On Predicting The Turbulence-induced Secondary Flows Using Nonlinear K-∈ Models

Low turbulent Reynolds number direct simulation data are used to calculate the invariants of the Reynolds stress and the turbulent dissipation rate in a square duct. The results show that, depending on the region where the analysis is carried out, the turbulent flow field comes close to one-, two-, and three-component states. Modeling such flows - even at higher Reynolds numbers - will require models that can approach all three states. A number of related nonlinear k-∈ models are tested a priori using the direct simulation data. The numerical simulation using Reynolds averaged Navier-Stokes equations with these models was performed. Their ability to predict the secondary flows, with a low-Reynolds k-∈ model, cannot be gauged from realizability. © 1996 American Institute of Physics.8718561868Speziale, C.G., Analytical methods for the developments of Reynoldsstress closures in turbulence (1991) Annu. Rev. 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Fluids, 6, p. 3144Gibson, M.M., Launder, B.E., Ground effects on pressure fluctuations in the atmospheric boundary layer (1979) J. Fluid Mech., 86, p. 491Cheesewright, R., McGrath, G., Petty, D.G., (1990) LDA Measurements of Turbulent Flow in a Duct of Square Cross Section at Low Reynolds Number, , Aeronautical Engineering Department, University of London, Report No. ER 101Huser, A., Biringen, S., Direct numerical simulation of turbulent flow in a square duct (1993) J. Fluid Mech., 257, p. 65Gavrilakis, S., Numerical simulation of low-Reynolds-number turbulent flow through a straight square duct (1992) J. Fluid Mech., 244, p. 101Gavrilakis, S., (1993) Turbulent Velocity Structures Derived from POD Analyses, , Institute de Machines Hydrauliques et de Mécanique des Fluides, École Polytechnique Fédérale de Lausanne, Report No. T-93-30Antonia, R.A., Kim, J., Browne, L.W.B., Some characteristics of small-scale turbulence in turbulent duct flow (1991) J. Fluid Mech., 233, p. 369Bradshaw, P., Blair Perot, J., A note on turbulent energy dissipation in viscous wall region (1993) Phys. Fluids, 5, p. 3305Kim, J., Moin, P., Moser, R., Turbulent statistics in fully developed channel flow at low Reynolds number (1987) J. Fluid Mech., 177, p. 133Tennekes, H., Lumley, J.L., (1972) A First Course in Turbulence, , MIT Press, Cambridge, MALumley, J.L., Computational Modeling of Turbulent Flows (1978) Advances in Applied Mechanics, 18, p. 123. , Academic Press. New YorkGavrilakis, S., Large-scale structures in the turbulent flow near a right-angled corner (1994) 1st ERCOFTAC Workshop on Direct and Large-Eddy Simulation, , SurreyGessner, F.B., The origin of secondary flow in turbulent flow along a corner (1973) J. Fluid Mech., 58, p. 1Speziale, C.G., The dissipation rate correlation and turbulent secondary flows in noncircular ducts (1986) Trans. Am. Soc. Mech. Eng. J. Fluid Eng., 108, p. 118Durbin, P.A., Near-wall turbulence closure modeling without damping functions (1991) Theor. Comput. Fluid Dyn., 3, p. 1Rodi, W., Mansour, N.N., Low Reynolds number k-∈ modeling with the aid of direct simulation (1993) J. Fluid Mech., 250, p. 509Mompean, G., Three-equation turbulence model for prediction of the mean square temperature variance in grid-generated flows and round jets (1994) Int. J. Heat Mass Transfer, 37, p. 1165Chien, K.Y., Prediction of channel and boundary-layer flows with a low-Reynolds-number turbulence model (1982) AIAA J., 20, p. 33Lam, C.K.G., Bremhorst, K., A modified form of the k-∈ model predicting wall turbulence (1981) Trans. Am. Soc. Mech. Eng. J. Fluid. Eng., 103, p. 456Reynolds, W.C., Computation of turbulent flows (1976) Annu. Rev. Fluid Mech., 8, p. 183Lindberg, P.A., (1994), private communicationNisizima, S., A numerical study of turbulent square-duct flow using an anisotropic k-∈ model (1990) Theor. Comput. 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Reduced-basis Output Bound Methods for Parametrised Partial Differential Equations

An efficient and reliable method for the prediction of outputs of interest of partial differential equations with affine parameter dependence is presented. To achieve efficiency we employ the reduced-basis method: a weighted residual Galerkin-type method, where the solution is projected onto low-dimensional spaces with certain problem-specific approximation properties. Reliability is obtained by a posteriori error estimation methods - relaxations of the standard error-residual equation that provide inexpensive but sharp and rigorous bounds for the error in outputs of interest. Special affine parameter dependence of the differential operator is exploited to develop a two-stage off-line/on-line blackbox computational procedure. In the on-line stage, for every new parameter value, we calculate the output of interest and an associated error bound. The computational complexity of the on-line stage of the procedure scales only with the dimension of the reduced-basis space and the parametric complexity of the partial differential operator; the method is thus ideally suited for the repeated and rapid evaluations required in the context of parameter estimation, design, optimization, and real-time control. The theory and corroborating numerical results are presented for: symmetric coercive problems (e.g. problems in conduction heat transfer), parabolic problems (e.g. unsteady heat transfer), noncoercive problems (e.g. the reduced-wave, or Helmholtz, equation), the Stokes problem (e.g flow of highly viscous fluids), and certain nonlinear equations (e.g. eigenvalue problems)

Murid herpesvirus 4 infection protects mice from the development of an anti-pneumovirus vaccine-induced TH2 immunopathology

Gammaherpesvirus imprintin

One-Point Probability Distribution Functions of Supersonic Turbulent Flows in Self-Gravitating Media

Turbulence is essential for understanding the structure and dynamics of molecular clouds and star-forming regions. There is a need for adequate tools to describe and characterize the properties of turbulent flows. One-point probability distribution functions (pdf's) of dynamical variables have been suggested as appropriate statistical measures and applied to several observed molecular clouds. However, the interpretation of these data requires comparison with numerical simulations. To address this issue, SPH simulations of driven and decaying, supersonic, turbulent flows with and without self-gravity are presented. In addition, random Gaussian velocity fields are analyzed to estimate the influence of variance effects. To characterize the flow properties, the pdf's of the density, of the line-of-sight velocity centroids, and of the line centroid increments are studied. This is supplemented by a discussion of the dispersion and the kurtosis of the increment pdf's, as well as the spatial distribution of velocity increments for small spatial lags. From the comparison between different models of interstellar turbulence, it follows that the inclusion of self-gravity leads to better agreement with the observed pdf's in molecular clouds. The increment pdf's for small spatial lags become exponential for all considered velocities. However, all the processes considered here lead to non-Gaussian signatures, differences are only gradual, and the analyzed pdf's are in addition projection dependent. It appears therefore very difficult to distinguish between different physical processes on the basis of pdf's only, which limits their applicability for adequately characterizing interstellar turbulence.Comment: 38 pages (incl. 17 figures), accepted for publication in ApJ, also available with full resolution figures at http://www.strw.leidenuniv.nl/~klessen/Preprint

Fungal and Bacterial Loads: Noninvasive Inflammatory Bowel Disease Biomarkers for the Clinical Setting

Malaltia inflamatòria intestinal; Càrrega microbiana; PrediccióEnfermedad inflamatoria intestinal; Carga microbiana; PredicciónInflammatory bowel disease; Microbial load; PredictionMicrobiome sequence data have been used to characterize Crohn's disease (CD) and ulcerative colitis (UC). Based on these data, we have previously identified microbiomarkers at the genus level to predict CD and CD relapse. However, microbial load was underexplored as a potential biomarker in inflammatory bowel disease (IBD). Here, we sought to study the use of fungal and bacterial loads as biomarkers to detect both CD and UC and CD and UC relapse. We analyzed the fecal fungal and bacterial loads of 294 stool samples obtained from 206 participants using real-time PCR amplification of the ITS2 region and the 16S rRNA gene, respectively. We combined the microbial data with demographic and standard laboratory data to diagnose ileal or ileocolonic CD and UC and predict disease relapse using the random forest algorithm. Fungal and bacterial loads were significantly different between healthy relatives of IBD patients and nonrelated healthy controls, between CD and UC patients in endoscopic remission, and between UC patients in relapse and non-UC individuals. Microbial load data combined with demographic and standard laboratory data improved the performance of the random forest models by 18%, reaching an average area under the receiver operating characteristic curve (AUC) of 0.842 (95% confidence interval [CI], 0.65 to 0.98), for IBD diagnosis and enhanced CD and UC discrimination and CD and UC relapse prediction. Our findings show that fecal fungal and bacterial loads could provide physicians with a noninvasive tool to discriminate disease subtypes or to predict disease flare in the clinical setting. IMPORTANCE Next-generation sequence data analysis has allowed a better understanding of the pathophysiology of IBD, relating microbiome composition and functions to the disease. Microbiome composition profiling may provide efficient diagnosis and prognosis tools in IBD. However, the bacterial and fungal loads of the fecal microbiota are underexplored as potential biomarkers of IBD. Ulcerative colitis (UC) patients have higher fecal fungal and bacterial loads than patients with ileal or ileocolonic CD. CD patients who relapsed harbor more-unstable fungal and bacterial loads than those of relapsed UC patients. Fecal fungal and bacterial load data improved prediction performance by 18% for IBD diagnosis based solely on clinical data and enhanced CD and UC discrimination and prediction of CD and UC relapse. Combined with existing laboratory biomarkers such as fecal calprotectin and C-reactive protein (CRP), microbial loads may improve the diagnostic accuracy of IBD and of ileal CD and UC disease activity and prediction of UC and ileal CD clinical relapse.This work was funded by Instituto de Salud Carlos III, grant PI17/00614, cofinanced by the European Regional Development Fund (ERDF) and by the PERIS (SLT002/16). F. Casellas has received research funding from AbbVie, Ferring, MSD, Shire, and Zambon and speaker fees from AbbVie, Chiesi, Ferring, Gebro, MSD, Shire, Takeda, and Zambon. S. Vermeire has received grant support from AbbVie, MSD, Pfizer, J&J, and Takeda; received speaker fees from AbbVie, MSD, Takeda, Ferring, Dr. Falk Pharma, Hospira, Pfizer Inc., and Tillots; and served as a consultant for AbbVie, MSD, Takeda, Ferring, Genentech/Roche, Robarts clinical trials, Gilead, Celgene, Prometheus, Avaxia, Prodigest, Shire, Pfizer Inc, Galapagos, Mundipharma, Hospira, Celgene, Second Genome, and Janssen. C. Manichanh has received financial support for research from Danone

Managing cancer patients during the COVID-19 pandemic: an ESMO multidisciplinary expert consensus.

We established an international consortium to review and discuss relevant clinical evidence in order to develop expert consensus statements related to cancer management during the severe acute respiratory syndrome coronavirus 2-related disease (COVID-19) pandemic. The steering committee prepared 10 working packages addressing significant clinical questions from diagnosis to surgery. During a virtual consensus meeting of 62 global experts and one patient advocate, led by the European Society for Medical Oncology, statements were discussed, amended and voted upon. When consensus could not be reached, the panel revised statements until a consensus was reached. Overall, the expert panel agreed on 28 consensus statements that can be used to overcome many of the clinical and technical areas of uncertainty ranging from diagnosis to therapeutic planning and treatment during the COVID-19 pandemic

Recruitment of latent pools of high-avidity CD8+ T cells to the antitumor immune response

A major barrier to successful antitumor vaccination is tolerance of high-avidity T cells specific to tumor antigens. In keeping with this notion, HER-2/neu (neu)-targeted vaccines, which raise strong CD8+ T cell responses to a dominant peptide (RNEU420-429) in WT FVB/N mice and protect them from a neu-expressing tumor challenge, fail to do so in MMTV-neu (neu-N) transgenic mice. However, treatment of neu-N mice with vaccine and cyclophosphamide-containing chemotherapy resulted in tumor protection in a proportion of mice. This effect was specifically abrogated by the transfer of neu-N–derived CD4+CD25+ T cells. RNEU420-429-specific CD8+ T cells were identified only in neu-N mice given vaccine and cyclophosphamide chemotherapy which rejected tumor challenge. Tetramer-binding studies demonstrated that cyclophosphamide pretreatment allowed the activation of high-avidity RNEU420-429-specific CD8+ T cells comparable to those generated from vaccinated FVB/N mice. Cyclophosphamide seemed to inhibit regulatory T (T reg) cells by selectively depleting the cycling population of CD4+CD25+ T cells in neu-N mice. These findings demonstrate that neu-N mice possess latent pools of high-avidity neu-specific CD8+ T cells that can be recruited to produce an effective antitumor response if T reg cells are blocked or removed by using approaches such as administration of cyclophosphamide before vaccination

Intraoperative ketorolac in high-risk breast cancer patients : A prospective, randomized, placebo-controlled clinical trial

Funding: This work is financed by grants received by PF, in the name of his institution: the Anticancer Fund (no grant number) (www.anticancerfund.org); the Belgian Society of Anaesthesia and Resuscitation (no grant number) (www.sarb.be); the Fondation Saint-Luc (no grant number) (www.uclouvain.be); the Commission du Patrimoine of the Université catholique de Louvain, St-Luc Hospital (exceptional grant, no number) (www.uclouvain.be). None of the funders had any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript except the scientific advise of GB, scientific director of the Anticancer Fund.Peer reviewedPublisher PD

Long-term response to second-line afatinib in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): Analysis of the LUX-Head & Neck 1 (LHN1) trial

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A phase 1 study of mTORC1/2 inhibitor BI 860585 as a single agent or with exemestane or paclitaxel in patients with advanced solid tumors

This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5–300 mg/day; Arm A), BI 860585 (40–220 mg/day; Arm B) with 25 mg/day exemestane, and BI 860585 (80–220 mg/day; Arm C) with 60–80 mg/m2 /week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD. Forty-one, 25, and 24 patients were treated (Arms A, B, and C). DLTs were observed in four (rash (n = 2), elevated alanine aminotransferase/aspartate aminotransferase, diarrhea), four (rash (n = 3), stomatitis, and increased gamma-glutamyl transferase), and two (diarrhea, increased blood creatine phosphokinase) patients in cycle 1. The BI 860585 MTD was 220 mg/day (Arm A) and 160 mg/day (Arms B and C). Nine patients achieved an objective response (Arm B: Four partial responses (PRs); Arm C: Four PRs; one complete response). The disease control rate was 20%, 28%, and 58% (Arms A, B, and C). The most frequent treatment-related adverse events (AEs) were hyperglycemia (54%) and diarrhea (39%) (Arm A); diarrhea (40%) and stomatitis (40%) (Arm B); fatigue (58%) and diarrhea (58%) (Arm C). The MTD was determined in all arms. Antitumor activity was observed with BI 860585 monotherapy and in combination with exemestane or paclitaxel