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.     

Disaster-readiness of medical facilities in Aichi Prefecture

One month following the Great Hanshin Earthquake of January 17, 1995, we conducted a survey of 173 hospitals in Aichi Prefecture to pinpoint problems related to their actual disaster-readiness and the medical backup systems in place to deal with such disasters. This study revealed that staff at 50% of the surveyed hospitals could reach the hospital within an hour, but that communication is almost entirely dependent on phone lines, suggesting that cordless/portable/mobile phones, radio systems, Internet, communications satellites and the like should be studied in the days to come for possible use as effective communication alternatives in times of disaster. Whereas 92% of the surveyed hospitals had manuals dealing with fire outbreaks, other areas were less well represented. For example, only 36.9% of surveyed hospitals had manuals for earthquakes, 31.7% had manuals for power outages and 14.2% had manuals to deal with flooding and water disasters. New manuals must be developed incorporating the key points garnered from experience (especially Hanshin) and be ready for use immediately. It is the time for each hospital to seriously rethink the measures it should take to deal with disasters.     

（2m，2，m）非线性等重码不是最佳检错码

本文证明了当ｍ＞４时（２ｍ，２，ｍ）非线性等重码不是最佳检错码。     

声光效应拉曼-内斯方程矩阵级数解法及声光调制器优化设计

提出一种求解正常声光相互作用拉曼 内斯 (Raman Nath)方程的矩阵级数解法 ,该解法直观方便且具有普遍性。计算结果表明 ,对Q =4 1π ,Bragg衍射的效率只有 97 5 % ;对非对称入射 ,以往的Raman Nath近似解误差较大 ;指出提高Bragg衍射效率的有效途径在于提高声光频率比并给出计算声光器件最优长度的计算公式。     

应用于生物医学的光声光谱技术的改进和实验研究

改进的光声光谱归一化技术，避免了普通的分光法归一化光声光谱技术中分束镜以及锁相放大器动态范围的影响和限制，实现宽光谱范围内准确的光谱测量。氙灯光源功率起伏用修正项修正，误差在5％以内，实现各次实验数据的可比性。     

USERS’ TWO-DIMENSIONAL INTEREST AND ITS STORAGE METHOD

The users‘ interest can be mined from the web cache and can be used widely.The interest can be specialized by the two-tuple(term,weight) in the simple interest model,in which the association relations are not mined.and then interest cannot be associated in expressing the users‘interest.Based on analyzing the WWW cache model,this letter brings forward a twodimensional interest model and gives the interrelated methods on how to store the two-dimensional interest model effectively.     

光纤通信在市内接入网的应用

先说明市内接入网的单位用户和住家用户两大类使用通信和电视、交互型和分配型业务的要求不相同，相应地对光纤传输的应用须作不同的考虑，文中认为；光纤从市内交换局直连办公大楼是合乎现实需要的，而对于居民住家，宜选用光纤连至路边或光纤与同轴结合和适当利用无源光网络等方案，俟将来时机成熟才实行光纤连至每一家，文末有概括总结，说明接入网不同于长途网，接入网的光纤系统可以使用常规单模光纤，工作于波长1．3μm，而光放大器和波分多路系统不是普遍需要，但光电子集成在光端机中是必要的。     

地下通风系统管理的新技术——系统特征图

本文介绍系统特征图的原理与方法 ,及其推广应用的前景     

连续梁的简便计算

利用三转角方程，对连续梁的内力进行精确的计算，该方法简捷明了，便于应用。     

Unicast-based multicast communication in wormhole-routed networks

Multicast communication, in which the same message is delivered from a source node to an arbitrary number of destination nodes, is being increasingly demanded in parallel computing. System supported multicast services can potentially offer improved performance, increased functionality, and simplified programming, and may in turn be used to support various higher-level operations for data movement and global process control. This paper presents efficient algorithms to implement multicast communication in wormhole-routed direct networks, in the absence of hardware multicast support, by exploiting the properties of the switching technology. Minimum-time multicast algorithms are presented for n-dimensional meshes and hypercubes that use deterministic, dimension-ordered routing of unicast messages. Both algorithms can deliver a multicast message to m-1 destinations in [log ₂ m] message passing steps, while avoiding contention among the constituent unicast messages. Performance results of implementations on a 64-node nCUBE-2 hypercube and a 168-node Symult 2010 2-D mesh are given