Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules

Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.     

红血球悬浮液流经平面狭缝的Fhraeus效应

本文论述了红血球悬浮液流经平面狭缝时其血球压积的变化规律,亦即片流Fahraeus效应。采用平面光学玻璃特制的二维狭缝装置、灌流管路、显微摄影记录及图象处理系统等组成实验系统。研究了厚度为4、7、12、25、36(μm)的五种狭缝中流过不同压积(H_f=2.00～31.00％)的红血球悬浮液时相对红血球压积的变化,发现了显著的片流Fahraeus效应及其规律并与管流Fahraeus效应进行了比较。本研究结论对“片流理论”及体液循环生理学具有重要意义。     

黄海周边河流的稀土元素地球化学及沉积物物源示踪

黄海周边的中韩主要河流悬浮沉积物中稀土元素组成不同, 韩国河流的稀土元素分异强于中国长江、黄河和鸭绿江, 表现为上陆壳标准化模式上明显的轻稀土相对富集. 不同级别的流域内源岩组成差异是形成这些河流稀土元素组成差异的主要因素. 稀土元素分异参数(La/Yb)_UCC和(Gd/Yb)_UCC, 以及稳定的La/Sc和Th/Sc元素比是识别进入黄海的中韩河流沉积物的可靠指标, 可以用于中国边缘海沉积物物源研究和古环境分析.     

Spatial aggregations for spatial based decision making in spatial data warehouses

For spatial based decision making such as choice of best place to construct a new department store, spatial data warehousing system is required more and more previous spatial data warehousing systems; however, provided decision making of non-spatial data on a map and so those cannot support enough spatial based decision making. The spatial aggregations are proposed for spatial based decision making in spatial data warehouses. The meaning of aggregation operators for applying spatial data was modified and new spatial aggregations were defined. These aggregations can support hierarchical concept of spatial measure. Using these aggregations, the spatial analysis classified by non-spatial data is provided. In case study, how to use these aggregations and how to support spatial based decision making are shown.     

Study for the Forming Principle of Logix Gear Tooth Profile and Its Mesh Performance

In recent years, a new type of gear named Logix gea r was developed. Actually, the tooth profile of this new type of gear is composed of lots of micro-segment involute curves, and on the profile, there exist lots of points, which their relative curvatures are equal to zero. This can result in the sliding coefficient smaller between two meshed Logix gears, and the mesh ch aracteristic becomes almost rolling transmission from sliding transmission accor dingly. So, this new type of gear has lots of advanta...     

An Integrated Die Casting Design System

Die casting process is one of the prime options for m anufacturing precisely dimensioned, sharply defined metal parts. The design of d ie casting dies comprises several stages and entails a large amount of time. Tra ditionally, the different stages of the die design were not integrated but exist as separate entities. Moreover, recurring modifications or even redesigns are r equired due to the complexity in achieving an accurate initial die design. As a result, die design is usually time-consuming and cos...     

近红外光谱技术结合主成分聚类鉴别海面溢油

鉴于目前没有一种方法能独立解决溢油鉴别的所有问题[1],本文提出近红外光谱技术结合主成分聚类分析鉴别溢油种类的方法.通过有机溶剂萃取出自行配制的汽油、柴油和润滑油模拟样品中的溢油后记录其近红外光谱,对5 800～6 200 cm-1区段范围内的近红外谱图经过多元散射校正(MSC),Norris一阶导数平滑预处理处理后求其主成分,并在主成分的基础上引入Ward聚类分析法(离差平方和法)对样品分类.     

GPS/INS integration: A performance sensitivity analysis

Inertial Navigation System (INS) and Global Positioning System (GPS) technologies have been widely used in a variety of positioning and navigation applications. Both systems have their unique features and shortcomings. Therefore, the integration of GPS with INS is now critical to overcome each of their drawbacks and to maximize each of their benefits. The integration of GPS with INS can be implemented using a Kalman filter in such modes as loosely, tightly and ultra-tightly coupled. In all these integration modes the INS error states, together with any navigation state (position, velocity, attitude) and other unknown parameters of interest, are estimated using GPS measurements. In a high performance system it is expected that all these unknown states will be precisely estimated. Although it has been noted that both the quality of the GPS measurements and the trajectory and/or manoeuvre characteristics of the problem will have impacts on system performance, a systematic sensitivity analysis is still lacking. This paper will address this issue through real data analyses. The performance analysisresults are very relevant to system design and platform trajectory and/or manoeuvre optimisation.     

Can cointegration‐based forecasting outperform univariate models? An application to Asian exchange rates

Conventional wisdom holds that restrictions on low‐frequency dynamics among cointegrated variables should provide more accurate short‐ to medium‐term forecasts than univariate techniques that contain no such information; even though, on standard accuracy measures, the information may not improve long‐term forecasting. But inconclusive empirical evidence is complicated by confusion about an appropriate accuracy criterion and the role of integration and cointegration in forecasting accuracy. We evaluate the short‐ and medium‐term forecasting accuracy of univariate Box–Jenkins type ARIMA techniques that imply only integration against multivariate cointegration models that contain both integration and cointegration for a system of five cointegrated Asian exchange rate time series. We use a rolling‐window technique to make multiple out of sample forecasts from one to forty steps ahead. Relative forecasting accuracy for individual exchange rates appears to be sensitive to the behaviour of the exchange rate series and the forecast horizon length. Over short horizons, ARIMA model forecasts are more accurate for series with moving‐average terms of order >1. ECMs perform better over medium‐term time horizons for series with no moving average terms. The results suggest a need to distinguish between ‘sequential’ and ‘synchronous’ forecasting ability in such comparisons. Copyright © 2002 John Wiley & Sons, Ltd.