Search results for "Computer simulation"
showing 10 items of 1054 documents
Extended Granger causality: a new tool to identify the structure of physiological networks.
2015
Granger causality (GC) is a very popular tool for assessing the presence of directional interactions between two time series of a multivariate data set. In its original formulation, GC does not account for zero-lag correlations possibly existing between the observed time series. In the present study we compare the GC with a novel measure, termed extended GC (eGC), able to capture instantaneous causal relationships. We present a two-step procedure for the practical estimation of eGC based on first detecting the existence of zero-lag correlations, and then assigning them to one of the two possible causal directions using pairwise measures of non-Gaussianity. The proposed method was validated …
Elevation in type I interferons inhibits HCN1 and slows cortical neuronal oscillations
2014
Central nervous system (CNS) inflammation involves the generation of inducible cytokines such as interferons (IFNs) and alterations in brain activity, yet the interplay of both is not well understood. Here, we show that in vivo elevation of IFNs by viral brain infection reduced hyperpolarization-activated currents (Ih) in cortical pyramidal neurons. In rodent brain slices directly exposed to type I IFNs, the hyperpolarization-activated cyclic nucleotide (HCN)-gated channel subunit HCN1 was specifically affected. The effect required an intact type I receptor (IFNAR) signaling cascade. Consistent with Ih inhibition, IFNs hyperpolarized the resting membrane potential, shifted the resonance fre…
Optical release of caged glutamate for stimulation of neurons in the in vitro slice preparation
2005
Optical stimulation techniques prove useful to map func- tional inputs in the in vitro brain slice preparation: Glutamate released by a focused beam of UV light induces action potentials, which can be detected in postsynaptic neurons. The direct activation effect is influenced by factors such as compound concentration, focus depth, light absorption in the tissue, and sensitivity of different neuronal do- mains. We analyze information derived from direct stimulation ex- periments in slices from rat barrel cortex and construct a computa- tional model of a layer V pyramidal neuron that reproduces the experimental findings. The model predictions concerning the influ- ence of focus depth on inpu…
Physiologically based metformin pharmacokinetics model of mice and scale-up to humans for the estimation of concentrations in various tissues
2020
Metformin is the primary drug for type 2 diabetes treatment and a promising candidate for other disease treatment. It has significant deviations between individuals in therapy efficiency and pharmacokinetics, leading to the administration of an unnecessary overdose or an insufficient dose. There is a lack of data regarding the concentration-time profiles in various human tissues that limits the understanding of pharmacokinetics and hinders the development of precision therapies for individual patients. The physiologically based pharmacokinetic (PBPK) model developed in this study is based on humans’ known physiological parameters (blood flow, tissue volume, and others). The missing tissue-s…
Using Virtual Reality to Distract Overweight Children from Bodily Sensations During Exercise
2016
This study analyzes the potential of virtual reality (VR) to enhance attentional distraction in overweight children as they experience bodily sensations during exercise. It has been suggested that one reason why obese children stop exercising is the perception of bodily sensations. In a counterbalanced design, a total of 109 children (33 overweight, 10-15 years old) were asked to walk twice for 6 minutes on a treadmill under one of two conditions: (a) traditional condition (TC)-focusing their attention on their physical feelings and sensations or (b) distraction condition (DC)-focusing their attention on a virtual environment. Attentional focus during exercise, bad-good feeling states (pre-…
Embryonic stem cell-related miRNAs are involved in differentiation of pluripotent cells originating from the germ line.
2010
Cells originating from the germ cell lineage retain the remarkable property under special culture conditions to give rise to cells with embryonic stem cell (ESC) properties, such as the multipotent adult germline stem cells (maGSCs) derived from adult mouse testis. To get an insight into the mechanisms that control pluripotency and differentiation in these cells, we studied how differences observed during in vitro differentiation between ESCs and maGSCs are associated with differences at the level of microRNAs (miRNAs). In this work, we provide for a first time a connection between germ cell origin of maGSCs and their specific miRNA expression profile. We found that maGSCs express higher le…
Quantifying male attractiveness
2003
Genetic models of sexual selection are concerned with a dynamic process in which female preference and male trait values coevolve. We present a rigorous method for characterizing evolutionary endpoints of this process in phenotypic terms. In our phenotypic characterization the mate-choice strategy of female population members determines how attractive females should find each male, and a population is evolutionarily stable if population members are actually behaving in this way. This provides a justification of phenotypic explanations of sexual selection and the insights into sexual selection that they provide. Furthermore, the phenotypic approach also has enormous advantages over a genetic…
Repeat expansion in spinocerebellar ataxia type 17 alleles of the TATA-box binding protein gene: an evolutionary approach.
2006
The variability and mutational changes of the CAG microsatellite in the TATA-box binding protein gene (TBP) were studied. We sequenced the microsatellite of the TBP gene of 25 unrelated individuals from northern Germany (10 SCA17 patients and 15 unaffected control individuals). In addition, the microsatellites were sequenced from individuals of 10 northern German families with at least one family member affected by SCA17. To study also the evolutionary history of this CAG/CAA microsatellite in nonhuman primates, the homologous regions were analysed from Pan troglodytes, Gorilla gorilla, Pongo pygmaeus, P. abellii, Hylobates lar, Nomascus leucogenys, Symphalangus syndactylus, Macaca mulatta,…
Shear stress alterations in the celiac trunk of patients with a continuous-flow left ventricular assist device as shown by in-silico and in-vitro flo…
2017
Background The use of left ventricular assist devices (LVADs) to treat advanced cardiac heart failure is constantly increasing, although this device leads to high risk for gastrointestinal bleeding. Methods Using in-silico flow analysis, we quantified hemodynamic alterations due to continuous-flow LVAD (HeartWare, Inc., Framingham, MA) in the celiac trunk and major branches of the abdominal aorta, and then explored the relationship between wall shear stress (WSS) and celiac trunk orientation. To assess outflow from the aortic branch, a 3-dimensional-printed patient-specific model of the celiac trunk reconstructed from an LVAD-supported patient was used to estimate echocardiographic outflow …
Chemometric and chemoinformatic analyses of anabolic and androgenic activities of testosterone and dihydrotestosterone analogues
2008
Predictive quantitative structure-activity relationship (QSAR) models of anabolic and androgenic activities for the testosterone and dihydrotestosterone steroid analogues were obtained by means of multiple linear regression using quantum and physicochemical molecular descriptors (MD) as well as a genetic algorithm for the selection of the best subset of variables. Quantitative models found for describing the anabolic (androgenic) activity are significant from a statistical point of view: R2 of 0.84 (0.72 and 0.70). A leave-one-out cross-validation procedure revealed that the regression models had a fairly good predictability [q2 of 0.80 (0.60 and 0.59)]. In addition, other QSAR models were …