Stability of compressible boundary layers in presence of smooth roughness and wall temperature effects

In natural laminar flow design, aircraft manufacturers aim to delay the laminar-to-turbulent transition by modifying the geometric features of the aircraft to stabilize the boundary layer. Yet, the transitional process is highly sensitive to surface imperfections; the presence of grooves, rivets or dimples, for instance, greatly affects the transitional properties of the flow and need to be considered for accurate predictive modelling. To this end, the nonlinear parabolized stability equations (NPSE) have shown promising predictive capabilities over a wide range of operating conditions. The NPSE are less dependent on experimental data, which is a step towards a generalizable transition model. Here, we first present a novel NPSE-based numerical framework, developed in-house but made open-source, to investigate transition in compressible flows. The code can handle complex geometries and only requires the coordinates of the wall to generate an orthonormal computational grid. The mesh spacing is refined based on the curvature of the wall. The model is formulated in dimensionless variables, and the disturbances are discretized using a finite-bandwidth approach. Written in Python and leveraging well-established libraries, the framework includes a laminar flow solver using the same numerical formulation as the modal stability solver to remain consistent. The code is validated against published cases and large-scale Direct Numerical Simulations (DNS). It can serve as the basis for the future development of modal stability-based problems in aerospace engineering, geophysical, and multiphase flows. The computational framework is used in combination with large-scale DNS to study the effect of smooth two-dimensional surface roughness on the stability characteristics of a canonical boundary layer flow under transonic conditions (M=0.714). In particular, the influence of two-dimensional smooth roughness on the stability of 2D Tollmien-Schlichting (T-S) waves is investigated with a particular emphasis on frequency content generation. The DNS reveals a stronger destabilizing effect of the disturbance higher frequencies for the case featuring the highest roughness amplitude. This causes a rapid growth of secondary instabilities which skips the standard T-S mechanism and give rise to a cyclical transitional pattern in which both late K-type structures and premature bypass transition are observable. The modal stability analysis also shows that, in the presence of two-dimensional smooth roughness, the mode experiencing the highest linear growth is three-dimensional. Finally, the coupling effect between roughness and wall temperature inhomogeneities is investigated at transonic condition using the nonlinear parabolized stability equations (NPSE). To this end, the effect of localized heating and cooling strips on the stability of a flat plate boundary layer with zero pressure gradient at M=0.714 is first investigated and confirms the stabilizing (destabilizing) effect of cooling (heating) strips. Then, the coupling effect between the wall roughness and heating strips is addressed by superimposing the effect of a smooth roughness patch, consisting of five sinusoidal, two-dimensional humps, to the numerical setup. The NPSE study reveals a catalytic coupling effect between the temperature strips and roughness. In other words, compared with the flat plate case, the stability of the flow is decreased in the presence of heating strips and roughness, and, inversely, increased in the presence of cooling strips and roughness

Vérification et validation d'une loi de paroi consistante du modèle de turbulence K-w SST

RÉSUMÉ Le modèle de turbulence k − ω SST est très répandu dans les codes de CFD modernes, car il offre de bonnes performances pour une vaste gamme de problèmes. Il fait notamment bonne figure dans les zones de fort gradient de pression adverse. La force de ce modèle réside dans sa capacité à exploiter les avantages des deux modèles de turbulence les plus populaires, le k −E et le k − ω. Le premier pour ses bonnes performances dans les zones d’écoulement libre, et le second pour sa pertinence dans les zones cisaillées, plus particulièrement dans les couches limites. Par ailleurs, le modèle k − ω SST est intégrable jusqu’à la paroi et donc compatible avec les modèles bas-Reynolds et l’approche des lois de paroi consistantes. Les lois de paroi consistantes présentent l’avantage, par rapport aux lois de paroi standard, d’être entièrement consistantes avec le modèle de turbulence avec lequel elles sont utilisées. En effet, dans l’ap- proche consistante des lois de paroi, les variables adimensionnelles de vitesse, température et de turbulence sont interpolées dans des tables spécifiques à chaque modèle de turbulence. Ces dernières sont produites à partir de la résolution des équations RANS 1D dans la couche limite. On s’assure ainsi d’imposer des conditions limites cohérentes en faisant un minimum d’hypothèse sur l’écoulement. Ce mémoire présente une formulation tout couplée pour le modèle de turbulence k − ω SST. Nous y proposons entre autres une démarche générale pour le développement et l’implémentation de lois de paroi consistantes et consistantes. Nous explorons au passage les principales étapes de l’implémentation d’un modèle de turbulence dans un code de CFD par éléments finis. En ce sens, nous dérivons la forme faible au sens de Galerkin ainsi que la forme stabilisée (Stabilized Upwind et Stabilized Upwind Petrov Galerkin) des équations aux dérivées partielles du modèle de turbulence k − ω SST. Nous traitons également du couplage des équations et des principaux algorithmes de résolution. Nous abordons ensuite le traitement des conditions limites en zone proche paroi et leur impact sur l’ordre de convergence de la méthode de Newton. Nous proposons également une stratégie d’adaptation selon les fonctions de pondération du modèle de turbulence k − ω SST. Enfin, nous abordons l’aspect vérification à l’aide de la technique des solutions manufacturées et finirons par faire la validation du modèle à l’aide de cas tests typiques en modélisation RANS.----------ABSTRACT The turbulence k − ω SST model is very common in modern CFD codes because of its good performance over a wide range of industrial problems. Particularly in areas of strong adverse pressure gradient. The strength of the model lies in its ability to take advantage of two of the most popular turbulence models, the k−E and the k−ω. The former for its good performance in free shear flows, and the second for its relevance in wall bounded flows, more specifically in boundary layers. Moreover, the k − ω SST model is valid in the whole boundary layer and is, therefore, compatible with low-Reynolds models and therefore the consistent wall law approach. The consistent wall function has the advantage, compared to the standard wall laws, to be entirely consistent with the turbulence model for which it has been derived. In the consistent wall law approach, the non-dimensional variables of speed, temperature and turbulence are interpolated from a model specific table unique to each turbulence model. Those tables are produced from the numerical resolution of the one-dimensional RANS equa- tions for turbulent Couette flow. In this way, we ensure the imposition of coherent boundary conditions for all variables up to the wall. In this master’s thesis, we present a fully coupled formulation of the k − ω SST turbulence model. We propose among others a general approach for the development and the implementation of consistent wall functions. We explore the main steps of the implementation of a turbulence model in a finite elements based CFD code. In this manner, we derive the weak form, in the sense of Galerkin, as well as its stabilized weak form of the k −ω SST equations. We also discuss the coupling of the equations and their main algorithms of resolution. We then discuss the treatment of boundary conditions in the near-wall region and their impact on the convergence of the Newton’s method. We also propose a mesh adaptation strategy according to the blending function of the k − ω SST model. Finally, we investigate the verification aspect using the technique of manufactured solutions and will validate the model using typical test cases in RANS modeling

Shell-model calculations and realistic effective interactions

A review is presented of the development and current status of nuclear shell-model calculations in which the two-body effective interaction is derived from the free nucleon-nucleon potential. The significant progress made in this field within the last decade is emphasized, in particular as regards the so-called V-low-k approach to the renormalization of the bare nucleon-nucleon interaction. In the last part of the review we first give a survey of realistic shell-model calculations from early to present days. Then, we report recent results for neutron-rich nuclei near doubly magic 132Sn and for the whole even-mass N=82 isotonic chain. These illustrate how shell-model effective interactions derived from modern nucleon-nucleon potentials are able to provide an accurate description of nuclear structure properties.Comment: 71 pages, to be published in Progress in Particle and Nuclear Physic

Discordance between testosterone measurement methods in castrated prostate cancer patients

Failure to suppress testosterone below 0.7 nM in castrated prostate cancer patients is associated with poor clinical outcomes. Testosterone levels in castrated patients are therefore routinely measured. Although mass spectrometry is the gold standard used to measure testosterone, most hospitals use an immunoassay method. In this study, we sought to evaluate the accuracy of an immunoassay method to measure castrate testosterone levels, with mass spectrometry as the reference standard. We retrospectively evaluated a cohort of 435 serum samples retrieved from castrated prostate cancer patients from April to September 2017. No follow-up of clinical outcomes was performed. Serum testosterone levels were measured in the same sample using liquid chromatography coupled with tandem mass spectrometry and electrochemiluminescent immunoassay methods. The mean testosterone levels were significantly higher with immunoassay than with mass spectrometry (0.672 ± 0.359 vs 0.461 ± 0.541 nM; P 0.7 nM was significantly higher with immunoassay (22.1%) than with mass spectrometry (13.1%; P 0.7 nM by immunoassay can result in an inaccurately identified castration status. Suboptimal testosterone levels in castrated patients should be confirmed by either mass spectrometry or an immunoassay method validated at low testosterone levels and interpreted with caution before any changes are made to treatment management

Technical Aspects of Flow Cytometry-based Measurable Residual Disease Quantification in Acute Myeloid Leukemia: Experience of the European LeukemiaNet MRD Working Party

Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll. The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories. The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment and are a next step toward further harmonization

Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly

The genetic causes of malformations of cortical development (MCD) remain largely unknown. Here we report the discovery of multiple pathogenic missense mutations in TUBG1, DYNC1H1 and KIF2A, as well as a single germline mosaic mutation in KIF5C, in subjects with MCD. We found a frequent recurrence of mutations in DYNC1H1, implying that this gene is a major locus for unexplained MCD. We further show that the mutations in KIF5C, KIF2A and DYNC1H1 affect ATP hydrolysis, productive protein folding and microtubule binding, respectively. In addition, we show that suppression of mouse Tubg1 expression in vivo interferes with proper neuronal migration, whereas expression of altered gamma-tubulin proteins in Saccharomyces cerevisiae disrupts normal microtubule behavior. Our data reinforce the importance of centrosomal and microtubule-related proteins in cortical development and strongly suggest that microtubule-dependent mitotic and postmitotic processes are major contributors to the pathogenesis of MCD

Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly.

International audienceThe genetic causes of malformations of cortical development (MCD) remain largely unknown. Here we report the discovery of multiple pathogenic missense mutations in TUBG1, DYNC1H1 and KIF2A, as well as a single germline mosaic mutation in KIF5C, in subjects with MCD. We found a frequent recurrence of mutations in DYNC1H1, implying that this gene is a major locus for unexplained MCD. We further show that the mutations in KIF5C, KIF2A and DYNC1H1 affect ATP hydrolysis, productive protein folding and microtubule binding, respectively. In addition, we show that suppression of mouse Tubg1 expression in vivo interferes with proper neuronal migration, whereas expression of altered γ-tubulin proteins in Saccharomyces cerevisiae disrupts normal microtubule behavior. Our data reinforce the importance of centrosomal and microtubule-related proteins in cortical development and strongly suggest that microtubule-dependent mitotic and postmitotic processes are major contributors to the pathogenesis of MCD

Eight previously unidentified mutations found in the OA1 ocular albinism gene

BACKGROUND: Ocular albinism type 1 (OA1) is an X-linked ocular disorder characterized by a severe reduction in visual acuity, nystagmus, hypopigmentation of the retinal pigmented epithelium, foveal hypoplasia, macromelanosomes in pigmented skin and eye cells, and misrouting of the optical tracts. This disease is primarily caused by mutations in the OA1 gene. METHODS: The ophthalmologic phenotype of the patients and their family members was characterized. We screened for mutations in the OA1 gene by direct sequencing of the nine PCR-amplified exons, and for genomic deletions by PCR-amplification of large DNA fragments. RESULTS: We sequenced the nine exons of the OA1 gene in 72 individuals and found ten different mutations in seven unrelated families and three sporadic cases. The ten mutations include an amino acid substitution and a premature stop codon previously reported by our team, and eight previously unidentified mutations: three amino acid substitutions, a duplication, a deletion, an insertion and two splice-site mutations. The use of a novel Taq polymerase enabled us to amplify large genomic fragments covering the OA1 gene. and to detect very likely six distinct large deletions. Furthermore, we were able to confirm that there was no deletion in twenty one patients where no mutation had been found. CONCLUSION: The identified mutations affect highly conserved amino acids, cause frameshifts or alternative splicing, thus affecting folding of the OA1 G protein coupled receptor, interactions of OA1 with its G protein and/or binding with its ligand

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN