Stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug

This review is written to evaluate the stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug. This discussion will be useful in the development of knowledge about stereoselective cutaneous hydrolysis and its influence on stereoselective transdermal transport of many other chiral prodrugs and drugs. Propranolol prodrugs undergo stereoselective hydrolysis in hairless mouse skin homogenate and in excised skin samples during permeation; the stereoselectivity is markedly biased towards hydrolysis of the (R) isomer. Unlike the liver, the esterase activity of the skin is high in its cytosolic fraction. Most of the lipophilic propranolol prodrugs cause stereoselective permeation across hairless mouse skin. A mechanism of stereoselective permeation of propranolol prodrug across the skin has been proposed, which indicates that the stereoselectivity in permeation is resulted from the stereoselective hydrolysis of lipophilic prodrug during permeation.     

Histochemical evaluation of placental dipeptidyl peptidase IV (CD26) in pre-eclampsia: enzyme activity in villous trophoblast indicates an enhanced likelihood of gestational hypertensive disorders

Nitric oxide (NO) acts as a modulator of neuronal transmission in mature neuronal systems, including the retina. Recently, NO has also been suggested to have a trophic function during development. We examined immunocytochemically the distribution of NO-producing cells in developing and transplanted rabbit retinas. An antibody detecting the neuronal isoform of its biosynthetic enzyme, nitric oxide synthase (NOS), was used on normal developing retinas [starting at embryonic day (E) 15] and on rabbit retinal transplants after various survival times (1-139 days after surgery). Weakly stained cell bodies were first observed in the proximal margin of the neuroblastic layer at E 29. Stained processes projecting towards a developing inner plexiform layer were also visible at this time point. Immunoreactive cells were located at later stages in the innermost part of the inner nuclear layer and in the ganglion cell layer, and are likely to correspond mainly to amacrine cells. NOS-labelled cells were also found in retinal transplants. The first NOS-labelled cells appeared, as in normal developing retinas, in ages corresponding to E 29 and were still detected in transplants corresponding to postnatal day 123. NOS-labelled cells were seen in areas between rosettes, where amacrine cells are located. NOS-labelled processes were at times seen to project for long distances, forming very distinct plexuses. NOS-containing amacrine cells thus appear both in the transplants and in developing retinas in the embryonic stages, long before synaptic function involving these cells can be expected, suggesting a role for NO not only in neuromodulation but also in retinal development.     

Imprudent linking weaves a tangled Web

Hypertext linking is often embraced uncritically by Web authors eager to explore the power of hypertext without first considering its effects on their readers' comprehension. Hypertext linking is not a substitute for thought-we think with ideas, not with dissociated snippets of raw information. Even the most germane bits of information cannot become ideas, regardless of how cleverly they are stacked, listed or linked. Ideas define relevance, provide context and establish patterns. With patterns, most concepts become intelligible, and we need continuity and stability of theme and context to recognize patterns. So, like most powerful technologies, hypertext links are a mixed blessing. Used improperly, they can be detrimental to Web sites. “Loose links” can drive away an audience, dilute the site's message, confuse the reader with irrelevant digressions and become a continuing maintenance headache for site authors and Webmasters     

Large-scale simulation studies in image pattern recognition

Many obstacles to progress in image pattern recognition result from the fact that per-class distributions are often too irregular to be well-approximated by simple analytical functions. Simulation studies offer one way to circumvent these obstacles. We present three closely related studies of machine-printed character recognition that rely on synthetic data generated pseudo-randomly in accordance with an explicit stochastic model of document image degradations. The unusually large scale of experiments - involving several million samples that makes this methodology possible have allowed us to compute sharp estimates of the intrinsic difficulty (Bayes risk) of concrete image recognition problems, as well as the asymptotic accuracy and domain of competency of classifiers     

Magnet Safety Assessment for ITER

The ITER magnet system consists of structurally linked sets of toroidal (TF) and poloidal (PF) field coils, central solenoid (CS), and various support structures. The coils are superconducting, force flow Helium cooled with a Kapton-Glass-Epoxy multilayer insulation system. The stored magnetic energy is about 100GJ in the TF system and 20GJ in the PF-CS. Coils and structure are maintained at 4 K by enclosing them in a vacuum cryostat. The cryostat, comprising an outer envelope to the magnets, forms most of the second radioactivity confinement barrier. The inner primary barrier is formed by the vacuum vessel, its ports and their extensions. To keep the machine size within acceptable bounds, it is essential that the magnets are in close proximity to both of the nuclear confinement barriers. The objective of the magnet design is that, although local damage to one of the barriers may occur in very exceptional circumstances, large scale magnet structural or thermal failure leading to simultaneous breaching of both barriers is not credible. Magnet accidents fall into three categories: thermal (which includes arcing arising from insulation failure and local overheating due to discharge failure in the event of a superconductor quench), structural (which includes component mechanical failure arising from material inadequacies, design errors and exceptional force patterns arising from coil shorts or control failures), and fluid (Helium release due to cooling line failure). After a preliminary survey to select initial faults conceivable within the present design, these faults are systematically analyzed to provide an assessment of the damage potential. The results of this damage assessment together with an assessment of the reliability of the monitoring and protective systems, shows that the magnets can operate with the required safety condition.     

Glial development in the Drosophila CNS requires concomitant activation of glial and repression of neuronal differentiation genes

Two classes of glial cells are found in the embryonic Drosophila CNS, midline glial cells and lateral glial cells. Midline glial development is triggered by EGF-receptor signalling, whereas lateral glial development is controlled by the gcm gene. Subsequent glial cell differentiation depends partly on the pointed gene. Here we describe a novel component required for all CNS glia development. The tramtrack gene encodes two zinc-finger proteins, one of which, ttkp69, is expressed in all non-neuronal CNS cells. We show that ttkp69 is downstream of gcm and can repress neuronal differentiation. Double mutant analysis and coexpression experiments indicate that glial cell differentiation may depend on a dual process, requiring the activation of glial differentiation by pointed and the concomitant repression of neuronal development by tramtrack.     

广钢转炉分厂2号方坯连铸机拉速问题的探讨

通过分析钢水在结晶器内凝固的不均匀性及对钢水结晶的热量平衡计算，讨论连铸中间包钢水温度、结晶器冷却水流量及进出水温差对拉坯速度的影响。