KIF5A and the contribution of susceptibility genotypes as a predictive biomarker for multiple sclerosis

There is increasing interest in the development of multiple sclerosis (MS) biomarkers that reflect central nervous system tissue injury to determine prognosis. We aimed to assess the prognostic value of kinesin superfamily motor protein KIF5A in MS by measuring levels of KIF5A in cerebrospinal fluid (CSF) combined with analysis of single nucleotide polymorphisms (SNPs; rs12368653 and rs703842) located within a MS susceptibility gene locus at chromosome 12q13–14 region. Enzyme-linked immunosorbent assay was used to measure KIF5A in CSF obtained from two independent biobanks comprising non-inflammatory neurological disease controls (NINDC), clinically isolated syndrome (CIS) and MS cases. CSF KIF5A expression was significantly elevated in progressive MS cases compared with NINDCs, CIS and relapsing–remitting MS (RRMS). In addition, levels of KIF5A positively correlated with change in MS disease severity scores (EDSS, MSSS and ARMSSS), in RRMS patients who had documented disease progression at 2-year clinical follow-up. Copies of adenine risk alleles (AG/AA; rs12368653 and rs703842) corresponded with a higher proportion of individuals in relapse at the time of lumbar puncture (LP), higher use of disease-modifying therapies post LP and shorter MS duration. Our study suggests that CSF KIF5A has potential as a predictive biomarker in MS and further studies into the potential prognostic value of analysing MS susceptibility SNPs should be considered

Isotope harvesting at heavy ion fragmentation facilities

Introduction The National Superconducting Cyclotron Laboratory (NSCL) is a national nuclear physics facility in which heavy ion beams are fragmented to produce exotic nuclei. In this process of fragmentation many nuclei are created, however, only one isotope is selected for experimentation. The remaining isotopes that are created go unused. The future upgrade of the NSCL to the Facility for Rare Isotope Beams (FRIB) will increase the incident energy of these heavy ion beams and amplify the current by three orders of magnitude. An aqueous beam dump will be created to collect the unused isotopes created in the process of fragmentation. Several of these isotopes are of interest for many applications including nuclear security, medical imaging, and therapy and are not currently available or are only available in very limited supply. Harvesting these isotopes from the aqueous beam dump could provide a consistent supply of these im-portant isotopes as an ancillary service to the existing experimental program. Material and Methods A liquid water target system was designed and tested to serve as a mock beam dump for exper-iments at the NSCL1. A 25 pnA 130 MeV/u 76Ge beam was fragmented using a 493 mg/cm2 thick beryllium production target. After fragmentation the beam was separated using the A1900 frag-ment separator2 set up for maximum 67Cu pro-duction using a 240 mg/cm2 aluminum wedge and a 2% momentum acceptance. The secondary beam was collected for four hours in the liquid water target system before being transferred to a collection vessel. Four additional four hour collections were made before finally shipping the five collections to Washington University and Hope College for chemical separation. Four of the five samples were separated using a two part separation scheme. First they were passed through and 3M Empore iminodiacetic acid functionalized chelation disk in a 1.25M ammonium acetate solution at pH 5. The flow through was collected and analyzed using an HPGe detector. Then 10mL of 6M HCl acid was passed through the chelation disk to remove the 2+ transition metals. The 10mL of 6M HCl acid was collected after passing through the disk and added to an anion-exchange column with 2.5 g AG1-X8 resin. The eluate was collected and then an additional 10mL of 6M HCl was passed through the column to remove the nickel. The 67Cu was then collected by passing 10mL of 0.5M HCl and the eluate was collected in 1mL fractions each analyzed by HPGe for 67Cu concentration and purity. The two highest 67Cu fractions were heated to dryness and reconstituted in 50 μL 0.1M ammonium acetate pH 5.5. 2 μL of 7.9 mg/mL NOTA-Bz-Trastuzumab was added to 45 μL of 67Cu and 3 μL 0.1M ammonium acetate pH 5.5. This solution was placed in a shaking incubator at 37 °C for twenty minutes and then analyzed by radio-instant thin layer chromatography in order to determine the per-cent of 67Cu bound to the antibody. Results and Conclusion 67Cu was collected into the liquid water target system with an average efficiency of 85 ± 5 %. The secondary beam was 73 % pure with the impurities, half-lives greater than 1 minute, listed in TABLE 1. Separation of 67Cu from the impurities resulted in an average recovery of 88 ± 3 % for a total recovery of 67Cu from the beam and separation of 75 ± 4 %. No detectable radioactive impurities were found in the final samples when analyzed using an HPGe detector. TABLE 2 shows the amount of 67Cu collected from the beam and the amount recovered decay corrected to end of bombardment. Labeling NOTA-Bz-Trastuzumab with 67Cu resulted in > 95 % radiochemical yield. Collection of the 73 % pure 67Cu beam in water and the resulting separation proved successful. These results demonstrate that radioisotopes can be collected from fragmented heavy ion beams and isolated in usable quantities and purity for many radiochemical applications. Further experimentation with an unpurified beam to better simulate conditions in the beam dump at the Facility for Rare Isotope Beams will be performed in the near future

Groundwater connectivity of a sheared gneiss aquifer in the Cauvery River basin, India

Connectivity of groundwater flow within crystalline-rock aquifers controls the sustainability of abstraction and baseflow to rivers, yet is often poorly constrained at a catchment scale. Here groundwater connectivity in a sheared gneiss aquifer is investigated by studying the intensively abstracted Berambadi catchment (84 km2) in the Cauvery River Basin, southern India, with geological characterisation, aquifer properties testing, hydrograph analysis, hydrochemical tracers and a numerical groundwater flow model. The study indicates a well-connected system, both laterally and vertically, that has evolved with high abstraction from a laterally to a vertically dominated flow system. Likely as a result of shearing, a high degree of lateral connectivity remains at low groundwater levels. Because of their low storage and logarithmic reduction in hydraulic conductivity with depth, crystalline-rock aquifers in environments such as this, with high abstraction and variable seasonal recharge, constitute a highly variable water resource, meaning farmers must adapt to varying water availability. Importantly, this study indicates that abstraction is reducing baseflow to the river, which, if also occurring in other similar catchments, will have implications downstream in the Cauvery River Basin

Measurement of inclusive D*+- and associated dijet cross sections in photoproduction at HERA

Inclusive photoproduction of D*+- mesons has been measured for photon-proton centre-of-mass energies in the range 130 < W < 280 GeV and a photon virtuality Q^2 < 1 GeV^2. The data sample used corresponds to an integrated luminosity of 37 pb^-1. Total and differential cross sections as functions of the D* transverse momentum and pseudorapidity are presented in restricted kinematical regions and the data are compared with next-to-leading order (NLO) perturbative QCD calculations using the "massive charm" and "massless charm" schemes. The measured cross sections are generally above the NLO calculations, in particular in the forward (proton) direction. The large data sample also allows the study of dijet production associated with charm. A significant resolved as well as a direct photon component contribute to the cross section. Leading order QCD Monte Carlo calculations indicate that the resolved contribution arises from a significant charm component in the photon. A massive charm NLO parton level calculation yields lower cross sections compared to the measured results in a kinematic region where the resolved photon contribution is significant.Comment: 32 pages including 6 figure

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Measurement of Jet Shapes in Photoproduction at HERA

The shape of jets produced in quasi-real photon-proton collisions at centre-of-mass energies in the range $134-277$ GeV has been measured using the hadronic energy flow. The measurement was done with the ZEUS detector at HERA. Jets are identified using a cone algorithm in the $\eta - \phi$ plane with a cone radius of one unit. Measured jet shapes both in inclusive jet and dijet production with transverse energies $E^{jet}_T>14$ GeV are presented. The jet shape broadens as the jet pseudorapidity ($\eta^{jet}$) increases and narrows as $E^{jet}_T$ increases. In dijet photoproduction, the jet shapes have been measured separately for samples dominated by resolved and by direct processes. Leading-logarithm parton-shower Monte Carlo calculations of resolved and direct processes describe well the measured jet shapes except for the inclusive production of jets with high $\eta^{jet}$ and low $E^{jet}_T$. The observed broadening of the jet shape as $\eta^{jet}$ increases is consistent with the predicted increase in the fraction of final state gluon jets.Comment: 29 pages including 9 figure

A Search for Dark Higgs Bosons

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb-1 of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the Standard Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots for b/w printin

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO