Nonlinear protein binding and enzyme heterogeneity: effects on hepatic drug removal

The kinetics of substrate removal by the liver and the resulting nonlinear changes in unbound fraction along the flow path at varying input drug concentrations were examined by a model simulation study. Specifically, we varied the binding association constant, KA, and the Michaelis-Menten constants (Km and Vmax) to examine the steady state drug removal (expressed as hepatic extraction ratio E) and changes in drug binding for (i) unienzyme systems and (ii) simple, parallel metabolic pathways; zonal metabolic heterogeneity was also added as a variable. At low KA, E declined with increasing input drug concentration, due primarily to saturation of enzymes; only small differences in binding were present across the liver. At high KA, a parabolic profile for E with concentration was observed; changes in unbound fraction between the inlet and the outlet of the liver followed in parallel fashion. Protein binding was the rate-determining step at low input drug concentrations, whereas enzyme saturation was the rate-controlling factor at high input drug concentration. Heterogeneous enzymic distribution modulated changes in unbound fraction within the liver and at the outlet. Despite marked changes in unbound fraction occurring within the liver for different enzymic distributions, the overall transhepatic differences were relatively small. We then investigated the logarithmic average unbound concentration and the length averaged concentration as estimates of substrate concentration in liver in the presence of nonlinear drug binding. Fitting of simulated data, with and without assigned random error (10%), to the Michaelis-Menten equation was performed; fitting was repeated for simulated data obtained with presence of a specific inhibitor of the high-affinity, anteriorly distributed pathway. Results were similar for both concentration terms: accurate estimates were obtained for anterior, high affinity pathways; an overestimation of parameters was observed for the lower affinity posteriorly distributed pathways. Improved estimations were found for posteriorly distributed pathways upon inhibition with specific inhibitors; with added random error, however, the improvement was much decreased. We applied the method for fitting of several sets of metabolic data obtained from rat liver perfusion studies performed with salicylamide (SAM) (i) without and (ii) with the presence of 2,6-dichloro-4-nitrophenol (DCNP), a SAM sulfation inhibitor. The fitted results showed that SAM sulfation was a high-affinity high-capacity pathway; SAM glucuronidation was of lower affinity but comparable capacity as the sulfation pathway, whereas SAM hydroxylation was of lower affinity and lower capacity.     

红外热图技术在气功研究中的应用

本文用红外技术研究发功时上肢体表温度变化的特点和它的规律。     

斗晏水电站混凝土面板堆石坝趾板设计

阐述了江西省重点建设项目斗晏水电站混凝土面板堆石趾板设计，并重点介绍较大断层上趾板设计处理方式。     

苯磺隆干悬浮剂技术浅析

通过对苯磺隆干悬浮剂项目的研究,进一步了解干悬浮剂的加工工艺和配方中各种助剂的相互作用;剖析助剂对主要技术指标的影响。     

挤压力对晶体生长速度及枝晶间距的影响

研究了挤压铸造时挤压力对宏观晶体生长速度的影响，给出了晶体生长速度表达式。结果表明：挤压力对合金宏观晶体生长速度的影响除与合金成分有关外，在某些挤压条件下，当形核率的增加幅度超过长大速度时，则挤压力可使宏观晶粒细化；反之，会使宏观晶粒变粗。随着挤压力的提高，合金凝固速度加快，一次枝晶间距和二次枝晶间距都随之减小，从而细化了树枝晶。     

无线技术的新领域--WUSB

无线USB(WUSB)技术是一个全新的无线传输标准.实现USB(通用串行总线)无线化以后,既可以保持有线USB的高速传输等优点,又可以去掉电缆的羁绊,给各种设备带来更大的便捷和移动性.文中首先介绍了WUSB技术的由来--UWB技术规范的标准化难以确定,然后对WUSB技术的规范标准进行了阐述,最后概述了WUSB技术的发展现状及目前和今后的技术研发重点,并对WUSB的发展前景进行了展望.     

Estimation for the number of components in a mixture model using stepwise split-and-merge EM algorithm

The main difficulty with EM algorithm for mixture model concerns the number of components, say g. This is the question of model selection, and the EM algorithm itself could not estimate g. On the contrary, the algorithm requires g to be specified before the remaining parameters can be estimated. To solve this problem, a new algorithm, which is called stepwise split-and-merge EM (SSMEM) algorithm, is proposed. The SSMEM algorithm alternately splits and merges components, estimating g and other parameters of components simultaneously. Also, two novel criteria are introduced to efficiently select the components for split or merge. Experimental results on simulated and real data demonstrate the effectivity of the proposed algorithm.     

岩土体斜(边)坡滑坡发生的机理

根据滑坡发生的初始条件、滑坡成因及方式表象,对常见的蠕变倾覆滑坡、卸荷滑坡、震动液化平推滑坡、潜蚀塌陷滑坡、溶蚀下陷滑坡、孔隙水压浮动滑坡和人工切蚀或冲(浪)蚀—加载滑坡等机理进行了分析.