291 research outputs found
Runx1 deficiency protects against adverse cardiac remodeling following myocardial infarction
Background: Myocardial infarction (MI) is a leading cause of heart failure and death worldwide. Preservation of contractile function and protection against adverse changes in ventricular architecture (cardiac remodeling) are key factors to limiting progression of this condition to heart failure. Consequently, new therapeutic targets are urgently required to achieve this aim. Expression of the Runx1 transcription factor is increased in adult cardiomyocytes after MI; however, the functional role of Runx1 in the heart is unknown.
Methods: To address this question, we have generated a novel tamoxifen-inducible cardiomyocyte-specific Runx1-deficient mouse. Mice were subjected to MI by means of coronary artery ligation. Cardiac remodeling and contractile function were assessed extensively at the whole-heart, cardiomyocyte, and molecular levels.
Results: Runx1-deficient mice were protected against adverse cardiac remodeling after MI, maintaining ventricular wall thickness and contractile function. Furthermore, these mice lacked eccentric hypertrophy, and their cardiomyocytes exhibited markedly improved calcium handling. At the mechanistic level, these effects were achieved through increased phosphorylation of phospholamban by protein kinase A and relief of sarco/endoplasmic reticulum Ca2+-ATPase inhibition. Enhanced sarco/endoplasmic reticulum Ca2+-ATPase activity in Runx1-deficient mice increased sarcoplasmic reticulum calcium content and sarcoplasmic reticulum–mediated calcium release, preserving cardiomyocyte contraction after MI.
Conclusions: Our data identified Runx1 as a novel therapeutic target with translational potential to counteract the effects of adverse cardiac remodeling, thereby improving survival and quality of life among patients with MI
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The diffusion of financial supervisory governance ideas
Who is watching the financial services industry? Since 1980, there have been multiple waves of thought about whether the ministry of finance, the central bank, a specialized regulator or some combination of these should have supervisory authority. These waves have been associated with the convergence of actual practices. How much and through what channels did internationally promoted ideas about supervisory 'best practice' influence institutional design choices? I use a new dataset of 83 countries and jurisdictions between the 1980s and 2007 to examine the diffusion of supervisory ideas. With this data, I employ Cox Proportional Hazard and Competing Risks Event History Analyses to evaluate the possible causal roles best practice policy ideas might have played. I find that banking crises and certain peer groups can encourage policy convergence on heavily promoted ideas
K0s K0s Final State in Two-Photon Collisions and Implications for Glueballs
The K0s K0s final state in two-photon collisions is studied with the L3
detector at LEP. The mass spectrum is dominated by the formation of the
f_2'(1525) tensor meson in the helicity-two state with a two-photon width times
the branching ratio into K Kbar of 76 +- 6 +- 11 eV. A clear signal for the
formation of the f_J(1710) is observed and it is found to be dominated by the
spin-two helicity-two state. No resonance is observed in the mass region around
2.2 GeV and an upper limit of 1.4 eV at 95% C.L. is derived for the two-photon
width times the branching ratio into K0s K0s for the glueball candidate
xi(2230)
Deuteron production in central Pb + Pb collisions at 158-A-GeV
Experimental results on deuteron emission from central Pb+Pb collisions (E_beam=158A GeV, fixed target), obtained by NA49 at the CERN SPS accelerator, are presented. The transverse mass m_t distribution was measured near mid-rapidity (2.0<y<2.5) in the range of 0<m_t-m_0<0.9 GeV/c2 (0<p_t<2.0 GeV/c) for the 4% most central collisions. An exponential fit gives an inverse slope T_d=(450ą30) MeV and a yield dN_d/dy=0.34ą0.03. The coalescence factor B2(m_t=m_0)=(3.5ą1.0)ˇ10^4 GeV^2 and its m_t-dependence are determined and discussed in terms of a model that includes the collective expansion of the source created in a collision. The derived Gaussian size parameter R_G of the emission volume is consistent with earlier HBT results on the source of pion emission
Copeptin for risk stratification in non-traumatic headache in the emergency setting: a prospective multicenter observational cohort study
In the emergency setting, non-traumatic headache is a benign symptom in 80% of cases, but serious underlying conditions need to be ruled out. Copeptin improves risk stratification in several acute diseases. Herein, we investigated the value of copeptin to discriminate between serious secondary headache and benign headache forms in the emergency setting.; Patients presenting with acute non-traumatic headache were prospectively enrolled into an observational cohort study. Copeptin was measured upon presentation to the emergency department. Primary endpoint was serious secondary headache defined by a neurologic cause requiring immediate treatment of the underlying disease. Secondary endpoint was the combination of mortality and hospitalization within 3 months. Two board-certified neurologist blinded to copeptin levels verified the endpoints after a structured 3-month-telephone interview.; Of the 391 patients included, 75 (19%) had a serious secondary headache. Copeptin was associated with serious secondary headache (OR 2.03, 95%CI 1.52-2.70, p < 0.0001). Area under the curve (AUC) for copeptin to identify the primary endpoint was 0.70 (0.63-0.76). After adjusting for age > 50, focal-neurological abnormalities, and thunderclap onset of symptoms, copeptin remained an independent predictive factor for serious secondary headache (OR 1.74, 95%CI 1.26-2.39, p = 0.001). Moreover, copeptin improved the AUC of the multivariate logistic clinical model (p-LR-test < 0.001). Even though copeptin values were higher in patients reaching the secondary endpoint, this association was not significant in multivariate logistic regression.; Copeptin was independently associated with serious secondary headache as compared to benign headaches forms. Copeptin may be a promising novel blood biomarker that should be further validated to rule out serious secondary headache in the emergency department.; Study Registration on 08/02/2010 as NCT01174901 at clinicaltrials.gov
Energy dependence of the differences between the quark and gluon jet fragmentation
Three jet events arising from decays of the Z boson, collected by the DELPHI detector, were used to measure differences in quark and gluon fragmentation. Gluon jets were anti-tagged by identifying b quark jets. Unbiased quark jets came from events with two jets plus one photon. Quark and gluon jet properties in different energy ranges were compared for the first time within the same detector. Quark and gluon jets of nearly the same energy in symmetric three jet event topologies were also compared. Using three independent methods, the average value of the ratio of the mean charged multiplicities of gluon and quark jets is Gluon jets are broader and produce fragments with a softer energy spectrum than quark jets of equivalent energy. The string effect has been observed in fully symmetric three jet events. The measured ratio R_{\gamma} of the charged particle flow in the q\overline{q} inter-jet region of the q\bar{q}g and q\bar{q}\gamma samples agrees with the perturbative QCD expectation. The dependence of the mean charged multiplicity on the hadronic center-of-mass energy was analysed in photon plus n-jet events. The value for \alpha_s(M_Z) determined from these data using a QCD prediction with corrections at leading and next-to-leading order is \[ \alpha_s(M_Z)=0.116 \pm 0.003\ (stat.) \pm 0.009\ (syst.). \
The NA49 large acceptance hadron detector
The NA49 detector is a wide acceptance spectrometer for the study of hadron production in p+p, p+A, and A+A collisions at the CERN SPS. The main components are 4 large volume TPCs for tracking and particle identification via . TOF scintillator arrays complement particle identification. Calorimeters for transverse energy determination and triggering, a detector for centrality selection in p+A collisions, and beam definition detectors complete the set-up. A description of all detector components is given with emphasis on new technical realizations. Performance and operational experience are discussed in particular with respect to the high track density environment of central Pb+Pb collisions
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Hadronic Expansion Dynamics in Central Pb+Pb Collisions at 158 GeV per Nucleon
Two-particle correlation functions of negative hadrons over wide phase space, and transverse mass spectra of negative hadrons and deuterons near mid-rapidity have been measured in central Pb+Pb collisions at 158 GeV per nucleon by the NA49 experiment at the CERN SPS. A novel Coulomb correction procedure for the negative two-particle correlations is employed making use of the measured oppositely charged particle correlation. Within an expanding source scenario these results are used to extract the dynamic characteristics of the hadronic source, resolving the ambiguities between the temperature and transverse expansion velocity of the source, that are unavoidable when single and two particle spectra are analysed separately. The source shape, the total duration of the source expansion, the duration of particle emission, the freeze-out temperature and the longitudinal and transverse expansion velocities are deduced
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