1,399 research outputs found

    Cystic fibrosis mice carrying the missense mutation G551D replicate human genotype phenotype correlations

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    We have generated a mouse carrying the human G551D mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR) by a one-step gene targeting procedure. These mutant mice show cystic fibrosis pathology but have a reduced risk of fatal intestinal blockage compared with 'null' mutants, in keeping with the reduced incidence of meconium ileus in G551D patients. The G551D mutant mice show greatly reduced CFTR-related chloride transport, displaying activity intermediate between that of cftr(mlUNC) replacement ('null') and cftr(mlHGU) insertional (residual activity) mutants and equivalent to approximately 4% of wild-type CFTR activity. The long-term survival of these animals should provide an excellent model with which to study cystic fibrosis, and they illustrate the value of mouse models carrying relevant mutations for examining genotype-phenotype correlations

    A geometric basis for the standard-model gauge group

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    A geometric approach to the standard model in terms of the Clifford algebra Cl_7 is advanced. A key feature of the model is its use of an algebraic spinor for one generation of leptons and quarks. Spinor transformations separate into left-sided ("exterior") and right-sided ("interior") types. By definition, Poincare transformations are exterior ones. We consider all rotations in the seven-dimensional space that (1) conserve the spacetime components of the particle and antiparticle currents and (2) do not couple the right-chiral neutrino. These rotations comprise additional exterior transformations that commute with the Poincare group and form the group SU(2)_L, interior ones that constitute SU(3)_C, and a unique group of coupled double-sided rotations with U(1)_Y symmetry. The spinor mediates a physical coupling of Poincare and isotopic symmetries within the restrictions of the Coleman--Mandula theorem. The four extra spacelike dimensions in the model form a basis for the Higgs isodoublet field, whose symmetry requires the chirality of SU(2). The charge assignments of both the fundamental fermions and the Higgs boson are produced exactly.Comment: 17 pages, LaTeX requires iopart. Accepted for publication in J. Phys. A: Math. Gen. 9 Mar 2001. Typos correcte

    'Help for hay fever', a goal-focused intervention for people with intermittent allergic rhinitis, delivered in Scottish community pharmacies: study protocol for a pilot cluster randomized controlled trial

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    <b>Background</b> Despite the availability of evidence-based guidelines for managing allergic rhinitis in primary care, management of the condition in the United Kingdom (UK) remains sub-optimal. Its high prevalence and negative effects on quality of life, school performance, productivity and co-morbid respiratory conditions (in particular, asthma), and high health and societal costs, make this a priority for developing novel models of care. Recent Australian research demonstrated the potential of a community pharmacy-based ā€˜goal-focusedā€™ intervention to help people with intermittent allergic rhinitis to self-manage their condition better, reduce symptom severity and improve quality of life. In this pilot study we will assess the transferability of the goal-focused intervention to a UK context, the suitability of the intervention materials, procedures and outcome measures and collect data to inform a future definitive UK randomized controlled trial (RCT). <p></p> <b>Methods/design</b> A pilot cluster RCT with associated preliminary economic analysis and embedded qualitative evaluation. The pilot trial will take place in two Scottish Health Board areas: Grampian and Greater Glasgow and Clyde. Twelve community pharmacies will be randomly assigned to intervention or usual care group. Each will recruit 12 customers seeking advice or treatment for intermittent allergic rhinitis. Pharmacy staff in intervention pharmacies will support recruited customers in developing strategies for setting and achieving goals that aim to avoid/minimize triggers for, and eliminate/minimize symptoms of allergic rhinitis. Customers recruited in non-intervention pharmacies will receive usual care. The co-primary outcome measures, selected to inform a sample size calculation for a future RCT, are: community pharmacy and customer recruitment and completion rates; and effect size of change in the validated mini-Rhinoconjunctivitis Quality of Life Questionnaire between baseline, one-week and six-weeks post-intervention. Secondary outcome measures relate to changes in symptom severity, productivity, medication adherence and self-efficacy. Quantitative data about accrual, retention and economic measures, and qualitative data about participantsā€™ experiences during the trial will be collected to inform the future RCT.<P></P> <b>Discussion</b> This work will lay the foundations for a definitive RCT of a community pharmacy-based ā€˜goal-focusedā€™ self-management intervention for people with intermittent allergic rhinitis. Results of the pilot trial are expected to be available in April 2013

    Topological transversals to a family of convex sets

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    Let F\mathcal F be a family of compact convex sets in Rd\mathbb R^d. We say that F\mathcal F has a \emph{topological Ļ\rho-transversal of index (m,k)(m,k)} (Ļ<m\rho<m, 0<kā‰¤dāˆ’m0<k\leq d-m) if there are, homologically, as many transversal mm-planes to F\mathcal F as mm-planes containing a fixed Ļ\rho-plane in Rm+k\mathbb R^{m+k}. Clearly, if F\mathcal F has a Ļ\rho-transversal plane, then F\mathcal F has a topological Ļ\rho-transversal of index (m,k),(m,k), for Ļ<m\rho<m and kā‰¤dāˆ’mk\leq d-m. The converse is not true in general. We prove that for a family F\mathcal F of Ļ+k+1\rho+k+1 compact convex sets in Rd\mathbb R^d a topological Ļ\rho-transversal of index (m,k)(m,k) implies an ordinary Ļ\rho-transversal. We use this result, together with the multiplication formulas for Schubert cocycles, the Lusternik-Schnirelmann category of the Grassmannian, and different versions of the colorful Helly theorem by B\'ar\'any and Lov\'asz, to obtain some geometric consequences

    Revisiting Clifford algebras and spinors III: conformal structures and twistors in the paravector model of spacetime

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    This paper is the third of a series of three, and it is the continuation of math-ph/0412074 and math-ph/0412075. After reviewing the conformal spacetime structure, conformal maps are described in Minkowski spacetime as the twisted adjoint representation of the group Spin_+(2,4), acting on paravectors. Twistors are then presented via the paravector model of Clifford algebras and related to conformal maps in the Clifford algebra over the lorentzian R{4,1}$ spacetime. We construct twistors in Minkowski spacetime as algebraic spinors associated with the Dirac-Clifford algebra Cl(1,3)(C) using one lower spacetime dimension than standard Clifford algebra formulations, since for this purpose the Clifford algebra over R{4,1} is also used to describe conformal maps, instead of R{2,4}. Although some papers have already described twistors using the algebra Cl(1,3)(C), isomorphic to Cl(4,1), the present formulation sheds some new light on the use of the paravector model and generalizations.Comment: 17 page

    Large-Scale Distributed Bayesian Matrix Factorization using Stochastic Gradient MCMC

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    Despite having various attractive qualities such as high prediction accuracy and the ability to quantify uncertainty and avoid over-fitting, Bayesian Matrix Factorization has not been widely adopted because of the prohibitive cost of inference. In this paper, we propose a scalable distributed Bayesian matrix factorization algorithm using stochastic gradient MCMC. Our algorithm, based on Distributed Stochastic Gradient Langevin Dynamics, can not only match the prediction accuracy of standard MCMC methods like Gibbs sampling, but at the same time is as fast and simple as stochastic gradient descent. In our experiments, we show that our algorithm can achieve the same level of prediction accuracy as Gibbs sampling an order of magnitude faster. We also show that our method reduces the prediction error as fast as distributed stochastic gradient descent, achieving a 4.1% improvement in RMSE for the Netflix dataset and an 1.8% for the Yahoo music dataset
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