Some overdetermined problems related to the anisotropic capacity

We characterize the Wulff shape of an anisotropic norm in terms of solutions to overdetermined problems for the Finsler p-capacity of a convex set Omega subset of R-N, with 1 < p < N. In particular we show that if the Finsler p-capacitary potential u associated to 0 has two homothetic level sets then 0 is Wulff shape. Moreover, we show that the concavity exponent of u is q = -(p - 1)/(N - p) if and only if Omega is Wulff shape

Upper bounds for the eigenvalues of Hessian equations

We prove some upper bounds for the Dirichlet eigenvalues of a class of fully nonlinear elliptic equations, namely the Hessian equationsComment: 15 pages, 1 figur

Imaging biomarkers of adiposity and sarcopenia as potential predictors for overall survival among patients with endometrial cancer treated with bevacizumab

Objective:To examine associations of body mass index (BMI), subcutaneous fat area (SFA) and density (SFD), visceral fat area (VFA) and density (VFD) and total psoas area (TPA) to outcomes among patients receiving chemotherapy with or without bevacizumab for advanced or recurrent endometrial cancer (EC). Methods:This was a multi-institutional, retrospective study of patients with EC treated with and without bevacizumab as part of front-line, platinum based chemotherapy. Demographics and clinical characteristics were collected. SFA, VFA, SFD, VFD, and TPA were determined from pre-treatment CT scans using a deep learning algorithm. Data was compared with overall survival (OS) and progression free survival (PFS). Results:Seventy-eight patients were analyzed. The majority were Caucasian (87.2%) with a mean BMI of 34.7 kg/m2. PFS and OS did not differ between patients with BMI, SFA, VFA, SFD, VFD, or TPA ≥ the 50th percentile compared to <50th percentile (p = 0.91, 0.45, 0.71, 0.74, 0.60, and 0.74 respectively) and (p = 0.99, 0.59, 0.14, 0.77, and 0.85 respectively). When adjusting for prognostic factors, elevated VFA trended towards shorter OS (25.1 vs 59.5 months, HR = 1.68 [0.92-3.05]).Patients receiving bevacizumab had similar OS compared to those who did not (37.6 vs 44.5 months, p = 0.409). When stratified by adiposity markers, no subset demonstrated benefit from bevacizumab. Conclusion:Obesity has been associated with increased levels of vascular endothelial growth factor (VEGF), the main target for bevacizumab therapy. Imaging measurements of VFA may provide prognostic information for patients with EC but no adiposity marker was predictive of improved response to bevacizumab

p 159analysis of early tumor shrinkage and depth of response in metastatic pancreatic cancer patients treated with first line modified folfirinox or gemcitabine nab paclitaxel

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Dystonia-ataxia syndrome with permanent torsional nystagmus caused by ECHS1 deficiency

Biallelic mutations in ECHS1, encoding the mitochondrial enoyl-CoA hydratase, have been associated with mitochondrial encephalopathies with basal ganglia involvement. Here, we describe a novel clinical presentation consisting of dystonia-ataxia syndrome with hearing loss and a peculiar torsional nystagmus observed in two adult siblings. The presence of a 0.9-ppm peak at MR spectroscopy analysis suggested the accumulation of branched-chain amino acids. Exome sequencing in index probands identified two ECHS1 mutations, one of which was novel (p.V82L). ECHS1 protein levels and residual activities were reduced in patients' fibroblasts. This paper expands the phenotypic spectrum observed in patients with impaired valine catabolism

In vitro and in vivo tetracycline-controlled myogenic conversion of NIH-3T3 cells: evidence of programmed cell death after muscle cell transplantation.

Ex vivo gene therapy of Duchenne muscular dystrophy based on autologous transplantation of genetically modified myoblasts is limited by their premature senescence. MyoD-converted fibroblasts represent an alternative source of myogenic cells. In this study the forced MyoD-dependent conversion of murine NIH-3T3 fibroblasts into myoblasts under the control of an inducible promoter silent in the presence of tetracycline was evaluated. After tetracycline withdrawal this promoter drives the transcription of MyoD in the engineered fibroblasts, inducing their myogenesis and giving rise to β-galactosidase-positive cells. MyoD-expressing fibroblasts withdrew from the cell cycle, but were unable to fuse in vitro into multinucleated myotubes. Five days following implantation of engineered fibroblasts in muscles of C57BL/10J mice we observed a sevenfold increase of β-galactosidase-positive regenerating myofibers in animals not treated with antibiotic compared with treated animals. After 1 week the number of positive fibers decreased and several apoptotic myonuclei were detected. Three weeks following implantation of MyoD-converted fibroblasts in recipient mice, no positive "blue" fiber was observed. Our results suggest that transactivation by tetracycline of MyoD may drive an in vivo myogenic conversion of NIH-3T3 fibroblasts and that, in this experimental setting, apoptosis plays a relevant role in limiting the efficacy of engineered fibroblast transplantation. This work opens the question whether apoptotic phenomena also play a general role as limiting factors of cellmediated gene therapy of inherited muscle disorders

Endothelin receptor B antagonists decrease glioma cell viability independently of their cognate receptor

Background: Endothelin receptor antagonists inhibit the progression of many cancers, but research into their influence on glioma has been limited. Methods: We treated glioma cell lines, LN-229 and SW1088, and melanoma cell lines, A375 and WM35, with two endothelin receptor type B (ETRB)-specific antagonists, A-192621 and BQ788, and quantified viable cells by the capacity of their intracellular esterases to convert non-fluorescent calcein AM into green-fluorescent calcein. We assessed cell proliferation by labeling cells with carboxyfluorescein diacetate succinimidyl ester and quantifying the fluorescence by FACS analysis. We also examined the cell cycle status using BrdU/propidium iodide double staining and FACS analysis. We evaluated changes in gene expression by microarray analysis following treatment with A-192621 in glioma cells. We examined the role of ETRB by reducing its expression level using small interfering RNA (siRNA). Results: We report that two ETRB-specific antagonists, A-192621 and BQ788, reduce the number of viable cells in two glioma cell lines in a dose- and time-dependent manner. We describe similar results for two melanoma cell lines. The more potent of the two antagonists, A-192621, decreases the mean number of cell divisions at least in part by inducing a G2/M arrest and apoptosis. Microarray analysis of the effects of A-192621 treatment reveals up-regulation of several DNA damage-inducible genes. These results were confirmed by real-time RT-PCR. Importantly, reducing expression of ETRB with siRNAs does not abrogate the effects of either A-192621 or BQ788 in glioma or melanoma cells. Furthermore, BQ123, an endothelin receptor type A (ETRA)-specific antagonist, has no effect on cell viability in any of these cell lines, indicating that the ETRB-independent effects on cell viability exhibited by A-192621 and BQ788 are not a result of ETRA inhibition. Conclusion: While ETRB antagonists reduce the viability of glioma cells in vitro, it appears unlikely that this effect is mediated by ETRB inhibition or cross-reaction with ETRA. Instead, we present evidence that A-192621 affects glioma and melanoma viability by activating stress/DNA damage response pathways, which leads to cell cycle arrest and apoptosis. This is the first evidence linking ETRB antagonist treatment to enhanced expression of DNA damage-inducible genes