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

Learning to collaborate: Can young children develop better communication strategies through collaboration with a more popular peer

Unpopular children are known to have poor communication skills and experience difficulty in collaborative situations. This study investigated whether pairing unpopular, 5 to 6 year-old, children with a more popular peer would promote more effective collaboration. The study also investigated differences in popular and unpopular children's verbal and non-verbal communication. Thirty-six girls and 36 boys were placed in one of 12 popular, 12 unpopular or 12 mixed pairs. There were no mixed gender pairs. Children were filmed playing a collaborative game. Collaboration in popular pairs was more successful and less disputational than in unpopular pairs. Boys in unpopular pairs broke the rules of the game more often, argued more and did not monitoring their partners' facial expressions effectively. With popular partners they argued less, were more likely to elaborate disagreements, looked at their partner for longer, smiled more and were more likely to offer him a small toy. Unpopular girls' interactions were not markedly disruptive but they clearly benefited from being paired with a child with good communication skills. Popular girls modified their behaviour to take into account an unpopular partner's need for support. These findings suggest that pairing popular and unpopular children may be a useful classroom organisation strategy

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

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

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

Measurement of the p-pbar -> Wgamma + X cross section at sqrt(s) = 1.96 TeV and WWgamma anomalous coupling limits

The WWgamma triple gauge boson coupling parameters are studied using p-pbar -> l nu gamma + X (l = e,mu) events at sqrt(s) = 1.96 TeV. The data were collected with the DO detector from an integrated luminosity of 162 pb^{-1} delivered by the Fermilab Tevatron Collider. The cross section times branching fraction for p-pbar -> W(gamma) + X -> l nu gamma + X with E_T^{gamma} > 8 GeV and Delta R_{l gamma} > 0.7 is 14.8 +/- 1.6 (stat) +/- 1.0 (syst) +/- 1.0 (lum) pb. The one-dimensional 95% confidence level limits on anomalous couplings are -0.88 < Delta kappa_{gamma} < 0.96 and -0.20 < lambda_{gamma} < 0.20.Comment: Submitted to Phys. Rev. D Rapid Communication

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 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

Monitoring boreal forest biomass and carbon storage change by integrating airborne laser scanning, biometry and eddy covariance data

AbstractThis study presents a comparison and integration of three methods commonly used to estimate the amount of forest ecosystem carbon (C) available for storage. In particular, we examine the representation of living above- and below-ground biomass change (net accumulation) using plot-level biometry and repeat airborne laser scanning (ALS) of three dimensional forest plot structure. These are compared with cumulative net CO2 fluxes (net ecosystem production, NEP) from eddy covariance (EC) over a six-year period within a jack pine chronosequence of four stands (~94, 30, 14 and 3years since establishment from 2005) located in central Saskatchewan, Canada. Combining the results of the two methods yield valuable observations on the partitioning of C within ecosystems. Subtracting total living biomass C accumulation from NEP results in a residual that represents change in soil and litter C storage. When plotted against time for the stands investigated, the curve produced is analogous to the soil C dynamics described in Covington (1981). Here, ALS biomass accumulation exceeds EC-based NEP measured in young stands, with the residual declining with age as stands regenerate and litter decomposition stabilizes. During the 50–70year age-period, NEP and live biomass accumulation come into balance, with the soil and litter pools of stands 70–100years post-disturbance becoming a net store of C. Biomass accumulation was greater in 2008–2011 compared to 2005–2008, with the smallest increase in the 94-year-old “old jack pine” stand and greatest in the 14-year-old “harvested jack pine 1994” stand, with values of 1.4 (±3.2) tCha−1 and 12.0 (±1.6) tCha−1, respectively. The efficiency with which CO2 was stored in accumulated biomass was lowest in the youngest and oldest stands, but peaked during rapid regeneration following harvest (14-year-old stand). The analysis highlights that the primary source of uncertainty in the data integration workflow is in the calculation of biomass expansion factors, and this aspect of the workflow needs to be implemented with caution to avoid large error propagations. We suggest that the adoption of integrated ALS, in situ and atmospheric flux monitoring frameworks is needed to improve spatio-temporal partitioning of C balance components at sub-decadal scale within rapidly changing forest ecosystems and for use in national carbon accounting programs