Open-air direct current plasma jet : scaling up, uniformity, and cellular control

Atmospheric-pressure plasma jets are commonly used in many fields from medicine to nanotechnology, yet the issue of scaling the discharges up to larger areas without compromising the plasma uniformity remains a major challenge. In this paper, we demonstrate a homogenous cold air plasmaglow with a large cross-section generated by a direct current power supply. There is no risk of glow-to-arc transitions, and the plasmaglow appears uniform regardless of the gap between the nozzle and the surface being processed. Detailed studies show that both the position of the quartz tube and the gas flow rate can be used to control the plasma properties. Further investigation indicates that the residual charges trapped on the inner surface of the quartz tube may be responsible for the generation of the air plasma plume with a large cross-section. The spatially resolved optical emission spectroscopy reveals that the air plasma plume is uniform as it propagates out of the nozzle. The remarkable improvement of the plasma uniformity is used to improve the bio-compatibility of a glass coverslip over a reasonably large area. This improvement is demonstrated by a much more uniform and effective attachment and proliferation of human embryonic kidney 293 (HEK 293) cells on the plasma-treated surface.

The dynamics of cellular automata on 2-manifolds is affected by topology

In this paper, we demonstrate that the distribution of Wolfram classes within a cellular automata rule space in the triangular tessellation is not consistent across different topological general. Using a statistical mechanics approach, cellular automata dynamical classes were approximated for cellular automata defined on genus-0, genus-1 and genus-2 2-manifolds. A distribution-free equality test for empirical distributions was applied to identify cases in which Wolfram classes were distributed differently across topologies. This result implies that global structure and local dynamics contribute to the long term evolution of cellular automata.

On the effect of topology on cellular automata rule spaces

This thesis presents an empirical study of the effects of topology on cellular automata rule spaces. The classical definition of a cellular automaton is restricted to that of a regular lattice, often with periodic boundary conditions. This definition is extended to allow for arbitrary topologies. The dynamics of cellular automata within the triangular tessellation were analysed when transformed to 2-manifolds of topological genus 0, genus 1 and genus 2. Cellular automata dynamics were analysed from a statistical mechanics perspective. The sample sizes required to obtain accurate entropy calculations were determined by an entropy error analysis which observed the error in the computed entropy against increasing sample sizes. Each cellular automata rule space was sampled repeatedly and the selected cellular automata were simulated over many thousands of trials for each topology. This resulted in an entropy distribution for each rule space. The computed entropy distributions are indicative of the cellular automata dynamical class distribution. Through the comparison of these dynamical class distributions using the E-statistic, it was identified that such topological changes cause these distributions to alter. This is a significant result which implies that both global structure and local dynamics play a important role in defining long term behaviour of cellular automata.

H2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype

BACKGROUND: About 1-5% of cancer patients suffer from significant normal tissue reactions as a result of radiotherapy (RT). It is not possible at this time to predict how most patients' normal tissues will respond to RT. DNA repair dysfunction is implicated in sensitivity to RT particularly in genes that mediate the repair of DNA double-strand breaks (DSBs). Phosphorylation of histone H2AX (phosphorylated molecules are known as gammaH2AX) occurs rapidly in response to DNA DSBs, and, among its other roles, contributes to repair protein recruitment to these damaged sites. Mammalian cell lines have also been crucial in facilitating the successful cloning of many DNA DSB repair genes; yet, very few mutant cell lines exist for non-syndromic clinical radiosensitivity (RS). METHODS: Here, we survey DNA DSB induction and repair in whole cells from RS patients, as revealed by gammaH2AX foci assays, as potential predictive markers of clinical radiation response. RESULTS: With one exception, both DNA focus induction and repair in cell lines from RS patients were comparable with controls. Using gammaH2AX foci assays, we identified a RS cancer patient cell line with a novel ionising radiation-induced DNA DSB repair defect; these data were confirmed by an independent DNA DSB repair assay. CONCLUSION: gammaH2AX focus measurement has limited scope as a pre-RT predictive assay in lymphoblast cell lines from RT patients; however, the assay can successfully identify novel DNA DSB repair-defective patient cell lines, thus potentially facilitating the discovery of novel constitutional contributions to clinical RS.

In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin’s lymphoma (NHL)

Background The analysis of cellular networks and pathways involved in oncogenesis has increased our knowledge about the pathogenic mechanisms that underlie tumour biology and has unmasked new molecular targets that may lead to the design of better anti-cancer therapies. Recently, using a high resolution loss of heterozygosity (LOH) analysis, we identified a number of potential tumour suppressor genes (TSGs) within common LOH regions across cases suffering from two of the most common forms of Non-Hodgkin’s lymphoma (NHL), Follicular Lymphoma (FL) and Diffuse Large B-cell Lymphoma (DLBCL). From these studies LOH of the protein tyrosine phosphatase receptor type J (PTPRJ) gene was identified as a common event in the lymphomagenesis of these B-cell lymphomas. The present study aimed to determine the cellular pathways affected by the inactivation of these TSGs including PTPRJ in FL and DLBCL tumourigenesis. Results Pathway analytical approaches identified that candidate TSGs located within common LOH regions participate within cellular pathways, which may play a crucial role in FL and DLBCL lymphomagenesis (i.e., metabolic pathways). These analyses also identified genes within the interactome of PTPRJ (i.e. PTPN11 and B2M) that when inactivated in NHL may play an important role in tumourigenesis. We also detected genes that are differentially expressed in cases with and without LOH of PTPRJ, such as NFATC3 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3). Moreover, upregulation of the VEGF, MAPK and ERBB signalling pathways was also observed in NHL cases with LOH of PTPRJ, indicating that LOH-driving events causing inactivation of PTPRJ, apart from possibly inducing a constitutive activation of these pathways by reduction or abrogation of its dephosphorylation activity, may also induce upregulation of these pathways when inactivated. This finding implicates these pathways in the lymphomagenesis and progression of FL and DLBCL. Conclusions The evidence obtained in this research supports findings suggesting that FL and DLBCL share common pathogenic mechanisms. Also, it indicates that PTPRJ can play a crucial role in the pathogenesis of these B-cell tumours and suggests that activation of PTPRJ might be an interesting novel chemotherapeutic target for the treatment of these B-cell tumours.

Numerical investigation of plant tissue porosity and its influence on cellular level shrinkage during drying

Dried plant food products are increasing in demand in the consumer market, leading to continuing research to develop better products and processing techniques. Plant materials are porous structures, which undergo large deformations during drying. For any given food material, porosity and other cellular parameters have a direct influence on the level of shrinkage and deformation characteristics during drying, which involve complex mechanisms. In order to better understand such mechanisms and their interrelationships, numerical modelling can be used as a tool. In contrast to conventional grid-based modelling techniques, it is considered that meshfree methods may have a higher potential for modelling large deformations of multiphase problem domains. This work uses a meshfree based microscale plant tissue drying model, which was recently developed by the authors. Here, the effects of porosity have been newly accounted for in the model with the objective of studying porosity development during drying and its influence on shrinkage at the cellular level. For simplicity, only open pores are modelled and in order to investigate the influence of different cellular parameters, both apple and grape tissues were used in the study. The simulation results indicated that the porosity negatively influences shrinkage during drying and the porosity decreases as the moisture content reduces (when open pores are considered). Also, there is a clear difference in the deformations of cells, tissues and pores, which is mainly influenced by the cell wall contraction effects during drying.

Evaluation of intra- and extra-epithelial secretory IgA in chlamydial infections

IgA is an important mucosal antibody that can neutralize mucosal pathogens by either preventing attachment to epithelia (immune exclusion) or alternatively inhibit intraepithelial replication following transcytosis by the polymeric immunoglobulin receptor (pIgR). Chlamydia trachomatis is a major human pathogen that initially targets the endocervical or urethral epithelium in women and men, respectively. As both tissues contain abundant SIgA we assessed the protection afforded by IgA targeting different chlamydial antigens expressed during the extra and intraepithelial stages of infection. We developed an in vitro model utilizing polarizing cells expressing the murine pIgR together with antigen-specific mouse IgA, and an in vivo model utilizing pIgR-/- mice. SIgA targeting the extraepithelial chlamydial antigen, the major outer membrane protein (MOMP), significantly reduced infection in vitro by 24 % and in vivo by 44 %. Conversely, pIgR-mediated delivery of IgA targeting the intraepithelial inclusion membrane protein A (IncA) bound to the inclusion but did not reduce infection in vitro or in vivo. Similarly, intraepithelial IgA targeting the secreted protease Chlamydia protease-like activity factor (CPAF) also failed to reduce infection. Together, these data suggest the importance of pIgR-mediated delivery of IgA targeting extra but not intraepithelial chlamydial antigens for protection against a genital tract infection.

Numerical investigation of case hardening of plant tissue during dying and its influence on the cellular level shrinkage

Dried plant food materials are one of the major contributors to the global food industry. Widening the fundamental understanding on different mechanisms of food material alterations during drying assists the development of novel dried food products and processing techniques. In this regard, case hardening is an important phenomenon, commonly observed during the drying processes of plant food materials, which significantly influences the product quality and process performance. In this work, a recent meshfree-based numerical model of the authors is further improved and used to simulate the influence of case hardening on shrinkage characteristics of plant tissues during drying. In order to model fluid and wall mechanisms in each cell, Smoothed Particle Hydrodynamics (SPH) and the Discrete Element Method (DEM) are used. The model is fundamentally more capable of simulating large deformation of multiphase materials, when compared with conventional grid-based modelling techniques such as Finite Element Methods (FEM) or Finite Difference Methods (FDM). Case hardening is implemented by maintaining distinct moisture levels in the different cell layers of a given tissue. In order to compare and investigate different factors influencing tissue deformations under case hardening, four different plant tissue varieties (apple, potato, carrot and grape) are studied. The simulation results indicate that the inner cells of any given tissue undergo limited shrinkage and cell wall wrinkling compared to the case hardened outer cell layers of the tissues. When comparing unique deformation characteristics of the different tissues, irrespective of the normalised moisture content, the cell size, cell fluid turgor pressure and cell wall characteristics influence the tissue response to case hardening.

A cellular automata model to investigate immune cell–tumor cell interactions in growing tumors in two spatial dimensions

We develop a hybrid cellular automata model to describe the effect of the immune system and chemokines on a growing tumor. The hybrid cellular automata model consists of partial differential equations to model chemokine concentrations, and discrete cellular automata to model cell–cell interactions and changes. The computational implementation overlays these two components on the same spatial region. We present representative simulations of the model and show that increasing the number of immature dendritic cells (DCs) in the domain causes a decrease in the number of tumor cells. This result strongly supports the hypothesis that DCs can be used as a cancer treatment. Furthermore, we also use the hybrid cellular automata model to investigate the growth of a tumor in a number of computational “cancer patients.” Using these virtual patients, the model can explain that increasing the number of DCs in the domain causes longer “survival.” Not surprisingly, the model also reflects the fact that the parameter related to tumor division rate plays an important role in tumor metastasis.