Targeting lentiviral vectors to antigen-specific immunoglobulins

Gene transfer into B cells by lentivectors can provide an alternative approach to managing B lymphocyte malignancies and autoreactive B cell-mediated autoimmune diseases. These pathogenic B cell Populations can be distinguished by their surface expression of monospecific immunoglobulin. Development of a novel vector system to deliver genes to these specific B cells could improve the safety and efficacy of gene therapy. We have developed an efficient rnethod to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and hi vivo. We were able to incorporate a model antigen CD20 and a fusogenic protein derived from the Sindbis virus as two distinct molecules into the lentiviral Surface. This engineered vector could specifically bind to cells expressing Surface immunoglobulin recognizing CD20 (αCD20), resulting in efficient transduction of target cells in a cognate antigen-dependent manner in vitro, and in vivo in a xenografted tumor model. Tumor suppression was observed in vivo, using the engineered lentivector to deliver a suicide gene to a xenografted tumor expressing αCD20. These results show the feasibility of engineering lentivectors to target immunoglobulin-specific cells to deliver a therapeutic effect. Such targeting lentivectors also Could potentially be used to genetically mark antigen-specific B cells in vivo to study their B cell biology

Strong Decays of Strange Quarkonia

In this paper we evaluate strong decay amplitudes and partial widths of strange mesons (strangeonia and kaonia) in the 3P0 decay model. We give numerical results for all energetically allowed open-flavor two-body decay modes of all nsbar and ssbar strange mesons in the 1S, 2S, 3S, 1P, 2P, 1D and 1F multiplets, comprising strong decays of a total of 43 resonances into 525 two-body modes, with 891 numerically evaluated amplitudes. This set of resonances includes all strange qqbar states with allowed strong decays expected in the quark model up to ca. 2.2 GeV. We use standard nonrelativistic quark model SHO wavefunctions to evaluate these amplitudes, and quote numerical results for all amplitudes present in each decay mode. We also discuss the status of the associated experimental candidates, and note which states and decay modes would be especially interesting for future experimental study at hadronic, e+e- and photoproduction facilities. These results should also be useful in distinguishing conventional quark model mesons from exotica such as glueballs and hybrids through their strong decays.Comment: 69 pages, 5 figures, 39 table

Omega-3 Index, fish consumption, use of fish oil supplements and first clinical diagnosis of central nervous system demyelination

Higher intakes of omega-3 polyunsaturated fatty acids (n3PUFAs) have been associated with lower MS risk. We aimed to test associations between the Omega-3 Index, blood levels of n3PUFAs, fish oil supplement use, and fish consumption with a first clinical diagnosis of CNS demyelination (FCD). Cases (n = 250) had a higher Omega-3 Index compared with a matched group of controls (n = 471) (average treatment effect (ATE)=0.31, p = 0.047, based on augmented inverse probability weighting). A higher percentage of cases than controls used fish oil supplements (cases=17% vs. controls=10%). We found that Omega-3 Index increased as time between FCD and study interview increased (e.g., at or below median (112 days), based on ATE, mean=5.30, 95% CI 5.08, 5.53; above median, mean=5.90, 95% CI 5.51, 6.30). Fish oil supplement use increased in a similar manner (at or below median (112 days), based on ATE, proportion=0.12, 95% CI 0.06, 0.18; above the median, proportion=0.21, 95% CI 0.14, 0.28). Our results suggest a behaviour change post FCD with increased use of fish oil supplements

Health inequalities, fundamental causes and power:Towards the practice of good theory

Reducing health inequalities remains a challenge for policy makers across the world. Beginning from Lewin’s famous dictum that “there is nothing as practical as a good theory”, this paper begins from an appreciative discussion of ‘fundamental cause theory’, emphasizing the elegance of its theoretical encapsulation of the challenge, the relevance of its critical focus for action, and its potential to support the practical mobilisation of knowledge in generating change. Moreover, it is argued that recent developments in the theory, provide an opportunity for further theoretical development focused more clearly on the concept of power (Dickie et al. 2015). A critical focus on power as the essential element in maintaining, increasing or reducing social and economic inequalities – including health inequalities – can both enhance the coherence of the theory, and also enhance the capacity to challenge the roots of health inequalities at different levels and scales. This paper provides an initial contribution by proposing a framework to help to identify the most important sources, forms and positions of power, as well as the social spaces in which they operate. Subsequent work could usefully test, elaborate and adapt this framework, or indeed ultimately replace it with something better, to help focus actions to reduce inequalities

Analysis of LIGO data for gravitational waves from binary neutron stars

We report on a search for gravitational waves from coalescing compact binary systems in the Milky Way and the Magellanic Clouds. The analysis uses data taken by two of the three LIGO interferometers during the first LIGO science run and illustrates a method of setting upper limits on inspiral event rates using interferometer data. The analysis pipeline is described with particular attention to data selection and coincidence between the two interferometers. We establish an observational upper limit of $\mathcal{R}<$1.7 \times 10^{2}$per year per Milky Way Equivalent Galaxy (MWEG), with 90coalescence rate of binary systems in which each component has a mass in the range 1--3$M_\odot$.Comment: 17 pages, 9 figure

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Lepton + Jets Events with Lifetime b-tagging

We present a measurement of the top quark pair ($t\bar{t}$) production cross section ($\sigma_{t\bar{t}}$) in $p\bar{p}$ collisions at $\sqrt{s}=1.96$ TeV using 230 pb$^{-1}$ of data collected by the D0 experiment at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), missing transverse energy, and jets in the final state. We employ lifetime-based b-jet identification techniques to further enhance the $t\bar{t}$ purity of the selected sample. For a top quark mass of 175 GeV, we measure $\sigma_{t\bar{t}}=8.6^{+1.6}_{-1.5}(stat.+syst.)\pm 0.6(lumi.)$ pb, in agreement with the standard model expectation.Comment: 7 pages, 2 figures, 3 tables Submitted to Phys.Rev.Let

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s} = 1.96 TeV using Kinematic Characteristics of Lepton + Jets Events

We present a measurement of the top quark pair ttbar production cross section in ppbar collisions at a center-of-mass energy of 1.96 TeV using 230 pb**{-1} of data collected by the DO detector at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), large missing transverse energy, and at least four jets, and extract the ttbar content of the sample based on the kinematic characteristics of the events. For a top quark mass of 175 GeV, we measure sigma(ttbar) = 6.7 {+1.4-1.3} (stat) {+1.6- 1.1} (syst) +/-0.4 (lumi) pb, in good agreement with the standard model prediction.Comment: submitted to Phys.Rev.Let

Measurement of the Isolated Photon Cross Section in p-pbar Collisions at sqrt{s}=1.96 TeV

The cross section for the inclusive production of isolated photons has been measured in p anti-p collisions at sqrt{s}=1.96 TeV with the D0 detector at the Fermilab Tevatron Collider. The photons span transverse momenta 23 to 300 GeV and have pseudorapidity |eta|<0.9. The cross section is compared with the results from two next-to-leading order perturbative QCD calculations. The theoretical predictions agree with the measurement within uncertainties.Comment: 7 pages, 5 figures, submitted to Phys.Lett.