25 research outputs found
Evaluation of refractory materials for a nuclear waste incinerator
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
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
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
A Fluorescently Labeled Dendronized PolymerâEnzyme Conjugate Carrying Multiple Copies of Two Different Types of Active Enzymes
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 PolymerâEnzyme Conjugates and Their Entrapment inside Giant Vesicles. Langmuir
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 denpolâHRP 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
Erratum: Corrigendum: Sustained gastrointestinal activity of dendronized polymerâenzyme conjugates
Upregulation of Key Molecules for Targeted Imaging and Therapy.
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