Cryo-Electron Tomographic Structure of an Immunodeficiency Virus Envelope Complex In Situ

The envelope glycoprotein (Env) complexes of the human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate viral entry and are a target for neutralizing antibodies. The receptor binding surfaces of Env are in large part sterically occluded or conformationally masked prior to receptor binding. Knowledge of the unliganded, trimeric Env structure is key for an understanding of viral entry and immune escape, and for the design of vaccines to elicit neutralizing antibodies. We have used cryo-electron tomography and averaging to obtain the structure of the SIV Env complex prior to fusion. Our result reveals novel details of Env organisation, including tight interaction between monomers in the gp41 trimer, associated with a three-lobed, membrane-distal gp120 trimer. A cavity exists at the gp41–gp120 trimer interface. Our model for the spike structure agrees with previously predicted interactions between gp41 monomers, and furthers our understanding of gp120 interactions within an intact spike

A Bayesian approach to single-particle electron cryo-tomography in RELION-4.0

We present a new approach for macromolecular structure determination from multiple particles in electron cryo-tomography (cryo-ET) data sets. Whereas existing subtomogram averaging approaches are based on 3D data models, we propose to optimise a regularised likelihood target that approximates a function of the 2D experimental images. In addition, analogous to Bayesian polishing and contrast transfer function (CTF) refinement in single-particle analysis, we describe the approaches that exploit the increased signal-to-noise ratio in the averaged structure to optimise tilt-series alignments, beam-induced motions of the particles throughout the tilt-series acquisition, defoci of the individual particles, as well as higher-order optical aberrations of the microscope. Implementation of our approaches in the open-source software package RELION aims to facilitate their general use, particularly for those researchers who are already familiar with its single-particle analysis tools. We illustrate for three applications that our approaches allow structure determination from cryo-ET data to resolutions sufficient for de novo atomic modelling.This work was funded by the UK Research and Innovation (UKRI) Medical Research Council (MC_UP_A025_1013 to SHWS; and MC_UP_1201/16 to JAGB), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC-CoG-2014, grant 648432, MEMBRANEFUSION to JAGB and ERC StG-2019, grant 852915 CRYTOCOP to GZ); the Swiss National Science Foundation (grant 205321_179041/1 to DC-D), the Max Planck Society (to JAGB) and the UKRI Biotechnology and Biological Sciences Research Council (grant BB/T002670/1 to GZ). TAMB is a recipient of a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (202231/Z/16/Z). JZ was partially funded by the European Union’s Horizon 2020 research and innovation program (ERC-ADG-2015, grant 692726, GlobalBioIm to Michael Unser)

Religion as practices of attachment and materiality: the making of Buddhism in contemporary London

This article aims to explore Buddhism’s often-overlooked presence on London’s urban landscape, showing how its quietness and subtlety of approach has allowed the faith to grow largely beneath the radar. It argues that Buddhism makes claims to urban space in much the same way as it produces its faith, being as much about the practices performed and the spaces where they are enacted as it is about faith or beliefs. The research across a number of Buddhist sites in London reveals that number of people declaring themselves as Buddhists has indeed risen in recent years, following the rise of other non-traditional religions in the UK; however, this research suggests that Buddhism differs from these in several ways. Drawing on Baumann’s (2002) distinction between traditionalist and modernist approaches to Buddhism, our research reveals a growth in each of these. Nevertheless, Buddhism remains largely invisible in the urban and suburban landscape of London, adapting buildings that are already in place, with little material impact on the built environment, and has thus been less subject to contestation than other religious movements and traditions. This research contributes to a growing literature which foregrounds the importance of religion in making contemporary urban and social worlds

Comparison of Different Methods for Estimating Cardiac Timings: A Comprehensive Multimodal Echocardiography Investigation

Cardiac time intervals are important hemodynamic indices and provide information about left ventricular performance. Phonocardiography (PCG), impedance cardiography (ICG), and recently, seismocardiography (SCG) have been unobtrusive methods of choice for detection of cardiac time intervals and have potentials to be integrated into wearable devices. The main purpose of this study was to investigate the accuracy and precision of beat-to-beat extraction of cardiac timings from the PCG, ICG and SCG recordings in comparison to multimodal echocardiography (Doppler, TDI, and M-mode) as the gold clinical standard. Recordings were obtained from 86 healthy adults and in total 2,120 cardiac cycles were analyzed. For estimation of the pre-ejection period (PEP), 43% of ICG annotations fell in the corresponding echocardiography ranges while this was 86% for SCG. For estimation of the total systolic time (TST), these numbers were 43, 80, and 90% for ICG, PCG, and SCG, respectively. In summary, SCG and PCG signals provided an acceptable accuracy and precision in estimating cardiac timings, as compared to ICG

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

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

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

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