Towards Constraining Parity-Violations in Gravity with Satellite Gradiometry

Parity violation in gravity, if existed, could have important implications, and it is meaningful to search and test the possible observational effects. Chern-Simons modified gravity serves as a natural model for gravitational parity-violations. Especially, considering extensions to Einstein-Hilbert action up to second order curvature terms, it is known that theories of gravitational parity-violation will reduce to the dynamical Chern-Simons gravity. In this letter, we outline the theoretical principles of testing the dynamical Chern-Simons gravity with orbiting gravity gradiometers, which could be naturally incorporated into future satellite gravity missions. The secular gravity gradient signals, due to the Mashhoon-Theiss (anomaly) effect, in dynamical Chern-Simons gravity are worked out, which can improve the constraint of the corresponding Chern-Simons length scale $\xi^{\frac{1}{4}}_{cs}$ obtained from such measurement scheme. For orbiting superconducting gradiometers or gradiometers with optical readout, a bound $\xi^{\frac{1}{4}}_{cs}\leq 10^6 \ km$ (or even better) could in principle be obtained, which will be at least 2 orders of magnitude stronger than the current one based on the observations from the GP-B mission and the LAGEOS I, II satellites.Comment: 15 pages, 6 figures. arXiv admin note: text overlap with arXiv:1606.0818

Multiple normalized solutions for quasi-linear Schr\"odinger equations

In this paper we prove the existence of two solutions having a prescribed $L^2$-norm for a quasi-linear Schr\"odinger equation. One of these solutions is a mountain pass solution relative to a constraint and the other one a minimum either local or global. To overcome the lack of differentiability of the associated functional, we rely on a perturbation method developed in [27]

Characterization of novel epigenetic targets in ovarian cancer

Le cancer épithélial de l’ovaire (CEO) représente 4% de tous les cancers chez la femme et est la première cause de décès parmi les tumeurs gynécologiques. Dans la plupart part des cas le CEO est diagnostiqué dans les stades avancés de la maladie. Le traitement repose sur la chirurgie cytoréductive suivie de la chimiothérapie combinant les dérivés de platine et de taxanes avec un taux de réponse de plus de 80%, cependant, la plupart part des patientes font une récidive par l’émergence de la résistance. Les bases moléculaires du déclenchement et de la progression du cancer de l’ovaire sont encore mal connues empêchant ainsi le développement de nouvelles approches thérapeutiques et de diagnostique. Au cours d’un cancer, l’hyperméthylation des ilots CpG de certains promoteurs géniques conduit souvent à l’inactivation des gènes suppresseurs de tumeur. L’hypométhylation des ilots CpG de certains promoteurs est également impliquée dans la réactivation des proto-oncogènes et des gènes pro-métastatiques. Cependant l’hypométhlation de l’ADN dans le cancer de l’ovaire est très peu étudiée. En utilisant la méthode d’immunoprécipitation de l'ADN méthylée combinée à une analyse sur puce (MeDIP-chip), nous avons trouvé que l’hyperméthylation de l'ADN se produit dans les stades précoces du cancer ovarien, tandis que les stades avancés de la maladie sont liés à l’hypométhylation de l’ADN des oncogènes impliqués dans la progression de la tumeur, l’invasion/métastase et probablement dans la chimiorésistance. Cette approche épigénomique a conduit à l’identification de nouveaux oncogènes hypométhylés dans le CEO. Dans cette étude, RUNX2 est identifié comme un gène hypométhylé dans les cellules post-chimiothérapeutiques et GALNT3 et BCAT1 sont parmi les gènes hypométhylés identifiés particulièrement dans le CEO de type séreux. L’analyse fonctionnelle de ces trois gènes montre qu’ils sont associés à la prolifération (y compris le contrôle du cycle cellulaire pour GALNT3 et BCAT1), de la migration et de l'invasion cellulaire dans le CEO séreux, suggérant qu’ils ont un fort potentiel oncogène dans la progression de la tumeur et pourraient être des nouvelles cibles thérapeutiques au niveau du CEO.Epithelial ovarian cancer (EOC) accounts for 4% of all cancers in women and is the leading cause of death from gynecologic malignancies. Most of EOC cases are diagnosed at advanced stage, which is associated with poor outcome. Despite the good initial response to chemotherapy, recurrence occurs in the majority of patients, resulting in chemotherapy resistance leading to a fatal disease. The molecular basis of EOC initiation and progression is still poorly understood, thus hindering the development of new diagnostic and therapeutic strategies for more effective EOC treatment. In cancer, the hypermethylation of gene promoter CpG islands leads to inactivation of tumor suppressor genes, and CpG islands hypomethylation is associated with proto-oncogenes and pro-metastasis genes. Similar to all malignancies, aberrant DNA methylation occurs in EOC. However, DNA hypomethylation in ovarian cancer is very briefly studied. Using methylated DNA immunoprecipitation (MeDIP) coupled to CpG island tiling arrays, we found that DNA hypermethylation occurred in less invasive/early stages of ovarian tumorigenesis, while advanced disease was associated with DNA hypomethylation of a number of oncogenes, implicated in cancer progression, invasion/metastasis and probably chemoresistance. This epigenomic approach has led to the identification of a number of novel oncogenes hypomethylated in EOC. In this thesis study, RUNX2 gene was identified as hypomethyleted gene in post-chemotherapy primary cells cultures and GALNT3 gene and BCAT1 gene were among the genes identified to be notably hypomethylated in serous EOC tumors. Subsequent functional analyses of these three genes demonstrated that they were associated with EOC cell proliferation (including cell cycle control for GALNT3 and BCAT1), migration and invasion, suggesting that they have strong oncogenic potential in serous EOC progression and that they might be novel EOC therapeutic targets

Molecular Mechanisms of TRAF6 Ubiquitination and Activation

The Tumor Necrosis Factor (TNF) Receptor Associated Factor 6 (TRAF6) is an intracellular signal transducers, being responsible for mediating many of the activation events initiated by TNF receptor (TNFR) and Toll-like/Interleukin-1 and 18 receptor (TIR) families, in which TRAF6 plays central roles in numerous biological processes including innate and adaptive immunity, osteoclastogenesis and bone development, CD40 signaling, neuronal cell development, and cancer cell progression. Acting as an E3 ubiquitin ligase, TRAF6 catalyzes lysine 63 linked poly-ubiquitination of itself and many other signal transducers upon association with upstream effectors possessing a short TRAF Interaction Motif (TIM) peptide sequence in the NF-KappaB signal transduction pathway. Ectopic over-expression of TRAF6 acts as a dominant-positive. However, the mechanism of TRAF6 activation by upstream activators or over-expression is unclear. This motivated our enthusiasm to study the role played by ubiquitination for TRAF6 in NF-KappaB signaling. We now demonstrate that two critical regions of TRAF6, the MATH domain required for TIM activator binding and the RING-Zinc region for downstream signaling, mutually interact and render the molecule structurally closed and inactive. Our results implicate that auto-ubiquitination disrupts such interaction, thus providing a means of sustaining the open conformation necessary for downstream signaling. However, excessive ubiquitination induced by TRAF6 over-expression results in formation of large cytoplasmic sequestosomes and its inactivation. Furthermore, the inferred cis nature of TRAF auto-ubiquitination is now demonstrated to act in trans and is regulated via its RING-Zinc and coiled-coil domains. We also demonstrate that both the RING-Zinc region and MATH domain of TRAF6 can be targeted for ubiquitination, but trans-ubiquitination of TRAF6 muteins is incapable of activating the NF-KappaB pathway, suggesting that ubiquitination, alone, is insufficient for activity