RESUMEN
The Materials Irradiation Experiment (MITE-E) was constructed at the University of Wisconsin-Madison Inertial Electrostatic Confinement Laboratory to test materials for potential use as plasma-facing materials (PFMs) in fusion reactors. PFMs in fusion reactors will be bombarded with x-rays, neutrons, and ions of hydrogen and helium. More needs to be understood about the interactions between the plasma and the materials to validate their use for fusion reactors. The MITE-E simulates some of the fusion reactor conditions by holding samples at temperatures up to 1000 °C while irradiating them with helium or deuterium ions with energies from 10 to 150 keV. The ion gun can irradiate the samples with ion currents of 20 µA-500 µA; the typical current used is 72 µA, which is an average flux of 9 × 10(14) ions/(cm(2) s). The ion gun uses electrostatic lenses to extract and shape the ion beam. A variable power (1-20 W), steady-state, Nd:YAG laser provides additional heating to maintain a constant sample temperature during irradiations. The ion beam current reaching the sample is directly measured and monitored in real-time during irradiations. The ion beam profile has been investigated using a copper sample sputtering experiment. The MITE-E has successfully been used to irradiate polycrystalline and single crystal tungsten samples with helium ions and will continue to be a source of important data for plasma interactions with materials.
RESUMEN
The Cynomolgus monkey may provide an alternative pharmacological model in which to evaluate the efficacy of novel inhibitors of the two known human steroid 5 alpha-reductase (SR) isoenzymes. To evaluate the suitability of this species at the level of the molecular targets, a Cynomolgus monkey prostate cDNA library was prepared and screened using human SR type 1 and 2 cDNAs as hybridization probes. Two distinct cDNA sequences were isolated encoding the monkey type 1 and 2 SR isoenzymes. These sequences share 93 and 95% amino acid sequence identity with their human enzyme counterparts, respectively. Difference in monkey type 1 SR, however, was found within the contiguous four amino acids corresponding to the regions in the human and rat sequences that have been proposed previously to influence steroid and inhibitor affinities. Subsequently, both monkey cDNAs were individually expressed in a mammalian cell (CHO) line. Enzyme activities of both monkey SRs were localized to the membrane fractions of CHO cell extracts. Like the human and rat enzymes, the monkey type 1 and type 2 SRs were most active at neutral and low pH, respectively. The results of inhibition studies with over 30 known SR inhibitors, including epristeride, 4MA, and finasteride, indicate that the monkey SR isoenzymes are functionally more similar to the human than the rat homologues. The results from initial velocity and inhibition studies as functions of pH with the human and monkey type 2 SRs also compare favorably. These results, together, suggest that the monkey SR isoenzymes are structurally and functionally comparable on a molecular level to their respective human counterparts, supporting the relevance and use of the Cynomolgus monkey as a pharmacological model for in vivo evaluation of SR inhibitors.
Asunto(s)
3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Isoenzimas/genética , Próstata/enzimología , Esteroides/metabolismo , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/clasificación , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/metabolismo , Inhibidores de 5-alfa-Reductasa , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Clonación Molecular , ADN Complementario/genética , Expresión Génica , Humanos , Concentración de Iones de Hidrógeno , Macaca fascicularis , Masculino , Datos de Secuencia Molecular , ARN Mensajero/genética , Ratas , Proteínas Recombinantes/metabolismo , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
Specificity of an enzyme inhibitor can have profound implications upon the compound's therapeutic potential, utility and safety profile. As potent inhibitors of human steroid 5 alpha-reductase (SR) the 3-androstene-3-carboxylic acids, or steroidal acrylates, may be useful in treatment of diseases such as benign prostatic hyperplasia for which 5 alpha-dihydrotestosterone (DHT) appears to be a causative agent. To determine its specificity profile, the interactions of a representative compound from this class, N-(t-butyl)androst-3,5-diene-17 beta-carboxamide-3-carboxylic acid (epristeride, SK&F 105657), have been studied with 7 other steroid processing enzymes and 5 steroid hormone receptors. The affinity of epristeride for each of these 12 potential targets was found to be at least 1000-fold weaker than that for SR, the intended target. In addition, using samples of the individually expressed two known forms of human SRs, epristeride has been shown to be a selective inhibitor of the recombinant human SR type 2, the predominant activity found in the prostate of man. Nonetheless, the mechanisms of SR inhibition for both isoenzymes involve formation of a ternary complex with epristeride, NADP+, and enzyme. Epristeride, consequently, has been shown to be an uncompetitive inhibitor versus steroid substrate of both human SR isoenzymes. These results suggest that this 3-androstene-3-carboxylic acid is a specific and selective inhibitor of the human type 2 SR, and that epristeride is an attractive compound for further investigation as a safe and effective therapeutic agent in the potential treatment of disease states associated with DHT-induced tissue growth.
Asunto(s)
Inhibidores de 5-alfa-Reductasa , Androstadienos/farmacología , Isoenzimas/antagonistas & inhibidores , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/metabolismo , Androstadienos/metabolismo , Animales , Humanos , Hígado/enzimología , Masculino , NADP/metabolismo , Ratas , Proteínas Recombinantes/antagonistas & inhibidoresRESUMEN
A theoretical description of the polarization characteristics of an altazimuth sky scanner optical system is presented based on Mueller-Stokes calculus. The theoretical results are verified experimentally. This unique computer-driven optical system was designed to perform laboratory studies of skylight as well as celestial objects during day or night and has the advantage that there are no space or weight limitations in the use of additional apparatus. The two parallel 45 degrees tilt mirrors that bring the light from any point of the sky down to the laboratory introduce some amount of intrinsic polarization, however. For that reason proper interpretation of the raw data requires a theoretical understanding of the polarization features of the instrument and accurate experimental determination of the elements of the Mueller-Stokes matrix describing the polarizing and depolarizing action of the system. This is especially true in the case of skylight intensity and polarization studies. A comparison of the theoretical and experimental results is given with an indication of the possible reasons for slight differences found between them.
RESUMEN
A method has been developed to determine total ozone from multispectral measurements of the direct solar irradiance. The total ozone is determined by a least squares fit to the spectrum between 290 nm and 380 nm. The aerosol extinction is accounted for by expanding it in a power series in wavelength; use of the linear term proved adequate. A mobile laboratory incorporating a sky scanner has been developed and used to obtain data to verify the method. Sun tracking, wavelength setting of the double monochromator, and data acquisition are under control of a minicomputer. Results obtained at Wallops Island, Virginia, and Palestine, Texas, agree well with simultaneous Dobson and Canterbury spectrometer and balloon ECC ozonesonde values. The wavelength calibration of the monochromator and the values for the normalized ozone absorption are the most important factors in an accurate determination of total ozone.
RESUMEN
An improved system has been implemented for measuring the ratio of the diffuse skylight to the direct sunlight in the biologically active region of the uv near the atmospheric limit. It combines a double monochromator employing holographic gratings for reduction of stray light with a cooled photomultiplier tube to provide a greatly improved SNR below 300 nm. Data may be obtained in either a scan mode or a narrowband photometry mode; in the latter mode accurate ratios have been obtained near 290 nm. Representative data are discussed along with a theoretical model of the ratio. The system is compact enough for use in a mobile monitoring system.