Mixed modeling for large-eddy simulation: The single-layer and two-layer minimum-dissipation-Bardina models

Predicting the behavior of turbulent flows using large-eddy simulation requires modeling of the subgrid-scale stress tensor. This tensor can be approximated using mixed models, which combine the dissipative nature of functional models with the capability of structural models to approximate out-of-equilibrium effects. We propose a mathematical basis to mix (functional) eddy-viscosity models with the (structural) Bardina model. By taking an anisotropic minimum-dissipation (AMD) model for the eddy viscosity, we obtain the (single-layer) AMD-Bardina model. In order to also obtain a physics-conforming model for wall-bounded flows, we further develop this mixed model into a two-layer approach: the near-wall region is parameterized with the AMD-Bardina model, whereas the outer region is computed with the Bardina model. The single-layer and two-layer AMD-Bardina models are tested in turbulent channel flows at various Reynolds numbers, and improved predictions are obtained when the mixed models are applied in comparison to the computations with the AMD and Bardina models alone. The results obtained with the two-layer AMD-Bardina model are particularly remarkable: both first- and second-order statistics are extremely well predicted and even the inflection of the mean velocity in the channel center is captured. Hence, a very promising model is obtained for large-eddy simulations of wall-bounded turbulent flows at moderate and high Reynolds numbers.Comment: 29 pages, 14 figures, 3 tables; revised, accepted manuscrip

A Comparison of Survey Methods for Documenting Presence of Myotis leibii (Eastern Small-Footed Bats) at Roosting Areas in Western Virginia

Many aspects of foraging and roosting habitat of Myotis leibii (Eastern Small-Footed Bat), an emergent rock roosting-obligate, are poorly described. Previous comparisons of effectiveness of acoustic sampling and mist-net captures have not included Eastern Small-Footed Bat. Habitat requirements of this species differ from congeners in the region, and it is unclear whether survey protocols developed for other species are applicable. Using data from three overlapping studies at two sampling sites in western Virginia’s central Appalachian Mountains, detection probabilities were examined for three survey methods (acoustic surveys with automated identification of calls, visual searches of rock crevices, and mist-netting) for use in the development of “best practices” for future surveys and monitoring. Observer effects were investigated using an expanded version of visual search data. Results suggested that acoustic surveys with automated call identification are not effective for documenting presence of Eastern Small-Footed Bats on talus slopes (basal detection rate of 0%) even when the species is known to be present. The broadband, high frequency echolocation calls emitted by Eastern Small-Footed Bat may be prone to attenuation by virtue of their high frequencies, and these factors, along with signal reflection, lower echolocation rates or possible misidentification to other bat species over talus slopes may all have contributed to poor acoustic survey success. Visual searches and mist-netting of emergent rock had basal detection probabilities of 91% and 75%, respectively. Success of visual searches varied among observers, but detection probability improved with practice. Additionally, visual searches were considerably more economical than mist-netting

Bat Echolocation Research: A handbook for planning and conducting acoustic studies

Echolocation provides an acoustic window on the behavior of most species of bats. Donald R. Griffin's book (Listening in the Dark: The Acoustic Orientation of Bats and Men) gave us a preview of what we might hear through this window. This Handbook illustrates how a small window has turned into a giant screen. The study of bat echolocation has progressed from a boutique curiosity and source of wonder to a discipline spanning areas of science from neurobiology through behavior, ecology, evolution, and environmental science. Many people who study bats use echolocation as a focus for their work. To some this means, for example, neurobiology, communication behavior, or environmental assessment. Whatever the goal, diversity is an underlying and overarching reality. At one level, diversity means that different species take quite different approaches to echolocation. At another level, individual differences remind us that echolocation is a conscious behavior. The same bat may, for instance, use quite different echolocation calls over the course of a night, a season, or its life. How much of echolocation behavior is inherited, and how much is learned

A forward genetic screen identifies host factors that influence the lysis-lysogeny decision in phage lambda

The lysis‐lysogeny decision made by bacteriophage lambda is one of the classic problems of molecular biology. Shortly after infecting a cell, the virus can either go down the lytic pathway and make more viruses, or go down the lysogenic pathway and integrate itself into the host genome. While much is known about how this decision takes place, the extent to which host physiology influences this decision and the mechanisms by which this influence takes place has remained mysterious. To answer this question, we performed a forward genetic screen to systematically identify all of the genes in E. coli that influence the lysis‐lysogeny decision. Our results demonstrate previously unknown links between host physiology and viral decision making and shed new light on this classic system

FIVA:Functional Information Viewer and Analyzer extracting biological knowledge from transcriptome data of prokaryotes

FIVA (Function Information Viewer and Analyzer) aids researchers in the prokaryotic community to quickly identify relevant biological processes following transcriptome analysis. Our software assists in functional profiling of large sets of genes and generates a comprehensive overview of affected biological processes.

Factors Affecting European Farmers’Participation in Biodiversity Policies

This article reports the major findings from an interdisciplinary research project that synthesises key insights into farmers’ willingness and ability to co-operate with biodiversity policies. The results of the study are based on an assessment of about 160 publications and research reports from six EU member states and from international comparative research.We developed a conceptual framework to systematically review the existent literature relevant for our purposes. This framework provides a common structure for analysing farmers’ perspectives regarding the introduction into farming practices of measures relevant to biodiversity. The analysis is coupled and contrasted with a survey of experts. The results presented above suggest that it is important to view support for practices oriented towards biodiversity protection not in a static sense – as a situation determined by one or several influencing factors – but rather as a process marked by interaction. Financial compensation and incentives function as a necessary, though clearly not sufficient condition in this process

Inhibition of ULK1/2 and Kras G12C Controls Tumor Growth in Preclinical Models of Lung Cancer

Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRASG12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRASG12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRASG12C signaling increases autophagy in KRASG12C-expressing lung cancer cells. Moreover, the combination of DCC-3116, a selective ULK1/2 inhibitor, plus sotorasib displays cooperative/synergistic suppression of human KRASG12C-driven lung cancer cell proliferation in vitro and superior tumor control in vivo. Additionally, in genetically engineered mouse models of KRASG12C-driven NSCLC, inhibition of either KRASG12C or ULK1/2 decreases tumor burden and increases mouse survival. Consequently, these data suggest that ULK1/2-mediated autophagy is a pharmacologically actionable cytoprotective stress response to inhibition of KRASG12C in lung cancer

Post-SARS-CoV-2-vaccination cerebral venous sinus thrombosis : an analysis of cases notified to the European Medicines Agency

Background and purpose Cerebral venous sinus thrombosis (CVST) has been described after vaccination against SARS-CoV-2. The clinical characteristics of 213 post-vaccination CVST cases notified to the European Medicines Agency are reported. Methods Data on adverse drug reactions after SARS-CoV-2 vaccination notified until 8 April 2021 under the Medical Dictionary for Regulatory Activities Term 'Central nervous system vascular disorders' were obtained from the EudraVigilance database. Post-vaccination CVST was compared with 100 European patients with CVST from before the COVID-19 pandemic derived from the International CVST Consortium. Results In all, 213 CVST cases were identified: 187 after AstraZeneca/Oxford (ChAdOx1 nCov-19) vaccination and 26 after a messenger RNA (mRNA) vaccination (25 with Pfizer/BioNTech, BNT162b2, and one with Moderna, mRNA-1273). Thrombocytopenia was reported in 107/187 CVST cases (57%, 95% confidence interval [CI] 50%-64%) in the ChAdOx1 nCov-19 group, in none in the mRNA vaccine group (0%, 95% CI 0%-13%) and in 7/100 (7%, 95% CI 3%-14%) in the pre-COVID-19 group. In the ChAdOx1 nCov-19 group, 39 (21%) reported COVID-19 polymerase chain reaction tests were performed within 30 days of CVST symptom onset, and all were negative. Of the 117 patients with a reported outcome in the ChAdOx1 nCov-19 group, 44 (38%, 95% CI 29%-47%) had died, compared to 2/10 (20%, 95% CI 6%-51%) in the mRNA vaccine group and 3/100 (3%, 95% CI 1%-8%) in the pre-COVID-19 group. Mortality amongst patients with thrombocytopenia in the ChAdOx1 nCov-19 group was 49% (95% CI 39%-60%). Conclusions Cerebral venous sinus thrombosis occurring after ChAdOx1 nCov-19 vaccination has a clinical profile distinct from CVST unrelated to vaccination. Only CVST after ChAdOx1 nCov-19 vaccination was associated with thrombocytopenia.Peer reviewe

A forward genetic screen identifies host factors that influence the lysis-lysogeny decision in phage lambda

The lysis‐lysogeny decision made by bacteriophage lambda is one of the classic problems of molecular biology. Shortly after infecting a cell, the virus can either go down the lytic pathway and make more viruses, or go down the lysogenic pathway and integrate itself into the host genome. While much is known about how this decision takes place, the extent to which host physiology influences this decision and the mechanisms by which this influence takes place has remained mysterious. To answer this question, we performed a forward genetic screen to systematically identify all of the genes in E. coli that influence the lysis‐lysogeny decision. Our results demonstrate previously unknown links between host physiology and viral decision making and shed new light on this classic system

Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic

IMPORTANCE Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism. OBJECTIVE To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies. EXPOSURES Diagnosis of cerebral venous sinus thrombosis. MAIN OUTCOMES AND MEASURES Frequencies of admission thrombocytopenia (platelet count 0.4, in a subset of patients with previously collected plasma samples). RESULTS Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 x10(3)/mu L) in 52 (6.0%), moderate (50-99 x10(3)/mu L) in 17 (2.0%), and severe ( CONCLUSIONS AND RELEVANCE In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopeniawas uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodieswere rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.Peer reviewe