Accelerator Design for the CHESS-U Upgrade

During the summer and fall of 2018 the Cornell High Energy Synchrotron Source (CHESS) is undergoing an upgrade to increase high-energy flux for x-ray users. The upgrade requires replacing one-sixth of the Cornell Electron Storage Ring (CESR), inverting the polarity of half of the CHESS beam lines, and switching to single-beam on-axis operation. The new sextant is comprised of six double-bend achromats (DBAs) with combined-function dipole-quadrupoles. Although the DBA design is widely utilized and well understood, the constraints for the CESR modifications make the CHESS-U lattice unique. This paper describes the design objectives, constraints, and implementation for the CESR accelerator upgrade for CHESS-U

Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration

Acknowledgements We are indebted to Jim Humphries, JennyCorrigan, LizDarley, Elizabeth Joynson, Natalie Walters, Sara Wells and the whole necropsy, histology, genotyping and MLC ward 6 teams at MRC Harwell for excellent technical assistance. We thank the staff of the WTSI Illumina Bespoke Team for the RNA-seq data, the Sanger Mouse Genetics Project for the initial mouse characterization and Dr David Adams for critical reading of the manuscript. We also thank KOMP for the mouse embryonic stem cells carrying the knockout first promoter-less allele (tm1a(KOMP)Wtsi) within Zfp016. Conflict of Interest statement. None declared. Funding This work was funded by the UK Medical Research Council (MRC) to A.A.-A. and a Motor Neurone Disease Association (MNDA) project grant to A.A.-A. and EMCF. D.L.H.B. is a Wellcome Trust Senior Clinical Scientist Fellow and P.F. is a MRC/MNDA Lady Edith Wolfson Clinician Scientist Fellow. Funding to pay the Open Access publication charges for this article was provided by the MRC grant number: MC_UP_A390_1106.Peer reviewedPublisher PD

Assessing MHC class I diversity in dairy cattle populations

The gene dense major histocompatibility complex (MHC) region, present in all jawed vertebrates, encodes molecules involved in self-non-self discrimination and the binding and presentation of antigenic peptides to T cells during the adaptive immune response. Variation in MHC genes is thought to be driven largely by pathogen-mediated selection, with diversity at MHC loci believed to benefit populations by allowing responses to rapidly evolving disease pathogens. However, in economically important dairy cattle, there are concerns that intensive selection for production and fitness traits may override natural selection. It had been hypothesised that these focussed dairy breeding practices may lead to a reduction in MHC diversity and leave cattle populations susceptible to new disease pathogens. The purpose of this study was to estimate current levels of MHC class I diversity in the UK Holstein-Friesian dairy cattle population, primarily through the assessment of diversity in bull populations with genetic input into the UK herd. In a sample of Canadian Holstein bulls, levels of class I allelic diversity were low given the size of the population sampled, but no significant loss of diversity over a twenty year period of selection was detected. Simulations of gene flow implicated trait selection as an influential force shaping diversity in the Canadian Holstein bull population. Haplotypes detected at high frequency were often negatively associated with selection traits indicating the action of heterozygote advantage. A SNP-based assay has been designed to facilitate rapid detection of common haplotypes and thus enable breeders to make more efficient selective breeding decisions whilst also maintaining MHC diversity in cattle populations. Investigations of class I diversity were expanded to incorporate the British Friesian bull population which were shown to have a markedly different pattern of class I diversity to that observed in the Canadian Holstein sample. A number of novel allele sequences and haplotypes were detected in the British Friesian bulls, the characterisation of which has contributed to our knowledge of the mechanisms driving diversity in the cattle class I region. MHC class I typing data from two bull populations and statistical analysis of trait associations with MHC haplotypes provides a comprehensive picture of MHC class I diversity in the wider UK herd and the selective forces integral to shaping diversity

Observation of the Dynamic Beta Effect at CESR with CLEO

Using the silicon strip detector of the CLEO experiment operating at the Cornell Electron-positron Storage Ring (CESR), we have observed that the horizontal size of the luminous region decreases in the presence of the beam-beam interaction from what is expected without the beam-beam interaction. The dependence on the bunch current agrees with the prediction of the dynamic beta effect. This is the first direct observation of the effect.Comment: 9 page uuencoded postscript file, postscritp file also available through http://w4.lns.cornell.edu/public/CLNS, submitted to Phys. Rev.

The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-Cell exhaustion

Fasciola hepatica infection of ruminants leads to non-resolving chronic infection, as patency develops, there is switching to a TGF-β and IL-10 led response. Here, we explore the responses of CD4 T-cells within the major draining lymph nodes. We found minimal expression of Foxp3 within CD4 cells but elevated levels within the γδ (WC1+) population. There is a strong T-cell-intrinsic exhaustion phenotype within the hepatic lymph node (HLN) characterized by a lack of antigen-specific proliferation and cytokine secretion. CD4 T-cells recovered from the HLN had high levels of PD-1 expression and low levels of IL-2 secretion. Exogenous IL-2 partially rescued this defect; when combined with neutralization of IL-10 and TGF-β, full restoration of proliferation, and cytokine production was achieved. Moreover, there is a clear uncoupling of the mechanisms that facilitate this regulation with parasite-specific proliferation and cytokine secretion being governed by independent means. These data would suggest that there is a CD4 T-cell-intrinsic regulation in place early in chronic infection, potentially leading to failure in resistance to reinfection