81 research outputs found

    Роль и место иностранного языка в профессиональной компетентности преподавателей технических специальностей

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    Раскрывается состав профессиональной компетентности преподавателей неязыковых вузов для выявления особенностей типологии ключевых компетенций, определяющих содержание иноязычного компонента. Автор предлагает рассматривать иноязычную профессионально-коммуникативную компетенцию как эффективное средство реализации иноязычной переподготовки преподавателей неязыковых вузов

    Selective killing of human immunodeficiency virus infected cells by non-nucleoside reverse transcriptase inhibitor-induced activation of HIV protease

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    <p>Abstract</p> <p>Background</p> <p>Current antiretroviral therapy against human immunodeficiency virus (HIV-1) reduces viral load and thereby prevents viral spread, but it cannot eradicate proviral genomes from infected cells. Cells in immunological sanctuaries as well as cells producing low levels of virus apparently contribute to a reservoir that maintains HIV persistence in the presence of highly active antiretroviral therapy. Thus, accelerated elimination of virus producing cells may represent a complementary strategy to control HIV infection. Here we sought to exploit HIV protease (PR) related cytotoxicity in order to develop a strategy for drug induced killing of HIV producing cells. PR processes the viral Gag and Gag-Pol polyproteins during virus maturation, but is also implicated in killing of virus producing cells through off-target cleavage of host proteins. It has been observed previously that micromolar concentrations of certain non-nucleoside reverse transcriptase inhibitors (NNRTIs) can stimulate intracellular PR activity, presumably by enhancing Gag-Pol dimerization.</p> <p>Results</p> <p>Using a newly developed cell-based assay we compared the degree of PR activation displayed by various NNRTIs. We identified inhibitors showing higher potency with respect to PR activation than previously described for NNRTIs, with the most potent compounds resulting in ~2-fold increase of the Gag processing signal at 250 nM. The degree of enhancement of intracellular Gag processing correlated with the compound's ability to enhance RT dimerization in a mammalian two-hybrid assay. Compounds were analyzed for their potential to mediate specific killing of chronically infected MT-4 cells. Levels of cytotoxicity on HIV infected cells determined for the different NNRTIs corresponded to the relative degree of drug induced intracellular PR activation, with CC<sub>50 </sub>values ranging from ~0.3 μM to above the tested concentration range (10 μM). Specific cytotoxicity was reverted by addition of PR inhibitors. Two of the most active compounds, VRX-480773 and GW-678248, were also tested in primary human cells and mediated cytotoxicity on HIV-1 infected peripheral blood mononuclear cells.</p> <p>Conclusion</p> <p>These data present proof of concept for targeted drug induced elimination of HIV producing cells. While NNRTIs themselves may not be sufficiently potent for therapeutic application, the results provide a basis for the development of drugs exploiting this mechanism of action.</p

    Electron-lattice interactions strongly renormalize the charge transfer energy in the spin-chain cuprate Li2_2CuO2_2

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    Strongly correlated insulators are broadly divided into two classes: Mott-Hubbard insulators, where the insulating gap is driven by the Coulomb repulsion UU on the transition-metal cation, and charge-transfer insulators, where the gap is driven by the charge transfer energy Δ\Delta between the cation and the ligand anions. The relative magnitudes of UU and Δ\Delta determine which class a material belongs to, and subsequently the nature of its low-energy excitations. These energy scales are typically understood through the local chemistry of the active ions. Here we show that the situation is more complex in the low-dimensional charge transfer insulator Li2_\mathrm{2}CuO2_\mathrm{2}, where Δ\Delta has a large non-electronic component. Combining resonant inelastic x-ray scattering with detailed modeling, we determine how the elementary lattice, charge, spin, and orbital excitations are entangled in this material. This results in a large lattice-driven renormalization of Δ\Delta, which significantly reshapes the fundamental electronic properties of Li2_\mathrm{2}CuO2_\mathrm{2}.Comment: Nature Communications, in pres

    Investigating the association between occupational exposure to asbestos and ovarian carcinoma: results from a pilot study in Germany

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    Background The aim of this pilot study was to assess the feasibility of a large-scale epidemiologic investigation elucidating the quantitative association between occupational exposure to asbestos and ovarian cancer in former German asbestos workers. Methods Between December 2017 and May 2018, a random sample of one thousand insured woman registered at the health service of a German trade association as formerly occupationally exposed to asbestos were invited to participate in a pilot study. Participation included a phone interview using a standardised questionnaire. The feasibility of the project was evaluated using a priori defined criteria. They included response, number of cases, eligibility of the questionnaire data for exact estimation of asbestos fibre-years, and availability of relevant medical documentation (imaging procedures, medical reports, and histologic materials). Results The response (17%) was clearly below the intended number of 60%. With six tumour suspects, of which two could be confirmed by medical documents, the number of cases was within the expected range of two to eleven cases. Exact asbestos fibre-year estimations could be performed for 29% of all interviewees, but only for one suspected case. Medical documentation could be collected for only few participants, while no histology reports could be obtained for all cases. Thus, only the feasibility criterion of the expected number of cases was fulfilled. Conclusion The results of the pilot study indicate that the planned project is feasible only to a very limited extent. For further planning of the study, measures to improve recruitment of participants are necessary

    A Minimally Replicative HIV-2 Live-Virus Vaccine ProtectsM. nemestrinafrom Disease after HIV-2287Challenge

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    AbstractM. nemestrinaimmunized with an apathogenic HIV-2 molecular clone (HIV-2KR) were protected from CD4 decline and disease upon challenge with HIV-2287, after any immunizing virus could be detected. Higher but not lower inocula of HIV-2KRwere protective against intravenous inoculation of either 105or 101TCID50of HIV-2287. Protected animals displayed substantial reductions in PBMC proviral burden (1–3 logs), viral titers (1–2 logs), and plasma viral RNA (2–4 logs) compared to unprotected or naive animals as early as 1 week postinfection. Plasma viral RNA became undetectable after 24 weeks in protected animals, but remained high in unprotected animals. No viral RNA was present in the spleen of the protected animal necropsied more than a year after challenge (though viral DNA was still present). No neutralizing responses could be demonstrated, but CTL activity was detected sooner and at higher levels after challenge in protected than in unprotected macaques. In this novel HIV-2 vaccine model, protection was clearly dose-dependent, and clearance of challenge virus RNA from the plasma did not require detectable ongoing replication of the immunizing virus at the time of challenge

    Overview of ASDEX Upgrade results

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    Recent results from the ASDEX Upgrade experimental campaigns 2001 and 2002 are presented. An improved understanding of energy and particle transport emerges in terms of a 'critical gradient' model for the temperature gradients. Coupling this to particle diffusion explains most of the observed behaviour of the density profiles, in particular, the finding that strong central heating reduces the tendency for density profile peaking. Internal transport barriers (ITBs) with electron and ion temperatures in excess of 20 keV (but not simultaneously) have been achieved. By shaping the plasma, a regime with small type II edge localized modes (ELMs) has been established. Here, the maximum power deposited on the target plates was greatly reduced at constant average power. Also, an increase of the ELM frequency by injection of shallow pellets was demonstrated. ELM free operation is possible in the quiescent H-mode regime previously found in DIII-D which has also been established on ASDEX Upgrade. Regarding stability, a regime with benign neoclassical tearing modes (NTMs) was found. During electron cyclotron current drive (ECCD) stabilization of NTMs, βN could be increased well above the usual onset level without a reappearance of the NTM. Electron cyclotron resonance heating and ECCD have also been used to control the sawtooth repetition frequency at a moderate fraction of the total heating power. The inner wall of the ASDEX Upgrade vessel has increasingly been covered with tungsten without causing detrimental effects on the plasma performance. Regarding scenario integration, a scenario with a large fraction of noninductively driven current (≥50%), but without ITB has been established. It combines improved confinement (τE/τITER98 ≈ 1.2) and stability (βN ≤ 3.5) at high Greenwald fraction (ne/nGW ≈ 0.85) in steady state and with type II ELMy edge and would offer the possibility for long pulses with high fusion power at reduced current in ITER
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