Positrons in gas filled traps and their transport in molecular gases

In this paper we give a review of two recent developments in positron transport, calculation of transport coefficients for a relatively complete set of collision cross sections for water vapour and for application of they Monte Carlo technique to model gas filled subexcitation positron traps such as Penning Malmberg Surko (Surko) trap. Calculated transport coefficients, very much like those for argon and other molecular gases show several new kinetic phenomena. The most important is the negative differential conductivity (NDC) for the bulk drift velocity when the flux drift velocity shows no sign of NDC. These results in water vapour are similar to the results in argon or hydrogen. The same technique that has been used for positron (and previously electron) transport may be applied to model development of particles in a Surko trap. We have provided calculation of the ensemble of positrons in the trap from an initial beam like distribution to the fully thermalised distribution. This model, however, does not include plasma effects (interaction between charged particles) and may be applied for lower positron densities

On new developments in the physics of positron swarms

Recently a new wave of swarm studies of positrons was initiated based on more complete scattering cross section sets. Initially some interesting and new physics was discovered, most importantly negative differential conductivity (NDC) that occurs only for the bulk drift velocity while it does not exist for the flux property. However the ultimate goal was to develop tools to model positron transport in realistic applications and the work that is progressing along these lines is reviewed here. It includes studies of positron transport in molecular gases, thermalization in generic swarm situations and in realistic gas filled traps and transport of positrons in crossed electric and magnetic fields. Finally we have extended the same technique of simulation (Monte Carlo) to studies of thermalization of positronium molecule. In addition, recently published first steps towards including effects of dense media on positron transport are summarized here

GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu

Deletion polymorphism of glutathione S-transferase M1 (GSTM1), a phase II detoxification and antioxidant enzyme, increases susceptibility to end-stage renal disease (ESRD) as well as the development of cardiovascular diseases (CVD) among ESRD patients and leads to their shorter cardiovascular survival. The mechanisms by which GSTM1 downregulation contributes to oxidative stress and inflammation in endothelial cells in uremic conditions have not been investigated so far. Therefore, the aim of the present study was to elucidate the effects of GSTM1 knockdown on oxidative stress and expression of a panel of inflammatory markers in human umbilical vein endothelial cells (HUVECs) exposed to uremic serum. Additionally, we aimed to discern whether GSTM1-null genotype is associated with serum levels of adhesion molecules in ESRD patients. HUVECs treated with uremic serum exhibited impaired redox balance characterized by enhanced lipid peroxidation and decreased antioxidant enzyme activities, independently of the GSTM1 knockdown. In response to uremic injury, HUVECs exhibited alteration in the expression of a series of inflammatory cytokines including retinol-binding protein 4 (RBP4), regulated on activation, normal T cell expressed and secreted (RANTES), C-reactive protein (CRP), angiogenin, dickkopf-1 (Dkk-1), and platelet factor 4 (PF4). GSTM1 knockdown in HUVECs showed upregulation of monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in the regulation of monocyte migration and adhesion. These cells also have shown upregulated intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1). In accordance with these findings, the levels of serum ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) were increased in ESRD patients lacking GSTM1, in comparison with patients with the GSTM1-active genotype. Based on these results, it may be concluded that incubation of endothelial cells in uremic serum induces redox imbalance accompanied with altered expression of a series of cytokines involved in arteriosclerosis and atherosclerosis. The association of GSTM1 downregulation with the altered expression of adhesion molecules might be at least partly responsible for the increased susceptibility of ESRD patients to CVD

Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

ContextPreeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.ObjectiveTo investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44.Design and interventionFKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling.Settings and participantsHuman samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid.Main outcome measuresPreeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed.ResultsThe CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis.ConclusionsThe FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes

Size Dependence of Current-Voltage Properties in Coulomb Blockade Networks

We theoretically investigate the current-voltage (I-V) property of two-dimensional Coulomb blockade (CB) arrays by conducting Monte Carlo simulations. The I-V property can be divided into three regions and we report the dependence of the aspect ratio delta (namely, the lateral size N_{y} over the longitudinal one N_{x}). We show that the average CB threshold obeys a power-law decay as a function of delta. Its exponent gamma corresponds to a sensitivity of the threshold depending on delta, and is inversely proportional to N_{x} (i.e., delta at fixed N_{y}). Further, the power-law exponent zeta, characterizing the nonlinearity of the I-V property in the intermediate region, logarithmically increases as delta increases. Our simulations describe the experimental result zeta=2.25 obtained by Parthasarathy et al. [Phys. Rev. Lett. 87 (2001) 186807]. In addition, the asymptotic I-V property of one-dimensional arrays obtained by Bascones et al. [Phys. Rev. B. 77 (2008) 245422] is applied to two-dimensional arrays. The asymptotic equation converges to the Ohm's law at the large voltage limit, and the combined tunneling-resistance is inversely proportional to delta. The extended asymptotic equation with the first-order perturbation well describes the experimental result obtained by Kurdak et al. [Phys. Rev. B 57 (1998) R6842]. Based on our asymptotic equation, we can estimate physical values that it is hard to obtain experimentally.Comment: 21 pages, 10 figures, accepted for publication in Journal of the Physical Society of Japa

Emerging Therapeutic Potential of Mesenchymal Stem/Stromal Cells in Preeclampsia.

Purpose of Review Preeclampsia is a dangerous pregnancy condition affecting both the mother and offspring. It is a multifactorial disease with poorly understood pathogenesis, lacking effective treatments. Maternal immune response, inflammation and oxidative stress leading to endothelial dysfunction are the most prominent pathogenic processes implicated in preeclampsia development. Here, we give a detailed overview of the therapeutic applications and mechanisms of mesenchymal stem/stromal cells (MSCs) as a potential new treatment for preeclampsia. Recent Findings MSCs have gained growing attention due to low immunogenicity, easy cultivation and expansion in vitro. Accumulating evidence now suggests that MSCs act primarily through their secretomes facilitating paracrine signalling that leads to potent immunomodulatory, pro-angiogenic and regenerative therapeutic effects. Summary MSCs have been studied in different animal models of preeclampsia demonstrating promising result, which support further investigations into the therapeutic effects and mechanisms of MSC-based therapies in preeclampsia, steering these therapies into clinical trials

Mechanisms of Key Innate Immune Cells in Early- and Late-Onset Preeclampsia.

Preeclampsia is a complex cardiovascular disorder of pregnancy with underlying multifactorial pathogeneses; however, its etiology is not fully understood. It is characterized by the new onset of maternal hypertension after 20 weeks of gestation, accompanied by proteinuria, maternal organ damage, and/or uteroplacental dysfunction. Preeclampsia can be subdivided into early- and late-onset phenotypes (EOPE and LOPE), diagnosed before 34 weeks or from 34 weeks of gestation, respectively. Impaired placental development in early pregnancy and subsequent growth restriction is often associated with EOPE, while LOPE is associated with maternal endothelial dysfunction. The innate immune system plays an essential role in normal progression of physiological pregnancy and fetal development. However, inappropriate or excessive activation of this system can lead to placental dysfunction or poor maternal vascular adaptation and contribute to the development of preeclampsia. This review aims to comprehensively outline the mechanisms of key innate immune cells including macrophages, neutrophils, natural killer (NK) cells, and innate B1 cells, in normal physiological pregnancy, EOPE and LOPE. The roles of the complement system, syncytiotrophoblast extracellular vesicles and mesenchymal stem cells (MSCs) are also discussed in the context of innate immune system regulation and preeclampsia. The outlined molecular mechanisms, which represent potential therapeutic targets, and associated emerging treatments, are evaluated as treatments for preeclampsia. Therefore, by addressing the current understanding of innate immunity in the pathogenesis of EOPE and LOPE, this review will contribute to the body of research that could lead to the development of better diagnosis, prevention, and treatment strategies. Importantly, it will delineate the differences in the mechanisms of the innate immune system in two different types of preeclampsia, which is necessary for a more personalized approach to the monitoring and treatment of affected women

Numerical Modeling of Thermalization of Positrons in Gas-Filled Surko Traps

In this paper, we present the results of our Monte Carlo-based numerical simulation of a Penning-Malmberg-Surko positron trap. The results of simulations show the effect that various processes (such as positronium (Ps) formation, annihilation, losses on walls, etc.) have on trapping efficiency. The thermalization profile is shown, along with the evolution of the energy distribution that morphs from a particle beam to a broad swarm-type distribution

Overlapping pathogenic signalling pathways and biomarkers in preeclampsia and cardiovascular disease

Objectives Preeclampsia is a cardiovascular pregnancy complication which occurs in 5-10% of pregnancies that can lead to a number of pregnancy complications including maternal and foetal death. Long-term, preeclampsia is associated with up to 8-fold increased risk of cardiovascular disease (CVD) for both mothers and their offspring. The lack of mechanistic data in relation to the causes or consequences of preeclampsia has prevented the development of effective therapeutic or monitoring strategies. Study design This study investigates common underlying mechanisms of preeclampsia and CVD, specifically hypertension and heart failure with preserved ejection fraction (HFpEF) using “in silico” approach of publicly available datasets. Integrated techniques were designed to mine data repositories and identify relevant biomarkers associated with these three conditions. Main outcomes measures The knowledge base tools were employed that enabled the analysis of these biomarkers to discover potential molecular and biological links between these three conditions. Results Our bioinformatics “in silico” analyses of the publically available datasets identified 76 common biomarkers between preeclampsia, hypertension and HFpEF. These biomarkers were representative of 29 pathways commonly enriched across the three conditions which were largely related to inflammation, metabolism, angiogenesis, remodelling, haemostasis, apoptosis and the renin-angiotensin-aldosterone (RAAS) system. Conclusions This bioinformatics approach which uses the wealth of scientific data available in public repositories can be helpful to gain a deeper understanding of the overlapping pathogenic mechanisms of associated diseases, which could be explored as biomarkers or targets to prevent long-term cardiovascular complications such as hypertension and HFpEF following preeclampsia

Association of Nrf2, SOD2 and GPX1 polymorphisms with biomarkers of oxidative distress and survival in end-stage renal disease patients

© 2019 by the authors. The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (GSTM1) deletion polymorphism, was further analyzed. Polymorphisms in Nrf2 (rs6721961), SOD2 (rs4880), GPX1 (rs1050450), and GSTM1 were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The SOD2 Val/Val genotype increased ESRD risk (OR = 2.01, p = 0.002), which was even higher in combination with the GPX1 Leu/Leu genotype (OR = 3.27, p = 0.019). Polymorphism in SOD2 also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the Nrf2 (C/C) and GPX1 (Leu/Leu) genotypes in addition to a patients’ age and GSTM1 polymorphism. Similarly, the GPX1 (Leu/Leu) genotype contributed to longer cardiovascular survival. Conclusions: Our results show that SOD2, GPX1, and Nrf2 polymorphisms are associated with ESRD development and can predict survival