Metabolism of Zidovudine

1. The anti-HIV drug zidovudine (3'-azido-2',3'-dideoxythymidine; ZDV) has three important pathways of metabolism. ZDV is a prodrug and must be phosphorylated in lymphocytes in order to exert its antiviral action. However, in quantitative terms this is a minor pathway probably accounting for less than 1% of the overall metabolic profile. The predominant pathway of metabolism is glucuronidation to GZDV and the metabolite is renally excreted. A further metabolite, derived by reduction of the azido moiety is 3'-amino-3'-deoxythymidine (AMT). 2. Zidovudine glucuronidation has been characterised in human liver microsomes. A number of drugs (e.g., naproxen, indomethacin and probenecid) have been shown to inhibit the in vitro conjugation of ZDV. Some of these drugs have also been co-administered with ZDV in HIV-positive patients. Significant pharmacokinetic interactions have been demonstrated with probenecid, naproxen and fluconazole. 3. 3'-amino-3'-deoxythymidine formation is probably mediated by both cytochrome P450 isozymes and NADPH-cytochrome P450 reductase. Peak plasma concentrations of AMT are approximately 10-15% of ZDV in patients. This is a potentially important metabolite because of its alleged cytotoxicity. 4. Measurement of intracellular ZDV phosphates in patients provides the key to our understanding of both the efficacy and toxicity of ZDV. Important recent work has demonstrated that as patients deteriorate (i.e., CD4 counts decrease below 100 x 10(6)/L), there is a corresponding increase in intracellular ZDV-monophosphate. This could have toxicological implications.     

Correlation of the reactivity,the active surface area and the total surface area of thin films of pyrolytic carbon

Using thin films of pyrolytic carbon the rate of the reaction with oxygen has been measured over the temperature range 625–740°C and at pressures of oxygen from 6–100 torr. The active surface area (ASA) of the films was measured from the total concentration of strongly-bound complexes with oxygen on the surface and the relative total surface area (TSA) was measured by low-temperature adsorption of nitrogen. A maximum in reactivity and in ASA was observed for films of average thickness of about 20 nm with a TSA of about 30 m² g^?1. At the maximum the ASA and TSA were essentially equal. The results are interpreted in terms of the mechanism of formation of pyrolytic carbon in the initial stages.     

Finite element analysis of tailored sheet forming processes considering laser welding zone

The finite element formulation for predicting strain distributions and weld line movements in the forming processes of tailored sheet metals is developed. The material properties of the welding zone such as strength coefficient, work-hardening exponent, and plastic anisotropic parameter are analytically obtained from those of base metals based on the tensile tests. The welding zone is modelled with the several, narrow finite elements called by weld elements. To verify the finite element formulation for tailored blanks, the forming processes of autobody door inner panel section and hemispherical dome are simulated. FEM predictions are compared and showed good agreements with experimental measurements.     

A disturbance observer based practical coordinated tracking controller for uncertain heterogeneous multi‐agent systems

This paper presents a coordinated tracking controller for multi‐agent systems. We assume that agents are uncertain, nonidentical, and affected by external disturbances. The information available to the tracking controller is a weighted sum of relative measurements. A coordinated tracking controller based on the disturbance observer, which is known as a robust output feedback controller, is designed so that the disturbances acting on agents are attenuated and at the same time the weighted sum of relative measurements approximately satisfies a differential equation defined by the leader's dynamics, which results in practical coordinated tracking. Systematic design procedures of the controller as well as numerical simulations are provided. Copyright © 2014 John Wiley & Sons, Ltd.     

The necessity of conducting to the end the activities of vector control in the onchocerciasis control program in west Africa: recall of the stakes and proposal of a minimum budget for the period 1998-2002

After a brief presentation of the Onchocerciasis Control Programme in West Africa (OCP), the authors realize the health and socioeconomic consequences that could follow a cessation of larvicide treatment before 2002 in the south-eastern and western extensions of the Programme. Taking into account that OCP activities are theoretically supported until 1997, but aware of financial constraints that will probably increase from now to 2002, this paper proposes an a minima estimation of the residual vector control activities for a "phasing out" spread out for five years (1998-2002). These estimations essentially concern the larvicide coverage, the insecticides used, the entomological surveillance, the logistical support and their financial aspects. As far as 48 U.S. $ million amount for 5 years are concerned, the budget allocated for vector control activities should not exceed the third of the global amount allocated to OCP for the actual fourth financial phase of the Programme (1992-1997).     

Efficient processing of spatial joins with DOT-based indexing

A spatial join is a query that searches for a set of object pairs satisfying a given spatial relationship from a database. It is one of the most costly queries, and thus requires an efficient processing algorithm that fully exploits the features of the underlying spatial indexes. In our earlier work, we devised a fairly effective algorithm for processing spatial joins with double transformation (DOT) indexing, which is one of several spatial indexing schemes. However, the algorithm is restricted to only the one-dimensional cases. In this paper, we extend the algorithm for the two-dimensional cases, which are general in Geographic Information Systems (GIS) applications. We first extend DOT to two-dimensional original space. Next, we propose an efficient algorithm for processing range queries using extended DOT. This algorithm employs the quarter division technique and the tri-quarter division technique devised by analyzing the regularity of the space-filling curve used in DOT. This greatly reduces the number of space transformation operations. We then propose a novel spatial join algorithm based on this range query processing algorithm. In processing a spatial join, we determine the access order of disk pages so that we can minimize the number of disk accesses. We show the superiority of the proposed method by extensive experiments using data sets of various distributions and sizes. The experimental results reveal that the proposed method improves the performance of spatial join processing up to three times in comparison with the widely-used R-tree-based spatial join method.     

Proving total correctness of nondeterministic programs in infinitary logic

Summary It is shown how the weakest precondition approach to proving total correctness of nondeterministic programs can be formalized in infinitary logic. The weakest precondition technique is extended to hierarchically structured programs by adding a new primitive statement for operational abstraction, the nondeterministic assignment statement, to the guarded commands of Dijkstra. The infinitary logic L ₁ is shown to be strong enough to express the weakest preconditions for Dijkstra's guarded commands, but too weak for the extended guarded commands. Two possible solutions are considered: going to the essentially stronger infinitary logic L ₁₁ and restricting the power of the nondeterministic assignment statement in a way which allows the weakest preconditions to be expressed in L ₁.