The simulation of stress fibre and focal adhesion development in cells on patterned substrates.

The remodelling of the cytoskeleton and focal adhesion (FA) distributions for cells on substrates with micro-patterned ligand patches is investigated using a bio-chemo-mechanical model. We investigate the effect of ligand pattern shape on the cytoskeletal arrangements and FA distributions for cells having approximately the same area. The cytoskeleton model accounts for the dynamic rearrangement of the actin/myosin stress fibres. It entails the highly nonlinear interactions between signalling, the kinetics of tension-dependent stress-fibre formation/dissolution and stress-dependent contractility. This model is coupled with another model that governs FA formation and accounts for the mechano-sensitivity of the adhesions from thermodynamic considerations. This coupled modelling scheme is shown to capture a variety of key experimental observations including: (i) the formation of high concentrations of stress fibres and FAs at the periphery of circular and triangular, convex-shaped ligand patterns; (ii) the development of high FA concentrations along the edges of the V-, T-, Y- and U-shaped concave ligand patterns; and (iii) the formation of highly aligned stress fibres along the non-adhered edges of cells on the concave ligand patterns. When appropriately calibrated, the model also accurately predicts the radii of curvature of the non-adhered edges of cells on the concave-shaped ligand patterns.     

A note on ‘a replenishment policy for items with price-dependent demand,time-proportional deterioration and no shortages’

In a recent paper, Begum et al. (2012 Begum, R., Sahoo, R.R., and Sahu, S.K. (2012), ‘A Replenishment Policy for Items with Price-Dependent Demand, Time-Proportional Deterioration and no Shortages’, International Journal of Systems Science, 43, 903–910.[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar], International Journal of Systems Science, 43, 903–910) established pricing and replenishment policy for an inventory system with price-sensitive demand rate, time-proportional deterioration rate which follows three parameters, Weibull distribution and no shortages. In their model formulation, it is observed that the retailer's stock level reaches zero before the deterioration occurs. Consequently, the model resulted in traditional inventory model with price sensitive demand rate and no shortages. Hence, the main purpose of this note is to modify and present complete model formulation for Begum et al. (2012) Begum, R., Sahoo, R.R., and Sahu, S.K. (2012), ‘A Replenishment Policy for Items with Price-Dependent Demand, Time-Proportional Deterioration and no Shortages’, International Journal of Systems Science, 43, 903–910.[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar]. The proposed model is validated by a numerical example and the sensitivity analysis of parameters is carried out.     

One-step photochemical synthesis of permanent, nonleaching, ultrathin antimicrobial coatings for textiles and plastics

Antimicrobial copolymers of hydrophobic N-alkyl and benzophenone containing polyethylenimines were synthesized from commercially available linear poly(2-ethyl-2-oxazoline), and covalently attached to surfaces of synthetic polymers, cotton, and modified silicon oxide using mild photo-cross-linking. Specifically, these polymers were applied to polypropylene, poly(vinyl chloride), polyethylene, cotton, and alkyl-coated oxide surfaces using solution casting or spray coating and then covalently cross-linked rendering permanent, nonleaching antimicrobial surfaces. The photochemical grafting of pendant benzophenones allows immobilization to any surface that contains a C-H bond. Incubating the modified materials with either Staphylococcus aureus or Escherichia coli demonstrated that the modified surfaces had substantial antimicrobial capacity against both Gram-positive and Gram-negative bacteria (>98% microbial death).     

PTEN Loss Enhances Error-Prone DSB Processing and Tumor Cell Radiosensitivity by Suppressing RAD51 Expression and Homologous Recombination

PTEN has been implicated in the repair of DNA double-strand breaks (DSBs), particularly through homologous recombination (HR). However, other data fail to demonstrate a direct role of PTEN in DSB repair. Therefore, here, we report experiments designed to further investigate the role of PTEN in DSB repair. We emphasize the consequences of PTEN loss in the engagement of the four DSB repair pathways—classical non-homologous end-joining (c-NHEJ), HR, alternative end-joining (alt-EJ) and single strand annealing (SSA)—and analyze the resulting dynamic changes in their utilization. We quantitate the effect of PTEN knockdown on cell radiosensitivity to killing, as well as checkpoint responses in normal and tumor cell lines. We find that disruption of PTEN sensitizes cells to ionizing radiation (IR). This radiosensitization is associated with a reduction in RAD51 expression that compromises HR and causes a marked increase in SSA engagement, an error-prone DSB repair pathway, while alt-EJ and c-NHEJ remain unchanged after PTEN knockdown. The G₂-checkpoint is partially suppressed after PTEN knockdown, corroborating the associated HR suppression. Notably, PTEN deficiency radiosensitizes cells to PARP inhibitors, Olaparib and BMN673. The results show the crucial role of PTEN in DSB repair and show a molecular link between PTEN and HR through the regulation of RAD51 expression. The expected benefit from combination treatment with Olaparib or BMN673 and IR shows that PTEN status may also be useful for patient stratification in clinical treatment protocols combining IR with PARP inhibitors.     

Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain

Manganese neurotoxicity has been reported to cause a neurodegenerative disease known as parkinsonism. Previous reports have shown that the expression of the KH-type splicing regulatory protein (KHSRP), a nucleic acid-binding protein, and NLRP3 is increased upon Mn exposure. However, the relation between these two during Mn toxicity has not been fully deduced. The mouse neuroblastoma (N2a) and SD rats are treated with LPS and MnCl₂ to evaluate the expression of KHSRP and NLRP3. Further, the effect of the NLRP3 inhibitor MCC950 is checked on the expression of NLRP3, KHSRP and pro-inflammatory markers (TNFα, IL-18 and IL-1β) as well as the caspase-1 enzyme. Our results demonstrated an increment in NLRP3 and KHSRP expression post-MnCl₂ exposure in N2a cells and rat brain, while on the other hand with LPS exposure only NLRP3 expression levels were elevated and KHSRP was found to be unaffected. An increased expression of KHSRP, NLRP3, pro-inflammatory markers and the caspase-1 enzyme was observed to be inhibited with MCC950 treatment in MnCl₂-exposed cells and rats. Manganese exposure induces NLRP3 and KHSRP expression to induce neuroinflammation, suggesting a correlation between both which functions in toxicity-related pathways. Furthermore, MCC950 treatment reversed the role of KHSRP from anti-inflammatory to pro-inflammatory.     

Analysis of free edge effects in composite laminates

Extensive work has been done in the field of free edge effects in composite laminates. The present paper reviews the modelling as well as the experimental work on this class of boundary value problems. The modelling techniques developed by a number of investigators and the experimental validation of the predictions made through these models are discussed.     

Antioxidant efficacy of chitosan/graphene functionalized superparamagnetic iron oxide nanoparticles

The antioxidant potential of superparamagnetic iron oxide nanoparticles functionalized with chitosan and graphene were examined in the present work. Coprecipitation technique was followed for the synthesis of iron oxide nanoparticles. Graphene-iron oxide nanocomposites were synthesized by mechanical mixing followed by the heat treatment at moderate temperature. The chitosan coated iron oxide nanoparticles were prepared by dispersing nanoparticles in chitosan solution. The nanoparticles/nanocomposites were characterized using XRD, SEM, TEM and HAADF-STEM for phase structure, morphology and elemental analysis. The superparamagnetic behavior of nanoparticles/nanocomposites were confirmed by magnetic measurements using vibrating sample magnetometry. Antioxidant efficacy of these nanoparticles/nanocomposites were investigated in terms of free radical scavenging and reducing potential using an array of in vitro assay system. Ferric reducing antioxidant power (FRAP) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) were used for the antioxidant capacity. The investigation suggests that the graphene improves the antiradical response of iron oxide nanoparticles at higher concentration which is almost comparable to the ascorbic acid used as standard.     

Parallel state-space search for a first solution with consistent linear speedups

Consider the problem of exploring a large state-space for a goal state where although many such states may exist in the state-space, finding any one state satisfying the requirements is sufficient. All the methods known until now for conducting such search in parallel using multiprocessors fail to provide consistent linear speedups over sequential execution. The speedups vary between sublinear to superlinear and from one execution to another. Further, adding more processors may sometimes lead to a slow-down rather than speedup, giving rise to speedup anomalies reported in literature. We present a prioritizing strategy which yields consistent speedups that are close toP withP processors, and that monotonically increase with the additon of processors. This is achieved by keeping the total number of nodes expanded during parallel search very close to that of a sequential search. In addition, the strategy requires substantially smaller memory relative to other methods. The performance of this strategy is demonstrated on a multiprocessor with several state-space search problems.This research has been supported in part by the National Science Foundation under Contract No. CCR-89-02496.