25 research outputs found

    Translational actomyosin research: fundamental insights and applications hand in hand

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    Evaluation of refractory materials for a nuclear waste incinerator

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    An experiment to find a suitable refractory lining for a nuclear waste incinerator has been completed. Eleven brick and six castable products were analyzed by optical and scanning microscopy. All the materials were fashioned into cup shapes and subjected to temperatures ranging from 800 to 1200/sup 0/C for as long as six weeks. Some of the cups were charged weekly with pellets made from ash materials that would contact an incinerator liner. Refractory products containing a high percentage of aluminum oxide had the greatest resistance to cracking and slag buildup. 35 figures

    Millville Wind Turbine Generator: failure analysis and corrective design modification

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    Fatigue cracks in the blade skins of the Millville Wind Turbine Generator were fractographically analyzed. It is believed they were caused by large flapwise deflections during a wind storm on December 4, 1978. The deflections caused the skin to buckle, which initiated rapidly growing fatigue cracks. Propagation continued to the leading edge, moving radially inward and outward along the leading edge radius. Communication between Rockwell and Millville resulted in a modified blade design which incorporates several corrective techniques

    A fluorescently labeled dendronized polymer-enzyme conjugate carrying multiple copies of two different types of active enzymes

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    A hybrid structure of a synthetic dendronized polymer, two different types of enzymes (superoxide dismutase and horseradish peroxidase), and a fluorescent dye (fluorescein) was synthesized. Thereby, a single polymer chain carried multiple copies of the two enzymes and the fluorescein. The entire attachment chemistry is based on UV/vis-quantifiable bis-aryl hydrazone bond formation that allows direct quantification of bound molecules: 60 superoxide dismutase, 120 horseradish peroxidase, and 20 fluorescein molecules on an average polymer chain of 2000 repeating units. To obtain other enzyme ratios the experimental conditions were altered accordingly. Moreover, it could be shown that both enzymes remained fully active and catalyzed a two-step cascade reaction

    PRECIPITATION CHARACTERISTICS OF ROCKY FLATS BERYLLIUM INGOT SHEET.

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    A Fluorescently Labeled Dendronized Polymer–Enzyme Conjugate Carrying Multiple Copies of Two Different Types of Active Enzymes

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    A hybrid structure of a synthetic dendronized polymer, two different types of enzymes (superoxide dismutase and horseradish peroxidase), and a fluorescent dye (fluorescein) was synthesized. Thereby, a single polymer chain carried multiple copies of the two enzymes and the fluorescein. The entire attachment chemistry is based on UV/vis-quantifiable bis-aryl hydrazone bond formation that allows direct quantification of bound molecules: 60 superoxide dismutase, 120 horseradish peroxidase, and 20 fluorescein molecules on an average polymer chain of 2000 repeating units. To obtain other enzyme ratios the experimental conditions were altered accordingly. Moreover, it could be shown that both enzymes remained fully active and catalyzed a two-step cascade reaction

    Structure and Enzymatic Properties of Molecular Dendronized Polymer−Enzyme Conjugates and Their Entrapment inside Giant Vesicles. Langmuir

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    Macromolecular hybrid structures were prepared in which two types of enzymes, horseradish peroxidase (HRP) and bovine erythrocytes Cu,Zn-superoxide dismutase (SOD), were linked to a fluorescently labeled, polycationic, dendronized polymer (denpol). Two homologous denpols of first and second generation were used and compared, and the activities of HRP and SOD of the conjugates were measured in aqueous solution separately and in combination. In the latter case the efficiency of the two enzymes in catalyzing a two-step cascade reaction was evaluated. Both enzymes in the two types of conjugates were highly active and comparable to free enzymes, although the efficiency of the enzymes bound to the second-generation denpol was significantly lower (up to a factor of 2) than the efficiency of HRP and SOD linked to the first-generation denpol. Both conjugates were analyzed by atomic force microscopy (AFM), confirming the expected increase in object size compared to free denpols and demonstrating the presence of enzyme molecules localized along the denpol chains. Finally, giant phospholipid vesicles with diameters of up to about 20 ÎŒm containing in their aqueous interior pool a first-generation denpol−HRP conjugate were prepared. The HRP of the entrapped conjugate was shown to remain active toward externally added, membrane-permeable substrates, an important prerequisite for the development of vesicular multienzyme reaction systems

    Upregulation of Key Molecules for Targeted Imaging and Therapy.

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    Targeted diagnosis and therapy enable precise tumor detection and treatment. Successful examples for precise tumor targeting are diagnostic and therapeutic radioligands. However, patients with tumors expressing low levels of the relevant molecular targets are deemed ineligible for such targeted approaches. METHODS We performed a screen for drugs that upregulate the somatostatin receptor subtype 2 (sstr2). Then, we characterized the effects of these drugs on transcriptional, translational, and functional levels in vitro and in vivo. RESULTS We identified 9 drugs that act as epigenetic modifiers, including the inhibitor of DNA methyltransferase decitabine as well as the inhibitors of histone deacetylase tacedinaline and romidepsin. In vitro, these drugs upregulated sstr2 on transcriptional, translational, and functional levels in a time- and dose-dependent manner. Thereby, their combinations revealed synergistic effects. In vivo, drug-based sstr2 upregulation improved the tumor-to-background and tumor-to-kidney ratios, which are the key determinants of successful sstr2-targeted imaging and radiopeptide therapy. CONCLUSION We present an approach that uses epigenetic modifiers to improve sstr2 targeting in vitro and in vivo. Translation of this method into the clinic may potentially convert patients ineligible for targeted imaging and therapy to eligible candidates
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