Description of the Scenario Machine

We present here an updated description of the "Scenario Machine" code. This tool is used to carry out a population synthesis of binary stars. Previous version of the description can be found at http://xray.sai.msu.ru/~mystery//articles/review/contents.htmlComment: 32 pages, 3 figures. Corrected typo

Therapeutic opportunities within the DNA damage response

The DNA damage response (DDR) is essential for maintaining the genomic integrity of the cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have been exploited therapeutically in the treatment of cancer with radiation therapies or genotoxic chemotherapies. More recently, protein components of the DDR systems have been identified as promising avenues for targeted cancer therapeutics. Here, we present an in-depth analysis of the function, role in cancer and therapeutic potential of 450 expert-curated human DDR genes. We discuss the DDR drugs that have been approved by the US Food and Drug Administration (FDA) or that are under clinical investigation. We examine large-scale genomic and expression data for 15 cancers to identify deregulated components of the DDR, and we apply systematic computational analysis to identify DDR proteins that are amenable to modulation by small molecules, highlighting potential novel therapeutic targets

Spatiotemporal progression of ubiquitin-proteasome system inhibition after status epilepticus suggests protective adaptation against hippocampal injury

BACKGROUND: The ubiquitin-proteasome-system (UPS) is the major intracellular pathway leading to the degradation of unwanted and/or misfolded soluble proteins. This includes proteins regulating cellular survival, synaptic plasticity and neurotransmitter signaling; processes controlling excitability thresholds that are altered by epileptogenic insults. Dysfunction of the UPS has been reported to occur in a brain region- and cell-specific manner and contribute to disease progression in acute and chronic brain diseases. Prolonged seizures, status epilepticus, may alter UPS function but there has been no systematic attempt to map when and where this occurs in vivo or to determine the consequences of proteasome inhibition on seizure-induced brain injury. METHOD: To determine whether seizures lead to an impairment of the UPS, we used a mouse model of status epilepticus whereby seizures are triggered by an intra-amygdala injection of kainic acid. Status epilepticus in this model causes cell death in selected brain areas, in particular the ipsilateral CA3 subfield of the hippocampus, and the development of epilepsy after a short latent period. To monitor seizure-induced dysfunction of the UPS we used a UPS inhibition reporter mouse expressing the ubiquitin fusion degradation substrate ubiquitin(G76V)-green fluorescent protein. Treatment with the specific proteasome inhibitor epoxomicin was used to establish the impact of proteasome inhibition on seizure-induced pathology. RESULTS AND CONCLUSIONS: Our studies show that status epilepticus induced by intra-amygdala kainic acid causes select spatio-temporal UPS inhibition which is most evident in damage-resistant regions of the hippocampus, including CA1 pyramidal and dentate granule neurons then appears later in astrocytes. In support of this exerting a beneficial effect, injection of mice with the proteasome inhibitor epoxomicin protected the normally vulnerable hippocampal CA3 subfield from seizure-induced neuronal death in the model. These studies reveal brain region- and cell-specific UPS impairment occurs after seizures and suggest UPS inhibition can protect against seizure-induced brain damage. Identifying networks or pathways regulated through the proteasome after seizures may yield novel target genes for the treatment of seizure-induced cell death and possibly epilepsy

Nucleation mechanism of GaN nanowires grown on (111) Si by molecular beam epitaxy

International audienceWe have performed a real-time in situ x-ray scattering study of the nucleation of GaN nanowires grown by plasma-assisted molecular beam epitaxy on AlN(0001)/Si(111). The intensity variation of the GaN diffraction peak as a function of time was found to exhibit three different regimes: (i) the deposition of a wetting layer, which is followed by (ii) a supralinear regime assigned to nucleation of almost fully relaxed GaN nanowires, eventually leading to (iii) a steady-state growth regime. Based on scanning electron microscopy and electron microscopy analysis, it is proposed that the granular character of the thin AlN buffer layer may account for the easy plastic relaxation of GaN, establishing that three-dimensional islanding and plastic strain relaxation of GaN are two necessary conditions for nanowire growth

Growth mechanism of catalyst-free 0001 GaN and AlN nanowires on Si by molecular beam epitaxy

International audienceReal-time in-situ X-rays scattering experiments were performed to study the nucleation process of GaN nanowires grown by plasma-assisted molecular beam epitaxy on AlN(0001)/Si(111). From the comparison between the case of nanowires and the case of GaN quantum dots, it is concluded that nanowire precursor islands are completely relaxed from the beginning. Next, based on high resolution electron microscopy analysis, it is demonstrated that relaxation of nanowire precursors is associated to formation of dislocations at the AlN/GaN interface, establishing that three-dimensional islanding and plastic strain relaxation of GaN are two necessary conditions for nanowire growth. Along the same lines, we demonstrate that three-dimensional islanding of AlN on SiO2 leads to formation of AlN nanowires with structural and optical properties characteristic of high quality relaxed material. (C) 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

RNB production at SPIRAL/GANIL

International audienceWe present the on-line production system and tests for the Phase-I of SPIRAL/GANIL (Radioactive Ion Production System with Acceleration on-Line) where exotic multicharged noble gas ion beams have been obtained with the ECRIS (Electron Cyclotron Resonance Ion Source) NANOGAN-III. A new ECRIS (MONO1000) for monocharged radioactive ions is also presented, together with the diffusion properties of different graphite targets for He and Ar isotopes