1,535 research outputs found

    2D cross-hole MMR - survey design and sensitivity analysis for cross-hole applications of the magnetometric resistivity method

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    The magnetometric resistivity (MMR) method measures low-level (typically < 1nT) magnetic fields associated with a low-frequency (1 - 20 Hz) electric current impressed into the ground to determine the subsurface resistivity structure. As a step towards the implementation of MMR for cross-hole imaging, in this Ph.D. thesis several aspects of survey design for near-surface applications are discussed. In numerical, laboratory and field studies the potential of MMR for advanced structural characterization and process monitoring at the field scale is assessed. The 2D cross-hole setup considers borehole measurements of the magnetic field as response to borehole current injection; in this case the magnetic field has only one non-zero component (perpendicular to the imaging plane – By_{y}). Optimal survey parameters are inferred from numerical studies regarding signal strength, source-generated noise level and resolving power. Modeling of MMR responses over 2D conductivity structures was performed using a newly developed 2.5D FE program MMRMod. It could be proven that current injection via vertical dipoles provides superior signal-to-noise ratio compared to other transmitter configurations. Analyzing resolving power in terms of sensitivity distribution reveals that dipole configurations reflect confined subsurface volumes, advantageous for tomographic surveys and that transmitter-receiver combinations exceeding an offset equal to the borehole separation do not contribute significantly to the overall crosshole resolution. With the assistance of laboratory testing two concepts for solving two major difficulties inherent in cross-hole MMR field surveying are derived: the correction for the arbitrary borehole sensor orientation and the correction for parasitic correlated noise fields induced by the measurement system itself. The (latter) measurement method with phase switching is thereby first-time successfully applied to the processing of MMR data. In addition, the proposed data processing procedure includes modern lock-in-technique and has proven to be an appropriate tool for an effective information extraction from the measured magnetic fields. Finally, cross-hole MMR data were collected during a water infiltration experiment at the Gorgonzola test site. Acquisition and processing are accomplished according to the developed tomographic measurement approach involving multiple-offset transmitter-receiver arrangements and repeated measurements with time (time-lapse mode). Data, obtained during initially conducted background measurement, are qualitatively validated based on two different conductivity models, one of which is obtained from the inversion of independently collected ERT data. Importantly, the comparison of field data with predicted model curves suggests better resolvability of contrasts by MMR than by ERT. Moreover, the analysis of time-lapse measurements reveals a clear spatiotemporal dependence of the anomalous MMRresponse (MMR response with respect to background value) based upon the water saturation

    Book Reviews

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    Wolfgang Weiss, Shakespeare in Bayern und auf Bairisch (Shakespeare in Bavaria and in Bavarian Regional Dialects), Passau: Verlag Karl Stutz, 2008, 1st ed. Pp. 201. ISBN: 978-3-88849-090-3. Manfred Pfister and Jürgen Gutsch (eds.), William Shakespeare’s Sonnets for the First Time Globally Reprinted: A Quatercentenary Anthology (with a DVD), Dozwil: Edition Signathur, 2009. Pp. 752. ISBN 978-3-908141-54-9. Re-playing Shakespeare in Asia, ed. Poonam Trivedi, Minami Ryuta, New York: Routledge 2010, 1st ed. Pp. 201. ISBN: 978-3-88849-090-3

    Cadets’ Perceptions of Gymnastics Instruction for Officer Development

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    The United States Military Academy has offered gymnastics instruction since 1838. Gymnastics continues to be an integral component of the physical education curriculum. The purpose of this study was to investigate cadets\u27 perceptions of their experiences in a required gymnastics course using the critical incident technique. Students described experiences in the gymnastics class that they believed had a positive or negative influence on their development as cadets and future Army officers. Key elements of their responses were classified into 16 positively perceived and 11 negatively perceived categories. The top positive categories were confidence, encouragement, fear management, modeling, additional instruction, and teamwork. The top negative categories included lack of time, helplessness, discouragement, lack of relevance, unfair grading, and injur

    Cancer cachexia-when proteasomal inhibition is not enough.

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    Myocyte Enhancer Factor 2 and Class II Histone Deacetylases Control a Gender-Specific Pathway of Cardioprotection Mediated by the Estrogen Receptor

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    Gender differences in cardiovascular disease have long been recognized and attributed to beneficial cardiovascular actions of estrogen. Class II histone deacetylases (HDACs) act as key modulators of heart disease by repressing the activity of the myocyte enhancer factor (MEF)2 transcription factor, which promotes pathological cardiac remodeling in response to stress. Although it is proposed that HDACs additionally influence nuclear receptor signaling, the effect of class II HDACs on gender differences in cardiovascular disease remains unstudied

    Tectonic significance of changes in post-subduction Pliocene-Quaternary magmatism in the south east part of the Carpathian-Pannonian Region

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    The south-eastern part of the Carpathian–Pannonian region records the cessation of convergence between the European platform/Moesia and the Tisza–Dacia microplate. Plio-Quaternary magmatic activity in this area, in close proximity to the ‘Vrancea zone’, shows a shift from normal calc-alkaline to much more diverse compositions (adakite-like calc-alkaline, K-alkalic, mafic Na-alkalic and ultrapotassic), suggesting a significant change in geodynamic processes at approximately 3 Ma. We review the tectonic setting, timing, petrology and geochemistry of the post-collisional volcanism to constrain the role of orogenic building processes such as subduction or collision on melt production and migration. The calc-alkaline volcanism (5.3–3.9 Ma) marks the end of normal subduction-related magmatism along the post-collisional Călimani–Gurghiu–Harghita volcanic chain in front of the European convergent plate margin. At ca. 3 Ma in South Harghita magma compositions changed to adakite-like calc-alkaline and continued until recent times (< 0.03 Ma) interrupted at 1.6–1.2 Ma by generation of Na and K-alkalic magmas, signifying changes in the source and melting mechanism. We attribute the changes in magma composition in front of the Moesian platform to two main geodynamic events: (1) slab-pull and steepening with opening of a tear window (adakite-like calc-alkaline magmas) and (2) renewed contraction associated with deep mantle processes such as slab steepening during post-collisional times (Na and K-alkalic magmas). Contemporaneous post-collisional volcanism at the eastern edge of the Pannonian Basin at 2.6–1.3 Ma was dominated by Na-alkalic and ultrapotassic magmas, suggesting a close relationship with thermal asthenospheric doming and strain partitioning related to the Adriatic indentation. Similar timing, magma chamber processes and volume for K-alkalic (shoshonitic) magmas in the South Apuseni Mountains (1.6 Ma) and South Harghita area at a distance of ca. 200 km imply a regional connection with the inversion tectonics

    Small-molecule inhibition of MuRF1 attenuates skeletal muscle atrophy and dysfunction in cardiac cachexia

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    Background; Muscle ring finger 1 (MuRF1) is a muscle‐specific ubiquitin E3 ligase activated during clinical conditions associated with skeletal muscle wasting. Yet, there remains a paucity of therapeutic interventions that directly inhibit MuRF1 function, particularly in vivo. The current study, therefore, developed a novel compound targeting the central coiled coil domain of MuRF1 to inhibit muscle wasting in cardiac cachexia. Methods; We identified small molecules that interfere with the MuRF1–titin interaction from a 130 000 compound screen based on Alpha Technology. A subset of nine prioritized compounds were synthesized and administrated during conditions of muscle wasting, that is, to C2C12 muscle cells treated with dexamethasone and to mice treated with monocrotaline to induce cardiac cachexia. Results; The nine selected compounds inhibited MuRF1–titin complexation with IC50 values <25 μM, of which three were found to also inhibit MuRF1 E3 ligase activity, with one further showing low toxicity on cultured myotubes. This last compound, EMBL chemical core ID#704946, also prevented atrophy in myotubes induced by dexamethasone and attenuated fibre atrophy and contractile dysfunction in mice during cardiac cachexia. Proteomic and western blot analyses showed that stress pathways were attenuated by ID#704946 treatment, including down‐regulation of MuRF1 and normalization of proteins associated with apoptosis (BAX) and protein synthesis (elF2B‐delta). Furthermore, actin ubiquitinylation and proteasome activity was attenuated. Conclusions; We identified a novel compound directed to MuRF1's central myofibrillar protein recognition domain. This compound attenuated in vivo muscle wasting and contractile dysfunction in cardiac cachexia by protecting de novo protein synthesis and by down‐regulating apoptosis and ubiquitin‐proteasome‐dependent proteolysis

    Activation of Tripartite Motif Containing 63 Expression by Transcription Factor EB and Transcription Factor Binding to Immunoglobulin Heavy Chain Enhancer 3 Is Regulated by Protein Kinase D and Class IIa Histone Deacetylases

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    Rationale: The ubiquitin-proteasome system (UPS) is responsible for skeletal muscle atrophy. We showed earlier that the transcription factor EB (TFEB) plays a role by increasing E3 ubiquitin ligase muscle really interesting new gene-finger 1(MuRF1)/tripartite motif-containing 63 (TRIM63) expression. MuRF 1 ubiquitinates structural proteins and mediates their UPS-dependent degradation. We now investigated how TFEB-mediated TRIM63 expression is regulated. Objective: Because protein kinase D1 (PKD1), histone deacetylase 5 (HDAC5), and TFEB belong to respective families with close structural, regulatory, and functional properties, we hypothesized that these families comprise a network regulating TRIM63 expression. Methods and Results: We found that TFEB and transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) activate TRIM63 expression. The class IIa HDACs HDAC4, HDAC5, and HDAC7 inhibited this activity. Furthermore, we could map the HDAC5 and TFE3 physical interaction. PKD1, PKD2, and PKD3 reversed the inhibitory effect of all tested class IIa HDACs toward TFEB and TFE3. PKD1 mediated nuclear export of all HDACs and lifted TFEB and TFE3 repression. We also mapped the PKD2 and HDAC5 interaction. We found that the inhibitory effect of PKD1 and PKD2 toward HDAC4, HDAC5, and HDAC7 was mediated by their phosphorylation and 14-3-3 mediated nuclear export. Conclusion: TFEB and TFE3 activate TRIM63 expression. Both transcription factors are controlled by HDAC4, HDAC5, HDAC7, and all PKD-family members. We propose that the multilevel PKD/HDAC/TFEB/TFE3 network tightly controls TRIM63 expression
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