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  • 1
    Publication Date: 2013-07-31
    Description: [1]  This paper supports studies of low frequency variability (LFV) within the thermosphere by deriving approximate integral and closed-form solutions of a nontrivial model of thermospheric temperature, density, and composition depending on altitude and time. We also provide a paradigm for applying dimensional analysis in such studies. The domain is the region between the mesopause and the exobase. The solutions emphasize the connectedness of the thermosphere, i.e., nonlocal influences of LFV in key physical parameters and phenomena. The present focus is seasonal variability (SV), within which the origin of a sizable semi-annual variation in the thermosphere remains under active investigation. Following from the thermodynamic differential equation for temperature is a filtered, integral solution consistent with the Π Theorem of dimensional analysis. A key result is the explicit demonstration that lower thermospheric boundary conditions affect low frequency variability throughout the thermosphere, making accurate boundary conditions essential to modeling LFV. In addition, LFV of the temperature varies inversely with variability of the net heating profile and has directly and inversely proportional contributions from variations in the thermal conductivity profile, which can include an " eddy diffusivity" component. Given a temperature profile, diffusive equilibrium defines model composition. For rapid calculations and transparency, we develop an approximate, closed-form solution for temperature, density, and composition depending only on a minimal set of observable parameters, and from that, we demonstrate the essential role of the phase and amplitude profile of the temperature LFV in determining the corresponding profile of variability in composition and density.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
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  • 2
    Publication Date: 2014-09-27
    Description: The basic helix-loop-helix transcription factor hASH1, encoded by the ASCL1 gene, plays an important role in neurogenesis and tumor development. Recent findings indicate that local oxygen tension is a critical determinant for the progression of neuroblastomas. Here we investigated the molecular mechanisms underlying the oxygen-dependent expression of hASH1 in neuroblastoma cells. Exposure of human neuroblastoma-derived Kelly cells to 1% O2 significantly decreased ASCL1 mRNA and hASH1 protein levels. Using reporter gene assays, we show that the response of hASH1 to hypoxia is mediated mainly by post-transcriptional inhibition via the ASCL1 mRNA 5′- and 3′-UTRs, whereas additional inhibition of the ASCL1 promoter was observed under prolonged hypoxia. By RNA pulldown experiments followed by MALDI/TOF-MS analysis, we identified heterogeneous nuclear ribonucleoprotein (hnRNP)-A2/B1 and hnRNP-R as interactors binding directly to the ASCL1 mRNA 5′- and 3′-UTRs and influencing its expression. We further demonstrate that hnRNP-A2/B1 is a key positive regulator of ASCL1, findings that were also confirmed by analysis of a large compilation of gene expression data. Our data suggest that a prominent down-regulation of hnRNP-A2/B1 during hypoxia is associated with the post-transcriptional suppression of hASH1 synthesis. This novel post-transcriptional mechanism for regulating hASH1 levels will have important implications in neural cell fate development and disease.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 3
    Publication Date: 2013-10-26
    Description: Signal transducer and activator of transcription 3 (Stat3) is a key mediator in the development of many cancers. For 20 years, it has been assumed that Stat3 mediates its biological activities as a nuclear localized transcription factor activated by many cytokines. However, recent studies from this laboratory and others indicate that Stat3 has an independent function in the mitochondria (mitoStat3) where it controls the activity of the electron transport chain (ETC) and mediates Ras-induced transformation of mouse embryo fibroblasts. The actions of mitoStat3 in controlling respiration and Ras transformation are mediated by the phosphorylation state of serine 727. To address the role of mitoStat3 in the pathogenesis of cells that are transformed, we used 4T1 breast cancer cells, which form tumors that metastasize in immunocompetent mice. Substitution of Ser-727 for an alanine or aspartate in Stat3 that has a mitochondrial localization sequence, MLS-Stat3, has profound effects on tumor growth, complex I activity of the ETC, and accumulation of reactive oxygen species (ROS). Cells expressing MLS-Stat3(S727A) display slower tumor growth, decreased complex I activity of the ETC, and increased ROS accumulation under hypoxia compared with cells expressing MLS-Stat3. In contrast, cells expressing MLS-Stat3(S727D) show enhanced tumor growth and complex I activity and decreased production of ROS. These results highlight the importance of serine 727 of mitoStat3 in breast cancer and suggest a novel role for mitoStat3 in regulation of ROS concentrations through its action on the ETC.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 4
    Publication Date: 2013-09-11
    Description: GABAB receptors (GABABRs) mediate slow inhibitory effects on neuronal excitability and synaptic transmission in the brain. However, the GABABR agonist baclofen can also promote excitability and seizure generation in human patients and animals models. Here we show that baclofen has concentration-dependent effects on the hippocampal network in a mouse model...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 5
    Publication Date: 2014-04-02
    Description: This study tested the possible relationship between reported visual awareness (“I see a visual stimulus in front of me”) and the social attribution of awareness to someone else (“That person is aware of an object next to him”). Subjects were tested in two steps. First, in an fMRI experiment, subjects...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2012-03-14
    Description: Pyrrole–imidazole (Py–Im) hairpin polyamides are a class of programmable, sequence-specific DNA binding oligomers capable of disrupting protein–DNA interactions and modulating gene expression in living cells. Methods to control the cellular uptake and nuclear localization of these compounds are essential to their application as molecular probes or therapeutic agents. Here, we explore modifications of the hairpin -aminobutyric acid turn unit as a means to enhance cellular uptake and biological activity. Remarkably, introduction of a simple aryl group at the turn potentiates the biological effects of a polyamide targeting the sequence 5'-WGWWCW-3' (W = A/T) by up to two orders of magnitude. Confocal microscopy and quantitative flow cytometry analysis suggest this enhanced potency is due to increased nuclear uptake. Finally, we explore the generality of this approach and find that aryl-turn modifications enhance the uptake of all polyamides tested, while having a variable effect on the upper limit of polyamide nuclear accumulation. Overall this provides a step forward for controlling the intracellular concentration of Py–Im polyamides that will prove valuable for future applications in which biological potency is essential.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
    Publication Date: 2011-10-20
    Description: A new general linear model of the climatology of the ionosphere's total electron content (TEC) is described, accounting simultaneously for the influences of solar and geomagnetic activity, oscillations at four frequencies and a secular trend. The model captures more than 98% of the variance in the daily averaged, global TEC derived from GPS observations during the 16 years from 1995 to 2010, and enables the reconstruction of TEC variations since 1950. Solar EUV irradiance variations, the dominant ionospheric influence, directly increase TEC by as much as 40 TECU from solar activity minimum to maximum and produce additional 27-day fluctuations of as much as 15 TECU (in October 2003). Semiannual and annual oscillations in TEC are comparable in magnitude to the 27-day fluctuations, with (peak to valley) amplitudes that increase from a few TECU at low solar activity to ∼17 TECU during solar activity maximum. The phase and amplitude of the semiannual oscillation are identical in the northern and southern geographic hemispheres (and hence globally). In contrast, the annual oscillation is twice as large in the southern hemisphere (where it peaks in December–January) than in the northern hemisphere (where it peaks in April–May). Seasonal, semiannual and annual anomalies in TEC are direct effects of semiannual and annual oscillations produced by orbitally driven photoionization and thermospheric composition changes, not of corresponding oscillations in solar or geomagnetic activity. Geomagnetic influences on daily averaged global TEC are relatively modest, with the maximum effect a reduction of 11 TECU (in October 2003) and only 11 episodes in excess of 5 TECU depletions during the past 16 years.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
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  • 8
    Publication Date: 2012-01-25
    Description: Nuclear factor κB (NF-κB) is a transcription factor that regulates various aspects of immune response, cell death, and differentiation as well as cancer. In this study we introduce the Py-Im polyamide 1 that binds preferentially to the sequences 5′-WGGWWW-3′ and 5′GGGWWW-3′. The compound is capable of binding to κB sites and reducing the expression of various NF-κB–driven genes including IL6 and IL8 by qRT-PCR. Chromatin immunoprecipitation experiments demonstrate a reduction of p65 occupancy within the proximal promoters of those genes. Genome-wide expression analysis by RNA-seq compares the DNA-binding polyamide with the well-characterized NF-κB inhibitor PS1145, identifies overlaps and differences in affected gene groups, and shows that both affect comparable numbers of TNF-α–inducible genes. Inhibition of NF-κB DNA binding via direct displacement of the transcription factor is a potential alternative to the existing antagonists.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
    Publication Date: 2011-05-14
    Description: Author(s): Isabella Gierz, Fabian Meier, J. Hugo Dil, Klaus Kern, and Christian R. Ast A giant spin splitting has been observed in surface alloys on noble metal (111) surfaces as a result of a strong structural modification at the surface as well as the large atomic spin-orbit interaction (SOI) of the alloy atoms. These surface alloys are an ideal playground to manipulate both the siz... [Phys. Rev. B 83, 195122] Published Fri May 13, 2011
    Keywords: Electronic structure and strongly correlated systems
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
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  • 10
    Publication Date: 2011-04-28
    Description: Author(s): Dandan Guan, Marco Bianchi, Shining Bao, Edward Perkins, Fabian Meier, J. Hugo Dil, Jürg Osterwalder, and Philip Hofmann The electron-phonon coupling strength of the ( sqrt[3] × sqrt[3] )R30^{°} Bi/Ag(111) surface alloy is investigated by temperature-dependent angle-resolved photoemission. The electron-phonon coupling strength for the Rashba-split surface state, as expressed by the mass-enhancement parameter λ, is ... [Phys. Rev. B 83, 155451] Published Wed Apr 27, 2011
    Keywords: Surface physics, nanoscale physics, low-dimensional systems
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
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