702 research outputs found

    Slow equivariant lump dynamics on the two sphere

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    The low-energy, rotationally equivariant dynamics of n CP^1 lumps on S^2 is studied within the approximation of geodesic motion in the moduli space of static solutions. The volume and curvature properties of this moduli space are computed. By lifting the geodesic flow to the completion of an n-fold cover of the moduli space, a good understanding of nearly singular lump dynamics within this approximation is obtained.Comment: 12 pages, 3 figure

    The geodesic approximation for lump dynamics and coercivity of the Hessian for harmonic maps

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    The most fruitful approach to studying low energy soliton dynamics in field theories of Bogomol'nyi type is the geodesic approximation of Manton. In the case of vortices and monopoles, Stuart has obtained rigorous estimates of the errors in this approximation, and hence proved that it is valid in the low speed regime. His method employs energy estimates which rely on a key coercivity property of the Hessian of the energy functional of the theory under consideration. In this paper we prove an analogous coercivity property for the Hessian of the energy functional of a general sigma model with compact K\"ahler domain and target. We go on to prove a continuity property for our result, and show that, for the CP^1 model on S^2, the Hessian fails to be globally coercive in the degree 1 sector. We present numerical evidence which suggests that the Hessian is globally coercive in a certain equivariance class of the degree n sector for n>1. We also prove that, within the geodesic approximation, a single CP^1 lump moving on S^2 does not generically travel on a great circle.Comment: 29 pages, 1 figure; typos corrected, references added, expanded discussion of the main function spac

    Application of pharmacogenomics and bioinformatics to exemplify the utility of human <i>ex vivo</i> organoculture models in the field of precision medicine

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    Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response

    Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases

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    In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance

    Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

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    A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN

    Lipoprotein‐Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

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    Background: We evaluated lipoprotein‐associated phospholipase A2 (Lp‐PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐PLA2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and Results: Plasma Lp‐PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐PLA2 activity levels and outcomes. At baseline, the median Lp‐PLA2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐PLA2 activity. There were no associations between on‐treatment Lp‐PLA2 activity or changes of Lp‐PLA2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐PLA2 activity or changes in Lp‐PLA2 activity levels and the effects of darapladib on outcomes. Conclusions: Although high Lp‐PLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐PLA2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐PLA2 activity

    Targeted kinase inhibition relieves slowness and tremor in a Drosophila model of LRRK2 Parkinson’s disease

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    Disease models: A reflex reaction A simple reflex in flies can be used to test the effectiveness of therapies that slow neurodegeneration in Parkinson’s disease (PD). Christopher Elliott and colleagues at the University of York in the United Kingdom investigated the contraction of the proboscis muscle which mediates a taste behavior response and is regulated by a single dopaminergic neuron. Flies bearing particular mutations in the PD-associated gene leucine-rich repeat kinase 2 (LRRK2) in dopaminergic neurons lost their ability to feed on a sweet solution. This was due to the movement of the proboscis muscle becoming slower and stiffer, hallmark features of PD. The authors rescued the impaired reflex reaction by feeding the flies l-DOPA or LRRK2 inhibitors. These findings highlight the proboscis extension response as a useful tool to identify other PD-associated mutations and test potential therapeutic compounds

    The Closed-Cone Pines of the Northern Channel Islands

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    Our interest in the pines of the Northern Channel Islands developed in the course of our work with the California closed-cone pines. The focus of these investigations has been Monterey pine (Pinus radiata D. Don.), a species which is widely planted as a forest tree in New Zealand, Australia, Chile, South Africa, and Spain. Despite its wide use, P. radiata is not well known genetically and its performance in California, its native home, has not been fully assessed. The first phase of the project on Pinus radiata entailed study and sampling of the three native stands on the mainland. Later, we sampled its southern variety {P. radiata var. binata Engelm.) on Guadalupe Island. This led to a consideration of the other insular populations of closed-cone pines and their relationship to mainland P. radiata and Bishop pine (P. muricata D. Don.). We thus became aware of the confusion and uncertainty relative to the taxonomic and biosystematic relationships within the P. radiata-muricata complex. In the past, California has relied on virgin and second-growth forests as a source of timber. In the future, artificial regeneration will become of increasing importance, and hitherto unused species may gain status as prime wood and fiber producers. Most insular populations of closed-cone pines occur on sites marginal for good tree growth. If planted on better sites, they may prove to be economically valuable. Furthermore, it may be possible to combine their ability to survive on poor sites with the fast-growth characteristics of other species or populations to produce strains suitable for wood production in less-than-optimal situations. The hybrid Pinus attenuata X P. radiata is a good example of the above possibility, combining the drought and cold resistance of knob-cone pine (P. attenuata Lemmon) with the fast growth of P. radiata. Such economic considerations, in addition to the biosystematic problems cited above, led us to study and sample the closed-cone pine populations on Guadalupe Island in February 1963. Cedros Island in April 1963, Santa Cruz Island in June 1964. and Santa Rosa Island in April 1965. This paper contains descriptions of the populations of closed-cone pines on Santa Cruz and Santa Rosa islands, and analyses of data from specimens collected on these islands as well as related mainland populations of Pinus muricata. Our results and observations are then discussed in the light of present knowledge of the California closed-cone pines.Linhart, Y. B., B. Burr, and M. T. Conkle. "The Closed-Cone Pines of the Northern Channel Islands." In: 1st Symposium on the Biology of the California Islands. National Park Service, 1965. 151-177

    Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

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    M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe
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