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  • 1
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    Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-02-05
    Description: Genome-wide transcript profiling was used to monitor signal transduction during yeast pheromone response. Genetic manipulations allowed analysis of changes in gene expression underlying pheromone signaling, cell cycle control, and polarized morphogenesis. A two-dimensional hierarchical clustered matrix, covering 383 of the most highly regulated genes, was constructed from 46 diverse experimental conditions. Diagnostic subsets of coexpressed genes reflected signaling activity, cross talk, and overlap of multiple mitogen-activated protein kinase (MAPK) pathways. Analysis of the profiles specified by two different MAPKs-Fus3p and Kss1p-revealed functional overlap of the filamentous growth and mating responses. Global transcript analysis reflects biological responses associated with the activation and perturbation of signal transduction pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, C J -- Nelson, B -- Marton, M J -- Stoughton, R -- Meyer, M R -- Bennett, H A -- He, Y D -- Dai, H -- Walker, W L -- Hughes, T R -- Tyers, M -- Boone, C -- Friend, S H -- New York, N.Y. -- Science. 2000 Feb 4;287(5454):873-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rosetta Inpharmatics, 12040 115th Avenue Northeast, Kirkland, WA 98034, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10657304" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Cycle Proteins ; Cyclin-Dependent Kinase Inhibitor Proteins ; Fungal Proteins/genetics/metabolism/physiology ; G1 Phase ; *Gene Expression Profiling ; *Gene Expression Regulation, Fungal ; Genome, Fungal ; Lipoproteins/pharmacology/physiology ; *MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/metabolism ; Multigene Family ; Oligonucleotide Array Sequence Analysis ; Peptides/pharmacology/physiology ; Pheromones ; Protein Kinase C/metabolism ; *Repressor Proteins ; Saccharomyces cerevisiae/cytology/*genetics/growth & development/physiology ; *Saccharomyces cerevisiae Proteins ; Transcription Factors/metabolism ; Transcriptional Activation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Evaluation of Seismic-Acoustic Analysis Methods for a Real-time UXO Monitoring System (2013)
    Environmental & Engineering Geophysical Society (EEGS)
    Details
    Publication Date: 2013-03-17
    Description: The Department of Defense (DoD) uses over two million rounds of high-explosive (HE) munitions per year ( Defense Science Board Task Force, 2003 ). A small percentage does not explode, thus generating unexploded ordnance (UXO) in current range areas at a substantial rate. As these ranges are closed, the DoD becomes responsible for the environmental restoration of the affected properties. Current methods of UXO remediation are costly because of high false alarm rates. Our current research is to develop a complementary technology that will alleviate false alarm rate by detecting, classifying, and locating UXO in near real time (less than 1 minute) as a munition impacts the range. This technology will utilize an array of buried seismic sensors in a calibrated range area, along with a set of algorithms based on theoretical and applied seismology and statistical analysis. Initial field tests at three sites focused on developing concepts of the seismic and acoustic location of ordnance impacts. Our research program developed from these initial field tests has four primary objectives: 1) fully implement a wired seismic-acoustic ordnance impact location system for live fire ranges; 2) develop a system capability to discriminate high-order (HE), low-order (partially exploded), and zero-order (UXO) events; 3) reduce location error to a stringent program metric of 1–2 m; and 4) investigate the feasibility of developing a wireless implementation of the technology. This paper describes the procedures and results from follow-on tests that were conducted in two locations at the U.S. Army Aberdeen Proving Ground (APG), Maryland. These tests were used to evaluate potential seismic-acoustic methods and system configurations for a Seismic-Acoustic Impact Monitoring Assessment (SAIMA) system for mitigating UXO hazards. Significant results from this work include: 1) seismic impulses from low-order impacts were detected at distances up to 1,000 meters; 2) classification features based on measurements of the amplitude of acoustic and seismic phases produce clear discrimination between HE and UXO impacts; 3) calculated location solutions for HE and UXO impacts yield an average location error of 10–20 meters; and 4) empirical observation and waveform modeling demonstrated that surface waves dominate the signal at all distances and therefore should be the primary phase used for all components of analysis. Furthermore, these tests demonstrated the current system design, allowing further enhancements, is capable of meeting the initial research objectives (1) and (2). Future research will focus on improving system performance with refinement of the sensor-layout geometry and the detection and location algorithms through system error analyses and follow-on field testing.
    Print ISSN: 1083-1363
    Electronic ISSN: 1943-2658
    Topics: Geosciences
    Published by Environmental & Engineering Geophysical Society (EEGS)
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  • 3
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    Reduction of polyglutamine toxicity by TDP-43, FUS and progranulin in Huntington's disease models (2013)
    Oxford University Press
    Details
    Publication Date: 2013-01-25
    Description: The DNA/RNA binding proteins TAR DNA-binding protein 43 (TDP-43) and fused-in-sarcoma (FUS) are genetically linked to amyotrophic lateral sclerosis and frontotemporal lobar dementia, while the inappropriate cytoplasmic accumulations of TDP-43 and FUS are observed in a growing number of late-onset pathologies including spinocerebellar ataxia 3, Alzheimer's and Huntington's diseases (HD). To investigate if TDP-43 and FUS contribute to neurodegenerative phenotypes, we turned to a genetically accessible Caenorhabditis elegans model of polyglutamine toxicity. In C. elegans , we observe that genetic loss-of-function mutations for nematode orthologs of TDP-43 or FUS reduced behavioral defects and neurodegeneration caused by huntingtin exon-1 with expanded polyglutamines. Furthermore, using striatal cells from huntingtin knock-in mice we observed that small interfering ribonucleic acid (siRNA) against TDP-43 or FUS reduced cell death caused by mutant huntingtin. Moreover, we found that TDP-43 and the survival factor progranulin (PGRN) genetically interact to regulate polyglutamine toxicity in C. elegans and mammalian cells. Altogether our data point towards a conserved function for TDP-43 and FUS in promoting polyglutamine toxicity and that delivery of PGRN may have therapeutic benefits.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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