Nickel: A very fast diffuser in silicon

Nickel is increasingly used in both IC and photovoltaic device fabrication, yet it has the potential to create highly recombination-active precipitates in silicon. For nearly three decades, the accepted nickel diffusivity in silicon has been DNi(T)=2.3×10exp−3 exp(−0.47 eV/kBT) cm2/s, a surprisingly low value given reports of rapid nickel diffusion in industrial applications. In this paper, we employ modern experimental methods to measure the higher nickel diffusivity DNi(T)=(1.69±0.74)×10exp−4 exp(−0.15±0.04 eV/kBT)  cm2/s. The measured activation energy is close to that predicted by first-principles theory using the nudged-elastic-band method. Our measured diffusivity of nickel is higher than previously published values at temperatures below 1150 °C, and orders of magnitude higher when extrapolated to room temperature.Peer reviewe

A systematic approach to identify host targets and rapidly deliver broad-spectrum antivirals.

peer reviewe

A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.

The unparalleled global effort to combat the continuing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic over the last year has resulted in promising prophylactic measures. However, a need still exists for cheap, effective therapeutics, and targeting multiple points in the viral life cycle could help tackle the current, as well as future, coronaviruses. Here, we leverage our recently developed, ultra-large-scale in silico screening platform, VirtualFlow, to search for inhibitors that target SARS-CoV-2. In this unprecedented structure-based virtual campaign, we screened roughly 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets. In addition to targeting the active sites of viral enzymes, we also targeted critical auxiliary sites such as functionally important protein-protein interactions

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Hygrome als Differentialdiagnose nicht entzündlicher Schwellungen der Halsweichteile

Einleitung: Unvermittelt auftretende Schwellungen des äußeren Halses bei Erwachsenen legen oft Verdacht auf ein entzündliches Geschehen nahe.Kasuistik: Fall 1: 46jährige Patientin mit plötzlicher, schmerzloser Schwellung des linken Halses, teigig palpabel, Labor o.B.. Sono und CT Hals ergeben Verdacht freier Flüssigkeit in den Faszien. Entschluss zur Intervention. Intraoperativ findet sich in den Halslogen serös-gelbliche Flüssigkeit ohne Hinweis auf zystische Strukturen, Einblutung oder Abszedierung. Es erfolgt Spülung und Verschluss mit Lascheneinlage. CT-Thorax zeigt ein das gesamte Mediastinum ausfüllendes Hygrom bis zur Clavicula, so dass von Spontanruptur ausgegangen werden kann. Postoperativer Verlauf regelrecht. Patientin lehnt weitere Operation ab, so dass thoraxchirurgischerseits MRT-Kontrollen geplant sind. Fall 2: 75 Jahre alte Patientin stellt sich mit seit 2 Monaten bestehender, plötzlich aufgetretener supraclaviculären Raumforderung links vor. Keine Schmerzen, Labor unauffällig, Durchführung CT Hals/Thorax zeigt große cystische, ovaläre Raumforderung bis infraclaviculär links reichend. Durch die Operation kann eine vollständige Exstirpation erzielt werden. Intraoperativ bestätigt sich die klinische Verdachtsdiagnose eines Hygroms. Postoperativer Verlauf regelrecht.Schlussfolgerung: Hygrome haben Urspung in ektopen Embryonalzellen des lymphatischen Systems. Sie treten spätestens im Jugendalter im Halsbereich auf. Selten Ausdehnungen in das obere Mediastinum. Somit muss bei schmerzlosen, nicht entzündlichen Halsschwellungen im Erwachsenenalter neben Halszysten bei entsprechender Anamnese auch ein Hygrom des oberen Mediastinums als seltene Differentialdiagnose berücksichtigt werden.Schlüsselwörter: Halsschwellung-Hygrom-Erwachsen

Cryo-EM structure of an activated GPCR-G protein complex in lipid nanodiscs.

G-protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane proteins and the targets of over 30% of currently marketed pharmaceuticals. Although several structures have been solved for GPCR-G protein complexes, few are in a lipid membrane environment. Here, we report cryo-EM structures of complexes of neurotensin, neurotensin receptor 1 and Gαi1β1γ1 in two conformational states, resolved to resolutions of 4.1 and 4.2 Å. The structures, determined in a lipid bilayer without any stabilizing antibodies or nanobodies, reveal an extended network of protein-protein interactions at the GPCR-G protein interface as compared to structures obtained in detergent micelles. The findings show that the lipid membrane modulates the structure and dynamics of complex formation and provide a molecular explanation for the stronger interaction between GPCRs and G proteins in lipid bilayers. We propose an allosteric mechanism for GDP release, providing new insights into the activation of G proteins for downstream signaling

Non-covalent SARS-CoV-2 Mpro inhibitors developed from in silico screen hits.

Mpro, the main protease of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is essential for the viral life cycle. Accordingly, several groups have performed in silico screens to identify Mpro inhibitors that might be used to treat SARS-CoV-2 infections. We selected more than five hundred compounds from the top-ranking hits of two very large in silico screens for on-demand synthesis. We then examined whether these compounds could bind to Mpro and inhibit its protease activity. Two interesting chemotypes were identified, which were further evaluated by characterizing an additional five hundred synthesis on-demand analogues. The compounds of the first chemotype denatured Mpro and were considered not useful for further development. The compounds of the second chemotype bound to and enhanced the melting temperature of Mpro. The most active compound from this chemotype inhibited Mpro in vitro with an IC50 value of 1 μM and suppressed replication of the SARS-CoV-2 virus in tissue culture cells. Its mode of binding to Mpro was determined by X-ray crystallography, revealing that it is a non-covalent inhibitor. We propose that the inhibitors described here could form the basis for medicinal chemistry efforts that could lead to the development of clinically relevant inhibitors