Involvement of cyclin-dependent kinase inhibitor p27Kip1 in growth inhibition of endometrium in the secretory phase and of hyperplastic endometrium treated with progesterone

A cyclin-dependent kinase (cdk) inhibitor, p27Kip1 (p27), binds to the cyclin E-cdk2 complex and functions as a suppressor of cell cycle promotion. Here, the involvement of p27 in the growth of normal human endometrium was immunohistochemically studied, and the findings were compared with those of Ki-67, cyclin E and cdk2. In addition, to elucidate the effect of progesterone on the expression of p27, tissues from patients with endometrial hyperplasia were examined before and after the administration of medroxyprogesterone acetate (MPA) for the treatment of this disease. In the glandular cells of the normal endometrium, p27 was negligible during the proliferative phase, whereas it was markedly increased in the secretory phase. The staining pattern of Ki-67 was the reverse. Cyclin E/cdk2-positive cells were observed throughout the menstrual cycle. In the secretory phase, the cyclin E/cdk2-positive cells were also positive for p27, suggesting an interaction between these molecules. Stromal cells, especially in the basalis, showed a consistent expression of p27 throughout the menstrual cycle. The expression of p27 in hyperplastic epithelia before the MPA treatment was negligible, whereas it was greatly increased after the treatment. The Ki-67 positivity decreased after the treatment. These findings suggest that p27 is involved in the progesterone-induced growth suppression of normal and hyperplastic endometria.     

Crystal structures of reaction intermediates of L-2-haloacid dehalogenase and implications for the reaction mechanism

Crystal structures of L-2-haloacid dehalogenase from Pseudomonas sp. YL complexed with monochloroacetate, L-2-chlorobutyrate, L-2-chloro-3-methylbutyrate, or L-2-chloro-4-methylvalerate were determined at 1.83-, 2.0-, 2.2-, and 2.2-A resolutions, respectively, using the complex crystals prepared with the S175A mutant, which are isomorphous with those of the wild-type enzyme. These structures exhibit unique structural features that correspond to those of the reaction intermediates. In each case, the nucleophile Asp-10 is esterified with the dechlorinated moiety of the substrate. The substrate moieties in all but the monochloroacetate intermediate have a D-configuration at the C2 atom. The overall polypeptide fold of each of the intermediates is similar to that of the wild-type enzyme. However, it is clear that the Asp-10-Ser-20 region moves to the active site in all of the intermediates, and the Tyr-91-Asp-102 and Leu-117-Arg-135 regions make conformational changes in all but the monochloroacetate intermediates. Ser-118 is located near the carboxyl group of the substrate moiety; this residue probably serves as a binding residue for the substrate carboxyl group. The hydrophobic pocket, which is primarily composed of the Tyr-12, Gln-42, Leu-45, Phe-60, Lys-151, Asn-177, and Trp-179 side chains, exists around the alkyl group of the substrate moiety. This pocket may play an important role in stabilizing the alkyl group of the substrate moiety through hydrophobic interactions, and may also play a role in determining the stereospecificity of the enzyme. Moreover, a water molecule, which is absent in the substrate-free enzyme, is present in the vicinities of the carboxyl carbon of Asp-10 and the side chains of Asp-180, Asn-177, and Ala-175 in each intermediate. This water molecule may hydrolyze the ester intermediate and its substrate. These findings crystallographically demonstrate that the enzyme reaction proceeds through the formation of an ester intermediate with the enzyme's nucleophile Asp-10.     

Gradient-index rod lens with high N.A

new gradient-index lens with high numerical aperture has been fabricated by a new ion-exchange technique. In this treatment, a glass rod doped with a highly polarizable ion (dopant A) is immersed into KNO3 salt doped with a medium polarizability ion (dopant B). Dopant B penetrates into the rod and modifies the refractive-index profile of the lens. This new lens has 0.6 N.A. and gives a 1.18-micron spot diam in the light-focusing system. This lens gives good results also in a light source coupling system and is useful in microoptic devices.     

Practical design of heat exchangers for dilution refrigerators: part 2

A dilution refrigerator with a He³ circulation rate 80–730 μmols^?1 and a minimum temperature of 2.85 mK which is continuously maintained has been built. Discrete heat exchangers with pressed metal (Cu and Ag) powder are used. The heat exchangers are newly developed, based on the analysis of Radebaugh and Siegwarth. The machine is designed for many purposes such as the base of nuclear cooling and studies of general solid state physics. The design, construction and performance of this refrigerator are described.     

一种基于贝叶斯分类原理的动态系统故障检测与诊断方法

基于贝叶斯分类原理提出一种能够同时检测与诊断动态系统的过程故障和传感器故障的新方法。给出的算法是递推形式的。仿真结果表明具有灵敏度高和响应速度快等优点。     

Synthesis of state machine diagrams from communication diagrams using Petri nets

Service-oriented architecture is an architecture style to build up a large-scale networked system composed of a set of components or functions, each of which is called a service. A problem to construct behavioral models of services from given global interaction specifications, called choreography, is known as the choreography realization problem. The constructed model is still an intermediate model in the process of system developments; the model will be corrected, modified, and enhanced further by designers. Therefore, we also have to consider readability of the constructed model. In this paper, we proposed a method to construct state machine models from choreographies described by a set of communication diagrams using Petri nets. The proposed method will try to use the composite states and the orthogonal regions of UML state machines for the readability.     

Robust output tracking of nonlinear systems with mismatched uncertainties

The problem of robust output tracking for a class of uncertain nonlinear systems which do not satisfy the conventional matching condition is considered. The main assumption on the uncertainty is that the triangularity condition is satisfied. Based on backstepping method and input/output linearization approach, we propose a class of non-adaptive state feedback controllers which can guarantee exponential stability of the tracking error for the uncertain nonlinear systems first. Next, adaptive control laws are developed so that no prior knowledge of the bounds on the uncertainties is required. By updating these upper bounds, we design a class of adaptive robust controllers. It is shown that under the proposed adaptive robust control the tracking error of the controlled system converges to zero as time approaches infinity.     

Safety analysis of a supercritical-pressure water-cooled fast reactor under supercritical pressure

The supercritical-pressure water-cooled fast reactor (SWFR) is a fast spectrum supercritical water-cooled reactor (SCWR) studied by the University of Tokyo. The SWFR is designed as a two-pass core with an outlet temperature 500 °C. The SWFR has fuel channels cooled by downward flow, higher power density, and smaller coolant density reactivity feedback compared with Super LWR. This paper describes the safety analyses of abnormal events for the SWFR. SPRAT-F code is used for the safety analysis at supercritical pressure considering the downward flow cooled seed fuel channel. This code is based on a 1-D node junction model with point kinetics and decay heat calculations. Flow redistribution among parallel paths is calculated by pressure-loss balance and momentum conservation. The initiating events are selected from those of LWRs. For the safety analysis, nine abnormal transients and four accidents are selected with considering types of abnormality. By the numerical analyses, it was found that the loss of flow events can be mitigated by the “water source” effect of the downward flow blanket channels in the abnormal transients and accidents. All the abnormal events satisfy the criteria with margin.     

Effects of stress on radiation hardening and microstructural evolution in A533B steel

Bent specimens of A533B steel (0.16 wt% Cu) were irradiated at 290 °C to 1 dpa with 6.4 MeV Fe³⁺ ions. Calculated tensile stresses at the irradiated surface were set to 0, 250, 500 and 750 MPa. The specimens were subjected to hardness measurements, transmission electron microscopy (TEM) observations and three-dimensional atom probe (3DAP) analysis. The radiation-induced hardening decreased with increasing stress to 500 MPa which was near the yield strength. TEM and 3DAP results showed that well-defined dislocation loops and solute clusters were formed. The diameter of dislocation loops increased and the number density decreased when the stress was applied, whereas the diameter and number density of solute clusters decreased. The hardening was mainly attributed to solute cluster formation. Application of tensile stress would control hardening by suppressing the solute cluster nucleation and growth.     

Numerical analysis of the onset of droplet entrainment in annular two-phase flow by hybrid method

A particle-grid hybrid method for simulating the onset of droplet entrainment is described. The air and liquid phases are expressed by grid and particle separately. The effects of surface tension and wall adhesion are calculated by the continuum surface force model. The fluid film variation and the droplet disengaging process are analyzed. The onset of entrainment criterion is obtained which has a good agreement with the correlation of Ishii and Grolmes (AIChE J., 21, 308–318). The influences of surface tension and gas phase density on the criterion are also studied. Several simulation flow fields are given for illustrating the efficiency of the method.