452 research outputs found

    Маркшейдерська школа Національного гірничого університету

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    Викладена історія створення та розвитку маркшейдерської школи в НГУ протягом 110 років.Изложена история создания и развития маркшейдерской школы в НГУ в течение 110 лет.History of creation and development ofsurveyor school is expounded in NMU during 110 years

    An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells.

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    Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells

    Performance and Mix Measurements of Indirect Drive Cu-Doped Be Implosions

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    The ablator couples energy between the driver and fusion fuel in inertial confinement fusion (ICF). Because of its low opacity, high solid density, and material properties, beryllium has long been considered an ideal ablator for ICF ignition experiments at the National Ignition Facility. We report here the first indirect drive Be implosions driven with shaped laser pulses and diagnosed with fusion yield at the OMEGA laser. The results show good performance with an average DD neutron yield of ~2 × 10[superscript 9] at a convergence ratio of R[subscript 0]/R ~ 10 and little impact due to the growth of hydrodynamic instabilities and mix. In addition, the effect of adding an inner liner of W between the Be and DD is demonstrated.United States. Dept. of Energy (Lawrence Livermore National Laboratory Contract DE-AC52-07NA27344

    Using least median of squares for structural superposition of flexible proteins

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    <p>Abstract</p> <p>Background</p> <p>The conventional superposition methods use an ordinary least squares (LS) fit for structural comparison of two different conformations of the same protein. The main problem of the LS fit that it is sensitive to outliers, i.e. large displacements of the original structures superimposed.</p> <p>Results</p> <p>To overcome this problem, we present a new algorithm to overlap two protein conformations by their atomic coordinates using a robust statistics technique: least median of squares (LMS). In order to effectively approximate the LMS optimization, the forward search technique is utilized. Our algorithm can automatically detect and superimpose the rigid core regions of two conformations with small or large displacements. In contrast, most existing superposition techniques strongly depend on the initial LS estimating for the entire atom sets of proteins. They may fail on structural superposition of two conformations with large displacements. The presented LMS fit can be considered as an alternative and complementary tool for structural superposition.</p> <p>Conclusion</p> <p>The proposed algorithm is robust and does not require any prior knowledge of the flexible regions. Furthermore, we show that the LMS fit can be extended to multiple level superposition between two conformations with several rigid domains. Our fit tool has produced successful superpositions when applied to proteins for which two conformations are known. The binary executable program for Windows platform, tested examples, and database are available from <url>https://engineering.purdue.edu/PRECISE/LMSfit</url>.</p

    Resonant nonlinear magneto-optical effects in atoms

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    In this article, we review the history, current status, physical mechanisms, experimental methods, and applications of nonlinear magneto-optical effects in atomic vapors. We begin by describing the pioneering work of Macaluso and Corbino over a century ago on linear magneto-optical effects (in which the properties of the medium do not depend on the light power) in the vicinity of atomic resonances, and contrast these effects with various nonlinear magneto-optical phenomena that have been studied both theoretically and experimentally since the late 1960s. In recent years, the field of nonlinear magneto-optics has experienced a revival of interest that has led to a number of developments, including the observation of ultra-narrow (1-Hz) magneto-optical resonances, applications in sensitive magnetometry, nonlinear magneto-optical tomography, and the possibility of a search for parity- and time-reversal-invariance violation in atoms.Comment: 51 pages, 23 figures, to appear in Rev. Mod. Phys. in Oct. 2002, Figure added, typos corrected, text edited for clarit

    Strengthening the research to policy and practice interface: exploring strategies used by research organisations working on sexual and reproductive health and HIV/AIDS

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    This commentary introduces the HARPS supplement on getting research into policy and practice in sexual and reproductive health (SRH). The papers in this supplement have been produced by the Sexual Health and HIV Evidence into Practice (SHHEP) collaboration of international research, practitioner and advocacy organizations based in research programmes funded by the UK Department for International Development

    Confab - Systematic generation of diverse low-energy conformers

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    <p>Abstract</p> <p>Background</p> <p>Many computational chemistry analyses require the generation of conformers, either on-the-fly, or in advance. We present Confab, an open source command-line application for the systematic generation of low-energy conformers according to a diversity criterion.</p> <p>Results</p> <p>Confab generates conformations using the 'torsion driving approach' which involves iterating systematically through a set of allowed torsion angles for each rotatable bond. Energy is assessed using the MMFF94 forcefield. Diversity is measured using the heavy-atom root-mean-square deviation (RMSD) relative to conformers already stored. We investigated the recovery of crystal structures for a dataset of 1000 ligands from the Protein Data Bank with fewer than 1 million conformations. Confab can recover 97% of the molecules to within 1.5 Å at a diversity level of 1.5 Å and an energy cutoff of 50 kcal/mol.</p> <p>Conclusions</p> <p>Confab is available from <url>http://confab.googlecode.com</url>.</p

    Professional development in teaching and learning for early career academic geographers: Contexts, practices and tensions

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    This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Geography in Higher Education on 16th May 2011, available online: doi: 10.1080/03098265.2011.563380This paper provides a review of the practices and tensions informing approaches to professional development for early career academic geographers who are teaching in higher education. We offer examples from Britain, Canada, Nigeria and the USA. The tensions include: institutional and departmental cultures; models that offer generic and discipline-specific approaches; the credibility of alternative settings for professional development in teaching and learning; the valuing of professional development and of teaching in academic systems of reward and recognition; and the challenges of balancing professional and personal life. We summarize concepts of good practice and suggest opportunities for future research
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