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Biological applications of triplex forming oligonucleotides will require the development of oligomers with high avidity and specificity. We examined the binding enhancement resulting from intercalator conjugation to both parallel design (polythymidine T15) and antiparallel design (polypurine AG15, for binding a 15 base pair polypurine-polypyrimidine sequence in the IL-2R alpha gene enhancer) oligomers under various ionic strength and temperature conditions. Oligonucleotides were conjugated through a urea link to 6,9 diamino-3-methoxy acridine (to give T15C and AG15C). Intercalator conjugation dramatically enhanced the specific triplex binding avidity (Kd = 5 nM for AG15C and 275 nM for T15C at 25 degrees C, compared to 2 microM for AG15 and > 50 microM for T15 at 25 degrees C), without detectable binding to an inappropriate target sequence. Surprisingly, triplex formation with AG15C occurred at lower Mg2+ concentrations than with T15C. AG15 and AG15C showed rapid Mg2+ dependent self association, but not T15C or T15. T15C triplex formation occurred rapidly (completion in less than 4 min), while AG15C bound to its target sequence more slowly over 20-24 h. Thus, binding constants in the low nanomolar range are now achievable with intercalator conjugated polypurine antiparallel binding oligonucleotides, a prerequisite for biological applications of such agents.  相似文献   
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Placing the radiators of antenna arrays closer than aggravates the problem of power mismatch. Based on efficiency considerations, a general analysis of this effect is presented, putting forward a simple tool to quantify, compare, and optimize the performance of antenna arrays. This analysis is not restricted with respect to the number of radiators or the degree of compactness. In order to improve power matching, a systematic approach for the design of lossless decoupling and matching networks based on 180 directional couplers is suggested for up to eight radiators. Implications of network losses, which have not yet received appropriate attention by researchers in the past, will be analyzed and discussed by means of a manufactured three-element prototype array.  相似文献   
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Cone-beam type X-ray computed tomography (CBCT) is a potential method to measure three-dimensional phase distributions in vessels. An example for that is the measurement of gas profiles in stirred chemical reactors. Such data are highly valuable for the assessment and evaluation of chemical processes, for optimisation of the reactor and stirrer design, and for evaluation of computational fluid dynamics codes used to model the fluid flow and heat transfer in reactive systems. However, there are considerable difficulties for accurate quantitative measurements due to beam hardening and radiation scattering effects. In a theoretical and experimental work we have investigated the non-linear effects of both physical phenomena and developed a suitable measurement setup as well as calibration and software correction methods to achieve a highly accurate measurement of void fraction profiles with CBCT.  相似文献   
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This paper addresses the problem of finding the parameters of the arrival law which most significantly influence expected occupation and loss of a finite capacity queue. The input process is supposed to be ergodic and wide sense stationary. We show that it is mostly possible to fit an MMPP(2) to the decisive parameters of observational data. Numerical examples illustrate the importance of the decisive parameters, called key parameters, and also show the accuracy of the proposed fitting procedure. Finally, in the appendix we present the solution of the finite capacity queueing problem with Special Semi Markov Process (SSMP) arrivals and a general service strategy.  相似文献   
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The response time of the instrument is a crucial parameter for the measurement of accurate morphology and latency of the acoustic reflex. An improved impedance meter accounting for this particular problem was designed for the measurement of the contralateral acoustic reflex. The temporal characteristic of the measurement apparatus is shown, as well as an example of an application in a normal hearing individual. The module can be incorporated into already existing instruments with some modifications  相似文献   
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Vancomycin hydrochloride (VCM) has an antibacterial action against Gram positive bacteria, e.g., Methicillin-resistant Staphylococcus aureus (MRSA). In the clinical situation, there are patients with serious infections, being infected with not only MRSA, but also with Gram negative bacteria like Pseudomonas aeruginosa. Because VCM has the adverse reaction of nephrotoxicity, we are apprehensive about using VCM with other antibiotics, which might increase this problem. Therefore, the nephrotoxic effects and pharmacokinetics of VCM were examined in rabbits and compared with those in rabbits administered with VCM and other antibiotics. Responses indicating nephrotoxicity such as increases of serum creatinine concentration and BUN and morphological changes of the kidney were induced by the single injection of VCM at 300 mg/kg, i.v. In contrast, no abnormality of clinical data and morphological alteration were observed in the groups injected with VCM and imipenem (IPM)-cilastatin sodium (CS), flomoxef sodium (FMOX) or fosfomycin sodium (FOM). This was not true for groups injected with VCM and ceftazidime, cefpimizole sodium (CPIZ) or cefoperazone sodium. Clearance of VCM increased obviously in the groups injected with VCM and IPM-CS, FMOX or FOM, but decreased in those given VCM and CPIZ. Since the renal concentrations of VCM in the groups that were administered VCM with IPM-CS, FMOX or FOM were lower than that in the control group, IPM-CS, FMOX and FOM may decrease the nephrotoxicity of VCM by inhibiting its uptake into the kidney.  相似文献   
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