333 research outputs found
Handbook of enzyme inhibitors Helmward Zollner; VCH Verlagsgesellschaft; Weinheim, 1989; xi + 440 pages; DM 194.00/£65.00
Superoxide-dependent formation of hydroxyl radicals in the presence of iron chelates Is it a mechanism for hydroxyl radical production in biochemical systems?
An investigation of the resource implications of the introduction of "new taylorism" into the Cleveland constabulary
The research is concerned with analysing the impact that organisational change' is having on the police service and in particular the effect that change has on individual systems within the Cleveland Constabulary. The theoretical part of the research examined the rationale for change within public sector organisations, the reasons for adopting this rationale and the likely effects on organisations that follow this programme. In order to place this in context a review of literature relating to private and public sector strategic management issues was carried out. The empirical part of the research involved interviews with a wide selection of senior police officers within the Cleveland Constabulary. This was followed by a forcewide survey of police officers of all ranks and a case study of the organisation. The focus of the research is to evaluate the cause and effect of change on all key elements that play a major part in determining the organisation’s strategic direction. The word strategy' has been given many different meanings and defined in many ways. One of the simplest and most used definition for defining an organisation’s strategy is given by Hofer and Schendel (1978):"Fundamental pattern of present and planned resource deployments and environmental interactions that indicates how the organisation will achieve its objectives." (Hofer and Schendel, 1978 :25)Corporate strategy can be regarded as the configuration of the activities of an organisation, allocating resources to each activity and co-ordinating the activities to meet the organisational objectives. The key elements of strategy are grouped under the generic headings of: human resources; financial resources; technological systems; and legal/political systems. The research has analysed the inter-relationships and effect that change has on the various elements by breaking it down into four specific areas for investigation: Overall efficiency - has the change resulted in increased or decreased overall efficiency; Resources - Has the change led to increased or decreased resource consumption; Operational efficiency - Has the change led to increased or decreased productivity; Bureaucracy - Has the change led to increased or decreased bureaucracy The purpose of the research is to develop a framework that can be applied to managerial issues and problems that are not amenable to rigorous analysis or are difficult to evaluate in strict mathematical terms. The framework developed can be regarded as a "heuristic' programme, that provides a significant contribution to determining the impact A at change can have on inter-related systems. It is hypothesised that if the impact of change programmes that have already been implemented can be evaluated, then we may learn from them, building these lessons into a model for determining the impact of future change. The main finding of the research was that the implementation of initiatives or techniques developed in the private sector, such as quality control, cost control and computerised production techniques, are not readily transferable to the public sector. Consequently, Ae projected cost savings and improvements in productivity failed to materialise. In many cases the introduction of new initiatives has resulted in: Increased cost; Decreased overall efficiency; Decreased productivity; Increased bureaucracy. There has been an identified drift into negative' efficiency, which is detrimental to the health of the organisation. The research identifies a need for immediate remedial action that can only take place when the organisation has developed the ability to recognise the symptoms. The organisation is progressive and will no doubt develop the focus to recognise the weaknesses inherent in its present strategies and those of the external bodies and agencies influencing the environment. This research provides a methodology to develop that focus and provides a framework to evaluate present and future strategies
Tamoxifen and related compounds decrease membrane fluidity in liposomes Mechanism for the antioxidant action of tamoxifen and relevance to its anticancer and cardioprotective actions?
AbstractTamoxifen and related compounds decrease membrane fluidity in ox-brain phospholipid liposomes: their order of effectiveness is, 4-hydroxytamoxifen > 17β-oestradiol > tamoxifen >cis-tamoxifen >N-desmethyltamoxifen > cholesterol. A good positive correlation was demonstrated between the decrease in membrane fluidity by these compounds and their antioxidant ability as inhibitors of liposomal and microsomal lipid peroxidation (correlation coefficient, r = 0.99, P < 0.001, in both cases). The ability of tamoxifen to decrease membrane fluidity is suggested to be the mechanism of its antioxidant action and is discussed in relation to its anticancer and cardioprotective actions
Tamoxifen and related compounds decrease membrane fluidity in liposomes Mechanism for the antioxidant action of tamoxifen and relevance to its anticancer and cardioprotective actions?
AbstractTamoxifen and related compounds decrease membrane fluidity in ox-brain phospholipid liposomes: their order of effectiveness is, 4-hydroxytamoxifen > 17β-oestradiol > tamoxifen >cis-tamoxifen >N-desmethyltamoxifen > cholesterol. A good positive correlation was demonstrated between the decrease in membrane fluidity by these compounds and their antioxidant ability as inhibitors of liposomal and microsomal lipid peroxidation (correlation coefficient, r = 0.99, P < 0.001, in both cases). The ability of tamoxifen to decrease membrane fluidity is suggested to be the mechanism of its antioxidant action and is discussed in relation to its anticancer and cardioprotective actions
Effect of oxidized glutathione on the inhibition of glucose-6-phosphate dehydrogenase by NADPH
Are mutagenic non D-loop direct repeat motifs in mitochondrial DNA under a negative selection pressure?
Non D-loop direct repeats (DRs) in mitochondrial DNA (mtDNA) have been commonly implicated in the mutagenesis of mtDNA deletions associated with neuromuscular disease and ageing. Further, these DRs have been hypothesized to put a constraint on the lifespan of mammals and are under a negative selection pressure. Using a compendium of 294 mammalian mtDNA, we re-examined the relationship between species lifespan and the mutagenicity of such DRs. Contradicting the prevailing hypotheses, we found no significant evidence that long-lived mammals possess fewer mutagenic DRs than short-lived mammals. By comparing DR counts in human mtDNA with those in selectively randomized sequences, we also showed that the number of DRs in human mtDNA is primarily determined by global mtDNA properties, such as the bias in synonymous codon usage (SCU) and nucleotide composition. We found that SCU bias in mtDNA positively correlates with DR counts, where repeated usage of a subset of codons leads to more frequent DR occurrences. While bias in SCU and nucleotide composition has been attributed to nucleotide mutational bias, mammalian mtDNA still exhibit higher SCU bias and DR counts than expected from such mutational bias, suggesting a lack of negative selection against non D-loop DR
Role of Direct Repeat and Stem-Loop Motifs in mtDNA Deletions: Cause or Coincidence?
Deletion mutations within mitochondrial DNA (mtDNA) have been implicated in degenerative and aging related conditions, such as sarcopenia and neuro-degeneration. While the precise molecular mechanism of deletion formation in mtDNA is still not completely understood, genome motifs such as direct repeat (DR) and stem-loop (SL) have been observed in the neighborhood of deletion breakpoints and thus have been postulated to take part in mutagenesis. In this study, we have analyzed the mitochondrial genomes from four different mammals: human, rhesus monkey, mouse and rat, and compared them to randomly generated sequences to further elucidate the role of direct repeat and stem-loop motifs in aging associated mtDNA deletions. Our analysis revealed that in the four species, DR and SL structures are abundant and that their distributions in mtDNA are not statistically different from randomized sequences. However, the average distance between the reported age associated mtDNA breakpoints and their respective nearest DR motifs is significantly shorter than what is expected of random chance in human (p<10−4) and rhesus monkey (p = 0.0034), but not in mouse (p = 0.0719) and rat (p = 0.0437), indicating the existence of species specific difference in the relationship between DR motifs and deletion breakpoints. In addition, the frequencies of large DRs (>10 bp) tend to decrease with increasing lifespan among the four mammals studied here, further suggesting an evolutionary selection against stable mtDNA misalignments associated with long DRs in long-living animals. In contrast to the results on DR, the probability of finding SL motifs near a deletion breakpoint does not differ from random in any of the four mtDNA sequences considered. Taken together, the findings in this study give support for the importance of stable mtDNA misalignments, aided by long DRs, as a major mechanism of deletion formation in long-living, but not in short-living mammals
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