The Charmonium Spectrum on the Lattice: A Status Report

We present our most recent results on the charmonium spectrum using relativistic Wilson fermions. We study the dependence of the spectrum on the charm quark mass and the Wohlert-Sheikholeslami improvement term.Comment: 4 pages, LaTeX, 5 figures (eps), needs espcrc2.sty, epsf.sty. FERMILAB-CONF-92/330-

Gastrointestinal Stromal Tumor Induced Hypercalcemia

Hypercalcemia in patients with cancer is a common laboratory finding affecting up to 44% of that patient population. 1,25-Dihydroxyvitamin D3 mediated hypercalcemia is one of the rare mechanisms of this endocrine emergency in cancer patients. It is even rarer for solid organ neoplasms to present with hypercalcemia mediated through the production of 1,25-dihydroxyvitamin D3. We report a case of a 77-year-old female who presented to the hospital with hypercalcemia and later was found to have metastatic gastrointestinal stromal tumor. There have been only 5 cases of gastrointestinal stromal tumor described in literature resulting in hypercalcemia. In our case, the mechanism of hypercalcemia was thought to be related to overproduction of 1,25-dihydroxyvitamin by tumor cells. The patient had a favorable response to imatinib with normalization of serum calcium level. Unfortunately, she developed fluid retention due to imatinib which was discontinued resulting in relapse of hypercalcemia that was resistant to all other treatment options

I felt that I deserved it - experiences and implications of disability hate crime

Purpose – The purpose of this paper is to summarise key findings and recommendations from the “Living in Fear” research project focusing on the experiences of people with learning disabilities and autism related to disability hate crime and the experience of the police in dealing with such incidents. Design/methodology/approach – Methods included: first, a postal survey with 255 people with learning disabilities or autism (or their carers for people with more severe disabilities), of whom 24 also took part in semi-structured interviews; and second, an electronic survey of the knowledge and experience of 459 police officers or support staff. Findings – Just under half of participants had experienced some form of victimisation. The Police reported problems with the definition of disability hate crime and challenges to responding effectively. Social implications – A case study from the research highlights some of the key findings and is linked to implications for people with learning disabilities and autism, carers, police and other agencies. Originality/value – Previous research has highlighted that victimisation is an issue for this group of people, but has never explored the prevalence and nature of such experiences in a representative sample. Neither has previous research brought together the perspectives of so many different agencies to offer recommendations that go across many sectors. The paper will be of interest to people with disabilities and their carers, professionals in health, social care and the Criminal Justice system

MT-HESS: an efficient Bayesian approach for simultaneous association detection in OMICS datasets, with application to eQTL mapping in multiple tissues.

MOTIVATION: Analysing the joint association between a large set of responses and predictors is a fundamental statistical task in integrative genomics, exemplified by numerous expression Quantitative Trait Loci (eQTL) studies. Of particular interest are the so-called ': hotspots ': , important genetic variants that regulate the expression of many genes. Recently, attention has focussed on whether eQTLs are common to several tissues, cell-types or, more generally, conditions or whether they are specific to a particular condition. RESULTS: We have implemented MT-HESS, a Bayesian hierarchical model that analyses the association between a large set of predictors, e.g. SNPs, and many responses, e.g. gene expression, in multiple tissues, cells or conditions. Our Bayesian sparse regression algorithm goes beyond ': one-at-a-time ': association tests between SNPs and responses and uses a fully multivariate model search across all linear combinations of SNPs, coupled with a model of the correlation between condition/tissue-specific responses. In addition, we use a hierarchical structure to leverage shared information across different genes, thus improving the detection of hotspots. We show the increase of power resulting from our new approach in an extensive simulation study. Our analysis of two case studies highlights new hotspots that would remain undetected by standard approaches and shows how greater prediction power can be achieved when several tissues are jointly considered. AVAILABILITY AND IMPLEMENTATION: C[Formula: see text] source code and documentation including compilation instructions are available under GNU licence at http://www.mrc-bsu.cam.ac.uk/software/

Challenges and Techniques for Simulating Line Emission

Modeling emission lines from the millimeter to the UV and producing synthetic spectra is crucial for a good understanding of observations, yet it is an art filled with hazards. This is the proceedings of “Walking the Line”, a 3-day conference held in 2018 that brought together scientists working on different aspects of emission line simulations, in order to share knowledge and discuss the methodology. Emission lines across the spectrum from the millimeter to the UV were discussed, with most of the focus on the interstellar medium, but also some topics on the circumgalactic medium. The most important quality of a useful model is a good synergy with observations and experiments. Challenges in simulating line emission are identified, some of which are already being worked upon, and others that must be addressed in the future for models to agree with observations. Recent advances in several areas aiming at achieving that synergy are summarized here, from micro-physical to galactic and circum-galactic scale

Easi-CRISPR: a robust method for one-step generation of mice carrying conditional and insertion alleles using long ssDNA donors and CRISPR ribonucleoproteins

Background Conditional knockout mice and transgenic mice expressing recombinases, reporters, and inducible transcriptional activators are key for many genetic studies and comprise over 90% of mouse models created. Conditional knockout mice are generated using labor-intensive methods of homologous recombination in embryonic stem cells and are available for only ~25% of all mouse genes. Transgenic mice generated by random genomic insertion approaches pose problems of unreliable expression, and thus there is a need for targeted-insertion models. Although CRISPR-based strategies were reported to create conditional and targeted-insertion alleles via one-step delivery of targeting components directly to zygotes, these strategies are quite inefficient. Results Here we describe Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR), a targeting strategy in which long single-stranded DNA donors are injected with pre-assembled crRNA + tracrRNA + Cas9 ribonucleoprotein (ctRNP) complexes into mouse zygotes. We show for over a dozen loci that Easi-CRISPR generates correctly targeted conditional and insertion alleles in 8.5–100% of the resulting live offspring. Conclusions Easi-CRISPR solves the major problem of animal genome engineering, namely the inefficiency of targeted DNA cassette insertion. The approach is robust, succeeding for all tested loci. It is versatile, generating both conditional and targeted insertion alleles. Finally, it is highly efficient, as treating an average of only 50 zygotes is sufficient to produce a correctly targeted allele in up to 100% of live offspring. Thus, Easi-CRISPR offers a comprehensive means of building large-scale Cre-LoxP animal resources

Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows

Abstract Background Susceptibility to Mycobacterium bovis infection in cattle is governed in part by host genetics. However, cattle diagnosed as infected with M. bovis display varying signs of pathology. The variation in host response to infection could represent a continuum since time of exposure or distinct outcomes due to differing pathogen handling. The relationships between host genetics and variation in host response and pathological sequelae following M. bovis infection were explored by genotyping 1966 Holstein-Friesian dairy cows at 538,231 SNPs with three distinct phenotypes. These were: single intradermal cervical comparative tuberculin (SICCT) test positives with visible lesions (VLs), SICCT-positives with undetected visible lesions (NVLs) and matched controls SICCT-negative on multiple occasions. Results Regional heritability mapping identified three loci associated with the NVL phenotype on chromosomes 17, 22 and 23, distinct to the region on chromosome 13 associated with the VL phenotype. The region on chromosome 23 was at genome-wide significance and candidate genes overlapping the mapped window included members of the bovine leukocyte antigen class IIb region, a complex known for its role in immunity and disease resistance. Chromosome heritability analysis attributed variance to six and thirteen chromosomes for the VL and NVL phenotypes, respectively, and four of these chromosomes were found to explain a proportion of the phenotypic variation for both the VL and NVL phenotype. By grouping the M. bovis outcomes (VLs and NVLs) variance was attributed to nine chromosomes. When contrasting the two M. bovis infection outcomes (VLs vs NVLs) nine chromosomes were found to harbour heritable variation. Regardless of the case phenotype under investigation, chromosome heritability did not exceed 8% indicating that the genetic control of bTB resistance consists of variants of small to moderate effect situated across many chromosomes of the bovine genome. Conclusions These findings suggest the host genetics of M. bovis infection outcomes is governed by distinct and overlapping genetic variants. Thus, variation in the pathology of M. bovis infected cattle may be partly genetically determined and indicative of different host responses or pathogen handling. There may be at least three distinct outcomes following M. bovis exposure in dairy cattle: resistance to infection, infection resulting in pathology or no detectable pathology

Observation of top quark pairs produced in association with a vector boson in pp collisions at s=8 √s=8TeV

Measurements of the cross sections for top quark pairs produced in association with a W or Z boson are presented, using 8 TeV pp collision data corresponding to an integrated luminosity of 19.5 fb −1 , collected by the CMS experiment at the LHC. Final states are selected in which the associated W boson decays to a charged lepton and a neutrino or the Z boson decays to two charged leptons. Signal events are identified by matching reconstructed objects in the detector to specific final state particles from t t ¯ W tt¯W or t t ¯ Z tt¯Z decays. The t t ¯ W tt¯W cross section is measured to be 382 − 102 + 117 fb with a significance of 4.8 standard deviations from the background-only hypothesis. The t t ¯ Z tt¯Z cross section is measured to be 242 − 55 + 65 fb with a significance of 6.4 standard deviations from the background-only hypothesis. These measurements are used to set bounds on five anomalous dimension-six operators that would affect the t t ¯ W tt¯W and t t ¯ Z tt¯Z cross sections