Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors

Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells. © 2010 MacTavish et al

Nucleation of Quark--Gluon Plasma from Hadronic Matter

The energy densities achieved during central collisions of large nuclei at Brookhaven's AGS may be high enough to allow the formation of quark--gluon plasma. Calculations based on relativistic nucleation theory suggest that rare events, perhaps one in every 10$^2$ or 10$^3$, undergo the phase transition. Experimental ramifications may include an enhancement in the ratio of pions to baryons, a reduction in the ratio of deuterons to protons, and a larger source size as seen by hadron interferometry.Comment: 22 pages, 7 figures available upon request, NUC--MINN--94/5--

Capillary pressure of van der Waals liquid nanodrops

The dependence of the surface tension on a nanodrop radius is important for the new-phase formation process. It is demonstrated that the famous Tolman formula is not unique and the size-dependence of the surface tension can distinct for different systems. The analysis is based on a relationship between the surface tension and disjoining pressure in nanodrops. It is shown that the van der Waals interactions do not affect the new-phase formation thermodynamics since the effect of the disjoining pressure and size-dependent component of the surface tension cancel each other.Comment: The paper is dedicated to the 80th anniversary of A.I. Rusano

Individual, unit and vocal clan level identity cues in sperm whale codas

Fieldwork was supported by Discovery and Equipment grants to H.W. from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Whale and Dolphin Conservation Society. S.G. and L.R. were supported by the Marine Alliance for Science and Technology for Scotland (MASTs) pooling initiative and their support is gratefully acknowledged. MASTs is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions. S.G. was also supported by an NSERC Postgraduate Scholarship (PGS-M), an NSERC Canadian Graduate Scholarship (CGS-D), the Izaak Killam Memorial Scholarship, the Patrick F. Lett Fund, the Dalhousie’s Presidents Award, and an FNU fellowship for the Danish Council for Independent Research from the Ministry of Higher Education and Science supplemented by a Sapere Aude Research Talent Award.The ‘social complexity hypothesis’ suggests that complex social structure is a driver of diversity in animal communication systems. Sperm whales have a hierarchically structured society in which the largest affiliative structures, the vocal clans, are marked on ocean-basin scales by culturally transmitted dialects of acoustic signals known as ‘codas’. We examined variation in coda repertoires among both individual whales and social units—the basic element of sperm whale society—using data from nine Caribbean social units across six years. Codas were assigned to individuals using photo-identification and acoustic size measurement, and we calculated similarity between repertoires using both continuous and categorical methods. We identified 21 coda types. Two of those (‘1+1+3’ and ‘5R1’) made up 65% of the codas recorded, were shared across all units and have dominated repertoires in this population for at least 30 years. Individuals appear to differ in the way they produce ‘5R1’ but not ‘1+1+3’ coda. Units use distinct 4-click coda types which contribute to making unit repertoires distinctive. Our results support the social complexity hypothesis in a marine species as different patterns of variation between coda types suggest divergent functions, perhaps representing selection for identity signals at several levels of social structure.Publisher PDFPeer reviewe

Feasibility of trial procedures for a randomised controlled trial of a community based group exercise intervention for falls prevention for visually impaired older people: the VIOLET study

Background Visually impaired older people (VIOP) have a higher risk of falling than their sighted peers, and are likely to avoid physical activity. The aim was to adapt the existing Falls Management Exercise (FaME) programme for VIOP, delivered in the community, and to investigate the feasibility of conducting a definitive randomised controlled trial (RCT) of this adapted intervention. Methods Two-centre randomised mixed methods pilot trial and economic evaluation of the adapted group-based FaME programme for VIOP versus usual care. A one hour exercise programme ran weekly over 12 weeks at the study sites (Newcastle and Glasgow), delivered by third sector (voluntary and community) organisations. Participants were advised to exercise at home for an additional two hours over the week. Those randomised to the usual activities group received no intervention. Outcome measures were completed at baseline, 12 and 24 weeks. The potential primary outcome was the Short Form Falls Efficacy Scale – International (SFES-I). Participants’ adherence was assessed by reviewing attendance records and self-reported compliance to the home exercises. Adherence with the course content (fidelity) by instructors was assessed by a researcher. Adverse events were collected in a weekly phone call. Results Eighteen participants, drawn from community-living VIOP were screened; 68 met the inclusion criteria; 64 participants were randomised with 33 allocated to the intervention and 31 to the usual activities arm. 94% of participants provided data at the 12 week visit and 92% at 24 weeks. Adherence was high. The intervention was found to be safe with 76% attending nine or more classes. Median time for home exercise was 50 min per week. There was little or no evidence that fear of falling, balance and falls risk, physical activity, emotional, attitudinal or quality of life outcomes differed between trial arms at follow-up. Conclusions The intervention, FaME, was implemented successfully for VIOP and all progression criteria for a main trial were met. The lack of difference between groups on fear of falling was unsurprising given it was a pilot study but there may have been other contributory factors including suboptimal exercise dose and apparent low risk of falls in participants. These issues need addressing for a future trial

Asymptotic Safety, Emergence and Minimal Length

There seems to be a common prejudice that asymptotic safety is either incompatible with, or at best unrelated to, the other topics in the title. This is not the case. In fact, we show that 1) the existence of a fixed point with suitable properties is a promising way of deriving emergent properties of gravity, and 2) there is a sense in which asymptotic safety implies a minimal length. In so doing we also discuss possible signatures of asymptotic safety in scattering experiments.Comment: LaTEX, 20 pages, 2 figures; v.2: minor changes, reflecting published versio

Number and mode of inheritance of QTL influencing backfat thickness on SSC2p in Sino-European pig pedigrees

<p>Abstract</p> <p>Background</p> <p>In the pig, multiple QTL associated with growth and fatness traits have been mapped to chromosome 2 (SSC2) and among these, at least one shows paternal expression due to the IGF2-intron3-G3072A substitution. Previously published results on the position and imprinting status of this QTL disagree between analyses from French and Dutch F2 crossbred pig populations obtained with the same breeds (Meishan crossed with Large White or Landrace).</p> <p>Methods</p> <p>To study the role of paternal and maternal alleles at the IGF2 locus and to test the hypothesis of a second QTL affecting backfat thickness on the short arm of SSC2 (SSC2p), a QTL mapping analysis was carried out on a combined pedigree including both the French and Dutch F2 populations, on the progeny of F1 males that were heterozygous (A/G) and homozygous (G/G) at the IGF2 locus. Simulations were performed to clarify the relations between the two QTL and to understand to what extent they can explain the discrepancies previously reported.</p> <p>Results</p> <p>The QTL analyses showed the segregation of at least two QTL on chromosome 2 in both pedigrees, i.e. the IGF2 locus and a second QTL segregating at least in the G/G F1 males and located between positions 30 and 51 cM. Statistical analyses highlighted that the maternally inherited allele at the IGF2 locus had a significant effect but simulation studies showed that this is probably a spurious effect due to the segregation of the second QTL.</p> <p>Conclusions</p> <p>Our results show that two QTL on SSC2p affect backfat thickness. Differences in the pedigree structures and in the number of heterozygous females at the IGF2 locus result in different imprinting statuses in the two pedigrees studied. The spurious effect observed when a maternally allele is present at the IGF2 locus, is in fact due to the presence of a second closely located QTL. This work confirms that pig chromosome 2 is a major region associated with fattening traits.</p

The production and consumption activities relating to the celebrity artist

This paper considers the impact of the celebrity artist on the associated production and consumption activities. It also considers the role which entrepreneurial marketing plays in helping to create the celebrity artist aura. The artist Thomas Kinkade is used to illustrate how this occurs in practice. Here, authenticity and nostalgia dimensions are also influential factors. Underpinning these relationships are the roles played out by the media, including communication of celebrity artist identity, and the catalysing of its commodification within the celebrity artist brandscape. An enduring celebrity brand results due to the market creation activities of the celebrity artist. A conceptual model is developed which synthesises the factors behind the production and consumption of the celebrity artist which can stimulate further research. This paper provides innovative insight into the world of the celebrity artist by interrogating the market making and shaping devices behind successful production and consumption practices

An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins

DNA methylation has a great potential for understanding the aetiology of common complex traits such as Type 2 diabetes (T2D). Here we perform genome-wide methylated DNA immunoprecipitation sequencing (MeDIP-seq) in whole-blood-derived DNA from 27 monozygotic twin pairs and follow up results with replication and integrated omics analyses. We identify predominately hypermethylated T2D-related differentially methylated regions (DMRs) and replicate the top signals in 42 unrelated T2D cases and 221 controls. The strongest signal is in the promoter of the MALT1 gene, involved in insulin and glycaemic pathways, and related to taurocholate levels in blood. Integrating the DNA methylome findings with T2D GWAS meta-analysis results reveals a strong enrichment for DMRs in T2D-susceptibility loci. We also detect signals specific to T2D-discordant twins in the GPR61 and PRKCB genes. These replicated T2D associations reflect both likely causal and consequential pathways of the disease. The analysis indicates how an integrated genomics and epigenomics approach, utilizing an MZ twin design, can provide pathogenic insights as well as potential drug targets and biomarkers for T2D and other complex traits.Funding support for this project was obtained from the European Research Council (project number 250157) and BGI. The study was also supported by TwinsUK, which is funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007-2013); and also receives support from the National Institute for Health Research (NIHR) BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas' NHS Foundation Trust and King’s College London. SNP Genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. M.M. is the holder of Wellcome Trust Senior Investigator Award (Wellcome 098381). T.D.S. is the holder of an ERC Advanced Principal Investigator award (ERC 250157). A.P.M. is a Wellcome Trust Senior Research Fellow in Basic Biomedical Science (grant number WT098017). Skeletal muscle 450k methylation project is supported by European Community's Seventh Framework Programme (FP7/2007-2013) under DEXLIFE project (grant agreement no. HEALTH-F2-2011-279228)

A comprehensive fracture prevention strategy in older adults : The European union geriatric medicine society (EUGMS) statement

Published also in Aging Clinical and Experimental Research, Vol.28, No.4, WOS: 000379034800030Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest group on falls and fracture prevention of the European union geriatric medicine society (EUGMS), in collaboration with the International association of gerontology and geriatrics for the European region (IAGG-ER), the European union of medical specialists (EUMS), the Fragility fracture network (FFN), the International osteoporosis foundation (IOF) - European society for clinical and economic aspects of osteoporosis and osteoarthritis (ECCEO), outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people. (C) 2016 Published by Elsevier Masson SAS.Peer reviewe