The proteosome inhibitor MG132 attenuates Retinoic Acid Receptor trans-activation and enhances trans-repression of Nuclear Factor κB. Potential relevance to chemo-preventive interventions with retinoids

BACKGROUND: Nuclear factor kappa B (NFκB) is a pro-malignant transcription factor with reciprocal effects on pro-metastatic and anti-metastatic gene expression. Interestingly, NFκB blockade results in the reciprocal induction of retinoic acid receptors (RARs). Given the established property of RARs as negative regulators of malignant progression, we postulated that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression. Using Line 1 tumor cells as a model for signal regulation of metastatic gene expression, we investigated the reciprocal interactions between NFκB and RARs in response to the pan-RAR agonist, all-trans retinoic acid (at-RA) and the pan-RAR antagonist, AGN193109. RESULTS: At-RA [0.1–1 μM] dose-dependently activated RAR and coordinately trans-repressed NFκB, while AGN193109 [1–10 μM] dose-dependently antagonized the effects of at-RA. At-RA and AGN193109 reciprocally regulate pro-metastatic matrix metalloprotease 9 (MMP 9) and its endogenous inhibitor, the tissue inhibitor of metalloprotease 1 (TIMP 1), in a manner consistent with the putative roles of NFκB and RAR in malignant progression. Activation of RAR concurs with its ubiquitination and proteosomal degradation. Accordingly, the proteosome inhibitor, MG132 [5 μM], blocked RAR degradation, quelled RAR trans-activation and enhanced RAR trans-repression of NFκB. CONCLUSION: We conclude that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression and propose that the dissociative effect of proteosome inhibitors could be harnessed towards enhancing the anticancer activity of retinoids

Improved sensitivity of H.E.S.S.-II through the fifth telescope focus system

The Imaging Atmospheric Cherenkov Telescope (IACT) works by imaging the very short flash of Cherenkov radiation generated by the cascade of relativistic charged particles produced when a TeV gamma ray strikes the atmosphere. This energetic air shower is initiated at an altitude of 10-30 km depending on the energy and the arrival direction of the primary gamma ray. Whether the best image of the shower is obtained by focusing the telescope at infinity and measuring the Cherenkov photon angles or focusing on the central region of the shower is a not obvious question. This is particularly true for large size IACT for which the depth of the field is much smaller. We address this issue in particular with the fifth telescope (CT5) of the High Energy Stereoscopic System (H.E.S.S.); a 28 m dish large size telescope recently entered in operation and sensitive to an energy threshold of tens of GeVs. CT5 is equipped with a focus system, its working principle and the expected effect of focusing depth on the telescope sensitivity at low energies (50-200 GeV) is discussed.Comment: In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil

Sensitivity to the KARMEN Timing Anomaly at MiniBooNE

We present sensitivities for the MiniBooNE experiment to a rare exotic pion decay producing a massive particle, Q^0. This type of decay represents one possible explanation for the timing anomaly reported by the KARMEN collaboration. MiniBooNE will be able to explore an area of the KARMEN signal that has not yet been investigated

Continuous Uniform Finite Time Stabilization of Planar Controllable Systems

Continuous homogeneous controllers are utilized in a full state feedback setting for the uniform finite time stabilization of a perturbed double integrator in the presence of uniformly decaying piecewise continuous disturbances. Semiglobal strong $\mathcal{C}^1$ Lyapunov functions are identified to establish uniform asymptotic stability of the closed-loop planar system. Uniform finite time stability is then proved by extending the homogeneity principle of discontinuous systems to the continuous case with uniformly decaying piecewise continuous nonhomogeneous disturbances. A finite upper bound on the settling time is also computed. The results extend the existing literature on homogeneity and finite time stability by both presenting uniform finite time stabilization and dealing with a broader class of nonhomogeneous disturbances for planar controllable systems while also proposing a new class of homogeneous continuous controllers

A Fixed-Target ExpeRiment at the LHC (AFTER@LHC) : luminosities, target polarisation and a selection of physics studies

We report on a future multi-purpose fixed-target experiment with the proton or lead ion LHC beams extracted by a bent crystal. The multi-TeV LHC beams allow for the most energetic fixed-target experiments ever performed. Such an experiment, tentatively named AFTER for "A Fixed-Target ExperRiment", gives access to new domains of particle and nuclear physics complementing that of collider experiments, in particular at RHIC and at the EIC projects. The instantaneous luminosity at AFTER using typical targets surpasses that of RHIC by more than 3 orders of magnitude. Beam extraction by a bent crystal offers an ideal way to obtain a clean and very collimated high-energy beam, without decreasing the performance of the LHC. The fixed-target mode also has the advantage of allowing for spin measurements with a polarised target and for an access over the full backward rapidity domain up to xF ~ - 1. Here, we elaborate on the reachable luminosities, the target polarisation and a selection of measurements with hydrogen and deuterium targets.Comment: 6 pages. Proceedings of the Sixth International Conference on Quarks and Nuclear Physics QNP2012 (16-20 April 2012, Ecole Polytechnique, Palaiseau,France

Spin physics at A Fixed-Target ExpeRiment at the LHC (AFTER@LHC)

We outline the opportunities for spin physics which are offered by a next generation and multi-purpose fixed-target experiment exploiting the proton LHC beam extracted by a bent crystal. In particular, we focus on the study of single transverse spin asymetries with the polarisation of the target.Comment: Contributed to the 20th International Spin Physics Symposium, SPIN2012, 17-22 September 2012, Dubna, Russia, 4 pages, LaTe

Thermodynamics of self-gravitating systems

Self-gravitating systems are expected to reach a statistical equilibrium state either through collisional relaxation or violent collisionless relaxation. However, a maximum entropy state does not always exist and the system may undergo a ``gravothermal catastrophe'': it can achieve ever increasing values of entropy by developing a dense and hot ``core'' surrounded by a low density ``halo''. In this paper, we study the phase transition between ``equilibrium'' states and ``collapsed'' states with the aid of a simple relaxation equation [Chavanis, Sommeria and Robert, Astrophys. J. 471, 385 (1996)] constructed so as to increase entropy with an optimal rate while conserving mass and energy. With this numerical algorithm, we can cover the whole bifurcation diagram in parameter space and check, by an independent method, the stability limits of Katz [Mon. Not. R. astr. Soc. 183, 765 (1978)] and Padmanabhan [Astrophys. J. Supp. 71, 651 (1989)]. When no equilibrium state exists, our relaxation equation develops a self-similar collapse leading to a finite time singularity.Comment: 54 pages. 25 figures. Submitted to Phys. Rev.

Prospectives for A Fixed-Target ExpeRiment at the LHC: AFTER@LHC

We argue that the concept of a multi-purpose fixed-target experiment with the proton or lead-ion LHC beams extracted by a bent crystal would offer a number of ground-breaking precision-physics opportunities. The multi-TeV LHC beams will allow for the most energetic fixed-target experiments ever performed. The fixed-target mode has the advantage of allowing for high luminosities, spin measurements with a polarised target, and access over the full backward rapidity domain --uncharted until now-- up to x_F ~ -1.Comment: 6 pages, 1 table, LaTeX. Proceedings of the 36th International Conference on High Energy Physics (ICHEP2012), 4-11 July 2012, Melbourne, Australi

Prediction of interaction between a side overflow and bed-load transport in a channel with semi-empirical approaches

Les seuils a deversoir lateral sont des structures de controle et de detournement a ecoulement libre regulierement utilisees en ingenierie de lutte contre les inondations. La perte laterale d'eau permet de reduire la capacite de transport de la charge de fond dans le chenal principal, engendrant ainsi une deposition locale des sediments pres du deversoir lateral. Le debordement servant aux calculs est donc augmente de maniere non controlee. Des experiences systematiques de canal sur appuis ont ete realisees puisque cette interaction ecoulement-sediments dans un tel canal n'avait jamais ete etudiee. Base sur ces experiences, un modele empirique bidimensionnel a ete developpe afin de decrire l'evolution longitudinale de la portion du canal alluvial a proximite du deversoir. De plus, une approche simple et explicite d'estimation directe de l'ecoulement lateral avec transport de la charge de fond a ete determinee. Pour etre applicables a l'ingenierie, les variables d'entree sont exprimees en termes de parametres sans dimensions. Finalement, l'utilisation des modeles est demontree sur une etude de cas du Rhone en Suisse