New Modeling Approaches to Investigate Cell Signaling in Radiation Response

Ionizing radiation damages individual cells and tissues leading to harmful biological effects. Among many radiation-induced lesions, DNA double-strand breaks (DSB) are considered the key precursors of most early and late effects [1] leading to direct mutation or aberrant signal transduction processes. In response to damage, a flow of information is communicated to cells not directly hit by the radiation through signal transduction pathways [2]. Non-targeted effects (NTE), which includes bystander effects and genomic instability in the progeny of irradiated cells and tissues, may be particularly important for space radiation risk assessment [1], because astronauts are exposed to a low fluence of heavy ions and only a small fraction of cells are traversed by an ion. NTE may also have important consequences clinical radiotherapy [3]. In the recent years, new simulation tools and modeling approaches have become available to study the tissue response to radiation. The simulation of signal transduction pathways require many elements such as detailed track structure calculations, a tissue or cell culture model, knowledge of biochemical pathways and Brownian Dynamics (BD) propagators of the signaling molecules in their micro-environment. Recently, the Monte-Carlo simulation code of radiation track structure RITRACKS was used for micro and nano-dosimetry calculations [4]. RITRACKS will be used to calculate the fraction of cells traversed by an ion and delta-rays and the energy deposited in cells in a tissue model. RITRACKS also simulates the formation of chemical species by the radiolysis of water [5], notably the .OH radical. This molecule is implicated in DNA damage and in the activation of the transforming growth factor beta (TGF), a signaling molecule involved in NTE. BD algorithms for a particle near a membrane comprising receptors were also developed and will be used to simulate trajectories of signaling molecules in the micro-environment and characterize autocrine and paracrine cell communication and signal transduction

GSFC Cutting Edge Avionics Technologies for Spacecraft

With the launch of NASA's first fiber optic bus on SAMPEX in 1992, GSFC has ushered in an era of new technology development and insertion into flight programs. Predating such programs the Lewis and Clark missions and the New Millenium Program, GSFC has spearheaded the drive to use cutting edge technologies on spacecraft for three reasons: to enable next generation Space and Earth Science, to shorten spacecraft development schedules, and to reduce the cost of NASA missions. The technologies developed have addressed three focus areas: standard interface components, high performance processing, and high-density packaging techniques enabling lower cost systems. To realize the benefits of standard interface components GSFC has developed and utilized radiation hardened/tolerant devices such as PCI target ASICs, Parallel Fiber Optic Data Bus terminals, MIL-STD-1773 and AS1773 transceivers, and Essential Services Node. High performance processing has been the focus of the Mongoose I and Mongoose V rad-hard 32-bit processor programs as well as the SMEX-Lite Computation Hub. High-density packaging techniques have resulted in 3-D stack DRAM packages and Chip-On-Board processes. Lower cost systems have been demonstrated by judiciously using all of our technology developments to enable "plug and play" scalable architectures. The paper will present a survey of development and insertion experiences for the above technologies, as well as future plans to enable more "better, faster, cheaper" spacecraft. Details of ongoing GSFC programs such as Ultra-Low Power electronics, Rad-Hard FPGAs, PCI master ASICs, and Next Generation Mongoose processors

Introducing the Living with Illness Group: A specialized treatment for patients with chronic schizophrenic conditions

This paper introduces a specialized psychotherapy/psychoeducational group treatment for patients with chronic psychotic symptoms who receive only partial benefit from psychotropic medications, psychotherapy, and milieu/activities therapy. The goal of the group is to assist patients to accurately identify the feelings, thoughts, and behaviors that are dysfunctional symptoms of their disability and then use the functional aspects of their brain as well as learned coping strategies to compensate for their disability. The group format, philosophy, procedures, and typical topics of discussion are detailed

Predicting Cell Death and Mutation Frequency for a Wide Spectrum of LET by Assuming DNA Break Clustering Inside Repair Domains

Cosmic radiation, which is composed of high charged and energy (HZE) particles, is responsible for cell death and mutation, which may be involved in cancer induction. Mutations are consequences of mis-repaired DNA breaks especially double-strand breaks (DSBs) that induce inter- and intra-chromosomal rearrangements (translocations, deletions, inversion). In this study, a computer simulation model is used to investigate the clustering of DSBs in repair domains, previously evidenced by our group in human breast cells [1]. This model is calibrated with experimental data measuring persistent 53BP1 radiation-induced foci (RIF) and is used to explain the high relative biological effectiveness (RBE) of HZE for both cell death and DNA mutation frequencies. We first validate our DSB cluster model using a new track structure model deployed on a simple geometrical configuration for repair domains in the nucleus; then we extend the scope from cell death to mutation induction. This work suggests that mechanism based on DSB repair process can explain several biological effects induced by HZE particles on different type of living cell

Prolégomènes à toute appréciation critique de CANDIDE

This text describes the CANDIDE model from three critical points of view. First, it presents the structure of the model with the aid of a table of "supersectors" and a flow chart. The discussion of the linkages between these supersectors brings out the general equilibrium character of the model.The center section of the paper deals with the theoretical foundations of the behavioural equations. A statement of the equation specification in each sector of the model is followed by a brief evaluation. The authors confess to an eclectic attitude and stress the practical difficulties of making stylized theories bring order in variegated facts. Exogenous influences on the model are discussed as well.The same eclectic approach is evident in the third part of the text which treats of estimation and validation. A variety of tests and checks—some novel ones included—are applied in the process of developing the model. The authors conclude with the observation that recent tumultuous developments in the economy raise fundamental questions about the validity and usefulness of models like CANDIDE

Connecting the time domain community with the Virtual Astronomical Observatory

The time domain has been identified as one of the most important areas of astronomical research for the next decade. The Virtual Observatory is in the vanguard with dedicated tools and services that enable and facilitate the discovery, dissemination and analysis of time domain data. These range in scope from rapid notifications of time-critical astronomical transients to annotating long-term variables with the latest modeling results. In this paper, we will review the prior art in these areas and focus on the capabilities that the VAO is bringing to bear in support of time domain science. In particular, we will focus on the issues involved with the heterogeneous collections of (ancillary) data associated with astronomical transients, and the time series characterization and classification tools required by the next generation of sky surveys, such as LSST and SKA.Comment: Submitted to Proceedings of SPIE Observatory Operations: Strategies, Processes and Systems IV, Amsterdam, 2012 July 2-