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  • 1
    Publication Date: 2013-12-10
    Description: Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930079/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930079/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roth, Theodore L -- Nayak, Debasis -- Atanasijevic, Tatjana -- Koretsky, Alan P -- Latour, Lawrence L -- McGavern, Dorian B -- ZIA NS003112-05/Intramural NIH HHS/ -- England -- Nature. 2014 Jan 9;505(7482):223-8. doi: 10.1038/nature12808. Epub 2013 Dec 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24317693" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Topical ; Animals ; Antioxidants/administration & dosage/therapeutic use ; Astrocytes/pathology ; Brain/drug effects/pathology ; Brain Injuries/*complications/diagnosis/drug therapy/*pathology ; Cell Death/drug effects ; Disease Models, Animal ; Encephalitis/complications/drug therapy/*pathology/*prevention & control ; Glasgow Coma Scale ; Glutathione/administration & dosage/therapeutic use ; Humans ; Intracranial Hemorrhages/complications/diagnosis ; Male ; Meninges/drug effects/pathology ; Mice ; Microglia/cytology/drug effects/physiology ; Neuroprotective Agents/administration & dosage/therapeutic use ; Neutrophils/drug effects/physiology ; Purinergic P2 Receptor Antagonists/administration & ; dosage/pharmacology/therapeutic use ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Receptors, Purinergic P2/metabolism ; Receptors, Purinergic P2X7/metabolism ; Skull/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-05-03
    Description: Transcription by RNA polymerase (RNAP) is interrupted by pauses that play diverse regulatory roles. Although individual pauses have been studied in vitro, the determinants of pauses in vivo and their distribution throughout the bacterial genome remain unknown. Using nascent transcript sequencing, we identified a 16-nucleotide consensus pause sequence in Escherichia coli that accounts for known regulatory pause sites as well as ~20,000 new in vivo pause sites. In vitro single-molecule and ensemble analyses demonstrate that these pauses result from RNAP-nucleic acid interactions that inhibit next-nucleotide addition. The consensus sequence also leads to pausing by RNAPs from diverse lineages and is enriched at translation start sites in both E. coli and Bacillus subtilis. Our results thus reveal a conserved mechanism unifying known and newly identified pause events.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108260/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108260/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Larson, Matthew H -- Mooney, Rachel A -- Peters, Jason M -- Windgassen, Tricia -- Nayak, Dhananjaya -- Gross, Carol A -- Block, Steven M -- Greenleaf, William J -- Landick, Robert -- Weissman, Jonathan S -- F32 GM100611/GM/NIGMS NIH HHS/ -- F32 GM108222/GM/NIGMS NIH HHS/ -- P50 GM102706/GM/NIGMS NIH HHS/ -- R01 GM038660/GM/NIGMS NIH HHS/ -- R01 GM102790/GM/NIGMS NIH HHS/ -- R37 GM057035/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):1042-7. doi: 10.1126/science.1251871. Epub 2014 May 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. ; Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA. ; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. ; Department of Biological Sciences, Stanford University, Stanford, CA 94025, USA. Department of Applied Physics; Stanford University, Stanford, CA 94025, USA. ; Department of Genetics, Stanford University, Stanford, CA 94025, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu. ; Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA. Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu. ; Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24789973" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Codon, Initiator/*genetics ; Consensus Sequence ; DNA-Directed RNA Polymerases/metabolism ; Escherichia coli/*genetics/*metabolism ; *Gene Expression Regulation, Bacterial ; Peptide Chain Initiation, Translational/*genetics ; *Regulatory Elements, Transcriptional ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2017-03-15
    Description: Although Cas9-mediated genome editing has proven to be a powerful genetic tool in eukaryotes, its application in Bacteria has been limited because of inefficient targeting or repair; and its application to Archaea has yet to be reported. Here we describe the development of a Cas9-mediated genome-editing tool that allows facile...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 4
    Publication Date: 2019
    Print ISSN: 1751-7362
    Electronic ISSN: 1751-7370
    Topics: Biology
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  • 5
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 78 (1995), S. 6135-6140 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Thin oxide on strained Si1−xGex surface has been grown using a nonelectron cyclotron resonance mode microwave plasma at low temperatures (150–200 °C). An optimized post-oxidation and post-metal annealing cycle has resulted in very low fixed oxide charge density (1.78×1010/cm2) and moderately low interface trap density (2.9×1011/cm2 eV). A controlled in situ hydrogen-plasma treatment to Si1−xGex has been found to be useful in improving the electrical properties of the oxide. The high electron injection phenomena of metal oxide semiconductor capacitors has been used for charge trapping studies of sites normally present in the SiGe oxides. From the position and the extent of current ledge observed as a function of ramped gate voltage, the capture cross section and the total number of traps have been determined. © 1995 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 76 (1994), S. 982-986 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The electrical and chemical properties of the interfaces of thin oxides grown on strained GexSi1−x layers are analyzed in detail using capacitance-voltage measurements and Auger electron spectroscopy. It is found that the electrical properties (interface states and fixed oxide charges) of the interface depend on various parameters such as oxidation temperature, oxidation time, Ge distribution near the interface, and Ge distribution in the entire epilayer. The Ge distribution at the interface can be described using concentration-dependent diffusivity of Ge in the epilayer. The electrical properties are improved with the increase in oxidation temperature, but for a given oxidation temperature, the quality of the interface degrades with the increase in oxidation time. At a very high oxidation temperature the Ge distribution in the entire epilayer is altered due to the high diffusivity of Ge.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 69 (1991), S. 6674-6678 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The experimental results of a molecular-beam epitaxy grown Si/GeSi p-n heterojunction are reported. It is found that the current flow in these p-n heterojunctions shows a nonideality factor of about 1.5 at room temperature and 2.35 at liquid nitrogen temperature. The nonideal behavior of the Si/GeSi p-n heterojunction is attributed to the charges that are trapped at the heterointerface. Annealing the samples at temperatures higher than the growth temperature results in an increase in the density of defects as well as an increase in the nonideal current. C-V measurements were employed to further investigate the behavior of the charges that are trapped in the interface. From C-V measurements under reverse bias it is found that increasing the annealing time and temperature increases the density of interface traps. In addition, a charge density of about 1012 cm−2 is found to be present at the Si/GeSi interface for the as-grown sample and increases with increasing annealing time and temperature.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 57 (1990), S. 369-371 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A cold-wall rapid thermal processor is used for the wet oxidation of the commensurately grown GexSi1−x layers on Si substrates. The rate of oxidation of the GexSi1−x layer is found to be significantly higher than that of pure Si, and the oxidation rate increases with the increase in the Ge content in GexSi1−x layer. The oxidation rate of GexSi1−x appears to decrease with increasing oxidation time for the time-temperature cycles considered here. Employing high-frequency and quasi-static capacitance-voltage measurements, it is found that a fixed negative oxide charge density in the range of 1011– 1012/cm2 and the interface trap level density (in the mid-gap region) of about 1012/cm2 eV are present. Further, the density of this fixed interface charge at the SiO2/GeSi interface is found to increase with the Ge concentration in the commensurately grown GeSi layers.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 56 (1990), S. 66-68 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The experimental results of the rapid thermal oxidation in the initial oxidation regime of molecular beam epitaxy grown GeSi strained layers are reported. It is shown that the dry oxidation rate of GeSi is the same as that of Si at different temperatures. After a very short initial time (∼10 s), the oxide thickness appears to be a linear function of time, which suggests that the kinetics of oxide growth during dry oxidation is limited by surface reaction controlled mechanisms. Further, the oxidation rate in the thin oxide regime is not affected by the Ge content up to 20% in the GeSi strained layer for dry oxidation. Using secondary-ion mass spectrometry, it is found that Ge is completely rejected out of the SiO2 layer which is formed during oxidation, and a Ge-rich layer is formed at the SiO2/GeSi interface. A significant amount of Ge is found to diffuse into the underlying GeSi layer during the growth of thin oxide films.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 70 (1997), S. 217-219 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Electron cyclotron resonance plasma oxidation of strained Si on relaxed Si1−xGex buffer layers in O2 ambient at room temperature is reported. The electrical properties of grown oxide have been characterized and compared with thermally grown oxides using a metal-oxide semiconductor structure. At a low field, the accumulation of holes in the buried Si1−xGex layer, due to the type-II band offset, has been observed. The experimental results from thermally grown oxides have been compared with the simulation results obtained using a heterostructure Poisson solver. © 1997 American Institute of Physics.
    Type of Medium: Electronic Resource
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