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Measurements of the Higgs boson production cross section and couplings in the W boson pair decay channel in proton-proton collisions at √=13TeV
Get PDFProduction cross sections of the standard model Higgs boson decaying to a pair of W bosons are measured in proton-proton collisions at a center-of-mass energy of 13TeV. The analysis targets Higgs bosons produced via gluon fusion, vector boson fusion, and in association with a W or Z boson. Candidate events are required to have at least two charged leptons and moderate missing transverse momentum, targeting events with at least one leptonically decaying W boson originating from the Higgs boson. Results are presented in the form of inclusive and differential cross sections in the simplified template cross section framework, as well as couplings of the Higgs boson to vector bosons and fermions. The data set collected by the CMS detector during 2016–2018 is used, corresponding to an integrated luminosity of 138fb−1. The signal strength modifier , defined as the ratio of the observed production rate in a given decay channel to the standard model expectation, is measured to be =0.95+0.10−0.09. All results are found to be compatible with the standard model within the uncertainties
Scenography for Alice By Heart: The Art of Growing Up
Get PDFAlice By Heart is a new musical by Duncan Sheik, Steven Sater, and Jessie Nelson. The story follows Alice, a young girl sheltering in an underground train station during the London Blitz of World War Two. There, she takes real refuge in retelling her favorite childhood book, Alice’s Adventures in Wonderland, to her dying best friend, Alfred. While venturing through her imagined world of Wonderland in an effort to save Alfred, Alice must confront what she has been avoiding: growing up. Her journey represents the trials of transitioning from adolescence to young adulthood, experiencing love, loss, grief, and, ultimately, self-discovery and actualization.My interpretation is that we are not meant to fully abandon childhood in favor of struggling through adulthood: rather, our childhood helps us to survive adulthood, and should be carried with us throughout life. The hope, imagination, enthusiasm, and energy of adolescence bring fulfillment to a life that is constantly bogged down by the realities and responsibilities of adulthood.This paper details my conceptualization, process, and final creation of scenography for Alice By Heart. My design both blends and contrasts the conditions of childhood and adulthood, calling us to embrace our inner child and embark on a life worth living
Boundary Work and Transactive Memory Systems in Teams: Moderating Effects of the Visibility Affordance
Get PDFIndividuals in work teams frequently cross boundaries across teams, often by using information and communication technologies (ICTs). The current study investigates the effects of members’ boundary work and the visibility affordance of teams’ ICTs on Transactive Memory Systems (TMS) in teams. Survey data from 212 full-time employees whose work hours were divided between multiple teams reveals that boundary spanning enhances the focal team’s TMS credibility and specialization and negatively influences TMS coordination. Additionally, boundary reinforcement positively affects TMS credibility and coordination. The visibility affordance has a direct positive impact on all three dimensions of TMS and a moderating effect for boundary reinforcement such that higher visibility overrides the positive direct effect of boundary reinforcement on TMS. These findings suggest that different types of boundary work contribute to different dimensions of TMS and that teams might consider prioritizing the use of ICTs with high visibility to enhance their TMS
Sex differences in infant vocalization and the origin of language
Get PDFSeeking to discern the earliest sex differences in language-related activities, our focus is vocal activity in the first two years of life, following up on recent research that unexpectedly showed boys produced significantly more speech-like vocalizations (protophones) than girls during the first year of life.We now bring a much larger body of data to bear on the comparison of early sex differences in vocalization, data based on automated analysis of all-day recordings of infants in their homes. The new evidence, like that of the prior study, also suggests boys produce more protophones than girls in the first year and offers additional basis for informed speculation about biological reasons for these differences. More broadly, the work offers a basis for informed speculations about foundations of language that we propose to have evolved in our distant hominin ancestors, foundations also required in early vocal development of modern human infants
Immunogenicity and protective efficacy of nanoparticle formulations of L-SseB against Salmonella infection
Get PDFSalmonella enterica, a Gram-negative pathogen, has over 2500 serovars that infect a wide range of hosts. In humans, S. enterica causes typhoid or gastroenteritis and is a major public health concern. In this study, SseB (the tip protein of the Salmonella pathogenicity island 2 type III secretion system) was fused with the LTA1 subunit of labile-toxin from enterotoxigenic E. coli to make the self-adjuvanting antigen L-SseB. Two unique nanoparticle formulations were developed to allow multimeric presentation of L-SseB. Mice were vaccinated with these formulations and protective efficacy determined via challenging the mice with S. enterica serovars. The polysaccharide (chitosan) formulation was found to elicit better protection when compared to the squalene nanoemulsion. When the polysaccharide formulation was used to vaccinate rabbits, protection from S. enterica challenge was elicited. In summary, L-SseB in a particulate polysaccharide formulation appears to be an attractive candidate vaccine capable of broad protection against S. enterica
Evaluation of AlphaFold-Multimer prediction on multi-chain protein complexes
Get PDFMotivation
Despite near-experimental accuracy on single-chain predictions, there is still scope for improvement among multimeric predictions. Methods like AlphaFold-Multimer and FoldDock can accurately model dimers. However, how well these methods fare on larger complexes is still unclear. Further, evaluation methods of the quality of multimeric complexes are not well established.
Results
We analysed the performance of AlphaFold-Multimer on a homology-reduced dataset of homo- and heteromeric protein complexes. We highlight the differences between the pairwise and multi-interface evaluation of chains within a multimer. We describe why certain complexes perform well on one metric (e.g. TM-score) but poorly on another (e.g. DockQ). We propose a new score, Predicted DockQ version 2 (pDockQ2), to estimate the quality of each interface in a multimer. Finally, we modelled protein complexes (from CORUM) and identified two highly confident structures that do not have sequence homology to any existing structures.
Availability and implementation
All scripts, models, and data used to perform the analysis in this study are freely available at https://gitlab.com/ElofssonLab/afm-benchmark
Targeting RNA-binding protein HuR to inhibit the progression of renal tubular fibrosis
Get PDFBackground
Upregulation of an RNA-binding protein HuR has been implicated in glomerular diseases. Herein, we evaluated whether it is involved in renal tubular fibrosis.
Methods
HuR was firstly examined in human kidney biopsy tissue with tubular disease. Second, its expression and the effect of HuR inhibition with KH3 on tubular injury were further assessed in a mouse model induced by a unilateral renal ischemia/reperfusion (IR). KH3 (50 mg kg−1) was given daily via intraperitoneal injection from day 3 to 14 after IR. Last, one of HuR-targeted pathways was examined in cultured proximal tubular cells.
Results
HuR significantly increases at the site of tubular injury both in progressive CKD in patients and in IR-injured kidneys in mice, accompanied by upregulation of HuR targets that are involved in inflammation, profibrotic cytokines, oxidative stress, proliferation, apoptosis, tubular EMT process, matrix remodeling and fibrosis in renal tubulointerstitial fibrosis. KH3 treatment reduces the IR-induced tubular injury and fibrosis, accompanied by the remarkable amelioration in those involved pathways. A panel of mRNA array further revealed that 519 molecules in mouse kidney following IR injury changed their expression and 71.3% of them that are involved in 50 profibrotic pathways, were ameliorated when treated with KH3. In vitro, TGFβ1 induced tubular HuR cytoplasmic translocation and subsequent tubular EMT, which were abrogated by KH3 administration in cultured HK-2 cells.
Conclusions
These results suggest that excessive upregulation of HuR contributes to renal tubulointerstitial fibrosis by dysregulating genes involved in multiple profibrotic pathways and activating the TGFß1/HuR feedback circuit in tubular cells. Inhibition of HuR may have therapeutic potential for renal tubular fibrosis
Identification of a novel transport system in Borrelia burgdorferi that links the inner and outer membranes
Get PDFBorrelia burgdorferi, the spirochete that causes Lyme disease, is a diderm organism that is similar to Gram-negative organisms in that it contains both an inner and outer membrane. Unlike typical Gram-negative organisms, however, B. burgdorferi lacks lipopolysaccharide (LPS). Using computational genome analyses and structural modeling, we identified a transport system containing six proteins in B. burgdorferi that are all orthologs to proteins found in the lipopolysaccharide transport (LPT) system that links the inner and outer membranes of Gram-negative organisms and is responsible for placing LPS on the surface of these organisms. While B. burgdorferi does not contain LPS, it does encode over 100 different surface-exposed lipoproteins and several major glycolipids, which like LPS are also highly amphiphilic molecules, though no system to transport these molecules to the borrelial surface is known. Accordingly, experiments supplemented by molecular modeling were undertaken to determine whether the orthologous LPT system identified in B. burgdorferi could transport lipoproteins and/or glycolipids to the borrelial outer membrane. Our combined observations strongly suggest that the LPT transport system does not transport lipoproteins to the surface. Molecular dynamic modeling, however, suggests that the borrelial LPT system could transport borrelial glycolipids to the outer membrane
Measurement of the mass dependence of the transverse momentum of lepton pairs in Drell–Yan production in proton–proton collisions at √=13TeV
Get PDFThe double differential cross sections of the Drell–Yan lepton pair (ℓ+ℓ−, dielectron or dimuon) production are measured as functions of the invariant mass ℓℓ, transverse momentum T(ℓℓ), and φ∗. The φ∗ observable, derived from angular measurements of the leptons and highly correlated with T(ℓℓ), is used to probe the low-T(ℓℓ) region in a complementary way. Dilepton masses up to 1TeV are investigated. Additionally, a measurement is performed requiring at least one jet in the final state. To benefit from partial cancellation of the systematic uncertainty, the ratios of the differential cross sections for various ℓℓ ranges to those in the Z mass peak interval are presented. The collected data correspond to an integrated luminosity of 36.3fb−1 of proton–proton collisions recorded with the CMS detector at the LHC at a centre-of-mass energy of 13TeV. Measurements are compared with predictions based on perturbative quantum chromodynamics, including soft-gluon resummation
The Auschwitz Report
Get PDFThe escape of Rudolf Vrba and Alfred Wetzler from Auschwitz on April 7, 1944, was extraordinary in its daring, courageous execution, and impact. The challenging task of the two escapees was to inform the world of previously unimaginable crimes, and to do so in a way that made the unbelievable believable. Because the deportations to Auschwitz were still in progress, it was essential to inform the threatened Jewish populations that they were slated by the Germans to be part of the “final solution.” When and how the transmission of the resulting Auschwitz Report took place, made all the difference, and that is this paper’s focus. Decisive transmissions involved secret networks in Switzerland and Hungary, taking place independently. Despite the presence of the Gestapo and the German army, finally, in early July, 1944, two independent, increasingly powerful efforts engendered by the report converged in Budapest. Only then could one of the most remarkable rescues of World War II take place. [email protected]