Flow coherent structures and frequency signature: Application of the dynamic modes decomposition to open cavity flow

International audienceThe dynamic dimension of an impinging flow may be significantly reduced by its boundary conditions and self-sustained oscillations they induce. The spectral signature is associated with remarkable spatial coherent structures. Dynamic modes decomposition (DMD) makes it possible to directly extract the dynamical properties of a non-linearly saturated flow. We apply DMD to highlight the spectral contribution of the longitudinal and transverse structures of an experimental open-cavity flow

Tumor-homing cytotoxic human induced neural stem cells for cancer therapy

Engineered neural stem cells (NSCs) are a promising approach to treating glioblastoma (GBM). The ideal NSC drug carrier for clinical use should be easily isolated and autologous to avoid immune rejection. We transdifferentiated (TD) human fibroblasts into tumor-homing early-stage induced NSCs (h-iNSCTE), engineered them to express optical reporters and different therapeutic gene products, and assessed the tumor-homing migration and therapeutic efficacy of cytotoxic h-iNSCTE in patient-derived GBM models of surgical and nonsurgical disease. Molecular and functional analysis revealed that our single-factor SOX2 TD strategy converted human skin fibroblasts into h-iNSCTE that were nestin+ and expressed pathways associated with tumor-homing migration in 4 days. Time-lapse motion analysis showed that h-iNSCTE rapidly migrated to human GBM cells and penetrated human GBM spheroids, a process inhibited by blockade of CXCR4. Serial imaging showed that h-iNSCTE delivery of the proapoptotic agent tumor necrosis factor-A-related apoptosis-inducing ligand (TRAIL) reduced the size of solid human GBM xenografts 250-fold in 3 weeks and prolonged median survival from 22 to 49 days. Additionally, h-iNSCTE thymidine kinase/ganciclovir enzyme/prodrug therapy (h-iNSCTE-TK) reduced the size of patient-derived GBM xenografts 20-fold and extended survival from 32 to 62 days. Mimicking clinical NSC therapy, h-iNSCTE-TK therapy delivered into the postoperative surgical resection cavity delayed the regrowth of residual GBMs threefold and prolonged survival from 46 to 60 days. These results suggest that TD of human skin into h-iNSCTE is a platform for creating tumor-homing cytotoxic cell therapies for cancer, where the potential to avoid carrier rejection could maximize treatment durability in human trials

Ginzburg-Landau Expansion in Non-Fermi Liquid Superconductors: Effect of the Mass Renormalization Factor

We reconsider the Ginzburg-Landau expansion for the case of a non-Fermi liquid superconductor. We obtain analytical results for the Ginzburg-Landau functional in the critical region around the superconducting phase transition, T <= T_c, in two special limits of the model, i.e., the spin-charge separation case and the anomalous Fermi liquid case. For both cases, in the presence of a mass renormalization factor, we derived the form and the specific dependence of the coherence length, penetration depth, specific heat jump at the critical point, and the magnetic upper critical field. For both limits the obtained results reduce to the usual BCS results for a two dimensional s-wave superconductor. We compare our results with recent and relevant theoretical work. The results for a d--wave symmetry order parameter do not change qualitatively the results presented in this paper. Only numerical factors appear additionally in our expressions.Comment: accepted for publication in Physical Review

Chemotherapy-induced CDA expression renders resistant non-small cell lung cancer cells sensitive to 5'-deoxy-5-fluorocytidine (5'-DFCR).

Pemetrexed (MTA) plus cisplatin combination therapy is considered the standard of care for patients with advanced non-small-cell lung cancer (NSCLC). However, in advanced NSCLC, the 5-year survival rate is below 10%, mainly due to resistance to therapy. We have previously shown that the fraction of mesenchymal-like, chemotherapy-resistant paraclone cells increased after MTA and cisplatin combination therapy in the NSCLC cell line A549. Cytidine deaminase (CDA) and thymidine phosphorylase (TYMP) are key enzymes of the pyrimidine salvage pathway. 5'-deoxy-5-fluorocytidine (5'-DFCR) is a cytidine analogue (metabolite of capecitabine), which is converted by CDA and subsequently by TYMP into 5-fluorouracil, a chemotherapeutic agent frequently used to treat solid tumors. The aim of this study was to identify and exploit chemotherapy-induced metabolic adaptations to target resistant cancer cells. Cell viability and colony formation assays were used to quantify the efficacy of MTA and cisplatin treatment in combination with schedule-dependent addition of 5'-DFCR on growth and survival of A549 paraclone cells and NSCLC cell lines. CDA and TYMP protein expression were monitored by Western blot. Finally, flow cytometry was used to analyze the EMT phenotype, DNA damage response activation and cell cycle distribution over time after treatment. CDA expression was measured by immunohistochemistry in tumor tissues of patients before and after neoadjuvant chemotherapy. We performed a small-scale screen of mitochondrial metabolism inhibitors, which revealed that 5'-DFCR selectively targets chemotherapy-resistant A549 paraclone cells characterized by high CDA and TYMP expression. In the cell line A549, CDA and TYMP expression was further increased by chemotherapy in a time-dependent manner, which was also observed in the KRAS-addicted NSCLC cell lines H358 and H411. The addition of 5'-DFCR on the second day after MTA and cisplatin combination therapy was the most efficient treatment to eradicate chemotherapy-resistant NSCLC cells. Moreover, recovery from treatment-induced DNA damage was delayed and accompanied by senescence induction and acquisition of a hybrid-EMT phenotype. In a subset of patient tumors, CDA expression was also increased after treatment with neoadjuvant chemotherapy. Chemotherapy increases CDA and TYMP expression thereby rendering resistant lung cancer cells susceptible to subsequent 5'-DFCR treatment

MEK1 drives oncogenic signaling and interacts with PARP1 for genomic and metabolic homeostasis in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a lethal malignancy etiologically caused by asbestos exposure, for which there are few effective treatment options. Although asbestos carcinogenesis is associated with reactive oxygen species (ROS), the bona fide oncogenic signaling pathways that regulate ROS homeostasis and bypass ROS-evoked apoptosis in MPM are poorly understood. In this study, we demonstrate that the mitogen-activated protein kinase (MAPK) pathway RAS-RAF-MEK-ERK is hyperactive and a molecular driver of MPM, independent of histological subtypes and genetic heterogeneity. Suppression of MAPK signaling by clinically approved MEK inhibitors (MEKi) elicits PARP1 to protect MPM cells from the cytotoxic effects of MAPK pathway blockage. Mechanistically, MEKi induces impairment of homologous recombination (HR) repair proficiency and mitochondrial metabolic activity, which is counterbalanced by pleiotropic PARP1. Consequently, the combination of MEK with PARP inhibitors enhances apoptotic cell death in vitro and in vivo that occurs through coordinated upregulation of cytotoxic ROS in MPM cells, suggesting a mechanism-based, readily translatable strategy to treat this daunting disease. Collectively, our studies uncover a previously unrecognized scenario that hyperactivation of the MAPK pathway is an essential feature of MPM and provide unprecedented evidence that MAPK signaling cooperates with PARP1 to homeostatically maintain ROS levels and escape ROS-mediated apoptosis

Primordial nucleosynthesis with a varying fine structure constant: An improved estimate

We compute primordial light-element abundances for cases with fine structure constant alpha different from the present value, including many sources of alpha dependence neglected in previous calculations. Specifically, we consider contributions arising from Coulomb barrier penetration, photon coupling to nuclear currents, and the electromagnetic components of nuclear masses. We find the primordial abundances to depend more weakly on alpha than previously estimated, by up to a factor of 2 in the case of ^7Li. We discuss the constraints on variations in alpha from the individual abundance measurements and the uncertainties affecting these constraints. While the present best measurements of primordial D/H, ^4He/H, and ^7Li/H may be reconciled pairwise by adjusting alpha and the universal baryon density, no value of alpha allows all three to be accommodated simultaneously without consideration of systematic error. The combination of measured abundances with observations of acoustic peaks in the cosmic microwave background favors no change in alpha within the uncertainties.Comment: Phys. Rev. D accepted version; minor changes in response to refere

Quantum Dot in the Kondo Regime coupled to p-wave superconductors

This paper studies the physics of junctions containing superconducting $(S)$ and normal $(N)$ leads weakly coupled to an Anderson impurity in the Kondo regime $(K)$. Special attention is devoted to the case where one of the leads is a $p-wave$ superconductor where mid-gap surface states play an important role in the tunneling processes and help the formation of Kondo resonance. The novel physics in these systems beyond that encountered in quantum dots coupled only to to normal leads is that electron transport at finite bias $eV$ in $SKN$ and $SKS$ junctions is governed by Andreev reflections. These enable the occurrence of dissipative current even when the bias $eV$ is smaller than the superconducting gap $\Delta$. Using the slave boson mean field approximation the current, shot-noise power and Fano factor are calculated as functions of the applied bias voltage in the sub-gap region $eV < \Delta$ and found to be strongly dependent on the ratio $t_K$ between the Kondo temperature $T_{K}$ and the superconducting gap $\Delta$. In particular, for large values of $t_K$ the attenuation of current due to the existence of the superconducting gap is compensated by the Kondo effect. This scenario is manifested also in the behavior of the Josephson current as function of temperature.Comment: 7 pages, 5 .eps figure

Biodiversity increases the resistance of ecosystem productivity to climate extremes

It remains unclear whether biodiversity buffers ecosystems against climate extremes, which are becoming increasingly frequent worldwide1. Early results suggested that the ecosystem productivity of diverse grassland plant communities was more resistant, changing less during drought, and more resilient, recovering more quickly after drought, than that of depauperate communities2. However, subsequent experimental tests produced mixed results3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13. Here we use data from 46 experiments that manipulated grassland plant diversity to test whether biodiversity provides resistance during and resilience after climate events. We show that biodiversity increased ecosystem resistance for a broad range of climate events, including wet or dry, moderate or extreme, and brief or prolonged events. Across all studies and climate events, the productivity of low-diversity communities with one or two species changed by approximately 50% during climate events, whereas that of high-diversity communities with 16–32 species was more resistant, changing by only approximately 25%. By a year after each climate event, ecosystem productivity had often fully recovered, or overshot, normal levels of productivity in both high- and low-diversity communities, leading to no detectable dependence of ecosystem resilience on biodiversity. Our results suggest that biodiversity mainly stabilizes ecosystem productivity, and productivity-dependent ecosystem services, by increasing resistance to climate events. Anthropogenic environmental changes that drive biodiversity loss thus seem likely to decrease ecosystem stability14, and restoration of biodiversity to increase it, mainly by changing the resistance of ecosystem productivity to climate events

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters