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1.
Whether a sulfonylurea may be used together with insulin for treating NIDDM has been controversial. One view, based on older studies, has been that the additional benefit is too small or the level of glucose control achieved usually too poor to recommend this method. More recent studies of a more specific way of combining a sulfonylurea with insulin are more supportive. When a single injection of insulin taken in the evening is added to a sulfonylurea at the time of secondary failure of the sulfonylurea alone, glycemic control is quite simply and consistently restored to acceptable levels. At this time in the natural history of NIDDM, evening insulin combined therapy is more effective than a single injection of insulin alone, and just as effective as a more complex multiple-injection regimen without an oral agent. A recent multicenter trial of a new sulfonylurea, glimepiride, in combination with a single injection of 70/30 insulin before dinner has confirmed that this approach is safe and more consistently effective than insulin alone for obese patients beginning insulin in a setting resembling clinical practice. The available evidence suggests this form of combined therapy is suitable for routine use.  相似文献   
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DNA topoisomerases have been proposed as the proteins involved in the formation of the DNA-protein cross-links detected after ultraviolet light (UV) irradiation of cellular DNA. This possibility has been investigated by studying the effects of UV-induced DNA damage on human DNA topoisomerase I action. UV lesions impaired the enzyme's ability to relax negatively supercoiled DNA. Decreased relaxation activity correlated with the stimulation of cleavable complexes. Accumulation of cleavable complexes resulted from blockage of the rejoining step of the cleavage-religation reaction. Mapping of cleavage sites on the pAT153 genome indicated UV-induced cleavage at discrete positions corresponding to sites stimulated also by the topoisomerase I inhibitor camptothecin, except for one. Subsequent analysis at nucleotide level within the sequence encompassing the UV-specific cleavage site revealed the precise positions of sites stimulated by camptothecin with respect to those specific for UV irradiation. Interestingly, one of the UV-stimulated cleavage sites was formed within a sequence that did not contain dimerized pyrimidines, suggesting transmission of the distortion, caused by photodamage to DNA, into the neighboring sequences. These results support the proposal that DNA structural alterations induced by UV lesions can be sufficient stimulus to induce cross-linking of topoisomerase I to cellular DNA.  相似文献   
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The geometric component of the point spread function (PSF) of a gamma camera collimator can be determined analytically, and the penetration component can be calculated readily by numerical ray-tracing. A Monte Carlo simulation of photon transport which includes collimator scatter is developed. The simulation was implemented with an array processor which propagates up to 1024 photons in parallel, allowing accurate estimates of the total radial PSF in less than a day. The simulation was tested by imaging monoenergetic point sources of Tc-99m, Cr-51, and Sr-85 (140, 320, and 514 keV, respectively) on a General Electric Star Cam with low-energy, general-purpose, and medium-energy collimators. Comparisons of measured and simulated PSFs demonstrate the validity of the model and the significance of collimator scatter in the degradation of image quality.  相似文献   
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The aim of this work is to demonstrate the use of a commercial finite element package, ABAQUS EXPLICIT, to model ultrasonic guided waves in structural components. The particular application of interest is modeling the interaction of a broadband vertical bending mode with transverse-type defects in railroad tracks. This topic is part of a broader project on high-speed defect detection in rails by long-range ultrasonic inspections. Reflection coefficient spectra in the 20–45 kHz range are obtained for four different sizes and three different orientations of transverse head flaws. A preliminary study of Lamb waves in a free plate helps drawing modeling guidelines for the rail.  相似文献   
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The effect of niobium implantation (2×1016 and 1017 ions/cm2) on the oxidation behavior of a -TiAl-based intermetallic alloy Ti–48Al–2Cr in air at 800°C has been examined. Isothermal studies with exposure times up to 200 hr and cyclic-oxidation tests up to 800 hr revealed a negligible effect for the low implantation dose. However, a remarkable decrease in oxidation rates was observed for the material implanted with 1017 Nb ions/cm2. The improvement in the oxidation resistance appeared to be similar to that obtained by alloying of the intermetallic with a few atomic percent niobium. Possible mechanisms for the effect of niobium on the oxidation resistance of TiAl-base intermetallics are discussed in view of the results obtained for the implanted material.  相似文献   
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The objectives of this study are to provide detailed information about green roof performance in the Mediterranean climate (retained volume, peak flow reduction, runoff delay) and to identify a suitable modelling approach for describing the associated hydrologic response. Data collected during a 13-month monitoring campaign and a seasonal monitoring campaign (September-December 2008) at the green roof experimental site of the University of Genova (Italy) are presented together with results obtained in quantifying the green roof hydrologic performance. In order to examine the green roof hydrologic response, the SWMS_2D model, that solves the Richards' equation for two-dimensional saturated-unsaturated water flow, has been implemented. Modelling results confirm the suitability of the SWMS_2D model to properly describe the hydrologic response of the green roofs. The model adequately reproduces the hydrographs; furthermore, the predicted soil water content profile generally matches the observed values along a vertical profile where measurements are available.  相似文献   
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Journal of Intelligent Manufacturing - Remanufacturing includes disassembly and reassembly of used products to save natural resources and reduce emissions. While assembly is widely understood in...  相似文献   
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Using the process of "antibody antigenization," we engineered two antibody molecules carrying in the third complementarity-determining region of the heavy chain variable domain a 7-mer or a 15-mer peptide epitope of the first extracellular domain (D1) of human CD4 receptor--namely, Ser-Phe-Leu-Thr-Lys-Gly-Pro-Ser (SFLTKGPS; positions 42 through 49) and Gly-Ser-Phe-Leu-Thr-Lys-Gly-Pro-Ser-Lys-Leu-Asn-Asp-Arg-Ala (GSFLTKGPSKLNDRA; positions 41 through 55). These amino acid sequences are contained in the consensus binding site for the human immunodeficiency virus (HIV) on CD4 receptor. Both antigenized antibodies (AgAbs) bound recombinant gp120 and were recognized by a prototype monoclonal antibody to CD4 whose binding site is within amino acid residues 41-55. AgAbs were then used as immunogens in rabbits and mice to elicit a humoral response against CD4. Only the AgAb carrying the sequence 41GSFLTKGPSKLN-DRA55 induced a response against CD4. The induced antibodies showed specificity for the amino acid sequence of CD4 engineered in the AgAb molecule, were able to inhibit the formation of syncytia between human CD4+ T cells MOLT-3 and 8E5 (T cells that are constitutively infected with HIV), and stained human CD4+ CEM T cells. Four murine monoclonal antibodies were used to analyze the relationship between syncytia inhibition and CD4 binding at the single antibody level, and indicated that recognition of native CD4 is not an absolute requirement for inhibition of syncytia. This study demonstrates that antigenized antibodies can be used as immunogens to elicit site-specific and biologically active immunity to CD4. The importance of this approach as a general way to induce anti-receptor immunity and as a possible new measure to immunointervention in HIV infection is discussed.  相似文献   
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