Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900's, which dramatically reduced disease prevalence. Continued use of these vaccines, however, threatens ultimate disease eradication and achievement of a polio-free world. Virus-like particles (VLPs) that lack a viral genome represent a safer potential vaccine, although they require particle stabilization.
View Article and Find Full Text PDFAfter L858R and ex19del epidermal growth factor receptor (EGFR) mutations, ex20ins mutations are the third most common class of driver-mutations in non-small cell lung cancer (NSCLC). Unfortunately, first-, second-, and third-generation EGFR tyrosine kinase inhibitors (TKIs) are generally ineffective for ex20ins patients due to insufficient mutant activity and selectivity over wild-type EGFR, leading to dose-limiting toxicities. While significant advances in recent years have been made toward identifying potent EGFR ex20ins mutant inhibitors, mutant vs wild-type EGFR selectivity remains a significant challenge.
View Article and Find Full Text PDFHeart failure with preserved ejection fraction (HFpEF) has recently emerged as an insidiously and increasingly prevalent heart failure phenotype. HFpEF often occurs in the context of hypertension and obesity and presents with diastolic dysfunction, ventricular hypertrophy, and myocardial fibrosis. Despite growing study of HFpEF, the causal links between early metabolic changes, bioenergetic perturbations, and cardiac structural remodeling remain unclear.
View Article and Find Full Text PDFA virus particle must work as a strongroom to protect its genome, but at the same time it must undergo dramatic conformational changes to infect the cell in order to replicate and assemble progeny. Thus, viruses are miniaturized wonders whose structural complexity requires investigation by a combination of different techniques that can tackle both static and dynamic processes. In this chapter, we will illustrate how major structural techniques such as X-ray crystallography and electron microscopy can be combined with other techniques to determine the structure of complex viruses.
View Article and Find Full Text PDFRobotic cholecystectomy (RC) using the da Vinci surgical system has been introduced as a potential alternative to the gold standard laparoscopic cholecystectomy (LC) for gallbladder removal. This systematic review aims to evaluate and compare the postoperative outcomes (operative time, bile leak, and postoperative complications) and cost-effectiveness between da Vinci RC and LC. A comprehensive search of electronic databases, including EMBASE, MEDLINE, Cochrane Library, and PubMed, used Medical Subject Headings terms and Boolean operators to identify relevant studies.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
November 2024
The first search for soft unclustered energy patterns (SUEPs) is performed using an integrated luminosity of 138 fb^{-1} of proton-proton collision data at sqrt[s]=13 TeV, collected in 2016-2018 by the CMS detector at the LHC. Such SUEPs are predicted by hidden valley models with a new, confining force with a large 't Hooft coupling. In events with boosted topologies, selected by high-threshold hadronic triggers, the multiplicity and sphericity of clustered tracks are used to reject the background from standard model quantum chromodynamics.
View Article and Find Full Text PDFCanine mast cell tumours (MCTs) are one of the most common skin cancers of dogs. Surgical removal is the primary treatment, but recurrence and metastasis can occur even with low-grade tumours. As a result, new treatment strategies are being sought.
View Article and Find Full Text PDFThe first search for the Z boson decay to ττμμ at the CERN LHC is presented, based on data collected by the CMS experiment at the LHC in proton-proton collisions at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138 fb^{-1}. The data are compatible with the predicted background. For the first time, an upper limit at the 95% confidence level of 6.
View Article and Find Full Text PDFFoot-and-mouth disease vaccination using inactivated virus is suboptimal, as the icosahedral viral capsids often disassemble into antigenically distinct pentameric units during long-term storage, or exposure to elevated temperature or lowered pH, and thus raise a response that is no longer protective. Furthermore, as foot-and-mouth disease virus (FMDV)'s seven serotypes are antigenically diverse, cross-protection from a single serotype vaccine is limited, and most existing mouse and bovine antibodies and camelid single-domain heavy chain-only antibodies are serotype-specific. For quality control purposes, there is a real need for pan-serotype antibodies that clearly distinguish between pentamer (12S) and protective intact FMDV capsid.
View Article and Find Full Text PDFUsing proton-proton collision data corresponding to an integrated luminosity of collected by the CMS experiment at , the decay is observed for the first time, with a statistical significance exceeding 5 standard deviations. The relative branching fraction, with respect to the decay, is measured to be , where the first uncertainty is statistical, the second is systematic, and the third is related to the uncertainties in and .
View Article and Find Full Text PDFA search for collective effects inside jets produced in proton-proton collisions is performed via correlation measurements of charged particles using the CMS detector at the CERN LHC. The analysis uses data collected at a center-of-mass energy of sqrt[s]=13 TeV, corresponding to an integrated luminosity of 138 fb^{-1}. Jets are reconstructed with the anti-k_{T} algorithm with a distance parameter of 0.
View Article and Find Full Text PDFThe replication of RNA viruses relies on the activity of RNA-dependent RNA polymerases (RdRps). Despite large variations in their genomic sequences, viral RdRps share a common architecture generally known as a closed right hand. The P2 polymerase of cystovirus φ6 is currently among the best characterized viral RdRps.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2024
Cellular processes are controlled by the thermodynamics of the underlying biomolecular interactions. Frequently, structural investigations use one monomeric binding partner, while ensemble measurements of binding affinities generally yield one affinity representative of a 1:1 interaction, despite the majority of the proteome consisting of oligomeric proteins. For example, viral entry and inhibition in SARS-CoV-2 involve a trimeric spike surface protein, a dimeric angiotensin-converting enzyme 2 (ACE2) cell-surface receptor and dimeric antibodies.
View Article and Find Full Text PDFChronic kidney disease (CKD) is a progressive disorder marked by a decline in kidney function. Obesity and sedentary behavior contribute to the development of CKD, though mechanisms by which this occurs are poorly understood. This knowledge gap is worsened by the lack of a reliable murine CKD model that does not rely on injury, toxin, or gene deletion to induce a reduction in kidney function.
View Article and Find Full Text PDFComput Softw Big Sci
September 2024
Energy correlators that describe energy-weighted distances between two or three particles in a hadronic jet are measured using an event sample of sqrt[s]=13 TeV proton-proton collisions collected by the CMS experiment and corresponding to an integrated luminosity of 36.3 fb^{-1}. The measured distributions are consistent with the trends in the simulation that reveal two key features of the strong interaction: confinement and asymptotic freedom.
View Article and Find Full Text PDFObjectives: We studied the immunogenicity after primary and booster vaccinations of the Abdala COVID-19 vaccine, a receptor-binding domain protein subunit vaccine, in Vietnamese people by determining the level of neutralization and cross-neutralization activities against the ancestral SARS-CoV-2 and its variants and SARS-CoV-1.
Methods: We performed a prospective observational study, enrolling adults aged 19-59 years in Dong Thap province, southern Vietnam, and collected blood samples from baseline until 4 weeks after the booster dose. We measured anti-nucleocapsid, anti-spike, and neutralizing antibodies against SARS-CoV-2 and assessed the cross-neutralization against 14 SARS-CoV-2 variants and SARS-CoV-1.
The production of ϒ(2S) and ϒ(3S) mesons in lead-lead (Pb-Pb) and proton-proton (pp) collisions is studied in their dimuon decay channel using the CMS detector at the LHC. The ϒ(3S) meson is observed for the first time in Pb-Pb collisions, with a significance above 5 standard deviations. The ratios of yields measured in Pb-Pb and pp collisions are reported for both the ϒ(2S) and ϒ(3S) mesons, as functions of transverse momentum and Pb-Pb collision centrality.
View Article and Find Full Text PDFThe first search for singly produced narrow resonances decaying to three well-separated hadronic jets is presented. The search uses proton-proton collision data corresponding to an integrated luminosity of 138 fb^{-1} at sqrt[s]=13 TeV, collected at the CERN LHC. No significant deviations from the background predictions are observed between 1.
View Article and Find Full Text PDFA strong and effective COVID-19 and future pandemic responses rely on global efforts to carry out surveillance of infections and emerging SARS-CoV-2 variants and to act accordingly in real time. Many countries in Southeast Asia lack capacity to determine the potential threat of new variants, or other emerging infections. Funded by Wellcome, the Southeast Asia initiative to combat SARS-CoV-2 variants (SEACOVARIANTS) consortium aims to develop and apply a multidisciplinary research platform in Southeast Asia (SEA) for rapid assessment of the biological significance of SARS-CoV-2 variants, thereby informing coordinated local, regional and global responses to the COVID-19 pandemic.
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