formation of black hole clusters, remaining in the Universe after decay of particles, from which they have originated. The dynamical evolution of such clusters discussed here is of the crucial importance. Such a model inherits all the advantages of the single PBHs like possible explanation of existence of supermassive black holes (origin of the early quasars), binary BH merges registered by LIGO/Virgo through gravitational waves, contribution to reionization of the Universe, but also has additional benefits. The cluster could alleviate or completely avoid existing constraints on the single PBH abundance making PBHs a real dark matter candidate. The most of existing constraints on (single) PBH density should be re-considered as applied to the clusters. Also unidentified cosmic gamma-ray point-like sources could be (partially) accounted for by them. One can conclude, that it seems really to be much more viable model with respect to the single PBHs.Comment: v2: both the text and bibliography are essentially extended, coincides with EPJC versio

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Военно-морская сила России на тихоокеанском направлении

The article gives the analytical consideration of the sea power of Russia in the Pacific Ocean in today’s period of international relations. After the collapse of the USSR, the main interest of Russia's foreign policy was focused on the European region and the waters of the Atlantic and the Arctic Ocean. The changes in the global structure of international relations caused Russia to revise the foundations of its policy in the Pacific region seas. The recognition that the economic “center of gravity” is shifting to the Asia-Pacific region is becoming widespread. That is why the determining the nature and scale of the naval forces of Russia in the Pacific direction seems relevant and timely.Статья посвящена аналитическому рассмотрению морской силы России на Тихом океане в текущий период развития международных отношений. После распада СССР основное внимание внешней политики России было приковано к европейскому региону и акватории Атлантического и Северного Ледовитого океана. После начала изменений глобальной структуры международных отношений, Россия приступила к пересмотру основ своей политики в акватории тихоокеанского региона. Признание того, что экономический «центр тяжести» смещается в АТР, становится повсеместным. Вот почему обращение к проблеме определения характера и масштабов военно-морской силы России на тихоокеанском направлении представляется актуальным и своевременным

The Correlation of Ten Immune Checkpoint Gene Expressions and Their Association with Gastric Cancer Development

In the immunotherapy based on immune checkpoint inhibition (IC), additional ICs are being studied to increase its effectiveness. An almost unstudied feature is the possible co-expression of ICs, which can determine the therapeutic efficacy of their inhibition. For the selection of promising ICs, information on the association of their expression with cancer development may be essential. We have obtained data on the expression correlation of ADAM17, PVR, TDO2, CD274, CD276, CEACAM1, IDO1, LGALS3, LGALS9, and HHLA2 genes in gastric cancer (GC). All but one, TDO2, have other IC genes with co-expression at some stage. At the metastatic stage, the expression of the IDO1 does not correlate with any other gene. The correlations are positive, but the expressions of the CD276 and CEACAM1 genes are negatively correlated. The expression of TDO2 and LGALS3 is associated with GC metastasis. The expression of TDO2 four-fold higher in metastatic tumors than in non-metastatic tumors, but LGALS3 was two-fold lower. The differentiation is associated with IDO1. The revealed features of TDO2, with a significant increase in expression at the metastatic stage and the absence of other IC genes with correlated expression indicates that the prospect of inhibiting TDO2 in metastatic GC. IDO1 may be considered for inhibition in low-differentiated tumors

Abrupt transition from fractional crystallization to magma mixing at Gorely volcano (Kamchatka) after caldera collapse

A series of large caldera-forming eruptions (361–38 ka) transformed Gorely volcano, southern Kamchatka Peninsula, from a shield-type system dominated by fractional crystallization processes to a composite volcanic center, exhibiting geochemical evidence of magma mixing. Old Gorely, an early shield volcano (700–361 ka), was followed by Young Gorely eruptions. Calc-alkaline high magnesium basalt to rhyolite lavas have been erupted from Gorely volcano since the Pleistocene. Fractional crystallization dominated evolution of the Old Gorely magmas, whereas magma mixing is more prominent in the Young Gorely eruptive products. The role of rechargeevacuation processes in Gorely magma evolution is negligible (a closed magmatic system); however, crustal rock assimilation plays a significant role for the evolved magmas. Most Gorely magmas differentiate in a shallow magmatic system at pressures up to 300 MPa, ∼3 wt% H2O, and oxygen fugacity of ∼QFM + 1.5 log units. Magma temperatures of 1123–1218 °C were measured using aluminum distribution between olivine and spinel in Old and Young Gorely basalts. The crystallization sequence of major minerals for Old Gorely was as follows: olivine and spinel (Ol + Sp) for mafic compositions (more than 5 wt% of MgO); clinopyroxene and plagioclase crystallized at ∼5 wt% of MgO (Ol +Cpx + Plag) and magnetite at ∼3.5 wt% of MgO (Ol + Cpx + Plag +Mt). We show that the shallow magma chamber evolution of Old Gorely occurs under conditions of decompression and degassing. We find that the caldera-forming eruption(s) modified the magma plumbing geometry. This led to a change in the dominant magma evolution process from fractional crystallization to magma mixing. We further suggest that disruption of the magma chamber and accompanying change in differentiation process have the potential to transform a shield volcanic system to that of composite cone on a global scale

Expression of Immune Checkpoints in Malignant Tumors: Therapy Targets and Biomarkers for the Gastric Cancer Prognosis

To increase the effectiveness of anticancer therapy based on immune checkpoint (IC) inhibition, some ICs are being investigated in addition to those used in clinic. We reviewed data on the relationship between PD-L1, B7-H3, B7-H4, IDO1, Galectin-3 and -9, CEACAM1, CD155, Siglec-15 and ADAM17 expression with cancer development in complex with the results of clinical trials on their inhibition. Increased expression of the most studied ICs—PD-L1, B7-H3, and B7-H4—is associated with poor survival; their inhibition is clinically significant. Expression of IDO1, CD155, and ADAM17 is also associated with poor survival, including gastric cancer (GC). The available data indicate that CD155 and ADAM17 are promising targets for immune therapy. However, the clinical trials of anti-IDO1 antibodies have been unsatisfactory. Expression of Galectin-3 and -9, CEACAM1 and Siglec-15 demonstrates a contradictory relationship with patient survival. The lack of satisfactory results of these IC inhibitor clinical trials additionally indicates the complex nature of their functioning. In conclusion, in many cases it is important to analyze the expression of other participants of the immune response besides target IC. The PD-L1, B7-H3, B7-H4, IDO1 and ADAM17 may be considered as candidates for prognosis markers for GC patient survival

Convergent In Vivo and In Vitro Selection of Ceftazidime Resistance Mutations at Position 167 of CTX-M-3 β-Lactamase in Hypermutable Escherichia coli Strains▿

We report on a novel CTX-M extended-spectrum β-lactamase (ESBL), designated CTX-M-42, with enhanced activity toward ceftazidime. CTX-M-42 was identified in a hypermutable Escherichia coli nosocomial isolate (isolate Irk2320) and is a Pro167Thr amino acid substitution variant of CTX-M-3. By molecular typing of ESBL-producing E. coli strains previously isolated in the same hospital ward, we were able to identify a putative progenitor (strain Irk1224) of Irk2320, which had a mutator phenotype and harbored the CTX-M-3 β-lactamase. To reproduce the natural evolution of CTX-M-3, we selected for ceftazidime resistance mutations in blaCTX-M-3 gene in vitro both in clinical isolate Irk1224 and in laboratory-derived hypermutable (mutD5) strain GM2995. These experiments yielded CTX-M-3Pro167Ser and CTX-M-3Asn136Lys mutants which conferred higher levels of resistance to ceftazidime than to cefotaxime. CTX-M-3Asn136Lys had a level of low activity toward ampicillin, which may explain its absence from clinical isolates. We conclude that the selection of CTX-M-42 could have occurred in vivo following treatment with ceftazidime and was likely facilitated by the hypermutable background

Hybrid Ultra-Low-Radioactive Material for Protecting Dark Matter Detector from Background Neutrons

A laboratory technology for a new ultra-low background hybrid material (HM) which meets the requirements for neutron absorption with simultaneous neutron detection has been developed. The technology and hybrid material can be useful for future low background underground detectors designed to directly search for dark matter with liquid noble gases. The HM is based on a polymethylmethacrylate (PMMA) polymer matrix in which gadolinium nuclei are homogeneously distributed up to 1.5 wt% concentration in polymer slabs of 5 cm thickness. To determine the 65 impurity elements by the inductively coupled plasma mass-spectrometry (ICP-MS) technique in the Gd-based preparations in 100–0.01 ppb range, the corresponding method has been developed. Limits of determination (LD) of 0.011 ppb for uranium, and 0.016 ppb for thorium were achieved. An analysis of Gd raw materials showed that the lowest contents of U and Th (1.2–0.2 ppb) were detected in commercial Gd-based preparations. They were manufactured either from secondary raw materials (extraction phosphoric acid) or from mineral raw materials formed in sedimentary rocks (phosphogypsum). To produce the Gd-doped HM the commercial GdCl3 was purified and used for synthesis of low-background coordination compound, namely, acetylacetonate gadolinium (Gd(acac)3) with U/Th contents less than LD. When dissolving Gd(acac)3 in methylmethacrylate, the true solution was obtained and its further thermal polymerization allowed fabrication of the Gd-doped PMMA with ultra-low background