462 research outputs found
Математическое моделирование воздействия природных пожаров на здания и сооружения
В данном исследовании создается двумерная математическая модель очага горения в лесном массиве, развивающегося во времени, тем самым подвергая тепловому воздействию рядом находящееся жилое здание. Проводятся многочисленные расчеты, на основании которых построены зависимости, по результатам получены безопасные расстояния от леса до постройки и распределения температуры на стенке здания.In this study, a two-dimensional mathematical model of a burning center in a forest that develops over time is created, thereby exposing a nearby residential building to heat. Numerous calculations are carried out, on the basis of which dependencies are built, according to the results, safe distances from the forest to the building and temperature distribution on the wall of the building are obtained
On the direction of transcription of cloned genes in Neurospora crassa.
On the direction of transcription of cloned genes in Neurospora crassa
Establishment of infectious HCV virion-producing cells with newly designed full-genome replicon RNA
Hepatitis C virus (HCV) replicon systems enable in-depth analysis of the life cycle of HCV. However, the previously reported full-genome replicon system is unable to produce authentic virions. On the basis of these results, we constructed newly designed full-genomic replicon RNA, which is composed of the intact 5′-terminal-half RNA extending to the NS2 region flanked by an extra selection marker gene. Huh-7 cells harboring this full-genomic RNA proliferated well under G418 selection and secreted virion-like particles into the supernatant. These particles, which were round and 50 nm in diameter when analyzed by electron microscopy, had a buoyant density of 1.08 g/mL that shifted to 1.19 g/mL after NP-40 treatment; these figures match the putative densities of intact virions and nucleocapsids without envelope. The particles also showed infectivity in a colony-forming assay. This system may offer another option for investigating the life cycle of HCV
Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents
Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs
Chiral corrections to the vector and axial couplings of quarks and baryons
We calculate chiral corrections to the semileptonic vector and axial quark
coupling constants using a manifestly Lorentz covariant chiral quark approach
up to order O(p4) in the two- and tree-flavor picture. These couplings are then
used in the evaluation of the corresponding couplings which govern the
semileptonic transitions between octet baryon states. In the calculation of
baryon matrix elements we use a general ansatz for the spatial form of the
quark wave function, without referring to a specific realization of
hadronization and confinement of quarks in baryons. Matching the physical
amplitudes calculated within our approach to the model-independent predictions
of baryon chiral perturbation theory (ChPT) allows one to deduce the connection
between our parameters and those of baryon ChPT.Comment: 28 pages, 4 figure
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Expanding the host range of hepatitis C virus through viral adaptation
Hepatitis C virus (HCV) species tropism is incompletely understood. We have previously shown that at the level of entry, human CD81 and occludin (OCLN) comprise the minimal set of human factors needed for viral uptake into murine cells. As an alternative approach to genetic humanization, species barriers can be overcome by adapting HCV to use the murine orthologues of these entry factors. We previously generated a murine tropic HCV (mtHCV or Jc1/mCD81) strain harboring three mutations within the viral envelope proteins that allowed productive entry into mouse cell lines. In this study, we aimed to characterize the ability of mtHCV to enter and infect mouse hepatocytes in vivo and in vitro Using a highly sensitive, Cre-activatable reporter, we demonstrate that mtHCV can enter mouse hepatocytes in vivo in the absence of any human cofactors. Viral entry still relied on expression of mouse CD81 and SCARB1 and was more efficient when mouse CD81 and OCLN were overexpressed. HCV entry could be significantly reduced in the presence of anti-HCV E2 specific antibodies, suggesting that uptake of mtHCV is dependent on viral glycoproteins. Despite mtHCV's ability to enter murine hepatocytes in vivo, we did not observe persistent infection, even in animals with severely blunted type I and III interferon signaling and impaired adaptive immune responses. Altogether, these results establish proof of concept that the barriers limiting HCV species tropism can be overcome by viral adaptation. However, additional viral adaptations will likely be needed to increase the robustness of a murine model system for hepatitis C. IMPORTANCE: At least 150 million individuals are chronically infected with HCV and are at risk of developing serious liver disease. Despite the advent of effective antiviral therapy, the frequency of chronic carriers has only marginally decreased. A major roadblock in developing a vaccine that would prevent transmission is the scarcity of animal models that are susceptible to HCV infection. It is poorly understood why HCV infects only humans and chimpanzees. To develop an animal model for hepatitis C, previous efforts focused on modifying the host environment of mice, for example, to render them more susceptible to HCV infection. Here, we attempted a complementary approach in which a laboratory-derived HCV variant was tested for its ability to infect mice. We demonstrate that this engineered HCV strain can enter mouse liver cells but does not replicate efficiently. Thus, additional adaptations are likely needed to construct a robust animal model for HCV
Meson Decay Constants from Isospin Mass Splittings in the Quark Model
Decay constants of and mesons are estimated within the framework of a
heavy-quark approach using measured isospin mass splittings in the , ,
and states to isolate the electromagnetic hyperfine interaction between
quarks. The values MeV and MeV are
obtained. Only experimental errors are given; possible theoretical ambiguities,
and suggestions for reducing them, are noted.Comment: 7 pages, LaTeX, EFI-92-3
Syndecan 4 Is Involved in Mediating HCV Entry through Interaction with Lipoviral Particle-Associated Apolipoprotein E
Hepatitis C virus (HCV) is a major cause of liver disease worldwide and HCV infection represents a major health problem. HCV associates with host lipoproteins forming host/viral hybrid complexes termed lipoviral particles. Apolipoprotein E (apoE) is a lipoprotein component that interacts with heparan sulfate proteoglycans (HSPG) to mediate hepatic lipoprotein uptake, and may likewise mediate HCV entry. We sought to define the functional regions of apoE with an aim to identify critical apoE binding partners involved in HCV infection. Using adenoviral vectors and siRNA to modulate apoE expression we show a direct correlation of apoE expression and HCV infectivity, whereas no correlation exists with viral protein expression. Mutating the HSPG binding domain (HSPG-BD) of apoE revealed key residues that are critical for mediating HCV infection. Furthermore, a novel synthetic peptide that mimics apoE's HSPG-BD directly and competitively inhibits HCV infection. Genetic knockdown of the HSPG proteins syndecan (SDC) 1 and 4 revealed that SDC4 principally mediates HCV entry. Our data demonstrate that HCV uses apoE-SDC4 interactions to enter hepatoma cells and establish infection. Targeting apoE-SDC interactions could be an alternative strategy for blocking HCV entry, a critical step in maintaining chronic HCV infection
Spin-Momentum Correlations in Inclusive Semileptonic Decays of Polarized Baryons
We consider spin-momentum correlations between the spin of the bottom baryon
and the momenta of its decay products in its inclusive
semileptonic decay. We define several polar and azimuthal spin-momentum
correlation measures in different event coordinate systems. The values of the
spin-momentum correlation measures are calculated up to
using the standard OPE und HQET methods. Some of the measures turn out to be
sufficiently large to make them good candidates for a determination of the
polarization of the in e.g. decays.Comment: 13 pages, 2 figures, more numerical results added; version published
as Phys. Rev. D60, 014021 (1999
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