Extreme bendability of DNA double helix due to bending asymmetry

Experimental data of the DNA cyclization (J-factor) at short length scales, as a way to study the elastic behavior of tightly bent DNA, exceed the theoretical expectation based on the wormlike chain (WLC) model by several orders of magnitude. Here, we propose that asymmetric bending rigidity of the double helix in the groove direction can be responsible for extreme bendability of DNA at short length scales and it also facilitates DNA loop formation at these lengths. To account for the bending asymmetry, we consider the asymmetric elastic rod (AER) model which has been introduced and parametrized in an earlier study (B. Eslami-Mossallam and M. Ejtehadi, Phys. Rev. E 80, 011919 (2009)). Exploiting a coarse grained representation of DNA molecule at base pair (bp) level, and using the Monte Carlo simulation method in combination with the umbrella sampling technique, we calculate the loop formation probability of DNA in the AER model. We show that, for DNA molecule has a larger J-factor compared to the WLC model which is in excellent agreement with recent experimental data.Comment: 8 pages, 9 figure

Fast and scalable inference of multi-sample cancer lineages.

Somatic variants can be used as lineage markers for the phylogenetic reconstruction of cancer evolution. Since somatic phylogenetics is complicated by sample heterogeneity, novel specialized tree-building methods are required for cancer phylogeny reconstruction. We present LICHeE (Lineage Inference for Cancer Heterogeneity and Evolution), a novel method that automates the phylogenetic inference of cancer progression from multiple somatic samples. LICHeE uses variant allele frequencies of somatic single nucleotide variants obtained by deep sequencing to reconstruct multi-sample cell lineage trees and infer the subclonal composition of the samples. LICHeE is open source and available at http://viq854.github.io/lichee

A Quantum-mechanical description of ion motion within the confining potentials of voltage gated ion channels

Voltage gated channel proteins cooperate in the transmission of membrane potentials between nerve cells. With the recent progress in atomic-scaled biological chemistry it has now become established that these channel proteins provide highly correlated atomic environments that may maintain electronic coherences even at warm temperatures. Here we demonstrate solutions of the Schr\"{o}dinger equation that represent the interaction of a single potassium ion within the surrounding carbonyl dipoles in the Berneche-Roux model of the bacterial \textit{KcsA} model channel. We show that, depending on the surrounding carbonyl derived potentials, alkali ions can become highly delocalized in the filter region of proteins at warm temperatures. We provide estimations about the temporal evolution of the kinetic energy of ions depending on their interaction with other ions, their location within the oxygen cage of the proteins filter region and depending on different oscillation frequencies of the surrounding carbonyl groups. Our results provide the first evidence that quantum mechanical properties are needed to explain a fundamental biological property such as ion-selectivity in trans-membrane ion-currents and the effect on gating kinetics and shaping of classical conductances in electrically excitable cells.Comment: 12 pages, 8 figure

Evaluation of acute and sub-chronic toxicity of Semelil (ANGIPARS�), a new phytotherapeutic drug for wound healing in rodents

Semelil (ANGIPARS�), an herbal formulation containing Melilotus officinalis extract, is a novel compound being developed for treatment of chronic wounds, particularly diabetic foot ulcers. The purpose of this study was to investigate toxicological, pharmacological, and pathomorphological effects of I.M. and I.P. administration of Semelil in animals. The acute toxicity parameters of Semelil diluted in normal saline (1:10 or 1:5) were determined after a single injection into BALB/c mice and Wistar rats in two steps. First, the LD50 was approximately assessed and then the precise lethal dose indices were estimated by the probit-analysis method. Specific single-dose effects of Semelil were monitored for clinical signs of toxicity, including general state of the animals, changes in their behavior, hematological and biochemical parameters for 14 days after drug administration. Then, subacute-chronic toxicity was evaluated in rats treated with Semelil for 3 months. In acute toxicity study, the calculated LD50 for drug diluted at 1:5 was in the range of 44-52 ml/kg. The adverse effects at drug doses close to the LD50 included depressed mood, narcosis, and sleep. No adverse pharmacological or toxicological effects of the drug diluted at 1:10 and administered in the single-dose (25-50 ml/kg body wt.) or chronically (daily doses of 0.07 and 0.21 ml/kg body wt.) were noted. Thus, the animal studies demonstrated a favorable safety profile for the phytotherapeutic Semelil

Nonimmune fetal hydrops and lysosomal storage disease: the finding of vacuolated lymphocytes in ascitic fluid in two cases

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102650/1/pd4274.pd

Investigation of Tractor Base Bleeding for Heavy Vehicle Aerodynamic Drag Reduction

One of the main contributors to the aerodynamic drag of a heavy vehicle is tractor-trailer gap drag, which arises when the vehicle operates within a crosswind. Under this operating condition, freestream flow is entrained into the tractor-trailer gap, imparting a momentum exchange to the vehicle and subsequently increasing the aerodynamic drag. While a number of add-on devices, including side extenders, splitter plates, vortex stabilizers, and gap sealers, have been previously tested to alleviate this source of drag, side extenders remain the primary add-on device of choice for reducing tractor-trailer gap drag. However, side extenders are not without maintenance and operational issues. When a heavy vehicle pivots sharply with respect to the trailer, as can occur during loading or unloading operations, the side extenders can become crushed against the trailer. Consequently, fleet operators are forced to incur additional costs to cover the repair or replacement of the damaged side extenders. This issue can be overcome by either shortening the side extenders or by devising an alternative drag reduction concept that can perform just as effectively as side extenders. To explore such a concept, we investigate tractor base bleeding as a means of reducing gap drag. Wind tunnel measurements are made on a 1:20 scale heavy vehicle model at a vehicle width-based Reynolds number of 420,000. The tractor bleeding flow, which is delivered through a porous material embedded within the tractor base, is introduced into the tractor-trailer gap at bleeding coefficients ranging from 0.0-0.018. To determine the performance of tractor base bleeding under more realistic operating conditions, computational fluid dynamics simulations are performed on a full-scale heavy vehicle within a crosswind for bleeding coefficients ranging from 0.0-0.13

Non-linear analysis of two-layer timber beams considering interlayer slip and uplift

A new mathematical model and its finite element formulation for the non-linear analysis of mechanical behaviour of a two-layer timber planar beam is presented. A modified principle of virtual work is employed in formulating the finite element method. The basic unknowns are strains. The following assumptions are adopted in the mathematical model: materials are taken to be non-linear and can differ from layer to layer; interacting shear and normal contact tractions between layers are derived from the non-linear shear contact traction-slip and the non-linear normal contact traction-uplift characteristics of the connectors; the geometrically linear and materially non-linear Bernoulli's beam theory is assumed for each layer. The formulation is found to be accurate, reliable and computationally effective. The suitability of the theory is validated by the comparison of the numerical solution and the experimental results of full-scale laboratory tests on a simply supported beam. An excellent agreement between measured and calculated results is observed for all load levels. The further objective of the paper is the analysis of the effect of different normal contact traction-uplift constitutive relationships on the kinematic and static quantities in a statically determined and undetermined structure. While the shear contact traction-slip constitutive relationship dictates the deformability of the composite beam and has a substantial influence on most of the static and kinematic quantities of the composite beam, a variable normal contact traction-uplift constitutive relationship is in most cases negligible

The clinical and environmental spread and diversity of toxigenic Clostridium difficile diarrhea in the region of the Middle East.

Stool samples of 1822 hospitalized patients with nosocomial diarrhea and 100 environmental samples were collected at three teaching hospitals and PCR amplification of rRNA intergenic spacer regions (ISR) was conducted. Bacterial cytotoxicity was assayed by conducting three assays namely toxigenic culture on vero cells, stool cytotoxin, and enzyme immunoassay. ISR was carried out using two universal primers complementary to conserved regions in the 16S and 23S rRNA genes. It was found that the toxigenic culture, stool cytotoxin and enzyme immunoassay showed close rates of detection of toxigenic C. difficile, 124, 121, and 122 /1822 (6.8, 6.64., and 6.7%) respectively. In addition, 32 different ribotypes for toxigenic C. difficile were detected, 28 in clinical and 6 in environmental isolates. The predominant ribotypes from the clinical isolates were 13-15, 35.6%, of isolates. Ribotypes were associated with age, location of isolation, and severity of symptoms of clostridial diarrhea (P<0.05). Ribotypes 6-9 affected children only. The most common ribotype of C. difficile , no. 13, as well as ribotypes 16, 20, and 4 covered almost the whole range of severity of symptoms. Ribotypes 21-27, 1, 3, 6, 7, 9, 11, 14, and 19 caused mild-moderate CDAD symptoms while ribotypes 5, 10 8, 12, 15, 17, and 28 were dominantly of severe symptoms (P<0.05). Environmental isolates showed 17% toxigenic strains composed of 4 different ribotypes while ribotypes 5 was shared with clinical isolates. These findings showed that C. difficile associated with diarrhea were genetically diverse and linked to environmental strains

Code Verification Results of an LLNL ASC Code on Some Tri-Lab Verification Test Suite Problems

As scientific codes become more complex and involve larger numbers of developers and algorithms, chances for algorithmic implementation mistakes increase. In this environment, code verification becomes essential to building confidence in the code implementation. This paper will present first results of a new code verification effort within LLNL's B Division. In particular, we will show results of code verification of the LLNL ASC ARES code on the test problems: Su Olson non-equilibrium radiation diffusion, Sod shock tube, Sedov point blast modeled with shock hydrodynamics, and Noh implosion