195 research outputs found
Signal generation and propagation in the olfactory bulb: Multicompartmental modeling
AbstractThe generation and propagation of action potentials in the two major cell types of the olfactory bulb, i.e., in the mitral and granule cells, are simulated by applying the multicompartmental modeling technique. The specific effects of the individual ionic currents, the propagation of the signals through the compartments, and several dynamic phenomena occurring in small networks (such as synchronized oscillation due to excitatory and inhibitory coupling) have been demonstrated
Fluid-Enhanced Annealing in the Subcontinental Lithospheric Mantle Beneath the Westernmost Margin of the Carpathian-Pannonian Extensional Basin System
Mantle xenoliths from the Styrian Basin Volcanic Field (Western Pannonian Basin, Austria) are mostly coarse granular amphibole-bearing spinel lherzolites with microstructures attesting for extensive annealing. Olivine and pyroxene CPO (crystal-preferred orientation) preserve nevertheless the record of coeval deformation during a preannealing tectonic event. Olivine shows transitional CPO symmetry from [010]-fiber to orthogonal type. In most samples with [010]-fiber olivine CPO symmetry, the [001] axes of the pyroxenes are also dispersed in the foliation plane. This CPO patterns are consistent with lithospheric deformation accommodated by dislocation creep in a transpressional tectonic regime. The lithospheric mantle deformed most probably during the transpressional phase after the Penninic slab breakoff in the Eastern Alps. The calculated seismic properties of the xenoliths indicate that a significant portion of shear wave splitting delay times in the Styrian Basin (0.5 s out of approximately 1.3 s) may originate in a highly annealed subcontinental lithospheric mantle. Hydroxyl content in olivine is correlated to the degree of annealing, with higher concentrations in the more annealed textures. Based on the correlation between microstructures and hydroxyl content in olivine, we propose that annealing was triggered by percolation of hydrous fluids/melts in the shallow subcontinental lithospheric mantle. A possible source of these fluids/melts is the dehydration of the subducted Penninic slab beneath the Styrian Basin. The studied xenoliths did not record the latest large-scale geodynamic events in the regionthe Miocene extension then tectonic inversion of the Pannonian Basin.We acknowledge the constructive criticism and helpful comments of Q‐K. Xia, an anonymous reviewer, and the Editor, John Geissman. We are grateful to F. Barou for his assistance during EBSD‐SEM analyses. L. E. Aradi is grateful to Bernardo Cesare, Levente Patkó, and Raúl Carampin for their help during the EPMA measurements. The FTIR analyses were carried out with the help of Judith Mihály and Csaba Németh. This research was partially granted by the Hungarian Science Foundation (OTKA, 78425 to Cs. Szabó). K. H.'s work was funded by the European Union Seventh Framework Programme Marie Curie postdoctoral fellowship (grant PIEFGA‐2012‐327226) and by the Juan de la Cierva Postdoctoral Fellowship (grant FPDI‐2013‐16253) of the Spanish Ministry of Economic and Competitiveness (MINECO). This project has been implemented with the support provided to I. J. Kovács from the National Research, Development and Innovation Fund of Hungary, financed under the K119740 funding scheme. The data used in this paper are listed in the references, tables, and supporting information. The raw EBSD and geochemical data are available from the corresponding author upon request. The FTIR spectra are available at the PULI (Pannonian Uniform Lithospheric Infrared spectral database) website (http://puli.mfgi.hu/). This is the 86 publication of the Lithosphere Fluid Research Lab (LRG)
Validity of models for Dreicer generation of runaway electrons in dynamic scenarios
Runaway electron modelling efforts are motivated by the risk these energetic
particles pose to large fusion devices. The sophisticated kinetic models can
capture most features of the runaway electron generation but have high
computational costs which can be avoided by using computationally cheaper
reduced kinetic codes. In this paper, we compare the reduced kinetic and
kinetic models to determine when the former solvers, based on analytical
calculations assuming quasi-stationarity, can be used. The Dreicer generation
rate is calculated by two different solvers in parallel in a workflow developed
in the European Integrated Modelling framework, and this is complemented by
calculations of a third code that is not yet integrated into the framework.
Runaway Fluid, a reduced kinetic code, NORSE, a kinetic code using non-linear
collision operator, and DREAM, a linearized Fokker-Planck solver, are used to
investigate the effect of a dynamic change in the electric field for different
plasma scenarios spanning across the whole tokamak-relevant range. We find that
on time scales shorter than or comparable to the electron collision time at the
critical velocity for runaway electron generation kinetic effects not captured
by reduced kinetic models play an important role. This characteristic time
scale is easy to calculate and can reliably be used to determine whether there
is a need for kinetic modelling, or cheaper reduced kinetic codes are expected
to deliver sufficiently accurate results. This criterion can be automated, and
thus it can be of great benefit for the comprehensive self-consistent modelling
frameworks that are attempting to simulate complex events such as tokamak
start-up or disruptions
A novel epilepsy mutation in the sodium channel SCN1A identifies a cytoplasmic domain for {beta} subunit interaction
A mutation in the sodium channel SCN1A was identified in a small Italian family with dominantly inherited generalized epilepsy with febrile seizures plus (GEFS+). The mutation, D1866Y, alters an evolutionarily conserved aspartate residue in the C-terminal cytoplasmic domain of the sodium channel {alpha} subunit. The mutation decreased modulation of the {alpha} subunit by {beta}1, which normally causes a negative shift in the voltage dependence of inactivation in oocytes. There was less of a shift with the mutant channel, resulting in a 10 mV difference between the wild-type and mutant channels in the presence of {beta}1. This shift increased the magnitude of the window current, which resulted in more persistent current during a voltage ramp. Computational analysis suggests that neurons expressing the mutant channels will fire an action potential with a shorter onset delay in response to a threshold current injection, and that they will fire multiple action potentials with a shorter interspike interval at a higher input stimulus. These results suggest a causal relationship between a positive shift in the voltage dependence of sodium channel inactivation and spontaneous seizure activity. Direct interaction between the cytoplasmic C-terminal domain of the wild-type{alpha} subunit with the {beta}1or {beta}3 subunit was first demonstrated by yeast two-hybrid analysis. The SCN1A peptide K1846-R1886 is sufficient for {beta} subunit interaction. Coimmunoprecipitation from transfected mammalian cells confirmed the interaction between the C-terminal domains of the {alpha} and {beta}1 subunits. The D1866Y mutation weakens this interaction, demonstrating a novel molecular mechanism leading to seizure susceptibility
Clinical outcomes in patients treated for coronary in-stent restenosis with drug-eluting balloons: Impact of high platelet reactivity.
BACKGROUND: The impact of high platelet reactivity (HPR) on clinical outcomes after elective percutaneous coronary interventions (PCI) with drug-eluting balloons (DEB) due to in-stent restenosis (ISR) is unknown. OBJECTIVE: We sought to evaluate the prognostic importance of HPR together with conventional risk factors in patients treated with DEB. METHODS: Patients treated with DEB due to ISR were enrolled in a single-centre, prospective registry between October 2009 and March 2015. Only patients with recent myocardial infarction (MI) received prasugrel, others were treated with clopidogrel. HPR was defined as an ADP-test >46U with the Multiplate assay and no adjustments were done based on results. The primary endpoint of the study was a composite of cardiovascular mortality, MI, any revascularization or stroke during one-year follow-up. RESULTS: 194 stable angina patients were recruited of whom 90% were treated with clopidogrel. Clinical characteristics and procedural data were available for all patients; while platelet function testing was performed in 152 subjects of whom 32 (21%) had HPR. Patients with HPR had a higher risk for the primary endpoint (HR: 2.45; CI: 1.01-5.92; p = 0.03). The difference was primarily driven by a higher risk for revascularization and MI. According to the multivariate analysis, HPR remained a significant, independent predictor of the primary endpoint (HR: 2.88; CI: 1.02-8.14; p = 0.04), while total DEB length and statin treatment were other independent correlates of the primary outcome. CONCLUSION: HPR was found to be an independent predictor of repeat revascularization and MI among elective patients with ISR undergoing PCI with DEB
Consistency and diversity of spike dynamics in the neurons of bed nucleus of Stria Terminalis of the rat: a dynamic clamp study
Neurons display a high degree of variability and diversity in the expression and regulation of their voltage-dependent ionic channels. Under low level of synaptic background a number of physiologically distinct cell types can be identified in most brain areas that display different responses to standard forms of intracellular current stimulation. Nevertheless, it is not well understood how biophysically different neurons process synaptic inputs in natural conditions, i.e., when experiencing intense synaptic bombardment in vivo. While distinct cell types might process synaptic inputs into different patterns of action potentials representing specific "motifs'' of network activity, standard methods of electrophysiology are not well suited to resolve such questions. In the current paper we performed dynamic clamp experiments with simulated synaptic inputs that were presented to three types of neurons in the juxtacapsular bed nucleus of stria terminalis (jcBNST) of the rat. Our analysis on the temporal structure of firing showed that the three types of jcBNST neurons did not produce qualitatively different spike responses under identical patterns of input. However, we observed consistent, cell type dependent variations in the fine structure of firing, at the level of single spikes. At the millisecond resolution structure of firing we found high degree of diversity across the entire spectrum of neurons irrespective of their type. Additionally, we identified a new cell type with intrinsic oscillatory properties that produced a rhythmic and regular firing under synaptic stimulation that distinguishes it from the previously described jcBNST cell types. Our findings suggest a sophisticated, cell type dependent regulation of spike dynamics of neurons when experiencing a complex synaptic background. The high degree of their dynamical diversity has implications to their cooperative dynamics and synchronization
Physics and chemistry of hydrogen in the vacancies of semiconductors
Hydrogen is well known to cause electrical passivation of lattice vacancies in semiconductors. This effect follows from the chemical passivation of the dangling bonds. Recently it was found that H in the carbon vacancy of SiC forms a three-center bond with two silicon neighbors in the vacancy, and gives rise to a new electrically active state. In this paper we examine hydrogen in the anion vacancies of BN, AlN, and GaN. We find that three-center bonding of H is quite common and follows clear trends in terms of the second-neighbor distance in the lattice, the typical (two-center) hydrogen-host-atom bond length, the electronegativity difference between host atoms and hydrogen, as well as the charge state of the vacancy. Three-center bonding limits the number of H atoms a nitrogen vacancy can capture to two, and prevents electric passivation in GaAs as well
The first biosimilar approved for the treatment of osteoporosis
To demonstrate the clinical comparability between RGB-10 (a biosimilar teriparatide) and the originator, a comparative pharmacokinetic trial was conducted. The study was successful in establishing bioequivalence. Marketing authorisation for RGB-10 (Terrosa®) was granted by the European Medicines Agency in 2017.Teriparatide, the first bone anabolic agent, is the biologically active fragment of human parathyroid hormone. The imminent patent expiry of the originator will open the door for biosimilars to enter the osteology market, thereby improving access to a highly effective, yet prohibitively expensive therapy.Subsequent to establishing comparability on the quality and non-clinical levels between RGB-10, a biosimilar teriparatide, and its reference product (Forsteo®), a randomised, double-blind, 2-way cross-over comparative study (duration: four days) was conducted in 54 healthy women (ages: 18 to 55 years) to demonstrate the pharmacokinetic/pharmacodynamic (PK/PD) equivalence and comparable safety of these products. Extents of exposure (AUC0-tlast) and peak exposure (Cmax), as measured by means of ELISA, were evaluated as co-primary PK endpoints, and serum calcium levels, as measured using standard automated techniques, were assessed for PD effects. Safety was monitored throughout the study.The 94.12% CIs for the ratio of the test to the reference treatments, used due to the two-stage design (85.20-98.60% and 85.51-99.52% for AUC0-tlast and Cmax, respectively), fell within the 80.00-125.00% acceptance range. The calcium PD parameters were essentially identical with geometric mean ratios (GMRs) of 99.93% and 99.87% for AUC and Cmax, respectively. Analysis of the safety data did not reveal any differences between RGB-10 and its reference.Based on the high level of similarity in the preclinical data and the results of this clinical study, marketing authorisation for RGB-10 (Terrosa®) was granted by the European Medicines Agency (EMA) in 2017
Atomistic simulations of self-trapped exciton formation in silicon nanostructures: The transition from quantum dots to nanowires
Using an approximate time-dependent density functional theory method, we
calculate the absorption and luminescence spectra for hydrogen passivated
silicon nanoscale structures with large aspect ratio. The effect of electron
confinement in axial and radial directions is systematically investigated.
Excited state relaxation leads to significant Stokes shifts for short nanorods
with lengths less than 2 nm, but has little effect on the luminescence
intensity. The formation of self-trapped excitons is likewise observed for
short nanostructures only; longer wires exhibit fully delocalized excitons with
neglible geometrical distortion at the excited state minimum.Comment: 10 pages, 4 figure
Boron Nitride Monolayer: A Strain-Tunable Nanosensor
The influence of triaxial in-plane strain on the electronic properties of a
hexagonal boron-nitride sheet is investigated using density functional theory.
Different from graphene, the triaxial strain localizes the molecular orbitals
of the boron-nitride flake in its center depending on the direction of the
applied strain. The proposed technique for localizing the molecular orbitals
that are close to the Fermi level in the center of boron nitride flakes can be
used to actualize engineered nanosensors, for instance, to selectively detect
gas molecules. We show that the central part of the strained flake adsorbs
polar molecules more strongly as compared with an unstrained sheet.Comment: 20 pages, 9 figure
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