Wavenumber-explicit continuity and coercivity estimates in acoustic scattering by planar screens

We study the classical first-kind boundary integral equation reformulations of time-harmonic acoustic scattering by planar sound-soft (Dirichlet) and sound-hard (Neumann) screens. We prove continuity and coercivity of the relevant boundary integral operators (the acoustic single-layer and hypersingular operators respectively) in appropriate fractional Sobolev spaces, with wavenumber-explicit bounds on the continuity and coercivity constants. Our analysis is based on spectral representations for the boundary integral operators, and builds on results of Ha-Duong (Jpn J Ind Appl Math 7:489--513 (1990) and Integr Equat Oper Th 15:427--453 (1992)).Comment: v2 has minor corrections compared to v1. arXiv admin note: substantial text overlap with arXiv:1401.280

Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model

Molecular basis of virus replication, viral pathogenesis and antiviral strategie

Phonon-mediated anisotropic superconductivity in the Y and Lu nickel borocarbides

We present scanning tunneling spectroscopy and microscopy measurements at low temperatures in the borocarbide materials RNi2B2C (R=Y, Lu). The characteristic strong coupling structure due to the pairing interaction is unambiguously resolved in the superconducting density of states. It is located at the superconducting gap plus the energy corresponding to a phonon mode identified in previous neutron scattering experiments. These measurements also show that this mode is coupled to the electrons through a highly anisotropic electron-phonon interaction originated by a nesting feature of the Fermi surface. Our experiments, from which we can extract a large electron-phonon coupling parameter lambda (between 0.5 and 0.8), demonstrate that this anisotropic electron-phonon coupling has an essential contribution to the pairing interaction. The tunneling spectra show an anisotropic s-wave superconducting gap function.Comment: 5 pages, 3 figure

Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses

Development of effective preventative interventions against SARS-CoV-2, the etiologic agent of COVID-19 is urgently needed. The viral surface spike (S) protein of SARS-CoV-2 is a key target for prophylactic measures as it is critical for the viral replication cycle and the primary target of neutralizing antibodies. We evaluated design elements previously shown for other coronavirus S protein-based vaccines to be successful, e.g., prefusion-stabilizing substitutions and heterologous signal peptides, for selection of a S-based SARS-CoV-2 vaccine candidate. In vitro characterization demonstrated that the introduction of stabilizing substitutions (i.e., furin cleavage site mutations and two consecutive prolines in the hinge region of S2) increased the ratio of neutralizing versus non-neutralizing antibody binding, suggestive for a prefusion conformation of the S protein. Furthermore, the wild-type signal peptide was best suited for the correct cleavage needed for a natively folded protein. These observations translated into superior immunogenicity in mice where the Ad26 vector encoding for a membrane-bound stabilized S protein with a wild-type signal peptide elicited potent neutralizing humoral immunity and cellular immunity that was polarized towards Th1 IFN-gamma. This optimized Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in a phase I clinical trial (ClinicalTrials.gov Identifier: NCT04436276).Molecular basis of virus replication, viral pathogenesis and antiviral strategie

The feasibility, proficiency, and mastery learning curves in 635 robotic pancreatoduodenectomies following a multicenter training program: "Standing on the Shoulders of Giants"

Objective: To assess the feasibility, proficiency, and mastery learning curves for robotic pancreatoduodenectomy (RPD) in "second-generation" RPD centers following a multicenter training program adhering to the IDEAL framework.Background: The long learning curves for RPD reported from "pioneering" expert centers may discourage centers interested in starting an RPD program. However, the feasibility, proficiency, and mastery learning curves may be shorter in "second-generation" centers that participated in dedicated RPD training programs, although data are lacking. We report on the learning curves for RPD in "second-generation" centers trained in a dedicated nationwide program.Methods: Post hoc analysis of all consecutive patients undergoing RPD in 7 centers that participated in the LAELAPS-3 training program, each with a minimum annual volume of 50 pancreatoduodenectomies, using the mandatory Dutch Pancreatic Cancer Audit (March 2016-December 2021). Cumulative sum analysis determined cutoffs for the 3 learning curves: operative time for the feasibility (1) risk-adjusted major complication (Clavien-Dindo grade >= III) for the proficiency, (2) and textbook outcome for the mastery, (3) learning curve. Outcomes before and after the cutoffs were compared for the proficiency and mastery learning curves. A survey was used to assess changes in practice and the most valued "lessons learned."Results: Overall, 635 RPD were performed by 17 trained surgeons, with a conversion rate of 6.6% (n=42). The median annual volume of RPD per center was 22.56.8. From 2016 to 2021, the nationwide annual use of RPD increased from 0% to 23% whereas the use of laparoscopic pancreatoduodenectomy decreased from 15% to 0%. The rate of major complications was 36.9% (n=234), surgical site infection 6.3% (n=40), postoperative pancreatic fistula (grade B/C) 26.9% (n=171), and 30-day/in-hospital mortality 3.5% (n=22). Cutoffs for the feasibility, proficiency, and mastery learning curves were reached at 15, 62, and 84 RPD. Major morbidity and 30-day/in-hospital mortality did not differ significantly before and after the cutoffs for the proficiency and mastery learning curves. Previous experience in laparoscopic pancreatoduodenectomy shortened the feasibility (-12 RPDs, -44%), proficiency (-32 RPDs, -34%), and mastery phase learning curve (-34 RPDs, -23%), but did not improve clinical outcome.Conclusions: The feasibility, proficiency, and mastery learning curves for RPD at 15, 62, and 84 procedures in "second-generation" centers after a multicenter training program were considerably shorter than previously reported from "pioneering" expert centers. The learning curve cutoffs and prior laparoscopic experience did not impact major morbidity and mortality. These findings demonstrate the safety and value of a nationwide training program for RPD in centers with sufficient volume.Surgical oncolog

Immunogenicity and efficacy of one and two doses of Ad26.COV2.S COVID vaccine in adult and aged NHP

Safe and effective coronavirus disease-19 (COVID-19) vaccines are urgently needed to control the ongoing pandemic. While single-dose vaccine regimens would provide multiple advantages, two doses may improve the magnitude and durability of immunity and protective efficacy. We assessed one-and two-dose regimens of the Ad26.COV2.S vaccine candidate in adult and aged nonhuman primates (NHPs). A two-dose Ad26.COV2.S regimen induced higher peak binding and neutralizing antibody responses compared with a single dose. In one-dose regimens, neutralizing antibody responses were stable for at least 14 wk, providing an early indication of durability. Ad26.COV2.S induced humoral immunity and T helper cell (Th cell) 1-skewed cellular responses in aged NHPs that were comparable to those in adult animals. Aged Ad26.COV2.S-vaccinated animals challenged 3 mo after dose 1 with a SARS-CoV-2 spike G614 variant showed near complete lower and substantial upper respiratory tract protection for both regimens. Neutralization of variants of concern by NHP sera was reduced for B.1.351 lineages while maintained for the B.1.1.7 lineage independent of Ad26.COV2.S vaccine regimen.Molecular basis of virus replication, viral pathogenesis and antiviral strategie

Nieuwe vondsten van de doornkaakzandbij Andrena trimmerana in Nederland (Hymenoptera: Apoidea: Andrenidae)

De doornkaakzandbij ziet er in het voorjaar een beetje anders uit dan in de zomer. Daarom worden de voorjaarsdieren door sommigen tot een andere soort beschouwd dan de zomerdieren. Uit Nederland zijn slechts drie exemplaren bekend: twee uit het voorjaar en één uit de zomer. Toevallig komen alle exemplaren uit hetzelfde gebied. Of is dit geen toeval

Cyclophilins and cyclophilin inhibitors in nidovirus replication

Molecular basis of virus replication, viral pathogenesis and antiviral strategie