220 research outputs found
Mechanisms linking short- and long-term electrical remodeling in the heart…is it a stretch?
Characterization of a novel, dominant negative KCNJ2 mutation associated with Andersen-Tawil syndrome
Andersen-Tawil syndrome is characterized by periodic paralysis, ventricular ectopy and dysmorphic features. Approximately 60% of patients exhibit loss-of-function mutations in KCNJ2, which encodes the inwardly rectifying K(+) channel pore forming subunit Kir2.1. Here, we report the identification of a novel KCNJ2 mutation (G211T), resulting in the amino acid substitution D71Y, in a patient presenting with signs and symptoms of Andersen-Tawil syndrome. The functional properties of the mutant subunit were characterized using voltage-clamp experiments on transiently transfected HEK-293 cells and neonatal mouse ventricular myocytes. Whole-cell current recordings of transfected HEK-293 cells demonstrated that the mutant protein Kir2.1-D71Y fails to form functional ion channels when expressed alone, but co-assembles with wild-type Kir2.1 subunits and suppresses wild-type subunit function. Further analysis revealed that current suppression requires at least two mutant subunits per channel. The D71Y mutation does not measurably affect the membrane trafficking of either the mutant or the wild-type subunit or alter the kinetic properties of the currents. Additional experiments revealed that expression of the mutant subunit suppresses native I(K1) in neonatal mouse ventricular myocytes. Simulations predict that the D71Y mutation in human ventricular myocytes will result in a mild prolongation of the action potential and potentially increase cell excitability. These experiments indicate that the Kir2.1-D71Y mutant protein functions as a dominant negative subunit resulting in reduced inwardly rectifying K(+) current amplitudes and altered cellular excitability in patients with Andersen-Tawil syndrome
Self-Energy Correction to the Two-Photon Decay Width in Hydrogenlike Atoms
We investigate the gauge invariance of the leading logarithmic radiative
correction to the two-photon decay width in hydrogenlike atoms. It is shown
that an effective treatment of the correction using a Lamb-shift "potential"
leads to equivalent results in both the length as well as the velocity gauges
provided all relevant correction terms are taken into account. Specifically,
the relevant radiative corrections are related to the energies that enter into
the propagator denominators, to the Hamiltonian, to the wave functions, and to
the energy conservation condition that holds between the two photons; the form
of all of these effects is different in the two gauges, but the final result is
shown to be gauge invariant, as it should be. Although the actual calculation
only involves integrations over nonrelativistic hydrogenic Green functions, the
derivation of the leading logarithmic correction can be regarded as slightly
more complex than that of other typical logarithmic terms. The dominant
radiative correction to the 2S two-photon decay width is found to be -2.020536
(alpha/pi) (Zalpha)^2 ln[(Zalpha)^-2] in units of the leading nonrelativistic
expression. This result is in agreement with a length-gauge calculation [S. G.
Karshenboim and V. G. Ivanov, e-print physics/9702027], where the coefficient
was given as -2.025(1).Comment: 9 pages, RevTe
Relativistic quantum dynamics in strong fields: Photon emission from heavy, few-electron ions
Recent progress in the study of the photon emission from highly-charged heavy
ions is reviewed. These investigations show that high- ions provide a unique
tool for improving the understanding of the electron-electron and
electron-photon interaction in the presence of strong fields. Apart from the
bound-state transitions, which are accurately described in the framework of
Quantum Electrodynamics, much information has been obtained also from the
radiative capture of (quasi-) free electrons by high- ions. Many features in
the observed spectra hereby confirm the inherently relativistic behavior of
even the simplest compound quantum systems in Nature.Comment: Version 18/11/0
Properties of metastable alkaline-earth-metal atoms calculated using an accurate effective core potential
The first three electronically excited states in the alkaline-earth-metal
atoms magnesium, calcium, and strontium comprise the (nsnp) triplet P^o_J
(J=0,1,2) fine-structure manifold. All three states are metastable and are of
interest for optical atomic clocks as well as for cold-collision physics. An
efficient technique--based on a physically motivated potential that models the
presence of the ionic core--is employed to solve the Schroedinger equation for
the two-electron valence shell. In this way, radiative lifetimes, laser-induced
clock shifts, and long-range interaction parameters are calculated for
metastable Mg, Ca, and Sr.Comment: 13 pages, 9 table
Quality of Reasoning in International Criminal Tribunals
It is not unreasonable to say that international criminal law is, for the most part, a judge made law. For better or worse, given the diffused nature of its sources of law as well as the institutions built to enforce it, the rising case law gave the international criminal courts a chance and a burden to develop international criminal law into an expansive, and familiar, branch of international law. In this Chapter, I attempt to analyse and elaborate the main vehicle through which this transformation has taken place – the judgements of the courts – in terms of the quality of their reasoning. I will piece together some general rules of thumb that have been created in the branch of international criminal law to assess the quality of reasoning of the different International Criminal Courts. My focus will be the work of the International Criminal Court, although the work of the ICC rests to a large degree on the work of the previous ad hoc tribunals. As such, I will analyse the criticisms that have been levelled at the international criminal tribunals in terms of their interpretation and reasoning, highlight some of the continuing concerns and assess the ICC’s current practice
Slowing and cooling molecules and neutral atoms by time-varying electric field gradients
A method of slowing, accelerating, cooling, and bunching molecules and
neutral atoms using time-varying electric field gradients is demonstrated with
cesium atoms in a fountain. The effects are measured and found to be in
agreement with calculation. Time-varying electric field gradient slowing and
cooling is applicable to atoms that have large dipole polarizabilities,
including atoms that are not amenable to laser slowing and cooling, to Rydberg
atoms, and to molecules, especially polar molecules with large electric dipole
moments. The possible applications of this method include slowing and cooling
thermal beams of atoms and molecules, launching cold atoms from a trap into a
fountain, and measuring atomic dipole polarizabilities.Comment: 13 pages, 10 figures. Scheduled for publication in Nov. 1 Phys. Rev.
Polarization correlation in the two-photon decay of atomic hydrogen: nonlocality versus entanglement
Association of Sex with Neurobehavioral Markers of Executive Function in 2-Year-Olds at High and Low Likelihood of Autism
Importance: Children with autism and their siblings exhibit executive function (EF) deficits early in development, but associations between EF and biological sex or early brain alterations in this population are largely unexplored. Objective: To investigate the interaction of sex, autism likelihood group, and structural magnetic resonance imaging alterations on EF in 2-year-old children at high familial likelihood (HL) and low familial likelihood (LL) of autism, based on having an older sibling with autism or no family history of autism in first-degree relatives. Design, Setting, and Participants: This prospective cohort study assessed 165 toddlers at HL (n = 110) and LL (n = 55) of autism at 4 university-based research centers. Data were collected from January 1, 2007, to December 31, 2013, and analyzed between August 2021 and June 2022 as part of the Infant Brain Imaging Study. Main Outcomes and Measures: Direct assessments of EF and acquired structural magnetic resonance imaging were performed to determine frontal lobe, parietal lobe, and total cerebral brain volume. Results: A total of 165 toddlers (mean [SD] age, 24.61 [0.95] months; 90 [54%] male, 137 [83%] White) at HL for autism (n = 110; 17 diagnosed with ASD) and LL for autism (n = 55) were studied. The toddlers at HL for autism scored lower than the toddlers at LL for autism on EF tests regardless of sex (mean [SE] B = -8.77 [4.21]; 95% CI, -17.09 to -0.45; η2p= 0.03). With the exclusion of toddlers with autism, no group (HL vs LL) difference in EF was found in boys (mean [SE] difference, -7.18 [4.26]; 95% CI, 1.24-15.59), but EF was lower in HL girls than LL girls (mean [SE] difference, -9.75 [4.34]; 95% CI, -18.32 to -1.18). Brain-behavior associations were examined, controlling for overall cerebral volume and developmental level. Sex differences in EF-frontal (B [SE] = 16.51 [7.43]; 95% CI, 1.36-31.67; η2p= 0.14) and EF-parietal (B [SE] = 17.68 [6.99]; 95% CI, 3.43-31.94; η2p= 0.17) associations were found in the LL group but not the HL group (EF-frontal: B [SE] = -1.36 [3.87]; 95% CI, -9.07 to 6.35; η2p= 0.00; EF-parietal: B [SE] = -2.81 [4.09]; 95% CI, -10.96 to 5.34; η2p= 0.01). Autism likelihood group differences in EF-frontal (B [SE] = -9.93 [4.88]; 95% CI, -19.73 to -0.12; η2p= 0.08) and EF-parietal (B [SE] = -15.44 [5.18]; 95% CI, -25.86 to -5.02; η2p= 0.16) associations were found in girls not boys (EF-frontal: B [SE] = 6.51 [5.88]; 95% CI, -5.26 to 18.27; η2p= 0.02; EF-parietal: B [SE] = 4.18 [5.48]; 95% CI, -6.78 to 15.15; η2p= 0.01). Conclusions and Relevance: This cohort study of toddlers at HL and LL of autism suggests that there is an association between sex and EF and that brain-behavior associations in EF may be altered in children at HL of autism. Furthermore, EF deficits may aggregate in families, particularly in girls
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