Leptogenesis in the two right-handed neutrino model revisited

We revisit leptogenesis in the minimal non-supersymmetric type I see-saw mechanism with two right-handed (RH) neutrinos, including flavour effects and allowing both RH neutrinos N_1 and N_2 to contribute, rather than just the lightest RH neutrino N_1 that has hitherto been considered. By performing scans over parameter space in terms of the single complex angle z of the orthogonal matrix R, for a range of PMNS parameters, we find that in regions around z \sim \pm \pi/2, for the case of a normal mass hierarchy, the N_2 contribution can dominate the contribution to leptogenesis, allowing the lightest RH neutrino mass to be decreased by about an order of magnitude in these regions, down to M_1 \sim 1.3*10^11 GeV for vanishing initial N_2-abundance, with the numerical results supported by analytic estimates. We show that the regions around z \sim \pm \pi /2 correspond to light sequential dominance, so the new results in this paper may be relevant to unified model building.Comment: 41 pages, 10 figures; v2 matches published version in PR

Using a fuzzy inference system to control a pumped storage hydro plant

The paper discusses the development of a fuzzy inference system (FIS) based governor control for a pumped storage hydroelectric plant. The First Hydro Company's plant at Dinorwig in North Wales is the largest of its kind in Europe and is mainly used for frequency control of the UK electrical grid. In previous investigations, a detailed model of the plant was developed using MATLAB(R)/SIMULINK(R) and this is now being used to compare FIS governor operation with the proportional-integral-derivative (PID) controller currently used. The paper describes the development of an FIS governor, and shows that its response to a step increase in load is superior to the PID under certain conditions of load. The paper proceeds to discuss the implications of these results in view of the possible practical application of an FIS governor at the Dinorwig plant

Modulation of endoglin expression in islets of langerhans by VEGF reveals a novel regulator of islet endothelial cell function

BACKGROUND: Endoglin/CD105 is an auxiliary receptor for transforming growth factor-β with established roles in vascular remodelling. It has recently been shown that heterozygous endoglin deficiency in mice decreases insulin secretion in an animal model of obesity, highlighting a potential role for endoglin in the regulation of islet function. We have previously identified two different populations of endoglin expressing cells in human and mouse islets which are: (i) endothelial cells (ECs) and (ii) islet mesenchymal stromal cells. The contribution of islet EC endoglin expression to islet development and sensitivity to VEGF is unknown and is the focus of this study. RESULTS: In vitro culture of mouse islets with VEGF164 for 48 h increased endoglin mRNA levels above untreated controls but VEGF did not modulate VEGFR2, CD31 or CD34 mRNA expression or islet viability. Removal of EC-endoglin expression in vivo reduced islet EC area but had no apparent effect on islet size or architecture. CONCLUSION: EC-specific endoglin expression in islets is sensitive to VEGF and plays partial roles in driving islet vascular development, however such regulation appears to be distinct to mechanisms required to modulate islet viability and size

The Association Between Personality Disorder Traits and Suicidality Following Sudden Bereavement: A National Cross-Sectional Survey

Personality disorder is associated with increased risk of suicidal behavior. The authors aimed to investigate the association between number of personality disorder traits and suicidality risk following sudden bereavement. A secondary analysis of cross-sectional data on 3,167 young adults in the United Kingdom who had experienced sudden bereavement investigated the association between number of traits (measured using a standardized screening instrument) and postbereavement suicide attempt and suicidal ideation. Using multivariable logistic regression, the authors found a linear relationship between number of traits and suicide attempt (adjusted odds ratio [AOR] = 1.36, 95% CI [1.23, 1.49]) and suicidal ideation (AOR = 1.31, 95% CI [1.25, 1.38]) following bereavement. This represented an increase in odds by 36% and 31%, respectively, for each additional personality trait. The authors suggest that individuals with a greater number of traits suggestive of a personality disorder diagnosis are at increased risk of suicidality after a negative life event

Clothing the New Poor Law workhouse in the nineteenth century

The workhouse remains a totemic institution for social historians, yet we still know very little about the day-to-day experiences of the indoor poor. Nowhere is this clearer than in discussions about workhouse clothing, which remain overwhelmingly negative in the literature and consistent with the predominant view of the workhouse as a place of suffering and humiliation. Yet more often than not, this view is based on relatively shallow empirical foundations and tends to rely on anecdotal evidence or on the uncritical use of subjective sources such as photographs, newspaper editorials and other cultural products. This article takes a different approach by looking again at the whole range of meanings that workhouse clothing held for paupers and those who oversaw its allocation, and at the practical and symbolic usages to which it was put by them. On the basis of this evidence the authors argue that, contrary to the orthodox view, workhouse clothing was rarely intended to be degrading or stigmatising; that it would have held very different meanings for different classes of paupers; and that, far from being a source of unbridled misery, paupers often found it to be a source of great strategic and practical value

Photoaffinity labeling of soluble auxin-binding proteins

The photoaffinity labeling agent azido-IAA (5-N3-[7-3H]indole-3-acetic acid), a biologically active analogue of the endogenous auxin indole-3-acetic acid, was used to search for auxin-binding proteins in the soluble fraction of Hyoscyamus muticus cells. Azido-IAA became covalently attached to three polypeptides with a high specific activity. The labeling was specific for IAA and not due to random tagging. Two polypeptides with molecular masses of 31 and 24 kDa in the 0-30% ammonium sulfate fraction were labeled after UV photolysis at 0 degree C but not at -196 degrees C, and appeared to have a high affinity indole-binding site(s) for which active, non-indole auxins were not good ligands. A third polypeptide with a molecular mass of 25 kDa present in the 50-60% ammonium sulfate fraction labeled exclusively at -196 degrees C and had a significant affinity for active auxins but not for inactive indoles. The azido-IAA labeling pattern, pI, competition results, and immunoprecipitation all indicate that the 31- and 24-kDa polypeptides are related to the basic form of endo-1,3-beta-glucanase (EC 3.2.1.39). Azido-IAA labeling polypeptides equivalent to the 31- and 24-kDa species were apparently also present in the cell wall. The low pH optimum for binding of azido-IAA to the 25-kDa polypeptide suggests the location of the active protein in a compartment such as the vacuole or a transport vesicle rather than in the cytosol

Modulation of Rab7a-mediated growth factor receptor trafficking inhibits islet beta cell apoptosis and autophagy under conditions of metabolic stress

Regenerative medicine approaches to enhancing beta cell growth and survival represent potential treatments for diabetes. It is known that growth factors such as insulin, IGF-1 and HGF support beta cell growth and survival, but in people with type 2 diabetes the destructive effects of metabolic stress predominate and beta cell death or dysfunction occurs. In this study we explore the novel hypothesis that regulation of growth factor receptor trafficking can be used to promote islet beta cell survival. Growth factor signalling is dependent on the presence of cell surface receptors. Endosomal trafficking and subsequent recycling or degradation of these receptors is controlled by the Rab GTPase family of proteins. We show that Rab7a siRNA inhibition enhances IGF-1 and HGF signalling in beta cells and increases expression of the growth factor receptors IGF-1R and c-Met. Furthermore, Rab7a inhibition promotes beta cell growth and islet survival, and protects against activation of apoptosis and autophagy pathways under conditions of metabolic stress. This study therefore demonstrates that Rab7a-mediated trafficking of growth factor receptors controls beta cell survival. Pharmaceutical Rab7a inhibition may provide a means to promote beta cell survival in the context of metabolic stress and prevent the onset of type 2 diabetes