Search results for " Simulation"
showing 10 items of 4034 documents
A Novel CCT5 Missense Variant Associated with Early Onset Motor Neuropathy
2020
Diseases associated with acquired or genetic defects in members of the chaperoning system (CS) are increasingly found and have been collectively termed chaperonopathies. Illustrative instances of genetic chaperonopathies involve the genes for chaperonins of Groups I (e.g., Heat shock protein 60, Hsp60) and II (e.g., Chaperonin Containing T-Complex polypeptide 1, CCT). Examples of the former are hypomyelinating leukodystrophy 4 (HLD4 or MitCHAP60) and hereditary spastic paraplegia (SPG13). A distal sensory mutilating neuropathy has been linked to a mutation [p.(His147Arg)] in subunit 5 of the CCT5 gene. Here, we describe a new possibly pathogenic variant [p.(Leu224Val)] of the same subunit b…
Drug connectivity mapping and functional analysis reveal therapeutic small molecules that differentially modulate myelination
2022
Disruption or loss of oligodendrocytes (OLs) and myelin has devastating effects on CNS function and integrity, which occur in diverse neurological disorders, including Multiple Sclerosis (MS), Alzheimer’s disease and neuropsychiatric disorders. Hence, there is a need to develop new therapies that promote oligodendrocyte regeneration and myelin repair. A promising approach is drug repurposing, but most agents have potentially contrasting biological actions depending on the cellular context and their dose-dependent effects on intracellular pathways. Here, we have used a combined systems biology and neurobiological approach to identify compounds that exert positive and negative effects on olig…
Surrogate Data Analysis for Assessing the Significance of the Coherence Function
2004
In cardiovascular variability analysis, the significance of the coupling between two time series is commonly assessed by setting a threshold level in the coherence function. While traditionally used statistical tests consider only the parameters of the adopted estimator, the required zero-coherence level may be affected by some features of the observed series. In this study, three procedures, based on the generation of surrogate series sharing given properties with the original but being structurally uncoupled, were considered: independent identically distributed (IID), Fourier transform (FT), and autoregressive (AR). IID surrogates maintained the distribution of the original series, while …
Different relaxations in myoglobin after photolysis
2004
To clarify the interplay of kinetic hole-burning (KHB), structural relaxation, and ligand migration in myoglobin (Mb), we measured time-resolved absorption spectra in the Soret region after photolysis of carbon monoxide Mb (MbCO) in the temperature interval 120-260 K and in the time window 350 ns to 200 ms. The spectral contributions of both photolyzed (Mb * ) and liganded Mb (MbCO) have been analyzed by taking into account homogeneous bandwidth, coupling to vibrational modes, and static conformational heterogeneity. We succeeded in separating the “time-dependent” spectral changes, and this work provides possibilities to identify the events in the process of ligand rebinding. KHB is domina…
Spectral broadening of the Soret band in myoglobin: an interpretation by the full spectrum of low-frequency modes from a normal modes analysis.
2005
In this work the temperature dependence of the Soret band line shape in carbon-monoxy myoglobin is re-analyzed by using both the full correlator approach in the time domain and the frequency domain approach. The new analyses exploit the full density of vibrational states of carbon-monoxy myoglobin available from normal modes analysis, and avoid the artificial division of the entire set of vibrational modes coupled to the Soret transition into "high-frequency" and "low-frequency" subsets; the frequency domain analysis, however, makes use of the so-called short-times approximation, while the time domain one avoids it. Time domain and frequency domain analyses give very similar results, thus s…
Dendritic Ih selectively blocks temporal summation of unsynchronized distal inputs in CA1 pyramidal neurons.
2004
The active dendritic conductances shape the input-output properties of many principal neurons in different brain regions, and the various ways in which they regulate neuronal excitability need to be investigated to better understand their functional consequences. Using a realistic model of a hippocampal CA1 pyramidal neuron, we show a major role for the hyperpolarization-activated current, I-h, in regulating the spike probability of a neuron when independent synaptic inputs are activated with different degrees of synchronization and at different distances from the soma. The results allowed us to make the experimentally testable prediction that the I-h in these neurons is needed to reduce ne…
Systematic uncertainties from halo asphericity in dark matter searches
2015
Although commonly assumed to be spherical, dark matter halos are predicted to be non-spherical by N-body simulations and their asphericity has a potential impact on the systematic uncertainties in dark matter searches. The evaluation of these uncertainties is the main aim of this work, where we study the impact of aspherical dark matter density distributions in Milky-Way-like halos on direct and indirect searches. Using data from the large N-body cosmological simulation Bolshoi, we perform a statistical analysis and quantify the systematic uncertainties on the determination of local dark matter density and the so-called $J$ factors for dark matter annihilations and decays from the galactic …
Improvement of neutron sensitivity for lithium formate ESR dosimeters: A Monte Carlo analysis
2023
This work presents the computational analysis of the sensitivity improvements that could be achieved in lithium formate monohydrate (LFM) electron paramagnetic resonance (EPR) dosemeters exposed to neutron beams. Monte Carlo (MC) simulations were performed on LFM pellets exposed to neutron beams with different energy spectra at various depths inside a water phantom. Various computations were carried out by considering different enrichments of 6Li inside the LFM matrix as well as addition of different amounts of gadolinium oxide inside the pellet blend. The energy released per unit mass was calculated with the aim of redicting the increase in dose achievable by the addition of sensitizers in…
Update of the search for supersymmetric particles in scenarios with Gravitino LSP and Sleptons NLSP
2001
An update of the search for sleptons, neutralinos and charginos in the context of scenarios where the lightest supersymmetric particle is the gravitino and the next-to-lightest supersymmetric particle is a slepton, is presented, together with the update of the search for heavy stable charged particles in light gravitino scenarios and Minimal Supersymmetric Standard Models. Data collected in 1999 with the DELPHI detector at centre-of-mass energies around 192, 196, 200 and 202 GeV were analysed. No evidence for the production of these supersymmetric particles was found. Hence, new mass limits were derived at 95% confidence level.
Search for supersymmetric particles in scenarios with a gravitino LSP and stau NLSP
2000
Sleptons, neutralinos and charginos were searched for in the context of scenarios where the lightest supersymmetric particle is the gravitino. It was assumed that the stau is the next-to-lightest supersymmetric particle. Data collected with the DELPHI detector at a centre-of-mass energy near 189 GeV were analysed combining the methods developed in previous searches at lower energies. No evidence for the production of these supersymmetric particles was found. Hence, limits were derived at 95% confidence level.