Gauge Five Brane Dynamics And Small Instanton Transitions In Heterotic Models

We present the first examples of cosmological solutions to four-dimensional heterotic models which include an evolving bundle modulus. The particular bundle modulus we consider corresponds to the width of a gauge five brane. As such our solutions can be used to describe the evolution in one of these models after a small instanton transition. We find that certain properties are generic to these solutions, regardless of initial conditions. This enables us to make some definite statements about the dynamics subsequent to a small instanton transition despite the fact that we cannot microscopically describe the process itself. We also show that an effective description of the small instanton transition by a continuous matching of fields and their first derivatives is precluded by the form of the respective low-energy theories before and after the transition.Comment: 16 pages, 3 figure

ON T CELL FATE DECISIONS: RETINOL, METABOLISM AND ITREG DIFFERENTIATION

The mammalian immune system is equipped to both eliminate pathogenic microorganisms and tumors, while remaining in homeostasis with commensal species at mucosal surfaces and tolerant towards self. Suppressor regulatory T cells (Tregs) are a major sentinel of this immunological tolerance. Induced Tregs (iTregs) arise in the periphery following the integration of cues from the metabolites, cytokines, etc. which make up its milieu. Dysregulation of iTreg development, function or homing underlies the etiology of many autoimmune diseases and immunopathologies. The amelioration or prevention of multiple murine disease models by boosting Treg cell numbers foreshadows clinical efficacy of iTreg therapy, but an incomplete understanding of Treg development has thus far prevented successful translation. Therefore, we considered the basic biology of T cell fate decision making from two unique, but integrated angles. First, we show that the stimulation of PPARγ in human T cells upregulates RDH10, a molecule which catalyzes the rate limiting step in the oxidation of retinol to transcriptionally active all-trans retinoic acid (ATRA), a positive regulator of iTreg development. This functionally intact pathway endows T cells the ability to autonomously sense and respond to retinoid signals present during Treg development and at tissue sites. Next, we asked questions about how T cells sense nutrient and oxygen availability as they differentiate. Tregs lacking the serine/threonine kinase PINK1 have limited activation-induced phosphorylation of Akt and oxidative phosphorylation rates, and reduced suppressor function. Notably, the uncoupling of iTreg function from normal FoxP3 expression reinforces the recent hypothesis that the PI3K/Akt/mTORC1 axis and metabolic checkpoints are decisive players in the acquisition of suppressor activity. Ultimately, the studies described herein converge on Akt and metabolism, and contribute to our understanding of how T cells integrate diverse signals present during fate determinism, provoking future Treg based therapeutics

Placement experience and learning motivations in Higher Education: a comparison between practical- and study-based programmes

Purpose - Placement-based learning is claimed to benefit educational outcomes in undergraduate programmes, with students gaining employability skills and the application of skill-sets in ‘real world’ situations. Most courses incorporate experiential learning; however, work placements remain exclusive to the aims of the academic programme. This report explores the changing learning motivations between students enrolled on: a) a practical-based programme, involving work placement (BA Adventure Education (Ad Ed)), and b) a study-based programme (BSc Sport and Exercise Science (SES)). In addition, motivation was examined between courses at each year. Design/methodology/approach - A 44 item Motivated Strategies for Learning Questionnaire was completed by first and final year undergraduates studying BA Ad Ed and BSc SES courses in the academic year 2011/12. Questionnaires were triangulated with focus groups, lecturer observations and statistical analyses. Findings - Learning motivation was influenced by: a) knowledge of academic grades, b) link between theoretical content and work experience, c) opportunity for reflection, and d) multidisciplinary nature of degree programmes. Furthermore, the majority of final year Ad Ed students showed understanding of the job market, degree transferability and career availability upon graduation. Originality/value - Where placement experience prepares British undergraduate learners for employment and provides insight into career demand, placements may also demotivate, particularly where careers do not necessitate degree qualification

Enhancement of primary production in the North Atlantic outside of the spring bloom, identified by remote sensing of ocean colour and temperature

Peer reviewedPublisher PD

The Milky Way Heart: Investigating molecular gas and gamma-ray morphologies in the Central Molecular Zone

Since the discovery of a broad distribution of very high energy (VHE; >0.1 TeV) gamma-rays in the Central Molecular Zone (CMZ) of the Galaxy in 2006 by the HESS collaboration, the correlation of this emission with the integrated intensity of the CS(1-0) molecular line emission has inferred a hadronic origin for the gamma-rays. Here we describe the beginning of our investigation into the strength of this correlation utilising new multi-line millimeter data from the Mopra CMZ and HOP surveys and multi-wavelength GBT radio continuum observations towards the CMZ and compare these in detail with the diffuse TeV gamma-ray emission from HESS. The benefit of these new data is that they allow us to simultaneously observe and analyse correlations using a large number (>10) of molecular species, some of which contain their isotopologue pairs. The use of isotopologue pairs is especially powerful, since it allows one to analyse the optical depth of a number of different molecular species, thus investigating the nature of the correlation over a range of different physical conditions. Here we begin by comparing the integrated line emission and continuum radio emission with the diffuse gamma-ray emission, and, by using isotopologue pairs such as HCN/H$^{13}$CN, obtain optical depths throughout the CMZ corresponding to regions of both strong and weak gamma-ray emission. We find that the radio continuum better matches the peak of the gamma-ray emission, which corresponds to the more compact -- compared to the relatively coarse resolution of the gamma-ray images -- sources in the CMZ. Using the isotopologue pairs, we find that the optical depth at all positions and velocities within the CMZ are about 2--4. This is similar to that found for the CS(1--0) line and would underestimate the mass of the CMZ, potentially explaining why molecular line emission peaks appear offset from the gamma-ray peaks.Comment: 8 pages, 5 figures. Accepted to the Proceedings of the 25th Texas Symposium on Relativistic Astrophysics (Heidelberg, 2010

Processes Contributing to the Maintenance of Flying Phobia: A Narrative Review

Flying phobia is a highly prevalent anxiety disorder, which causes sufferers significant distress and life interference. The processes which maintain flying phobia remain poorly understood. A systematic search of the literature was performed to identify what research has been conducted into the processes which may be involved in the fear of flying and whether processes which are believed to maintain other anxiety disorder diagnoses have been investigated in flying phobia. The results of the literature review are presented and related to existing cognitive behavioural theory and research. The results indicate that little research has been conducted into a number of areas considered important in the wider cognitive behavioural literature on anxiety disorders: namely attention, mental imagery, memory, worry and safety-seeking behaviours. The review proposes a hypothetical model, derived from cognitive behavioural theory, for the processes which may be involved in maintaining flying phobia, and considers a number of areas for future research

Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal fat cells - Activation of protein kinase B by wortmannin-sensitive and -insensittve mechanisms

Previous studies using L6 myotubes have suggested that glycogen synthase kinase-3 (GSK-3) is phosphoryl ated and inactivated in response to insulin by protein kinase B (PKB, also known as Akt or RAG) (Cross, D, A, E., Alessi, D, R., Cohen, P., Andjelkovic, M., and Hemmings, B, A. (1995) Nature 378, 785-789), In the present study, marked increases in the activity of PKB have been shown to occur in insulin-treated rat epididymal fat cells with a time course compatible with the observed decrease in GSK-3 activity, Isoproterenol, acting primarily through beta(3)-adrenoreceptors, was found to decrease GSK-3 activity to a similar extent (approximately 50%) to insulin, However, unlike the effect of insulin, the inhibition of GSK by isoproterenol was not found to be sensitive to inhibition by the phosphatidylinositol 3'-kinase inhibitors, wortmannin or LY 294002, The change in GSK-3 activity brought about by isoproterenol could not be mimicked by the addition of permeant cyclic AMP analogues or forskolin to the cells, although at the concentrations used, these agents were able to stimulate lipolysis. Isoproterenol, but again not the cyclic AMP analogues, was found to increase the activity of PKB, although to a lesser extent than insulin. While wortmannin abolished the stimulation of PKB activity by insulin, it was without effect on the activation seen in response to isoproterenol, The activation of PKB by isoproterenol was not accompanied by any detectable change in the electrophoretic mobility of the protein on SDS-polyacrylamide gel electrophoresis. It would therefore appear that distinct mechanisms exist for the stimulation of PKB by insulin and isoproterenol in rat fat cells