Variational Two Fermion Wave Equations in QED: Muonium Like Systems

We consider a reformulation of QED in which covariant Green functions are used to solve for the electromagnetic field in terms of the fermion fields. The resulting modified Hamiltonian contains the photon propagator directly. A simple Fock-state variational trial function is used to derive relativistic two-fermion equations variationally from the expectation value of the Hamiltonian of the field theory. The interaction kernel of the equation is shown to be, in essence, the invariant M-matrix in lowest order. Solutions of the two-body equations are presented for muonium like system for small coupling strengths. The results compare well with the observed muonium spectrum, as well as that for hydrogen and muonic hydrogen. Anomalous magnetic moment effects are discussed

Viscoelastic response of contractile filament bundles

The actin cytoskeleton of adherent tissue cells often condenses into filament bundles contracted by myosin motors, so-called stress fibers, which play a crucial role in the mechanical interaction of cells with their environment. Stress fibers are usually attached to their environment at the endpoints, but possibly also along their whole length. We introduce a theoretical model for such contractile filament bundles which combines passive viscoelasticity with active contractility. The model equations are solved analytically for two different types of boundary conditions. A free boundary corresponds to stress fiber contraction dynamics after laser surgery and results in good agreement with experimental data. Imposing cyclic varying boundary forces allows us to calculate the complex modulus of a single stress fiber.Comment: Revtex with 24 pages, 7 Postscript figures included, accepted for publication in Phys. Rev.

Human placental renin-angiotensin system in normotensive and pre-eclamptic pregnancies at high altitude and after acute hypoxia-reoxygenation insult.

A functioning placental renin-angiotensin system (RAS) appears necessary for uncomplicated pregnancy and is present during placentation, which occurs under low oxygen tensions. Placental RAS is increased in pre-eclampsia (PE), characterised by placental dysfunction and elevated oxidative stress. We investigated the effect of high altitude hypoxia on the RAS and hypoxia-inducible factors (HIFs) by measuring mRNA and protein expression in term placentae from normotensive (NT) and PE women who delivered at sea level or above 3100 m, using an explant model of hypoxia-reoxygenation to assess the impact of acute oxidative stress on the RAS and HIFs. Protein levels of prorenin (P = 0.049), prorenin receptor (PRR; P = 0.0004), and angiotensin type 1 receptor (AT1R, P = 0.006) and type 2 receptor (AT2R, P = 0.002) were all significantly higher in placentae from NT women at altitude, despite mRNA expression being unaffected. However, mRNA expression of all RAS components was significantly lower in PE at altitude than at sea level, yet PRR, angiotensinogen (AGT) and AT1R proteins were all increased. The increase in transcript and protein expression of all the HIFs and NADPH oxidase 4 seen in PE compared to NT at sea level was blunted at high altitude. Experimentally induced oxidative stress stimulated AGT mRNA (P = 0.04) and protein (P = 0.025). AT1R (r = 0.77, P < 0.001) and AT2R (r = 0.81, P < 0.001) mRNA both significantly correlated with HIF-1β, whilst AT2R also correlated with HIF-1α (r = 0.512, P < 0.013). Our observations suggest that the placental RAS is responsive to changes in tissue oxygenation: this could be important in the interplay between reactive oxygen species as cell-signalling molecules for angiogenesis and hence placental development and function.HDM is supported by an ERA-EDTA Fellowship (ERA LTF 137-2013).This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1113/JP27104

Maternal Dexamethasone Treatment Alters Tissue and Circulating Components of the Renin-Angiotensin System in the Pregnant Ewe and Fetus.

Antenatal synthetic glucocorticoids promote fetal maturation in pregnant women at risk of preterm delivery and their mechanism of action may involve other endocrine systems. This study investigated the effect of maternal dexamethasone treatment, at clinically relevant doses, on components of the renin-angiotensin system (RAS) in the pregnant ewe and fetus. From 125 days of gestation (term, 145 ± 2 d), 10 ewes carrying single fetuses of mixed sex (3 female, 7 male) were injected twice im, at 10-11 pm, with dexamethasone (2 × 12 mg, n = 5) or saline (n = 5) at 24-hour intervals. At 10 hours after the second injection, maternal dexamethasone treatment increased angiotensin-converting enzyme (ACE) mRNA levels in the fetal lungs, kidneys, and heart and ACE concentration in the circulation and lungs, but not kidneys, of the fetuses. Fetal cardiac mRNA abundance of angiotensin II (AII) type 2 receptor decreased after maternal dexamethasone treatment. Between the two groups of fetuses, there were no significant differences in plasma angiotensinogen or renin concentrations; in transcript levels of renal renin, or AII type 1 or 2 receptors in the lungs and kidneys; or in pulmonary, renal or cardiac protein content of the AII receptors. In the pregnant ewes, dexamethasone administration increased pulmonary ACE and plasma angiotensinogen, and decreased plasma renin, concentrations. Some of the effects of dexamethasone treatment on the maternal and fetal RAS were associated with altered insulin and thyroid hormone activity. Changes in the local and circulating RAS induced by dexamethasone exposure in utero may contribute to the maturational and tissue-specific actions of antenatal glucocorticoid treatment.The study was supported by the Biotechnology and Biological Sciences Research Council and Tommy’s, the baby charity.This is the final version. It was first published by the Endocrine Society at http://press.endocrine.org/doi/abs/10.1210/en.2015-119

Measurement of the total angiotensinogen and its reduced and oxidised forms in human plasma using targeted LC-MS/MS.

Angiotensinogen (AGT) is a critical protein in the renin-angiotensin-aldosterone system and may have an important role in the pathogenesis of pre-eclampsia. The disulphide linkage between cysteines 18 and 138 has a key role in the redox switch of AGT which modulates the release of angiotensin I with consequential effects on blood pressure. In this paper, we report a quantitative targeted LC-MS/MS method for the reliable measurement of the total AGT and its reduced and oxidised forms in human plasma. AGT was selectively enriched from human plasma using two-dimensional chromatography employing concanavalin A lectin affinity and reversed phase steps and then deglycosylated using PNGase F. A differential alkylation approach was coupled with targeted LC-MS/MS method to identify the two AGT forms in the plasma chymotryptic digest. An additional AGT proteolytic marker peptide was identified and used to measure total AGT levels. The developed MS workflow enabled the reproducible detection of total AGT and its two distinct forms in human plasma with analytical precision of ≤ 15%. The LC-MS/MS assay for total AGT in plasma showed a linear response (R2 = 0.992) with a limit of quantification in the low nanomolar range. The method gave suitable validation characteristics for biomedical application to the quantification of the oxidation level and the total level of AGT in plasma samples collected from normal and pre-eclamptic patients

Proposal for mu p scattering experiment at NAL

It is proposed to use a muon beam at NAL to study inelastic scattering. The muon beam will have an energy 100 {+-} 2.5 GeV, with 10{sup 6} instantaneous, 3 x 10{sup 5} average, muons per second. If a beam of 10{sup 7}/sec becomes available it is possible that improved technology will immediately allow its use. The scattered muons and the electro-produced hadrons will be detected in a spectrometer system consisting of a large magnet equipped with a set of wire spark chambers and scintillation counters. It is proposed to use both hydrogen and deuterium targets, of length 200 cms. The experiment has in particular the following goals: (1) Measure the structure function W{sub 2}(q{sup 2}, {upsilon}) over the range 20 GeV &lt; {upsilon} &lt; 90 GeV, and 0.2 &lt; q &lt; 20 (GeV/c){sup 2}. (2) Study rho electroproduction in such a manner as to obtain the density matrix elements as a function of q{sup 2}, t, and {upsilon}. (3) Study the momentum spectrum and multiplicity of the electro-produced hadrons. (4) Use the recoil protons to make a study of the electroproduction of forward going mesons. It is estimated that these measurements will require 800 hours of running time

In Vivo RNA Interference Screens Identify Regulators of Antiviral CD4+ and CD8+ T Cell Differentiation

SummaryClassical genetic approaches to examine the requirements of genes for T cell differentiation during infection are time consuming. Here we developed a pooled approach to screen 30–100+ genes individually in separate antigen-specific T cells during infection using short hairpin RNAs in a microRNA context (shRNAmir). Independent screens using T cell receptor (TCR)-transgenic CD4+ and CD8+ T cells responding to lymphocytic choriomeningitis virus (LCMV) identified multiple genes that regulated development of follicular helper (Tfh) and T helper 1 (Th1) cells, and short-lived effector and memory precursor cytotoxic T lymphocytes (CTLs). Both screens revealed roles for the positive transcription elongation factor (P-TEFb) component Cyclin T1 (Ccnt1). Inhibiting expression of Cyclin T1, or its catalytic partner Cdk9, impaired development of Th1 cells and protective short-lived effector CTL and enhanced Tfh cell and memory precursor CTL formation in vivo. This pooled shRNA screening approach should have utility in numerous immunological studies

Proposed atomic cascade experimental test of symmetric local hidden-variables theories

The proposal is made of replacing the usual auxiliary assumptions needed for the derivation of testable Bell inequalities by an assumption resting only on symmetry considerations. It is shown that reliable atomic cascade tests of symmetric local hidden-variables theories should combine high statistics, cascades of type 0→1→0, and calcite polarizers. The three conditions have been achieved in experiments already performed, but never before simultaneously

'Education, education, education' : legal, moral and clinical

This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students