Immunogenicity of a universal HIV-1 vaccine vectored by DNA, MVA and CHADV-63 in a Phase I/IIA clinical trial

Background The major challenge facing both antibody and T cell-eliciting vaccines against HIV-1 is the extreme variability of the HIV-1 genome: a successful vaccine has to effectively target diverse HIV-1 strains circulating in the population and then must deal with ongoing virus escape in infected individuals. To address these issues, we assembled a vaccine immunogen HIVconsv from the functionally most conserved regions (not epitopes) of the HIV-1 proteome. Methods A gene coding for the HIVconsv immunogen was inserted into plasmid DNA (D), modified vaccinia virus Ankara (MVA; M) and non-replicating adenovirus of a chimpanzee origin ChAdV-63 (C). Currently, combined heterologous prime-boost regimens of these vaccines, namely CM, DDDCM and DDDMC, are being evaluated in a phase I/IIa trial HIV-CORE002 in healthy HIV-1/2-negative volunteers in Oxford. Results Preliminary data indicate that the vaccines are well tolerated and show high immunogenicity. Following the CM regimen, vaccine-induced T cell frequencies reached a median of 5150 (range 1475 to 16495) SFU/106 PMBC ex vivo one week post MVA vaccination. DNA priming increased subsequent T cell responses to ChAdV-63 vaccination (median: C 577 and DDDC 1328 SFU/106 PBMC) and ELISpot responses again peaked 1 week following MVA (median 4500; range 2260-7960 SFU/106 PBMC). Matrix analyses of the participants following CM vaccination showed that T cells responded to a range of peptides across the length of HIVconsv. The CM regimen elicited IFN-γ in both CD4+ and CD8+ T cell subsets and polyfunctional (IFN-γ & TNF-α) responses to HIVconsv peptides. Conclusion Presented data will be very much work in progress. Nevetheless, the HIVconsv vaccines have so far induced T cell responses superior to other HIV-1 vaccine candidates tested to date. ChAdV-63 is the first adenovirus of chimp origin delivering an HIV-1-derived immunogen that has reached the clinic. The work is supported by Medical Research Council UK

First-principles extrapolation method for accurate CO adsorption energies on metal surfaces

We show that a simple first-principles correction based on the difference between the singlet-triplet CO excitation energy values obtained by DFT and high-level quantum chemistry methods yields accurate CO adsorption properties on a variety of metal surfaces. We demonstrate a linear relationship between the CO adsorption energy and the CO singlet-triplet splitting, similar to the linear dependence of CO adsorption energy on the energy of the CO 2$\pi$* orbital found recently {[Kresse {\em et al.}, Physical Review B {\bf 68}, 073401 (2003)]}. Converged DFT calculations underestimate the CO singlet-triplet excitation energy $\Delta E_{\rm S-T}$, whereas coupled-cluster and CI calculations reproduce the experimental $\Delta E_{\rm S-T}$. The dependence of $E_{\rm chem}$ on $\Delta E_{\rm S-T}$ is used to extrapolate $E_{\rm chem}$ for the top, bridge and hollow sites for the (100) and (111) surfaces of Pt, Rh, Pd and Cu to the values that correspond to the coupled-cluster and CI $\Delta E_{\rm S-T}$ value. The correction reproduces experimental adsorption site preference for all cases and obtains $E_{\rm chem}$ in excellent agreement with experimental results.Comment: Table sent as table1.eps. 3 figure

Anthropogenic alteration of nutrient supply increases the global freshwater carbon sink

Lakes have a disproportionate effect on the global carbon (C) cycle relative to their area, mediating C transfer from land to atmosphere, and burying organic-C in their sediments. The magnitude and temporal variability of C burial is, however, poorly constrained, and the degree to which humans have influenced lake C cycling through landscape alteration has not been systematically assessed. Here, we report global and biome specific trajectories of lake C sequestration based on 516 lakes and show that some lake C burial rates (i.e., those in tropical forest and grassland biomes) have quadrupled over the last 100 years. Global lake C-sequestration (~0.12 Pg year-1) has increased by ~72 Tg year-1 since 1900, offsetting 20% of annual CO2 freshwater emissions rising to ~30% if reservoirs are included and contributing to the residual continental C sink. Nutrient availability explains ~70% of the observed increase, while rising temperatures have a minimal effect

Global mobility of professionals and the transfer of tacit knowledge in multinational service firms

Purpose: The use of expatriates to transfer individual and organizational know-how and knowledge is a practice widely used by multinational enterprises (MNEs). However, for service firms, the mobility of employees across national borders depends on the commitments made by countries under the General Agreement on Trade in Services (GATS). In particular, the Mode 4 form of supply under GATS can limit the ability of professionals to enter a particular country and can restrict the intra-organizational transfer of knowledge in multinational service firms. The purpose of this paper is to investigate how MNEs attempt to overcome these barriers and transfer knowledge through their global network. Design/methodology/approach: Using Nonaka and Takeuchi’s SECI model of knowledge transfer, the authors study the intra-organizational knowledge transfer practices of an Indian multinational service firm. Semi-structured interviews were conducted with 20 key informants involved with the organization. Findings: The company uses global teams to transfer tacit knowledge and facilitates inpatriation through an internship program that helps the firm overcome nationality requirement that restricts the movement of their managers to other countries, which in turn limits their ability to transfer knowledge in the intra-organizational setting. The company uses the services of a not-for-profit youth organization that helps recruit interns for the program and also facilitates the relationship with the Indian Government, which provides support for this initiative by reducing barriers to entry for the interns. Originality/value: This study takes the unique approach of studying barriers to movement of professionals and a firm’s strategic response. It identifies the pressures and barriers that companies face in the global economy and highlights the role of government agencies and other stakeholders in facilitating or restricting the transfer of knowledge within a firm’s international network. The paper articulates the implications for policy and practice, and a future research agenda

Grasping the phenomenology of sporting bodies

The last two decades have witnessed a vast expansion in research and writing on the sociology of the body and on issues of embodiment. Indeed, both sociology in general and the sociology of sport specifically have well heeded the long-standing and vociferous calls ‘to bring the body back in’ to social theory. It seems particularly curious therefore that the sociology of sport has to-date addressed this primarily at a certain abstract, theoretical level, with relatively few accounts to be found that are truly grounded in the corporeal realities of the lived sporting body; a ‘carnal sociology’ of sport, to borrow Crossley’s (1995) expression. To portray and understand more fully this kind of embodied perspective, it is argued, demands engaging with the phenomenology of the body, and this article seeks to contribute to a small but growing literature providing this particular form of ‘embodied’ analysis of the body in sport. Here we identify some useful intellectual resources for developing a phenomenology of sporting experience, specifically its sensory elements, and also subsequently examine the potential for its evocative portrayal and effective analysis via different kinds of textual forms. Key words: phenomenology; sociology of the sporting body; embodiment; the sense

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters