G1 phase arrest by the phosphatidylinositol 3-kinase inhibitor LY 294002 is correlated to up-regulation of p27Kip1 and inhibition of G1 CDKs in choroidal melanoma cells

AbstractWe have investigated the effect of the flavonoid derivative LY 294002, a potent and selective phosphatidylinositol 3-kinase inhibitor, on cell cycle progression in human choroidal melanoma cells. We demonstrate that LY 294002 induces a specific G1 block in asynchronously growing cells leading to an almost complete inhibition of cell proliferation after three days of treatment. When melanoma cells are released from a nocodazole-induced G2/M block, LY 294002 is shown to delay and greatly restrain the G1/S transition. The inhibitor is able to exert its action as long as it is added during the G1 progression and before the cells enter in S phase. We report that the LY 294002-induced G1 arrest is closely correlated to inhibition of CDK4 and CDK2 activities leading to the impairment of pRb phosphorylation which normally occurs during G1 progression. While the inhibition of CDK4 may be attributed at least in part to the decline in CDK4 protein level, CDK2 activity reduction is rather due to the up-regulation of the CDK inhibitor p27Kip1 and to its increased association to CDK2

Vulnerability of CMOS image sensors in megajoule class laser harsh environment

CMOS image sensors (CIS) are promising candidates as part of optical imagers for the plasma diagnostics devoted to the study of fusion by inertial confinement. However, the harsh radiative environment of Megajoule Class Lasers threatens the performances of these optical sensors. In this paper, the vulnerability of CIS to the transient and mixed pulsed radiation environment associated with such facilities is investigated during an experiment at the OMEGA facility at the Laboratory for Laser Energetics (LLE), Rochester, NY, USA. The transient and permanent effects of the 14 MeV neutron pulse on CIS are presented. The behavior of the tested CIS shows that active pixel sensors (APS) exhibit a better hardness to this harsh environment than a CCD. A first order extrapolation of the reported results to the higher level of radiation expected for Megajoule Class Laser facilities (Laser Megajoule in France or National Ignition Facility in the USA) shows that temporarily saturated pixels due to transient neutron-induced single event effects will be the major issue for the development of radiation-tolerant plasma diagnostic instruments whereas the permanent degradation of the CIS related to displacement damage or total ionizing dose effects could be reduced by applying well known mitigation techniques

Vulnerability of optical detection systems to megajoule class laser radiative environment

The Laser MegaJoule (LMJ) facility will host inertial confinement fusion experiments in order to achieve ignition by imploding a Deuterium-Tritium filled microballoon [1]. In this context an X-ray imaging system is necessary to diagnose the core size and the shape of the target in the 10-100 keV band. Such a diagnostic will be composed of two parts: an X-ray optical system and a detection assembly. The survivability of each element of this diagnostic has to be ensured within the mixed pulse consisting of X-rays, gamma rays and 14 MeV neutrons created by fusion reactions. The design of this diagnostic will take into account optics and detectors vulnerability to neutron yield of at least 1016. In this work, we will present the main results of our vulnerability studies and of our hardening-by-system and hardening-by-design studies

Hardening approach to use CMOS image sensors for fusion by inertial confinement diagnostics

A hardening method is proposed to enable the use of CMOS image sensors for Fusion by Inertial Confinement Diagnostics. The mitigation technique improves their radiation tolerance using a reset mode implemented in the device. The results obtained evidence a reduction of more than 70% in the number of transient white pixels induced in the pixel array by the mixed neutron and γ-ray pulsed radiation environment

Interaction between the C-terminal domains of N and P proteins of measles virus investigated by NMR.

International audienceIn this paper we investigate the interaction between the C-terminal domains of the measles virus phosphoprotein (XD) and nucleoprotein (N(TAIL)) by using nuclear magnetic resonance chemical shift perturbation experiments. Using both N(TAIL) constructs and peptides, we show that contrary to the conserved Box2 region (N(489-506)), the C-terminal region of N(TAIL) (N(513-525)) does not directly interact with XD, and yet affects binding to XD. We tentatively propose a model where the C-terminus of N(TAIL) would stabilize the N(TAIL)-XD complex either via a functional coupling with N(489-506) or by reducing the entropic penalty associated to the binding-coupled-to-folding process

Light Extraction and Brightness Enhancement of Luminescent Rectangular Slabs

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