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21.
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   
22.
This paper addresses the BIBO (bounded-input bounded-output) stability of a class of discrete 2-D quarter-plane filters in the presence of nonessential singularities of the second kind (NSSK's) on the unit bidisk. Conditions under which the double bilinear transformation (DBT) preserves stability are derived. The results presented here also extend the class of systems whose stability can be predicted. Use of the inverse DBT to produce a continuous equivalent of the discrete 2-D transfer function allows easy application of a continuous-domain equivalent of a criterion developed by Dautov. The necessary and sufficient condition for stability derived in this work provides a simple check for the class of systems under consideration. From this class of systems, it is also possible to construct stable pairs of mutually inverse transfer functions.  相似文献   
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Sleep deprivation and fragmentation occurring in the hospital setting may have a negative impact on the respiratory system by decreasing respiratory muscle function and ventilatory response to CO2. Sleep deprivation in a patient with respiratory failure may, therefore, impair recovery and weaning from mechanical ventilation. We postulate that light, sound, and interruption levels in a weaning unit are major factors resulting in sleep disorders and possibly circadian rhythm disruption. As an initial test of this hypothesis, we sampled interruption levels and continuously monitored light and sound levels for a minimum of seven consecutive days in a medical ICU, a multiple bed respiratory care unit (RCU) room, a single-bed RCU room, and a private room. Light levels in all areas maintained a day-night rhythm, with peak levels dependent on window orientation and shading. Peak sound levels were extremely high in all areas representing values significantly higher than those recommended by the Environmental Protection Agency as acceptable for a hospital environment. The number of sound peaks greater than 80 decibels, which may result in sleep arousals, was especially high in the intensive and respiratory care areas, but did show a day-night rhythm in all settings. Patient interruptions tended to be erratic, leaving little time for condensed sleep. We conclude that the potential for environmentally induced sleep disruption is high in all areas, but especially high in the intensive and respiratory care areas where the negative consequences may be the most severe.  相似文献   
25.
We report two cases of metastatic non-functioning pancreatic endocrine tumour with very elevated plasma levels of alpha-fetoprotein. In these two cases, serial plasma levels of alpha-fetoprotein, initially normal, correlated well with hepatic tumour progression and were associated with fatal outcome. These results suggest that elevated plasma concentration of alpha-fetoprotein may be caused by metastatic pancreatic endocrine tumour and than alpha-fetoprotein serial measurement may be useful in prognostic evaluation.  相似文献   
26.
In the verified architecture microprocessor (VAMP) project we have designed, functionally verified, and synthesized a processor with full DLX instruction set, delayed branch, Tomasulo scheduler, maskable nested precise interrupts, pipelined fully IEEE compatible dual precision floating point unit with variable latency, and separate instruction and data caches. The verification has been carried out in the theorem proving system PVS. The processor has been implemented on a Xilinx FPGA. A shorter version of this article with the title “Instantiating uninterpreted functional units and memory system: functional verification of the VAMP” appeared in [8]. The work reported here was done while all the authors were with Saarland University.  相似文献   
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Total phosphorus (TP) inputs to Lake Simcoe have led to hypolimnetic dissolved oxygen (DO) depletion and loss of cold water fish habitat. Since 1990, efforts have been made to reduce the total TP input to the lake below a defined target of 75 t/year, which was predicted to lead to reductions in spring TP concentration and improvements in end-of-summer hypolimnetic DO concentrations. The total TP load to the lake during the most recent period of record (1998/99-2003/04) ranged from 53 to 76 t/yr and averaged 67 t/yr, compared to an average of 114 t/yr estimated between 1990/91 and 1997/98 (range 85-157 t/yr). Reductions in TP loads from the catchment via tributary discharge (∼26 t) accounted for the majority of the decrease in total load between the two time periods. Total P concentrations decreased significantly in four out of six long-term monitored tributaries; however, concentrations in all six tributaries remain above the level recommended to avoid nuisance plant growth (30 μg/L). Although TP loads to the lake are currently below the target 75 t/yr, excessive growths of filamentous algae and macrophytes continue to be a problem in the nearshore zone. End-of-summer minimum hypolimnetic DO concentrations (average 4.3 mg/L, 1998/99-2003/04) remain substantially below the level (7 mg/L) that is considered protective of lake trout. Efforts to reduce TP loads to the lake therefore need to continue.  相似文献   
29.
When humans plan to execute a tool-use action, they can only specify the bodily movement parameters by taking into account the external target or goal of the tool-use action and the target-movement mapping implemented by the tool. In this study, the authors used the movement precuing method to investigate how people prepare for actions made with tools. More specifically, they asked whether people would be able to specify the spatial target and the target-movement mapping of the tool-use action independently of each other, and to what degree they would be able to prepare these components in advance. In 3 experiments, they precued either the target or the target-movement mapping of tool-use actions involving either a compatible or an incompatible target-movement mapping. Results indicate that participants benefit from partial advance information about the target-movement mapping, whereas no significant effects were found for precuing the spatial target of the action. These results occurred regardless of whether the target-movement mapping was compatible or incompatible and provide evidence for the notion that the target-movement mapping of a tool-use action is part of its cognitive representation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
30.
阿维斯塔波莱瑞特厂正在进行一个现代化改造项目,以提高炉卷轧机的生产能力,达到年产100万吨。但是,由于在阿维斯塔波莱瑞特厂炉卷轧机上的现有技术已达到极限,只有通过对轧机及自动化系统进行现代化的改造才有可能提高和增强轧机的利用率和易维护性。  相似文献   
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