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51.
Chromosomal effects of adeno-associated virus vector integration. 总被引:17,自引:0,他引:17
Adeno-associated virus (AAV) vectors are currently being used in several clinical gene-therapy trials (see the NIH OBA Human Gene Transfer Clinical Trials Database); however, little is known about the chromosomal effects of vector integration. Here we report that integrated vector proviruses are associated with chromosomal deletions and other rearrangements and are frequently located on chromosome 19 (although not at the wildtype AAV integration site). 相似文献
52.
Fibulin-5/DANCE is essential for elastogenesis in vivo. 总被引:19,自引:0,他引:19
Tomoyuki Nakamura Pilar Ruiz Lozano Yasuhiro Ikeda Yoshitaka Iwanaga Aleksander Hinek Susumu Minamisawa Ching-Feng Cheng Kazuhiro Kobuke Nancy Dalton Yoshikazu Takada Kei Tashiro John Ross Jr Tasuku Honjo Kenneth R Chien 《Nature》2002,415(6868):171-175
The elastic fibre system has a principal role in the structure and function of various types of organs that require elasticity, such as large arteries, lung and skin. Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta-binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood. Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand, is an essential determinant of elastic fibre organization. fibulin-5-/- mice generated by gene targeting exhibit a severely disorganized elastic fibre system throughout the body. fibulin-5-/- mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphysema, and loose skin (cutis laxa). These tissues contain fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibres. Fibulin-5 interacts directly with elastic fibres in vitro, and serves as a ligand for cell surface integrins alphavbeta3, alphavbeta5 and alpha9beta1 through its amino-terminal domain. Thus, fibulin-5 may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibres in the skin, lung and vasculature. 相似文献
53.
Jacob W. Ulvila 《Journal of forecasting》1985,4(4):377-385
Recent years have seen an increasing cross-fertilization between the fields of decision analysis and forecasting. Decision-analytic models often require forecasts as inputs, and aspects of the Bayesian decision-theoretic framework underlying decision analysis have proved useful to forecasting, particularly in contexts where subjective judgemental inputs are required. This paper describes the use of decision tree analysis for forecasting and illustrates its use for corporate divisional forecasting and planning. A specialized decision-analytic technique, acts as events, is also described and illustrated to forecast a new product's earnings. Conclusions are drawn about the applicability of decision analysis for forecasting. 相似文献
54.
J. W. Faigle H. Stierlin H. Mory T. Winkler H. -P. Kriemler 《Cellular and molecular life sciences : CMLS》1985,41(4):476-478
Summary Indoxyl derivatives were detected as minor products among the urinary metabolites of two trial drugs, a benzodiazepine (GP 55 129) and a benzophenone (CGP 11 952). Their structures were elucidated by NMR and mass spectroscopy. Presumably, metabolites containing potential aldehyde functions react spontaneously with endogenous indoxyl. Such derivatives have not hitherto been encountered in drug metabolism. 相似文献
55.
The melatonin rhythm: both a clock and a calendar 总被引:24,自引:0,他引:24
R. J. Reiter 《Cellular and molecular life sciences : CMLS》1993,49(8):654-664
The paper briefly reviews the data which shows that the circadian production and secretion of melatonin by the pineal gland can impart both daily, i.e., clock, and seasonal, i.e., calendar, information to the organism. The paper summarizes the 3 patterns of nocturnal melatonin production that have been described. Clearly, regardless of the pattern of nocturnal melatonin production a particular species normally displays, the duration of nightime elevated melatonin is proportional to the duration of the night length. Since daylength under natural conditions changes daily the melatonin rhythm, which adjusts to the photoperiod sends time of year information to the organism. The melatonin receptors which subserve the clock message sent by the pineal gland in the form of a melatonin cycle may reside in the biological clock itself, namely, the suprachiasmatic nuclei (SCN). The melatonin receptors that mediate seasonal changes in reproductive physiology are presumably those that are located on the pars tuberalis cells of the anterior pituitary gland. Besides these receptors which likely mediate clock and calendar information, melatonin receptors have been described in other organs. Interestingly, the distribution of melatonin receptors is highly species-specific. Whereas the clock and calendar information that the melatonin cycle imparts to the organism relies on cell membrane receptors, a fact that is of some interest considering the high lipophilicity of melatonin, recent studies indicate that other functions of melatonin may require no receptor whatsoever. 相似文献
56.
57.
卢武星 《北京师范大学学报(自然科学版)》1994,(4)
1.0MeV208Pb离子在非晶Si中的投影射程RP和射程偏差ΔRP作为注量和温度二者的函数用背散射法进行测定.注量的变化范围为5×1013~7×1014cm-2.注入是在室温和t=-120℃下完成的.由由实验所确定的投影射程,射程偏差与注量或温度无关,并且分别等于295和72.2nm.与TRIM86的计算结果相比较,发现RP的偏离为18%,而ΔRP的偏离为36%.RP和ΔRP二者与注量及温度的无关性,排除了所观察到的与TRIM的矛盾是由于注入期间辐射增强扩散或离子束混合效应而引起的解释。 相似文献
58.
Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition 总被引:2,自引:0,他引:2
K. Brune W. S. Beck G. Geisslinger S. Menzel-Soglowek B. M. Peskar B. A. Peskar 《Cellular and molecular life sciences : CMLS》1991,47(3):257-261
Summary Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that prostaglandin synthesis inhibition is primarily mediating the anti-inflammatory activity but prostaglandin synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited prostaglandin synthesis, inflammation and nociception in rats. The R-form had much less effect on prostaglandin synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics. 相似文献
59.
Non-Minimum Phase Nonlinear System Predictive Control Based on Local Recurrent Neural Networks 总被引:3,自引:0,他引:3
Abstract: After a recursive multi-step-ahead predictor for nonlinear systems based on local recurrent neural networks isintroduced, an intelligent PID controller is adopted to correct the errors including identified model errors and accumulatederrors produced in the recursive process. Characterized by predictive control, this method can achieve a good controlaccuracy and has good robustness. A simulation study shows that this control algorithm is very effective. 相似文献
60.
Dynamic Characteristics of Inter-Satellite Links in LEO Networks 总被引:1,自引:0,他引:1
To establish an efficient inter-satellite link (ISL) in an LEO network, the effect of geometric characteristics of ISL on the ISLs and the devices on the LEO satellite should be examined. Because of the continuous movement of the LEO satellite, the time-varying behaviours of the ISL's geometric charactersistics continuously change with the changes of the satellite's position on the orbit. These dynamic geometric characteristics of the ISLs are important for ISL's performance analyzing and the design of the devices on the LEO satellite. This paper describes dynamic geometric characteristics of ISL, analyzes the impact of these regulations on the tracking system of the satellite's antenna and the power adjusting system of the satellite's transmitter, with the Iridium system as an example. 相似文献