Dynamics and calcium association to the N-terminal regulatory domain of human cardiac troponin C: a multiscale computational study.

Troponin C (TnC) is an important regulatory molecule in cardiomyocytes. Calcium binding to site II in TnC initiates a series of molecular events that result in muscle contraction. The most direct change upon Ca(2+) binding is an opening motion of the molecule that exposes a hydrophobic patch on the surface allowing for Troponin I to bind. Molecular dynamics simulations were used to elucidate the dynamics of this crucial protein in three different states: apo, Ca(2+)-bound, and Ca(2+)-TnI-bound. Dynamics between the states are compared, and the Ca(2+)-bound system is investigated for opening motions. On the basis of the simulations, NMR chemical shifts and order parameters are calculated and compared with experimental observables. Agreement indicates that the simulations sample the relevant dynamics of the system. Brownian dynamics simulations are used to investigate the calcium association of TnC. We find that calcium binding gives rise to correlative motions involving the EF hand and collective motions conducive of formation of the TnI-binding interface. We furthermore indicate the essential role of electrostatic steering in facilitating diffusion-limited binding of Ca(2+)

NLO QCD+EW predictions for 2ℓ\ell2v diboson signatures at the LHC

We present next-to-leading order (NLO) calculations including QCD and electroweak (EW) corrections for 2$\ell$2ν diboson signatures with two opposite-charge leptons and two neutrinos. Specifically, we study the processes $pp \to e^+\mu^-\nu_e\overline{\nu}_{\mu}$ and $pp \to e^+e^-\nu\overline{\nu}$, including all relevant off-shell diboson channels, $W^+W^-, ZZ, \gamma Z$, as well as non-resonant contributions. Photon-induced processes are computed at NLO EW, and we discuss subtle differences related to the definition and the renormalisation of the coupling α for processes with initial- and final-state photons. All calculations are performed within the automated Munich/Sherpa+OpenLoops frameworks, and we provide numerical predictions for the LHC at 13 TeV. The behaviour of the corrections is investigated with emphasis on the high-energy regime, where NLO EW effects can amount to tens of percent due to large Sudakov logarithms. The interplay between $W$ $W$and $ZZ$ contributions to the same-flavour channel, $pp \to e^+e^-\nu\overline{\nu}$, is discussed in detail, and a quantitative analysis of photon-induced contributions is presented. Finally, we consider approximations that account for all sources of large logarithms, at high and low energy, by combining virtual EW corrections with a YFS soft-photon resummation or a QED parton shower

NNLO QCD + NLO EW with Matrix+OpenLoops: precise predictions for vector-boson pair production

We present the first combination of NNLO QCD and NLO EW corrections for vector-boson pair production at the LHC. We consider all final states with two, three and four charged leptons, including resonant and non-resonant diagrams, spin correlations and off-shell effects. Detailed predictions are discussed for three representative channels corresponding to W+W−, W±Z and Z Z production. Both QCD and EW corrections are very significant, and the details of their combination can play a crucial role to achieve the level of precision demanded by experimental analyses. In this context we point out nontrivial issues that arise at large transverse momenta, where the EW corrections are strongly enhanced by Sudakov logarithms and the QCD corrections can feature so-called giant K -factors. Our calculations have been carried out in the Matrix+OpenLoops framework and can be extended to the production of an arbitrary colour singlet in hadronic collisions, provided that the required two-loop QCD amplitudes are available. Combined NNLO QCD and NLO EW predictions for the full set of massive diboson processes will be made publicly available in the next release of Matrix and will be instrumental in advancing precision diboson studies and new-physics searches at the LHC and future hadron colliders

Top-quark mass effects in H+jet and H+2 jets production

We present calculations of Higgs boson production via gluon-gluon fusion in association with one or two additional jets at next-to-leading order in QCD. The calculation of H+jet is exact in the treatment of the top-quark mass, whereas for the H+2 jets calculation the two-loop virtual amplitudes are approximated via a reweighting with leading-order mass effects, while keeping all top-quark mass effects in the real radiation contributions. For H+jet production, this study extends a previous calculation, revealing an error in the previous results. For total and differential cross sections, we present new results and compare the QCD corrections with the infinite top-mass limit, for which we find a strikingly good agreement if all amplitudes are rescaled by the leading-order mass dependence

Top-quark mass effects in H+jet and H+2 jets production

We present calculations of Higgs boson production via gluon-gluon fusion in association with one or two additional jets at next-to-leading order in QCD. The calculation of H+jet is exact in the treatment of the top-quark mass, whereas for the H+2 jets calculation the two-loop virtual amplitudes are approximated via a reweighting with leading-order mass effects, while keeping all top-quark mass effects in the real radiation contributions. For H+jet production, this study extends a previous calculation, revealing an error in the previous results. For total and differential cross sections, we present new results and compare the QCD corrections with the infinite top-mass limit, for which we find a strikingly good agreement if all amplitudes are rescaled by the leading-order mass dependence

Uncovering Shakespeare\u27s Sisters in Special Collections and College Archives, Musselman Library

Foreword by Professor Suzanne J. Flynn I have taught the first-year seminar, Shakespeare’s Sisters, several times, and over the years I have brought the seminar’s students to the Folger Shakespeare Library in Washington, D.C. There, the wonderful librarians have treated the students to a special exhibit of early women’s manuscripts and first editions, beginning with letters written by Elizabeth I and proceeding through important works by seventeen and eighteenth-century women authors such as Aemelia Lanyer, Anne Finch, Aphra Behn, and Mary Wollstonecraft. This year I worked with Carolyn Sautter, the Director of Special Collections and College Archives, to give my 2018 seminar students the opportunity to produce a sequel to the Folger exhibit of early modern women writers. Special Collections houses an impressive array of first editions from the nineteenth and twentieth centuries, many of them acquired from Thomas Y. Cooper, the former editor of the Hanover Evening Sun newspaper, who donated over 1600 items to Musselman Library in 1965. Working with Kerri Odess-Harnish, we chose first editions of eight significant works of literature written by American and British women from the mid-nineteenth through the mid-twentieth centuries. The students worked in pairs, researching a single book and producing a report that outlines important biographical facts about the author, the book’s publication and reception history, and finally the significance of the book in the years since its publication. We hope that our project will draw attention to the wealth of literary treasures housed in Special Collections at Musselman Library, but especially to these works by eight of “Shakespeare’s Sisters.

Considerable interlaboratory variation in PD-L1 positivity in a nationwide cohort of non-small cell lung cancer patients

Objectives: Immunohistochemical expression of programmed death-ligand 1 (PD-L1) is used as a predictive biomarker for prescription of immunotherapy to non-small cell lung cancer (NSCLC) patients. Accurate assessment of PD-L1 expression is therefore crucial. In this study, the extent of interlaboratory variation in PD-L1 positivity in the Netherlands was assessed, using real-world clinical pathology data. Materials and Methods: Data on all NSCLC patients in the Netherlands with a mention of PD-L1 testing in their pathology report from July 2017 to December 2018 were extracted from PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands. PD-L1 positivity rates were determined for each laboratory that performed PD-L1 testing, with separate analyses for histological and cytological material. Two cutoffs (1% and 50%) were used to determine PD-L1 positivity. Differences between laboratories were assessed using funnel plots with 95% confidence limits around the overall mean. Results: 6,354 patients from 30 laboratories were included in the analysis of histology data. At the 1% cutoff, maximum interlaboratory variation was 39.1% (32.7%-71.8%) and ten laboratories (33.3%) differed significantly from the mean. Using the 50% cutoff, four laboratories (13.3%) differed significantly from the mean and maximum variation was 23.1% (17.2%-40.3%). In the analysis of cytology data, 1,868 patients from 23 laboratories were included. Eight laboratories (34.8%) differed significantly from the mean in the analyses of both cutoffs. Maximum variation was 41.2% (32.2%-73.4%) and 29.2% (14.7%-43.9%) using the 1% and 50% cutoffs, respectively. Conclusion: Considerable interlaboratory variation in PD-L1 positivity was observed. Variation was largest using the 1% cutoff. At the 50% cutoff, analysis of cytology data demonstrated a higher degree of variation than the analysis of histology data

A comparative study of Higgs boson production from vector-boson fusion

The data taken in Run II at the Large Hadron Collider have started to probe Higgs boson production at high transverse momentum. Future data will provide a large sample of events with boosted Higgs boson topologies, allowing for a detailed understanding of electroweak Higgs boson plus two-jet production, and in particular the vector-boson fusion mode (VBF). We perform a detailed comparison of precision calculations for Higgs boson production in this channel, with particular emphasis on large Higgs boson transverse momenta, and on the jet radius dependence of the cross section. We study fixed-order predictions at next-to-leading order and next-to-next-to-leading order QCD, and compare the results to NLO plus parton shower (NLOPS) matched calculations. The impact of the NNLO corrections on the central predictions is mild, with inclusive scale uncertainties of the order of a few percent, which can increase with the imposition of kinematic cuts. We find good agreement between the fixed-order and matched calculations in non-Sudakov regions, and the various NLOPS predictions also agree well in the Sudakov regime. We analyze backgrounds to VBF Higgs boson production stemming from associated production, and from gluon-gluon fusion. At high Higgs boson transverse momenta, the ∆yjj and/or mjj cuts typically used to enhance the VBF signal over background lead to a reduced efficiency. We examine this effect as a function of the jet radius and using different definitions of the tagging jets. QCD radiative corrections increase for all Higgs production modes with increasing Higgs boson pT, but the proportionately larger increase in the gluon fusion channel results in a decrease of the gluon-gluon fusion background to electroweak Higgs plus two jet production upon requiring exclusive two-jet topologies. We study this effect in detail and contrast in particular a central jet veto with a global jet multiplicity requirement

A comparative study of Higgs boson production from vector-boson fusion

The data taken in Run II at the Large Hadron Collider have started to probe Higgs boson production at high transverse momentum. Future data will provide a large sample of events with boosted Higgs boson topologies, allowing for a detailed understanding of electroweak Higgs boson plus two-jet production, and in particular the vector-boson fusion mode (VBF). We perform a detailed comparison of precision calculations for Higgs boson production in this channel, with particular emphasis on large Higgs boson transverse momenta, and on the jet radius dependence of the cross section. We study fixed-order predictions at next-to-leading order and next-to-next-to-leading order QCD, and compare the results to NLO plus parton shower (NLOPS) matched calculations. The impact of the NNLO corrections on the central predictions is mild, with inclusive scale uncertainties of the order of a few percent, which can increase with the imposition of kinematic cuts. We find good agreement between the fixed-order and matched calculations in non-Sudakov regions, and the various NLOPS predictions also agree well in the Sudakov regime. We analyze backgrounds to VBF Higgs boson production stemming from associated production, and from gluon-gluon fusion. At high Higgs boson transverse momenta, the ∆yjj and/or mjj cuts typically used to enhance the VBF signal over background lead to a reduced efficiency. We examine this effect as a function of the jet radius and using different definitions of the tagging jets. QCD radiative corrections increase for all Higgs production modes with increasing Higgs boson pT, but the proportionately larger increase in the gluon fusion channel results in a decrease of the gluon-gluon fusion background to electroweak Higgs plus two jet production upon requiring exclusive two-jet topologies. We study this effect in detail and contrast in particular a central jet veto with a global jet multiplicity requirement

Warfare, Fiscal Capacity, and Performance

We exploit differences in casualties sustained in pre-modern wars to estimate the impact of fiscal capacity on economic performance. In the past, states fought different amounts of external conflicts, of various lengths and magnitudes. To raise the revenues to wage wars, states made fiscal innovations, which persisted and helped to shape current fiscal institutions. Economic historians claim that greater fiscal capacity was the key long-run institutional change brought about by historical conflicts. Using casualties sustained in pre-modern wars to instrument for current fiscal institutions, we estimate substantial impacts of fiscal capacity on GDP per worker. The results are robust to a broad range of specifications, controls, and sub-samples