Formation and inhibition of free radicals in electrically stressed and aged insulating polymers

Previous work has shown that prebreakdown, electrical aging, and breakdown phenomena are directly associated with charge carriers injected from electrical contacts and their subsequent dissociative trapping and recombination. In addition, the energy released from each trapping or recombination event is dissipated in the breaking of the bonds of macromolecules, thus forming free radicals and new traps in the electrically stressed insulating polymers, as predicted by Kao's model. It is this gradual degradation process that leads to electrical aging and destructive breakdown. New experimental results are presented to confirm previous findings and a new approach to inhibit the degradation process by the incorporation of suitable dopants into the polymer. The concentration of free radicals in the polymer increases with an increasing electric field at a fixed stress time of 250 h and with increasing stress time at a fixed electric field of 833 kV cm^?1. The concentration of free radicals is directly related to the concentration of new traps created by stress. However, when suitable dopants are incorporated, the initiation voltage for the occurrence of electrical treeing and the breakdown strength are both increased. The dopants tend to create shallow traps and have little effect on the deep trap concentration. This implies that the dopants act as free‐radical scavengers that tend to satisfy the unpaired electrons of the broken bonds, which create new acceptor‐like electron traps and new shallow traps. By doing so, the shallow traps screen the deep traps, thereby reducing the energy released during trapping and recombination and the probability of breaking the macromolecular bonds and causing structural degradation. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3416–3425, 2003     

An evolutionary algorithm for large traveling salesman problems

This work proposes an evolutionary algorithm, called the heterogeneous selection evolutionary algorithm (HeSEA), for solving large traveling salesman problems (TSP). The strengths and limitations of numerous well-known genetic operators are first analyzed, along with local search methods for TSPs from their solution qualities and mechanisms for preserving and adding edges. Based on this analysis, a new approach, HeSEA is proposed which integrates edge assembly crossover (EAX) and Lin-Kernighan (LK) local search, through family competition and heterogeneous pairing selection. This study demonstrates experimentally that EAX and LK can compensate for each other's disadvantages. Family competition and heterogeneous pairing selections are used to maintain the diversity of the population, which is especially useful for evolutionary algorithms in solving large TSPs. The proposed method was evaluated on 16 well-known TSPs in which the numbers of cities range from 318 to 13509. Experimental results indicate that HeSEA performs well and is very competitive with other approaches. The proposed method can determine the optimum path when the number of cities is under 10,000 and the mean solution quality is within 0.0074% above the optimum for each test problem. These findings imply that the proposed method can find tours robustly with a fixed small population and a limited family competition length in reasonable time, when used to solve large TSPs.     

The band areas of proteins determined by fluorescent scanning in the commercial automated gel electrophoresis apparatus

An automated gel electrophoresis apparatus, recently available commercially, allows one to follow the band during electrophoresis in real time, and lends itself therefore to an evaluation of bandwidth as a function of migration time (the dispersion coefficient), resolution and band shape. These determinations assume the constancy of band area with migration time and at various gel concentrations. The purpose of the present study was to verify these assumptions. Representative proteins and sodium dodecyl sulfate (SDS)-proteins, either natively fluorescent or fluorescein carboxylate labeled, were found to exhibit band areas which approach constancy as a function of migration time in both agarose and polyacrylamide gel electrophoresis, provided that (i) the protein concentration under the band was low enough to obviate self-quenching of fluorescence; (ii) the separation of the protein of interest from contaminants had progressed sufficiently during the time at which band areas were measured; (iii) the baseline under the peak was sufficiently well defined. However, band areas decrease with increasing gel concentration. Protein peaks exhibited leading and trailing tails. The ratio of the combined tail area to total area appeared to be near-constant at varying migration times. However, that ratio increases with increasing gel concentration. The tail area does not appear to be an artifact of fluorometric detection since it is reproduced upon fluorimetric analysis of the protein eluted from gel slices after electrophoresis. However, it may be due to photochemical destruction under the conditions of repetitive fluorometric peak detection.     

Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains

T-cell receptors (TCRs) upon binding to peptide-MHC ligands transduce signals in T lymphocytes. Tyrosine phosphorylations in the cytoplasmic domains of the CD3 (gammadeltaepsilon) and zeta subunits of the TCR complex by Src family kinases initiate the signaling cascades via docking and activation of ZAP-70 kinase and other signaling components. We examined the role of the low-density detergent-insoluble membranes (DIMs) in TCR signaling. Using mouse thymocytes as a model, we characterized the structural organization of DIMs in detail. We then demonstrated that TCR engagement triggered an immediate increase in the amount of TCR/CD3 present in DIMs, which directly involves the engaged receptor complexes. TCR/CD3 recruitment is accompanied by the accumulation of a series of prominent tyrosine-phosphorylated substrates and by an increase of the Lck activity in DIMs. Upon TCR stimulation, the DIM-associated receptor complexes are highly enriched in the hyperphosphorylated p23 zeta chains, contain most of the TCR/CD3-associated, phosphorylation-activated ZAP-70 kinases and seem to integrate into higher order, multiple tyrosine-phosphorylated substrate-containing protein complexes. The TCR/CD3 recruitment was found to depend on the activity of Src family kinases. We thus provide the first demonstration of recuitment of TCR/CD3 to DIMs upon receptor stimulation and propose it as a mechanism whereby TCR engagement is coupled to downstream signaling cascades.     

Grand Coulee Dam 70 Years Later: What Can We Learn?

This paper presents key findings from a case study on the Grand Coulee Dam conducted by the authors for the World Commission on Dams. The analysis demonstrates that the distribution of project benefits has been tilted in favour of irrigation interests and hydroelectric power users and that the project's major cost bearers have been riparian-based indigenous tribes of the Upper Columbia River. The study identifies lessons learned that are applicable to many large multi-purpose water resources development projects. Within the paper, the impacts of the following factors are discussed: low stakeholder participation in decision making; absence of just compensation to Native Americans and Canadian First Nations adversely affected by the loss of fishery resources; modernization of agricultural technology; differing stakeholder perceptions of project costs and benefits; and changes in values attached to anadromous fish. The lessons highlight the need for careful, broad-based a priori assessments of the irreversible and cumulative impacts of large water resources development projects as well as planned re-evaluations of water allocations and project operations.     

Effect of deformation route on microstructural development in aluminum processed by equal channel angular extrusion

Aluminum has been deformed by equal channel angular extrusion (ECAE) to obtain submicron-grained structures under different deformation routes. The deformation routes were varied by rotating billets through 0, 90, and 180 deg between each extrusion pass, and were designated as route A, B_C, and C, respectively. Based on quantitative microstructural analysis, the effectiveness of the deformation route is shown to depend upon the different definition used. The order of effectiveness is (a) A > B_C > C for both 90 and 120 deg dies, in terms of the generation of high-angle grain boundaries (HAGBs); (b) B_C > C > A for both 90 and 120 deg dies, in terms of the formation of equiaxed shape of grains; and (c) B_C > A > C for 90 deg die and B_C ∼ A > C for 120 die, in terms of reducing grain size. It is suggested that the generation of HAGBs can be related to the accumulation of nonredundant strain, while the shape and orientation of grains may be linked to the shearing patterns of the deformation route.     

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.