Brane Tilings, M2-branes and Orbifolds

Brane Tilings represent one of the largest classes of superconformal theories with known gravity duals in 3+1 and also 2+1 dimensions. They provide a useful link between a large class of quiver gauge theories and their moduli spaces, which are the toric Calabi-Yau (CY) singularities. This thesis includes a discussion of an algorithm that can be used to generate all brane tilings with any given number of superpotential terms. All tilings with at most 8 superpotential terms have been generated using an implementation of this method. Orbifolds are a subject of central importance in string theory. It is widely known that there may be two or more orbifolds of a space by a finite group. Abelian Calabi-Yau orbifolds of the form C³/Γ can be counted according to the size of the group |Γ|. Three methods of counting these orbifolds will be given. A brane tiling together with a set of Chern Simons levels is sufficient to define a quiver Chern-Simons theory which describes the worldvolume theory of the M2-brane probe. A forward algorithm exists which allows us to easily compute the toric data associated to the moduli space of the quiver Chern-Simons theory from knowledge of the tiling and Chern-Simons levels. This forward algorithm will be discussed and illustrated with a few examples. It is possible that two different Chern-Simons theories have the same moduli-space. This effect, sometimes known as 'toric duality' will be described further. We will explore how two Chern-Simons theories (corresponding to brane tilings) can be related to each other by the Higgs mechanism and how brane tilings (with CS levels) that correspond to 14 fano 3-folds have been constructed. The idea of 'child' and 'parent' brane tilings will be introduced and we will discuss how it has been possible to count 'children' using the symmetry of the 'parent' tiling

Response to: 'On the approach for determining association between changes in marital quality and cardiovascular disease risk factors' by MM Pike

No abstract available

The cationic region of Rhes mediates its interactions with specific Gβ subunits

Ras homologue enriched in striatum (Rhes) is a small monomeric G protein which functions in a variety of cellular processes, including attenuation of G protein-coupled receptor (GPCR)signalling. There have been many studies into the effects of Rhes, but there is no molecular information about how Rhes might bring about these effects. Rhes shares striking sequence homology to AGS1 (activator of G protein signalling 1) and we considered whether the two proteins function in similar ways. AGS1 binds to the Gβ1 subunit of heterotrimeric G proteins and we have used yeast two-hybrid studies to show that Rhes binds selectively to Gβ1, Gβ2 and Gβ3 subunits. Binding to the Gβ subunits involves the cationic regions of AGS1 and Rhes, and we used Rhes-AGS1 chimeras to show that their different cationic regions determine the Gβ-specificity of the interactions. Possible implications of this interaction for the activity of Rhes are discussed

Epigenome-wide Association Studies and the Interpretation of Disease -Omics

Epigenome-wide association studies represent one means of applying genome-wide assays to identify molecular events that could be associated with human phenotypes. The epigenome is especially intriguing as a target for study, as epigenetic regulatory processes are, by definition, heritable from parent to daughter cells and are found to have transcriptional regulatory properties. As such, the epigenome is an attractive candidate for mediating long-term responses to cellular stimuli, such as environmental effects modifying disease risk. Such epigenomic studies represent a broader category of disease -omics, which suffer from multiple problems in design and execution that severely limit their interpretability. Here we define many of the problems with current epigenomic studies and propose solutions that can be applied to allow this and other disease -omics studies to achieve their potential for generating valuable insights

Podoconiosis in East and West Gojam Zones, Northern Ethiopia

Background: Podoconiosis is a neglected tropical disease (NTD) that is prevalent in red clay soil-covered highlands of tropical Africa, Central and South America, and northern India. It is estimated that up to one million cases exist in Ethiopia. This study aimed to estimate the prevalence of podoconiosis in East and West Gojam Zones of Amhara Region in northern Ethiopia. Methodology/Principal Findings: A cross-sectional household survey was conducted in Debre Eliyas and Dembecha woredas (districts) in East and West Gojam Zones, respectively. The survey covered all 17,553 households in 20 kebeles (administrative subunits) randomly selected from the two woredas. A detailed structured interview was conducted on 1,704 cases of podoconiosis identified in the survey. Results: The prevalence of podoconiosis in the population aged 15 years and above was found to be 3.3% (95% CI, 3.2% to 3.6%). 87% of cases were in the economically active age group (15–64 years). On average, patients sought treatment five years after the start of the leg swelling. Most subjects had second (42.7%) or third (36.1%) clinical stage disease, 97.9% had mossy lesions, and 53% had open wounds. On average, patients had five episodes of acute adenolymphangitis (ALA) per year and spent a total of 90 days per year with ALA. The median age of first use of shoes and socks were 22 and 23 years, respectively. More men than women owned more than one pair of shoes (61.1% vs. 50.5%; x2 = 11.6 p = 0.001). At the time of interview, 23.6% of the respondents were barefoot, of whom about two-thirds were women. Conclusions: This study showed high prevalence of podoconiosis and associated morbidities such as ALA, mossy lesions and open wounds in northern Ethiopia. Predominance of cases at early clinical stage of podoconiosis indicates the potential for reversing the swelling and calls for disease prevention interventions

Special features of RAD Sequencing data:implications for genotyping

Restriction site-associated DNA Sequencing (RAD-Seq) is an economical and efficient method for SNP discovery and genotyping. As with other sequencing-by-synthesis methods, RAD-Seq produces stochastic count data and requires sensitive analysis to develop or genotype markers accurately. We show that there are several sources of bias specific to RAD-Seq that are not explicitly addressed by current genotyping tools, namely restriction fragment bias, restriction site heterozygosity and PCR GC content bias. We explore the performance of existing analysis tools given these biases and discuss approaches to limiting or handling biases in RAD-Seq data. While these biases need to be taken seriously, we believe RAD loci affected by them can be excluded or processed with relative ease in most cases and that most RAD loci will be accurately genotyped by existing tools

Changes in marital quality over 6 years and its association with cardiovascular disease risk factors in men: findings from the ALSPAC prospective cohort study

Background: Marital relationship quality has been suggested to have independent effects on cardiovascular health outcomes. This study investigates the association between changes in marital relationship quality and cardiovascular disease (CVD) risk factors in men. Methods: We used data from The Avon Longitudinal Study of Parents and Children, a prospective birth cohort study (Bristol, UK). Our baseline sample was restricted to married study fathers with baseline relationship and covariate data (n=2496). We restricted final analysis (n=620) to those with complete outcome, exposure and covariate data, who were married and confirmed the study child’s father at 6.4 years and 18.8 years after baseline. Relationship quality was measured at baseline and 6.4 years and operationalised as consistently good, improving, deteriorating or consistently poor relationship. We measured CVD risk factors of blood pressure, resting heart rate, body mass index, lipid profile and fasting glucose at 18.8 years after baseline. Results: Improving relationships were associated with lower levels of low-density lipoprotein (−0.25 mmol/L, 95% CI −0.46 to −0.03) and relative reduction of body mass index (−1.07 kg/m2, 95% CI −1.73 to −0.42) compared with consistently good relationships, adjusting for confounders. Weaker associations were found between improving relationships and total cholesterol (−0.24 mmol/L, 95% CI −0.48 to 0.00) and diastolic blood pressure (−2.24 mm Hg, 95% CI −4.59 to +0.11). Deteriorating relationships were associated with worsening diastolic blood pressure (+2.74 mm Hg, 95% CI 0.50 to 4.98). Conclusions: Improvement and deterioration of longitudinal relationship quality appears associated with respectively positive and negative associations with a range of CVD risk factors

Differential effects of RGS proteins on Gαq and Gα11 activity

Heterotrimeric G proteins play a pivotal role in GPCR signalling; they link receptors to intracellular effectors and their inactivation by RGS proteins is a key factor in resetting the pathway following stimulation. The precise GPCR:G protein:RGS combination determines the nature and duration of the response. Investigating the activity of particular combinations is difficult in cells which contain multiples of each component. We have therefore utilised a previously characterised yeast system to express mammalian proteins in isolation. Human Gαq and Gα11 spontaneously activated the yeast pheromone-response pathway by a mechanism which required the formation of Gα-GTP. This provided an assay for the specific activity of human RGS proteins. RGS1, RGS2, RGS3 and RGS4 inhibited the spontaneous activity of both Gαq and Gα11 but, in contrast, RGS5 and RGS16 were much less effective against Gα11 than Gαq. Interestingly, RGS2 and RGS3 were able to inhibit signalling from the constitutively active Gαq QL/Gα11 QL mutants, confirming the GAP-independent activity of these RGS proteins. To determine if the RGS-Gα specificity was maintained under conditions of GPCR stimulation, minor modifications to the C-terminus of Gαq/Gα11 enabled coupling to an endogenous receptor. RGS2 and RGS3 were effective inhibitors of both Gα subunits even at high levels of receptor stimulation, emphasising their GAP-independent activity. At low levels of stimulation RGS5 and RGS16 retained their differential Gα activity, further highlighting that RGS proteins can discriminate between two very closely related Gα subunits