3,051 research outputs found
CaMKII inhibition rectifies arrhythmic phenotype in a patient-specific model of catecholaminergic polymorphic ventricular tachycardia
Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro 'patient-specific cell-based system' that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of a cardiac model of CPVT through the generation of iPSC from a CPVT patient carrying a heterozygous mutation in the cardiac ryanodine receptor gene (RyR2) and their subsequent differentiation into cardiomyocytes (CMs). Whole-cell patch-clamp and intracellular electrical recordings of spontaneously beating cells revealed the presence of delayed afterdepolarizations (DADs) in CPVT-CMs, both in resting conditions and after β-adrenergic stimulation, resembling the cardiac phenotype of the patients. Furthermore, treatment with KN-93 (2-[N-(2-hydroxyethyl)]-N-(4methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), an antiarrhythmic drug that inhibits Ca(2+)/calmodulin-dependent serine-threonine protein kinase II (CaMKII), drastically reduced the presence of DADs in CVPT-CMs, rescuing the arrhythmic phenotype induced by catecholaminergic stress. In addition, intracellular calcium transient measurements on 3D beating clusters by fast resolution optical mapping showed that CPVT clusters developed multiple calcium transients, whereas in the wild-type clusters, only single initiations were detected. Such instability is aggravated in the presence of isoproterenol and is attenuated by KN-93. As seen in our RyR2 knock-in CPVT mice, the antiarrhythmic effect of KN-93 is confirmed in these human iPSC-derived cardiac cells, supporting the role of this in vitro system for drug screening and optimization of clinical treatment strategies
Measurement of Time-Dependent CP-Violating Parameters in B0 -> K0S K0S decays
We report a measurement of the CP-violating parameters in B0->K0S K0S decays
based on a data sample of 657 million BBbar pairs collected at the Y(4S)
resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider.
In this study, one neutral B meson is fully reconstructed in the B0->K0S K0S
decay mode, and the flavor of the accompanying B meson is identified by its
decay products. The CP-violating parameters are measured from the asymmetry in
the distributions of the proper-time interval between the two B decays: S =
-0.38 +0.69-0.77(stat) +-0.09(syst) and A = -0.38 +-0.38(stat) +-0.05(syst).Comment: 5pages, 2figures, submitted to PR
Measurement of CP violating asymmetries in B^0 -> K^+K^- K^0_S decays with a time-dependent Dalitz approach
We report a measurement of violating asymmetries in decays with a time-dependent Dalitz approach. This analysis
is based on a data sample of pairs accumulated
at the resonance with the Belle detector at the KEKB
asymmetric-energy collider. As the result of an unbinned maximum
likelihood fit to the selected candidates, the mixing-induced and direct
violation parameters, and are obtained for
, and other decays. We find four solutions that describe the data. There are
\{eqnarray*} \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (32.2 \pm 9.0 \pm
2.6 \pm 1.4)^{\circ}; \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (26.2 \pm
8.8 \pm 2.7 \pm 1.2)^{\circ};\\ \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = &
(27.3 \pm 8.6 \pm 2.8 \pm 1.3)^{\circ}\; {\rm and}\\ \phi_1^{\rm eff}(B^0\to
\phi(1020) K^0_S) & = & (24.3 \pm 8.0 \pm 2.9 \pm 5.2)^{\circ}.{eqnarray*}\ The
values for the violating phase in are similar
but other properties of the Dalitz plot are quite different for the four
solutions. These four solutions have consistent values for
all three meson decay channels and none of them deviates significantly from
the values measured in decays with the currently
available statistics. In addition, we find no significant direct
violation.Comment: submitted to PR
Measurement of CP violating asymmetries in B^0 -> K^+K^- K^0_S decays with a time-dependent Dalitz approach
We report a measurement of violating asymmetries in decays with a time-dependent Dalitz approach. This analysis
is based on a data sample of pairs accumulated
at the resonance with the Belle detector at the KEKB
asymmetric-energy collider. As the result of an unbinned maximum
likelihood fit to the selected candidates, the mixing-induced and direct
violation parameters, and are obtained for
, and other decays. We find four solutions that describe the data. There are
\{eqnarray*} \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (32.2 \pm 9.0 \pm
2.6 \pm 1.4)^{\circ}; \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (26.2 \pm
8.8 \pm 2.7 \pm 1.2)^{\circ};\\ \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = &
(27.3 \pm 8.6 \pm 2.8 \pm 1.3)^{\circ}\; {\rm and}\\ \phi_1^{\rm eff}(B^0\to
\phi(1020) K^0_S) & = & (24.3 \pm 8.0 \pm 2.9 \pm 5.2)^{\circ}.{eqnarray*}\ The
values for the violating phase in are similar
but other properties of the Dalitz plot are quite different for the four
solutions. These four solutions have consistent values for
all three meson decay channels and none of them deviates significantly from
the values measured in decays with the currently
available statistics. In addition, we find no significant direct
violation.Comment: submitted to PR
Search for Time-Dependent CPT Violation in Hadronic and Semileptonic B Decays
We report a new sensitive search for CPT violation, which includes improved
measurements of the CPT-violating parameter z and the total decay-width
difference normalized to the averaged width DeltaGamma_d/Gamma_d of the two Bd
mass eigenstates. The results are based on a data sample of 535 x 10^6 BBbar
pairs collected at the Upsilon(4S) resonance with the Belle detector at the
KEKB asymmetric-energy e^+e^- collider. We obtain Re(z) = [+1.9 +/- 3.7 (stat)
+/- 3.3 (syst)] x 10^{-2}, Im(z) = [-5.7 +/- 3.3 (stat) +/- 3.3 (syst)] x
10^{-3}, and DeltaGamma_d/Gamma_d = [-1.7 +/- 1.8 (stat) +/- 1.1 (syst)] x
10^{-2}, all of which are consistent with zero. This is the most precise single
measurement of these parameters in the neutral B-meson system to date.Comment: 7 pages, 3 figures, 2 tables, LaTeX; addition of supplemental
information, corrections of typos, results unchange
Angular analysis of
We present a measurement of angular observables, , , ,
, in the decay , where
is either or . The analysis is performed on
a data sample corresponding to an integrated luminosity of
containing pairs, collected
at the resonance with the Belle detector at the
asymmetric-energy collider KEKB. Four angular observables,
are extracted in five bins of the invariant mass squared of the
lepton system, . We compare our results for with Standard
Model predictions including the region in which the LHCb collaboration
reported the so-called anomaly.Comment: Conference paper for LHC Ski 2016. SM prediction for
corrected and reference for arXiv:1207.2753 adde
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