Isolation and characterization of the mouse gene for the type 3 iodothyronine deiodinase

The type 3 iodothyronine deiodinase (D3) is a selenoenzyme that inactivates thyroid hormones by removing a iodine from the 5-position of the tyrosyl ring. D3 is highly expressed in many tissues during the early stages of development, and its activity is regulated by selected growth factors and various hormones. To gain further insights into the structure, functional role, and regulation of this enzyme, we screened a mouse liver genomic library with a rat D3 complementary DNA probe and isolated a 12-kb clone coding for the Dio3. Restriction analysis followed by Southern blotting and nucleotide sequencing demonstrated that the Dio3 contains a single exon, 1853 bp in length, that encodes the entire length of the messenger RNA expressed in murine placenta and neonatal skin. Primer extension experiments identified two potential transcriptional start sites located 77 and 60 nt upstream of the ATG translational start codon. The region immediately 5' to the start sites contains consensus TATA, CAAT, and GC elements. Furthermore, a 526-nucleotide genomic fragment from this region was demonstrated to efficiently drive a luciferase reporter construct when transfected into COS-7, XTC-2, or XL-2 cells or into primary cultures of rat preadipocytes derived from neonatal brown fat. In conclusion, D3 transcripts in the placenta and skin are encoded by the Dio3 gene from a single exon whose expression is regulated by an upstream region that contains several consensus promoter elements. Further characterization of this gene will provide new insights into the factors regulating the unique pattern of D3 expression during development

Performance Evaluation of Adaptive Scientific Applications using TAU

Fueled by increasing processor speeds and high speed interconnection networks, advances in high performance computer architectures have allowed the development of increasingly complex large scale parallel systems. For computational scientists, programming these systems efficiently is a challenging task. Understanding the performance of their parallel applications i

Dual Mechanisms of Regulation of Type I lodothyronine 5'-Deiodinase in the Rat Kidney, Liver, and Thyroid Gland Implications for the Treatment of Hyperthyroidism with Radiographic Contrast Agents

Abstract Introduction Alterations in thyroid hormone status and the administration of radiographic contrast agents can markedly influence iodothyronine metabolism and, in particular, the activity of type I 5'-deiodinase (51I). In the present studies, the mechanisms responsible for these effects have been reassessed. As previously reported, the addition of iopanoic acid (1OP) to broken cell preparations resulted in a competitive pattern of 5DI inhibition. However, the in vivo administration to rats of IOP or 3,3',5'-triiodothyronine (rT3) resulted in a noncompetitive pattern of inhibition of 51)I in the liver, kidney, and thyroid gland, whereby marked decreases in maximal enzyme velocity (Vx) were noted, with no change in the value of the Michaelis-Menten constant. In rats rendered hyperthyroid by the injection of 3,5,3'-triiodothyronine (T3), 5DI activity was significantly increased in the liver and the kidney. Alterations in thyroid hormone status also have important and direct "autoregulatory" effects on the cellular processes that metabolize these hormones (2). In the rat, hyperthyroidism results in a marked increase in the rate of "local" T3 production in the liver (3, 4). This effect is secondary, in part, to an increase in activity of type I 5'-deiodinase (51DI), the principal enzymatic process responsible for hepatic thyroxine (T4) to T3 conversion (5). In contrast to this activating effect of thyroid hormones on 5'DI in the liver (and kidney Radiographic contrast agents such as iopanoic acid (IOP) and sodium ipodate (NaIp) inhibit T4 to T3 conversion in man (7-9) and experimental animals (10-12), and offer an alternative to the thionamides in the treatment ofGraves' disease In tissue homogenates, IOP and NaIp act as competitive inhibitors of both 5D

Performance analysis integration in the Uintah software development cycle

ManuscriptThe increasing complexity of high-performance computing environments and programming methodologies presents challenges for empirical performance evaluation. Evolving parallel and distributed systems require performance technology that can be flexibly configured to observe different events and associated performance data of interest. It must also be possible to integrate performance evaluation techniques with the programming paradigms and software engineering methods. This is particularly important for tracking performance on parallel software projects involving many code teams over many stages of development. This paper describes the integration of the TAU and XPARE tools in the Uintah Computational Framework (UCF). Discussed is the use of performance mapping techniques to associate low-level performance data to higher levels of abstraction in UCF and the use of performance regression testing to provides a historical portfolio of the evolution of application performance. A scalability study shows the benefits of integrating performance technology in building large-scale parallel applications

Flight Development for Cryogenic Fluid Management in Support of Exploration Missions

This paper describes the results of the "Experimentation for the Maturation of Deep Space Cryogenic Refueling Technology" study. The purposes of this study were to identify cryogenic fluids management technologies requiring low gravity flight experiments to bring to technology readiness level (TRL) 5-6; to study many possible flight experiment options; and to develop near-term low-cost flight experiment concepts to mature core technologies of refueling. A total of twenty-five white papers were prepared in the course of this study. Each white paper is briefly summarized and relevant references cited. A total of 90 references are cited

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

A SUTRA Model of Seawater Intrusion in Western Long Island, New York

Program for the Tenth Conference on Geology of Long Island and Metropolitan New Yor

Pharmacological Effects of Asiatic acid in Glioblastoma Cells under Hypoxia

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide (TMZ) and cisplatin, the median survival rate remains low (<16 months). Combined with increasing drug resistance and the inability of some compounds to cross the blood brain barrier (BBB), novel compounds are being sought for the treatment of this disease. Here, we aimed to examine the pharmacological effect of Asiatic acid (AA) in glioblastoma under hypoxia. To investigate the effects of AA on cell viability, proliferation, apoptosis and wound healing, SVG p12 fetal glia and U87-MG grade IV glioblastoma cells were cultured under normoxic (21% O2) and hypoxic (1% O2) conditions. In normoxia, AA reduced cell viability in U87-MG cells in a time and concentration-dependent manner. A significant decrease in viability, compared to cisplatin, was observed following 2hrs of AA treatment with no significant changes in cell proliferation or cell cycle progression observed. Under hypoxia, a significantly greater number of cells underwent apoptosis in comparison to cisplatin. While cisplatin showed a reduction in wound healing in normoxia, a significantly greater reduction was observed following AA treatment. An overall reduction in wound healing was observed under hypoxia. The results of this study show that AA has cytotoxic effects on glioma cell lines and has the potential to become an alternative treatment for glioblastoma

Systematic review of the effects of the intestinal microbiota on selected nutrients and non-nutrients

The systematic review demonstrates that the IM plays a major role in the breakdown and transformation of the dietary substrates examined. However, recent human data are limited with the exception of data from studies examining fibres and polyphenols. Results observed in relation with dietary substrates were not always consistent or coherent across studies and methodological limitations and differences in IM analyses made comparisons difficult. Moreover, non-digestible components likely to reach the colon are often not well defined or characterised in studies making comparisons between studies difficult if not impossible. Going forward, further rigorously controlled randomised human trials with well-defined dietary substrates and utilizing omic-based technologies to characterise and measure the IM and their functional activities will advance the field. Current evidence suggests that more detailed knowledge of the metabolic activities and interactions of the IM hold considerable promise in relation with host health

Radiometric measurements of the microwave emissivity of foam

Includes bibliographical references.Radiometric measurements of the microwave emissivity of foam were conducted during May 2000 at the Naval Research Laboratory's Chesapeake Bay Detachment using radiometers operating at 10.8 and 36.5 GHz. Horizontal and vertical polarization measurements were performed at 36.5 GHz; horizontal, vertical, +45°, ­45°, left-circular, and right-circular polarization measurements were obtained at 10.8 GHz. These measurements were carried out over a range of incidence angles from 30° to 60°. Surface foam was generated by blowing compressed air through a matrix of gas-permeable tubing supported by an aluminum frame and floats. Video micrographs of the foam were used to measure bubble size distribution and foam layer thickness. A video camera was boresighted with the radiometers to determine the beam-fill fraction of the foam generator. Results show emissivities that were greater than 0.9 and approximately constant in value over the range of incidence angles for vertically polarized radiation at both 10.8 and 36.5 GHz, while emissivities of horizontally polarized radiation showed a gradual decrease in value as incidence angle increased. Emissivities at +45°, ­45°, left-circular, and right-circular polarizations were all very nearly equal to each other and were in turn approximately equal to the average values of the horizontal and vertical emissivities in each case.This work was sponsored by the Department of the Navy, Office of Naval Research under Award N0014-00-1-280 to the University of Massachusetts, Award N00014-00-0152 to the University of Washington, and Award N0001400WX21032 to the Naval Research Laboratory