Numerical study of lipid translocation driven by nanoporation due to multiple high-intensity, ultrashort electrical pulses

AbstractThe dynamical translocation of lipids from one leaflet to another due to membrane permeabilization driven by nanosecond, high-intensity (>100kV/cm) electrical pulses has been probed. Our simulations show that lipid molecules can translocate by diffusion through water-filled nanopores which form following high voltage application. Our focus is on multiple pulsing, and such simulations are relevant to gauge the time duration over which nanopores might remain open, and facilitate continued lipid translocations and membrane transport. Our results are indicative of a N½ scaling with pulse number for the pore radius. These results bode well for the use of pulse trains in biomedical applications, not only due to cumulative behaviors and in reducing electric intensities and pulsing hardware, but also due to the possibility of long-lived thermo-electric physics near the membrane, and the possibility for pore coalescence

Numerical Study of Lipid Translocation Driven by Nanoporation Due to Multiple High-Intensity, Ultrashort Electrical Pulses

The dynamical translocation of lipids from one leaflet to another due to membrane permeabilization driven by nanosecond, high-intensity (\u3e100 kV/cm) electrical pulses has been probed. Our simulations show that lipid molecules can translocate by diffusion through water-filled nanopores which form following high voltage application. Our focus is on multiple pulsing, and such simulations are relevant to gauge the time duration over which nanopores might remain open, and facilitate continued lipid translocations and membrane transport. Our results are indicative of a N1/2 scaling with pulse number for the pore radius. These results bode well for the use of pulse trains in biomedical applications, not only due to cumulative behaviors and in reducing electric intensities and pulsing hardware, but also due to the possibility of long-lived thermo-electric physics near the membrane, and the possibility for pore coalescence. © 2013 Elsevier B.V. All rights reserved

Simulations of Transient Membrane Behavior in Cells Subjected to a High-Intensity Ultrashort Electric Pulse

A molecular dynamics (MD) scheme is combined with a distributed circuit model for a self-consistent analysis of the transient membrane response for cells subjected to an ultrashort (nanosecond) high-intensity (approximately 0.01-V/nm spatially averaged field) voltage pulse. The dynamical, stochastic, many-body aspects are treated at the molecular level by resorting to a course-grained representation of the membrane lipid molecules. Coupling the Smoluchowski equation to the distributed electrical model for current flow provides the time-dependent transmembrane fields for the MD simulations. A good match between the simulation results and available experimental data is obtained. Predictions include pore formation times of about 5-6 ns. It is also shown that the pore formation process would tend to begin from the anodic side of an electrically stressed membrane. Furthermore, the present simulations demonstrate that ions could facilitate pore formation. This could be of practical importance and have direct relevance to the recent observations of calcium release from the endoplasmic reticulum in cells subjected to such ultrashort, high-intensity pulses

Integrated analytical models for flexible manufacturing systems

Product form queueing networks (PFQN) and generalized stochastic Petri nets (GSPN) have emerged as the principal performance modelling tools for flexible manufacturing systems (FMS). In this paper, we present integrated PFQN-GSPN models, which combine the computational efficiency of PFQN and representational power of GSPN by employing the principle of flow-equivalence. We show that FMS that include non-product form characteristics such as dynamic routing and synchronization can be evaluated efficiently and accurately using the integrated models

Computational approaches for modeling human intestinal absorption and permeability

Human intestinal absorption (HIA) is an important roadblock in the formulation of new drug substances. Computational models are needed for the rapid estimation of this property. The measurements are determined via in vivo experiments or in vitro permeability studies. We present several computational models that are able to predict the absorption of drugs by the human intestine and the permeability through human Caco-2 cells. The training and prediction sets were derived from literature sources and carefully examined to eliminate compounds that are actively transported. We compare our results to models derived by other methods and find that the statistical quality is similar. We believe that models derived from both sources of experimental data would provide greater consistency in predictions. The performance of several QSPR models that we investigated to predict outside the training set for either experimental property clearly indicates that caution should be exercised while applying any of the models for quantitative predictions. However, we are able to show that the qualitative predictions can be obtained with close to a 70% success rate

Reference evapotranspiration in the irrigated perimeters of the state of Sergipe

O conhecimento da evapotranspiração de referência (ETo) é essencial no manejo de irrigação de culturas agrícolas em todo o mundo. Neste trabalho se utilizaram dados meteorológicos diários de evaporação do tanque "Classe A", temperaturas máximas e mínimas, insolação, velocidade do vento a 2 m de altura e umidade relativa do ar, referentes ao período de 1989 a 1993, coletados em quatro perímetros irrigados do Estado de Sergipe, para estimativa da ETo com base nos métodos do Tanque Classe "A", Radiação Solar, Hargreaves & Samani, Linacre e Penman-Monteith (FAO/56). Comparam-se os valores diários da ETo para a região estudada, através dos quais, quando comparados com o modelo de Penman-Monteith (FAO/56) se obtiveram os melhores desempenhos com os métodos que utilizam a radiação solar como dado de entrada no modelo. O método do Tanque Classe "A" não apresentou desempenho satisfatório em nenhum perímetro irrigado estudado. _________________________________________________________________________________________ ABSTRACT: The knowledge of reference evapotranspiration (ETo) is essential for the irrigation scheduling of crops throughout the world. This work used daily meteorological data of Class A pan evaporation, maximum and minimum air temperatures, insolation, wind speed at 2 m above surface and relative humidity from 1989 to 1993 for four irrigated perimeters of Sergipe. These data were used for estimating ETo based on the following methods: Class A pan evaporation, Solar Radiation, Hargreaves & Samani, Linacre and Penman-Monteith (FAO/56). The daily values of ETo were compared to those obtained by FAO Penman-Monteith method in order to choose the best method of estimating ETo for the region. The best performance was obtained for those models which used the solar radiation as the data input. The Class A pan evaporation method did not show favorable performance in any irrigated perimeter

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk