Metastable Flux Configurations and de Sitter Spaces

We derive stability conditions for the critical points of the no-scale scalar potential governing the dynamics of the complex structure moduli and the axio-dilaton in compactifications of type IIB string theory on Calabi-Yau three-folds. We discuss a concrete example of a T^6 orientifold. We then consider the four-dimensional theory obtained from compactifications of type IIB string theory on non-geometric backgrounds which are mirror to rigid Calabi-Yau manifolds and show that the complex structure moduli fields can be stabilized in terms of H_{RR} only, i.e. with no need of orientifold projection. The stabilization of all the fields at weak coupling, including the axio-dilaton, may require to break supersymmetry in the presence of H_{NS} flux or corrections to the scalar potential.Comment: 24 page

Application of passive seismic to the detection of buried hollows

Pilot studies involving the use of passive seismic techniques in a range of geological settings and applications, e.g., mapping bedrock, studies of soil erosion and Quaternary mapping have shown that it is a versatile, non-invasive and economic technique. This paper presents the findings of three case studies that trialled the use of passive seismic techniques for the detection and characterisation of buried hollows in carbonate rocks, comprising: i) a buried hollow in the Cretaceous Chalk at Ashford Hill in the Kennet Valley, a tributary of the River Thames, UK; ii) buried karst in the foundation excavations for wind turbines in Carboniferous Limestone at Brassington, Wirksworth, Derbyshire, UK, and iii) defining the extent of solution hollows that host terrestrial Miocene deposits, near Friden, Newhaven, Derbyshire, UK. Whilst case studies ii) and iii) are focused on areas of buried dolines, the geological context of the Ashford Hill site is more complex; comprising a deformation hollow with an uplifted “pinnacle” of chalk bedrock at the centre. The data were collected using a (Tromino), a three-component, broadband seismometer to measure background ambient noise (microtremors induced by wind, ocean waves, industrial machinery, road and rail traffic, etc.). The Tromino is small, portable with an operating range of 0.1 Hz to 1,024 Hz and interpreted using proprietary software (Grilla), which subjects the data to Fourier transformation and smoothing. Where possible, estimated shear wave velocities used in the Grilla Software modelling, based on peaks identified on the H/V spectrum, have been calibrated using borehole data or parallel geophysical techniques. In each case, the karst features were defined by Nakamura’s horizontal to vertical (H/V) spectral ratio technique, where microtremors are converted to show impedance contrasts (velocity x density), or a pseudo layered seismic stratigraphy of the near surface along each profile. An additional benefit of the use of this technique is its depth of penetration and potential for defining the structural and lithological context of the hollows, thereby contributing to the process understanding associated with their formation. To this end the technique has helped define discontinuity (fault, joint or bedding) guidance of the hollows.S. Castellaro, Mrs J. Renwick, West Coast Energy Ltd (GDF Suez), Mr Roger Durrant (Raymond Brown Construction Ltd

Effects of Excess Brain-Derived Human α-Synuclein on Synaptic Vesicle Trafficking

α-Synuclein is a presynaptic protein that regulates synaptic vesicle trafficking under physiological conditions. However, in several neurodegenerative diseases, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, α-synuclein accumulates throughout the neuron, including at synapses, leading to altered synaptic function, neurotoxicity, and motor, cognitive, and autonomic dysfunction. Neurons typically contain both monomeric and multimeric forms of α-synuclein, and it is generally accepted that disrupting the balance between them promotes aggregation and neurotoxicity. However, it remains unclear how distinct molecular species of α-synuclein affect synapses where α-synuclein is normally expressed. Using the lamprey reticulospinal synapse model, we previously showed that acute introduction of excess recombinant monomeric or dimeric α-synuclein impaired distinct stages of clathrin-mediated synaptic vesicle endocytosis, leading to a loss of synaptic vesicles. Here, we expand this knowledge by investigating the effects of native, physiological α-synuclein isolated from the brain of a neuropathologically normal human subject, which comprised predominantly helically folded multimeric α-synuclein with a minor component of monomeric α-synuclein. After acute introduction of excess brain-derived human α-synuclein, there was a moderate reduction in the synaptic vesicle cluster and an increase in the number of large, atypical vesicles called “cisternae.” In addition, brain-derived α-synuclein increased synaptic vesicle and cisternae sizes and induced atypical fusion/fission events at the active zone. In contrast to monomeric or dimeric α-synuclein, the brain-derived multimeric α-synuclein did not appear to alter clathrin-mediated synaptic vesicle endocytosis. Taken together, these data suggest that excess brain-derived human α-synuclein impairs intracellular vesicle trafficking and further corroborate the idea that different molecular species of α-synuclein produce distinct trafficking defects at synapses. These findings provide insights into the mechanisms by which excess α-synuclein contributes to synaptic deficits and disease phenotypes

Perfect weddings abroad

Approximately 16% of UK couples are currently married abroad. However, academic or practitioner focused research that explores the complex nature of a couple’s buying preferences or the development of innovative marketing strategies by businesses operating within the weddings abroad niche sector, is almost non-existent. This exploratory paper examines the role and relevance of marketing within the weddings abroad sector. The complex nature of customer needs in this high emotional and involvement experience, are identified and explored. A case study of Perfect Weddings Abroad Ltd highlights distinctive features and characteristics. Social networking and the use of home-workers, with a focus on reassurance and handholding are important tools used to develop relationships with customers. These tools and techniques help increase the tangibility of a weddings abroad package. Clusters of complementary services that are synergistic and provide sources of competitive advantage are identified and an agenda for future research is developed

The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers

This is the final version of the article. Available from Springer Nature via the DOI in this record.The dataset generated during the current study are available from the corresponding author on reasonable request.Acute nicotine abstinence in cigarette smokers results in deficits in performance on specific cognitive processes, including working memory and impulsivity which are important in relapse. Cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, has shown pro-cognitive effects and preliminary evidence has indicated it can reduce the number of cigarettes smoked in dependent smokers. However, the effects of CBD on cognition have never been tested during acute nicotine withdrawal. The present study therefore aimed to investigate if CBD can improve memory and reduce impulsivity during acute tobacco abstinence. Thirty, non-treatment seeking, dependent, cigarette smokers attended two laboratory-based sessions after overnight abstinence, in which they received either 800 mg oral CBD or placebo (PBO), in a randomised order. Abstinence was biologically verified. Participants were assessed on go/no-go, delay discounting, prose recall and N-back (0-back, 1-back, 2-back) tasks. The effects of CBD on delay discounting, prose recall and the N-back (correct responses, maintenance or manipulation) were null, confirmed by a Bayesian analysis, which found evidence for the null hypothesis. Contrary to our predictions, CBD increased commission errors on the go/no-go task. In conclusion, a single 800 mg dose of CBD does not improve verbal or spatial working memory, or impulsivity during tobacco abstinence.This research was funded by a PhD Studentship from the Medical Research Council (MRC) to the C.H. and an MRC DPFS award (MR/K015524/1) to HVC and CJAM.TPF is funded by a Senior Academic Fellowship from the Society for the Study of Addiction

Q methodology and a Delphi poll: a useful approach to researching a narrative approach to therapy

Q methodology and a Delphi poll combined qualitative and quantitative methods to explore definitions of White and Epston's (1990) narrative approach to therapy among a group of UK practitioners. A Delphi poll was used to generate statements about narrative therapy. The piloting of statements by the Delphi panel identified agreement about theoretical ideas underpinning narrative therapy and certain key practices. A wider group of practitioners ranked the statements in a Q sort and made qualitative comments about their sorting. Quantitative methods (principal components analysis) were used to extract eight accounts of narrative therapy, five of which are qualitatively analysed in this paper. Agreement and differences were identified across a range of issues, including the social construction of narratives, privileging a political stance or narrative techniques and the relationship with other therapies, specifically systemic psychotherapy. Q methodology, combined with the Delphi poll, was a unique and innovative feature of this study

Factors associated with crisis pregnancies in Ireland: Findings from three nationally representative sexual health surveys

Background: Findings on the demographic and sexual health characteristics associated with the experience of a crisis pregnancy is important to inform the public health policy of a country, including Ireland. Findings from other jurisdictions have suggested that certain demographic groups are at risk for unintended pregnancies and the disparity between the groups have been growing in recent years. Ireland is a country which experienced much economic and societal change in the first decade of the 21st century, changes which are likely to have affected demographic variables pertaining to sexual health. The current study had two aims: to investigate changes in the socioeconomic characteristics associated with crisis pregnancies over a seven year period [2003 to 2010], and to investigate the recent [2010] socioeconomic risk factors associated with crisis pregnancies in Ireland. Methods: The study compared the results from 18-45 year old women using data from three broadly similar nationally representative Irish sexual health surveys carried out in 2003, 2004-2006 and 2010. Chi square analysis compared of the socioeconomic characteristics across the seven year period and found that a higher proportion of women with two or more children and women for whom religion was not important reported a crisis pregnancy in 2010 compared with earlier years. A logistic regression then investigated the sexual health history and socioeconomic factors associated with the experience of a recent crisis pregnancy using the most recent 2010 data. Results: Receipt of sex education and contraception use at first sex significantly predicted the experiencing of a recent crisis pregnancy. Younger women and those with a lower level of education were more likely to report having experienced a recent crisis pregnancy. Conclusion: Similar demographic groups are at risk for experiencing a crisis pregnancy in Ireland compared with international research, yet the disparities between demographic groups who have experienced a crisis pregnancy appear to be decreasing rather than increasing over a seven year period. Recommendations are made with regard to the provision of continued sex education throughout the lifespan, particularly for those women who are at an increased risk of experiencing a crisis pregnancy

Social richness, socio-technical tension and the virtual commissioning of NHS research

<p>Abstract</p> <p>Background</p> <p>This paper draws on a recent study that evaluated the process of commissioning NHS funded research using virtual committees. Building on an earlier paper that reported our evaluation, here we focus on the effects of asynchronous computer mediated communication (CMC) when used to support group work.</p> <p>Methods</p> <p>To do this the discussion focuses on how CMC affected three key group factors, building relationships, group cohesion and group commitment. The notion of socio-technical tension is elaborated and the paper explores how social richness can act to counter the socially impoverishing and time extending effects of asynchronous CMC.</p> <p>Results</p> <p>We argue that social richness in this context results from the presence of five principal influences. These are: a dynamic range of participant aspirations and personal agendas; participant commitment to and identification with the work and ideals of the group; a rich diversity of social, professional and work-related backgrounds; a website designed to enhance participation and interaction and the mediating effects of an effective chairperson.</p> <p>Conclusion</p> <p>If virtual work groups are to be used by the NHS in the future, then there is a need for more research into the role of social context and its relationship to the effectiveness of newly formed virtual groups. Equally as important are studies that examine the effects of socio-technical interaction on groups undertaking tasks in the real world of work.</p

Protein interactions in Xenopus germ plasm RNP particles

Hermes is an RNA-binding protein that we have previously reported to be found in the ribonucleoprotein (RNP) particles of Xenopus germ plasm, where it is associated with various RNAs, including that encoding the germ line determinant Nanos1. To further define the composition of these RNPs, we performed a screen for Hermes-binding partners using the yeast two-hybrid system. We have identified and validated four proteins that interact with Hermes in germ plasm: two isoforms of Xvelo1 (a homologue of zebrafish Bucky ball) and Rbm24b and Rbm42b, both RNA-binding proteins containing the RRM motif. GFP-Xvelo fusion proteins and their endogenous counterparts, identified with antisera, were found to localize with Hermes in the germ plasm particles of large oocytes and eggs. Only the larger Xvelo isoform was naturally found in the Balbiani body of previtellogenic oocytes. Bimolecular fluorescence complementation (BiFC) experiments confirmed that Hermes and the Xvelo variants interact in germ plasm, as do Rbm24b and 42b. Depletion of the shorter Xvelo variant with antisense oligonucleotides caused a decrease in the size of germ plasm aggregates and loosening of associated mitochondria from these structures. This suggests that the short Xvelo variant, or less likely its RNA, has a role in organizing and maintaining the integrity of germ plasm in Xenopus oocytes. While GFP fusion proteins for Rbm24b and 42b did not localize into germ plasm as specifically as Hermes or Xvelo, BiFC analysis indicated that both interact with Hermes in germ plasm RNPs. They are very stable in the face of RNA depletion, but additive effects of combinations of antisense oligos suggest they may have a role in germ plasm structure and may influence the ability of Hermes protein to effectively enter RNP particles

Extensive sequence-influenced DNA methylation polymorphism in the human genome

Background: Epigenetic polymorphisms are a potential source of human diversity, but their frequency and relationship to genetic polymorphisms are unclear. DNA methylation, an epigenetic mark that is a covalent modification of the DNA itself, plays an important role in the regulation of gene expression. Most studies of DNA methylation in mammalian cells have focused on CpG methylation present in CpG islands (areas of concentrated CpGs often found near promoters), but there are also interesting patterns of CpG methylation found outside of CpG islands. Results: We compared DNA methylation patterns on both alleles between many pairs (and larger groups) of related and unrelated individuals. Direct observation and simulation experiments revealed that around 10% of common single nucleotide polymorphisms (SNPs) reside in regions with differences in the propensity for local DNA methylation between the two alleles. We further showed that for the most common form of SNP, a polymorphism at a CpG dinucleotide, the presence of the CpG at the SNP positively affected local DNA methylation in cis. Conclusions: Taken together with the known effect of DNA methylation on mutation rate, our results suggest an interesting interdependence between genetics and epigenetics underlying diversity in the human genome