On the decay of turbulence in plane Couette flow

The decay of turbulent and laminar oblique bands in the lower transitional range of plane Couette flow is studied by means of direct numerical simulations of the Navier--Stokes equations. We consider systems that are extended enough for several bands to exist, thanks to mild wall-normal under-resolution considered as a consistent and well-validated modelling strategy. We point out a two-stage process involving the rupture of a band followed by a slow regression of the fragments left. Previous approaches to turbulence decay in wall-bounded flows making use of the chaotic transient paradigm are reinterpreted within a spatiotemporal perspective in terms of large deviations of an underlying stochastic process.Comment: ETC13 Conference Proceedings, 6 pages, 5 figure

Transition from the Couette-Taylor system to the plane Couette system

We discuss the flow between concentric rotating cylinders in the limit of large radii where the system approaches plane Couette flow. We discuss how in this limit the linear instability that leads to the formation of Taylor vortices is lost and how the character of the transition approaches that of planar shear flows. In particular, a parameter regime is identified where fractal distributions of life times and spatiotemporal intermittency occur. Experiments in this regime should allow to study the characteristics of shear flow turbulence in a closed flow geometry.Comment: 5 pages, 5 figure

Management of the axilla in breast cancer:\ua0outcome analysis in a series of ductal versus lobular invasive cancers

Introduction: Axillary lymph node dissection (ALND) has been considered essential for the staging of breast cancer (BC). As the impact of tumor biology on clinical outcomes is recognized, a surgical de-escalation approach is being implemented. We performed a retrospective study focused on surgical management of the axilla in invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). Materials and methods: 1151 newly diagnosed BCs, IDCs (79.6%) or ILCs (20.4%), were selected among patients treated at our Breast Cancer Unit from 2012 to 2018. Tumor characteristics and clinical information were collected and predictors of further metastasis after positive sentinel lymph node biopsy (SLNB) analyzed in relation to disease-free survival (DFS) and overall survival (OS). Results: 27.5% of patients with ILC had 65 3 metastatic lymph nodes at ALND after positive SLNB versus 11.48% of IDCs (p = 0.04). Risk predictors of further metastasis at ALND were the presence of > 2 positive lymph nodes at SLNB (OR = 4.72, 95% CI 1.15\u201319.5 p = 0.03), T3\u2013T4 tumors (OR = 4.93, 95% CI 1.10\u201322.2, p = 0.03) and Non-Luminal BC (OR = 2.74, 95% CI 1.16\u20136.50, p = 0.02). The lobular histotype was not associated with the risk of further metastasis at ALND (OR = 1.62, 95% CI 0.77\u20133.41, p = 0.20). Conclusions: ILC histology is not associated with higher risk of further metastasis at ALND in our analysis. However, surgical management decisions should be taken considering tumor histotype, biology and expected sensitivity to adjuvant therapies

Current Status of Fibroblast Growth Factor Receptor-Targeted Therapies in Breast Cancer

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is an urgent need for better knowledge of the biology leading to the disease, which can lead to the design of increasingly accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. The Fibroblast Growth Factor Receptors/Fibroblast Growth Factors (FGFRs/FGFs) axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of FGFR mutations, which lead to tumor formation and summarizes the state-of-the-art therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC

The melting curve of iron at extreme pressures: implications for planetary cores

Exoplanets with masses similar to that of Earth have recently been discovered in extrasolar systems. A first order question for understanding their dynamics is to know whether they possess Earth like liquid metallic cores. However, the iron melting curve is unknown at conditions corresponding to planets of several times the Earth's mass (over 1500 GPa for planets with 10 times the Earth's mass (ME)). In the density-temperature region of the cores of those super-Earths, we calculate the iron melting curve using first principle molecular dynamics simulations based on density functional theory. By comparing this melting curve with the calculated thermal structure of Super Earths, we show that planets heavier than 2ME, have solid cores, thus precluding the existence of an internal metallic-core driven magnetic field. The iron melting curve obtained in this study exhibits a steeper slope than any calculated planetary adiabatic temperature profile rendering the presence of molten metallic cores less likely as sizes of terrestrial planets increase

Evolution of turbulent spots in a parallel shear flow

The evolution of turbulent spots in a parallel shear flow is studied by means of full three-dimensional numerical simulations. The flow is bounded by free surfaces and driven by a volume force. Three regions in the spanwise spot cross-section can be identified: a turbulent interior, an interface layer with prominent streamwise streaks and vortices and a laminar exterior region with a large scale flow induced by the presence of the spot. The lift-up of streamwise streaks which is caused by non-normal amplification is clearly detected in the region adjacent to the spot interface. The spot can be characterized by an exponentially decaying front that moves with a speed different from that of the cross-stream outflow or the spanwise phase velocity of the streamwise roll pattern. Growth of the spots seems to be intimately connected to the large scale outside flow, for a turbulent ribbon extending across the box in downstream direction does not show the large scale flow and does not grow. Quantitatively, the large scale flow induces a linear instability in the neighborhood of the spot, but the associated front velocity is too small to explain the spot spreading.Comment: 10 pages, 10 Postscript figure

TGS1 mediates 2,2,7-trimethyl guanosine capping of the human telomerase RNA to direct telomerase dependent telomere maintenance

Pathways that direct the selection of the telomerase-dependent or recombination-based, alternative lengthening of telomere (ALT) maintenance pathway in cancer cells are poorly understood. Using human lung cancer cells and tumor organoids we show that formation of the 2,2,7-trimethylguanosine (TMG) cap structure at the human telomerase RNA 5′ end by the Trimethylguanosine Synthase 1 (TGS1) is central for recruiting telomerase to telomeres and engaging Cajal bodies in telomere maintenance. TGS1 depletion or inhibition by the natural nucleoside sinefungin impairs telomerase recruitment to telomeres leading to Exonuclease 1 mediated generation of telomere 3′ end protrusions that engage in RAD51-dependent, homology directed recombination and the activation of key features of the ALT pathway. This indicates a critical role for 2,2,7-TMG capping of the RNA component of human telomerase (hTR) in enforcing telomerase-dependent telomere maintenance to restrict the formation of telomeric substrates conductive to ALT. Our work introduces a targetable pathway of telomere maintenance that holds relevance for telomere-related diseases such as cancer and aging