24 research outputs found

    A decision-based perspective for the design of methods for systems design

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    Organization of material, a definition of decision based design, a hierarchy of decision based design, the decision support problem technique, a conceptual model design that can be manufactured and maintained, meta-design, computer-based design, action learning, and the characteristics of decisions are among the topics covered

    Isolation of a Human Anti-HIV gp41 Membrane Proximal Region Neutralizing Antibody by Antigen-Specific Single B Cell Sorting

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    Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER). We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb) against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673–680) and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (VH1-69) and variable kappa light chain (VK3-20) gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672–680). These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection

    A study of CP violation in B-+/- -> DK +/- and B-+/- -> D pi(+/-) decays with D -> (KSK +/-)-K-0 pi(-/+) final states

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    A first study of CP violation in the decay modes B±→[KS0K±π∓]Dh±B^\pm\to [K^0_{\rm S} K^\pm \pi^\mp]_D h^\pm and B±→[KS0K∓π±]Dh±B^\pm\to [K^0_{\rm S} K^\mp \pi^\pm]_D h^\pm, where hh labels a KK or π\pi meson and DD labels a D0D^0 or D‟0\overline{D}^0 meson, is performed. The analysis uses the LHCb data set collected in pppp collisions, corresponding to an integrated luminosity of 3 fb−1^{-1}. The analysis is sensitive to the CP-violating CKM phase Îł\gamma through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of Îł\gamma using other decay modes

    Studies of beauty baryon decays to D0ph− and Λ+ch− final states

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    Study of forward Z + jet production in pp collisions at √s=7 TeV

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    A measurement of the Z(→Ό+Ό−)Z(\rightarrow\mu^+\mu^-)+jet production cross-section in pppp collisions at a centre-of-mass energy s=7\sqrt{s} = 7 TeV is presented. The analysis is based on an integrated luminosity of 1.0 fb−11.0\,\text{fb}^{-1} recorded by the LHCb experiment. Results are shown with two jet transverse momentum thresholds, 10 and 20 GeV, for both the overall cross-section within the fiducial volume, and for six differential cross-section measurements. The fiducial volume requires that both the jet and the muons from the Z boson decay are produced in the forward direction (2.0<η<4.52.0<\eta<4.5). The results show good agreement with theoretical predictions at the second-order expansion in the coupling of the strong interaction.A measurement of the Z(→Ό+Ό−)Z(\rightarrow\mu^+\mu^-)+jet production cross-section in pppp collisions at a centre-of-mass energy s=7\sqrt{s} = 7 TeV is presented. The analysis is based on an integrated luminosity of 1.0 fb−11.0\,\text{fb}^{-1} recorded by the LHCb experiment. Results are shown with two jet transverse momentum thresholds, 10 and 20 GeV, for both the overall cross-section within the fiducial volume, and for six differential cross-section measurements. The fiducial volume requires that both the jet and the muons from the Z boson decay are produced in the forward direction (2.0<η<4.52.0<\eta<4.5). The results show good agreement with theoretical predictions at the second-order expansion in the coupling of the strong interaction

    Measurement of Upsilon production in collisions at root s=2.76 TeV

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    The production of ΄(1S)\Upsilon(1S), ΄(2S)\Upsilon(2S) and ΄(3S)\Upsilon(3S) mesons decaying into the dimuon final state is studied with the LHCb detector using a data sample corresponding to an integrated luminosity of 3.3 pb−1pb^{-1} collected in proton-proton collisions at a centre-of-mass energy of s=2.76\sqrt{s}=2.76 TeV. The differential production cross-sections times dimuon branching fractions are measured as functions of the ΄\Upsilon transverse momentum and rapidity, over the ranges $p_{\rm T} Upsilon(1S) X) x B(Upsilon(1S) -> mu+mu-) = 1.111 +/- 0.043 +/- 0.044 nb, sigma(pp -> Upsilon(2S) X) x B(Upsilon(2S) -> mu+mu-) = 0.264 +/- 0.023 +/- 0.011 nb, sigma(pp -> Upsilon(3S) X) x B(Upsilon(3S) -> mu+mu-) = 0.159 +/- 0.020 +/- 0.007 nb, where the first uncertainty is statistical and the second systematic

    Contemporary developments in Green (environmental) HRM scholarship

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    This article reviews the contemporary literature on Green Human Resource Management (GHRM) to contextually frame the seven articles appearing in this Special Issue. Review findings reveal the embedded nature of GHRM workplace- level practices and additional research needing to focus on HR systems, individual behaviors and emerging theoretical lenses. As a set, the articles herein span green recruitment, competencies, employee participation, financial/environmental performance links, and contextual issues utilizing national culture, paradox, and stake- holder theories. By recognizing such multi-level dynamics, HRM scholars and practitioners can enhance GHRM initiatives that stimulate progress toward work- place environmental sustainability. Keywords: environment; green; human resources; organizations; sustainabilit

    The 3T3 neutral red uptake phototoxicity test:practical experience and implications for phototoxicity testing - the report of an ECVAM-EFPIA workshop

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    This is the report from the “ECVAM-EFPIA workshop on 3T3 NRU Phototoxicity Test: Practical Experience and Implications for Phototoxicity Testing”, jointly organized by ECVAM and EFPIA and held on the 25-27 October 2010 in Somma Lombardo, Italy. The European Centre for the Validation of Alternative Methods (ECVAM) was established in 1991 within the European Commission Joint Research, based on a Communication from the European Commission1. The main objective of ECVAM is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine and replace the use of laboratory animals. The European Federation of Pharmaceuticals Industries and Association (EFPIA) represent the pharmaceutical industry operating in Europe. Through its direct membership of 31 national associations and 40 leading pharmaceutical companies, EFPIA is the voice on the EU scene of 2,200 companies committed to researching, developing and bringing to patients new medicines that improve health and the quality of life around the world. The workshop, co-chaired by Joachim Kreysa (ECVAM) and Phil Wilcox (GSK, EFPIA) involved thirty-five experts from academia, regulatory authorities and industry that were invited to contribute with their experiences in the field. The main objectives of the workshop were: - to present 'in use' experience of the pharmaceutical industry with the 3T3 Neutral Red Uptake Phototoxicity Test (3T3 NRU-PT), - to discuss why it differs from the results in the original validation exercise, - to discuss technical issues and - consider ways to improve the usability of the 3T3 NRU-PT for (non-topical) pharmaceuticals, e.g. by modifying technical aspects of the assay or adjusting the criteria used to classify for a positive response. During the workshop, the assay methodology was reviewed by comparing the OECD Test Guideline with the actual protocol used, data from EFPIA and JPMA ‘surveys’ were presented and possible reasons for the outcomes were discussed. Experts from cosmetics and pharmaceutical industries presented their experience with the 3T3 NRU-PT and evidence was presented for phototoxic clinical symptoms that could be linked to certain relevant molecules. Brainstorming sessions discussed if the 3T3 NRU-PT needed to be improved and whether alternatives to the 3T3 NRU-PT exist. Finally, the view point from EU and US regulators was also presented. In the final session, the conclusions of the meeting were summarised with action points. It was concluded that the 3T3 NRU-PT is a hazard-based assay with a high level of sensitivity. It is relevant and an accepted test that correctly identifies non-phototoxic materials. However, positive results in the 3T3 NRU-PT often do not translate into a clinical phototoxicity risk. Possible ways to improve the practical use of this assay include: (i.) implementation of absorption criteria as a means to reduce the number of materials tested, (ii.) limit the highest concentration tested, and (iii.) consider modifying the criteria used to identify “positives” in the test.JRC.I.5-Systems Toxicolog
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