Effect of somatic mutation on DNA binding properties of anti-DNA autoantibodies

Autoantibodies that bind DNA are a hallmark of systemic lupus erythematosus. A subset of autoantibody•DNA complexes localize to kidney tissue and lead to damage and even death. 11F8, 9F11, and 15B10 are clonally related anti-DNA autoantibodies isolated from an autoimmune mouse. 11F8 binds ssDNA in a sequence-specific manner and causes tissue damage, while 9F11 and 15B10 bind ssDNA non-specifically and are benign. Among these antibodies, DNA binding properties are mediated by five amino acid differences in primary sequence. Thermodynamic and kinetic parameters associated with recognition of structurally different DNA sequences were determined for each antibody to provide insight toward recognition strategies, and to explore a link between binding properties and disease pathogenesis. A model of 11F8 bound to its high affinity consensus sequence provides a foundation for understanding the differences in thermodynamic and kinetic parameters between the three mAbs. Our data suggest that 11F8 utilizes the proposed ssDNA recognition motif including Y32 V L , a hydrogen bonding residue at 91 V L , and an aromatic residue at the tip of the third heavy chain complementarity determining region. Interestingly, a somatic mutation to arginine at 31 V H in 11F8 may afford additional binding site contacts including R31 V H , R96 V H , and R98 V H that could determine specificity. © 2007 Wiley Periodicals, Inc. Biopolymers 85: 471–480, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected] Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55984/1/20691_ftp.pd

Effectiveness of a quality improvement collaborative in reducing time to surgery for patients requiring emergency cholecystectomy.

Background:Acute gallstone disease is a high-volume emergency general surgery presentation with wide variations in the quality of care provided across the UK. This controlled cohort evaluation assessed whether participation in a quality improvement collaborative approach reduced time to surgery for patients with acute gallstone disease to fewer than 8 days from presentation, in line with national guidance. Methods:Patients admitted to hospital with acute biliary conditions in England and Wales between 1 April 2014 and 31 December 2017 were identified from Hospital Episode Statistics data. Time series of quarterly activity were produced for the Cholecystectomy Quality Improvement Collaborative (Chole-QuIC) and all other acute National Health Service hospitals (control group). A negative binomial regression model was used to compare the proportion of patients having surgery within 8 days in the baseline and intervention periods. Results:Of 13 sites invited to join Chole-QuIC, 12 participated throughout the collaborative, which ran from October 2016 to January 2018. Of 7944 admissions, 1160 patients had a cholecystectomy within 8 days of admission, a significant improvement (P < 0·050) from baseline performance. This represented a relative change of 1·56 (95 per cent c.i. 1·38 to 1·75), compared with 1·08 for the control group. At the individual site level, eight of the 12 Chole-QuIC sites showed a significant improvement (P < 0·050), with four sites increasing their 8-day surgery rate to over 20 per cent of all emergency admissions, well above the mean of 15·3 per cent for control hospitals. Conclusion:A surgeon-led quality improvement collaborative approach improved care for patients requiring emergency cholecystectomy

The clonal root system of balsam poplar in upland sites of Quebec and Alberta

Balsam poplar seeds are short-lived and require moist seedbeds soon after they are released to germinate. In addition to sexual reproduction, balsam poplar stands can regenerate clonally by root suckering. The origin of stands will in turn affect their genetic structure and root system architecture, which are poorly understood for upland forest stands. Three stands were hydraulically excavated in Quebec (moist) and Alberta (dry) to determine the origin of trees and to characterize root systems with respect to presence of parental roots and root grafts connections. Clones were identified using single-nucleotide polymorphism (SNPs), and all stems, roots and root grafts were aged using dendrochronology techniques. All 82 excavated trees were of sucker origin, and four of the six stands contained a single clone. Parental root connections were found between 22% and 25% of excavated trees, and 53% and 48% of trees were linked with a root graft between the same or different clones, in Alberta and Quebec, respectively. Mean distance between trees connected by parental root was significantly lower than the distance between unconnected trees (0.47 ± 0.25 m vs. 3.14 ± 0.15 m and 1.55 ± 0.27 m vs. 4.25 ± 0.13 m) in Alberta and in Quebec, respectively. The excavations also revealed many dead stumps with live roots, maintained through root connections with live trees. This research highlights that balsam poplar growing in upland stands is a clonal species that can maintain relatively high genotypic diversity, with frequent root connections between trees at maturity. Maintaining an extensive root system through root connections increases the chances of a clone surviving when the above ground tree is dead and may also enhance the resilience of balsam poplar stands after disturbance

Drinking in the dark: shedding light on young people’s alcohol consumption experiences

This paper draws on 12 months of ethnographic research to explore the drinking experiences of young people, aged 15-24, living in the suburban case study locations of Chorlton and Wythenshawe, Manchester, UK. This paper moves beyond the contemporary geographical imaginary of alcohol consumption as a city-centre issue, to explore suburban indoor and outdoor drinking cultures. Through paying attention to atmospheres of darkness and lightness, I show how drinkscapes are active constituents of young people’s drinking occasions, rather than passive backdrops. More than this, I illustrate how young people transform dark and light drinkscapes, thereby shaping the drinking practices of themselves and others. Through looking at the interplay between the curating of an atmosphere, and the experience of that atmosphere when bodies, and practices are inserted into it, this paper offers a different take on the ‘drinking at home is bad, drinking in public spaces is good’ argument, with original policy suggestions

Forward pi^0 Production and Associated Transverse Energy Flow in Deep-Inelastic Scattering at HERA

Deep-inelastic positron-proton interactions at low values of Bjorken-x down to x \approx 4.10^-5 which give rise to high transverse momentum pi^0 mesons are studied with the H1 experiment at HERA. The inclusive cross section for pi^0 mesons produced at small angles with respect to the proton remnant (the forward region) is presented as a function of the transverse momentum and energy of the pi^0 and of the four-momentum transfer Q^2 and Bjorken-x. Measurements are also presented of the transverse energy flow in events containing a forward pi^0 meson. Hadronic final state calculations based on QCD models implementing different parton evolution schemes are confronted with the data.Comment: 27 pages, 8 figures and 3 table

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde