Showing papers by "King's College London published in 1996"

Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer.

Abstract: It is increasingly proposed that reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a key role in human cancer development [1–6], especially as evidence is growing that antioxidants may prevent or delay the onset of some types of cancer (reviewed in [7,8]). ROS is a collective term often used by biologists to include oxygen radicals [superoxide (O # J−), hydroxyl (OHJ), peroxyl (RO # J) and alkoxyl (ROJ)] and certain nonradicals that are either oxidizing agents and}or are easily converted into radicals, such as HOCl, ozone (O $ ), peroxynitrite (ONOO−), singlet oxygen ("O # ) and H # O # . RNS is a similar collective term that includes nitric oxide radical (NOJ), ONOO−, nitrogen dioxide radical (NO # J), other oxides of nitrogen and products arising when NOJ reacts with O # J−, ROJ and RO # J. ‘Reactive ’ is not always an appropriate term; H # O # , NOJ and O # J− react quickly with very few molecules, whereas OHJ reacts quickly with almost anything. RO # J, ROJ, HOCl, NO # J, ONOO− and O $ have intermediate reactivities. ROS and RNS have been shown to possess many characteristics of carcinogens [4] (Figure 1). Mutagenesis by ROS}RNS could contribute to the initiation of cancer, in addition to being important in the promotion and progression phases. For example, ROS}RNS can have the following effects. (1) Cause structural alterations in DNA, e.g. base pair mutations, rearrangements, deletions, insertions and sequence amplification. OHJ is especially damaging, but "O # , RO # J, ROJ, HNO # , O $ , ONOO− and the decomposition products of ONOO− are also effective [9–13]. ROS can produce gross chromosomal alterations in addition to point mutations and thus could be involved in the inactivation or loss of the second wild-type allele of a mutated proto-oncogene or tumour-suppressor gene that can occur during tumour promotion and progression, allowing expression of the mutated phenotype [4]. (2) Affect cytoplasmic and nuclear signal transduction pathways [14,15]. For example, H # O # (which crosses cell and organelle membranes easily) can lead to displacement of the inhibitory subunit from the cytoplasmic transcription factor nuclear factor κB, allowing the activated factor to migrate to the nucleus [14]. Nitration of tyrosine residues by ONOO− may block phosphorylation. (3) Modulate the activity of the proteins and genes that respond to stress and which act to regulate the genes that are related to cell proliferation, differentiation and apoptosis [4,14–17]. For example, H # O # can stimulate transcription of c-jun

Antioxidants in human health and disease

Abstract: Free radicals and antioxidants are widely discussed in the clinical and nutritional literature. Antioxidants are needed to prevent the formation and oppose the actions of reactive oxygen and nitrogen species, which are generated in vivo and cause damage to DNA, lipids, proteins, and other biomolecules. Endogenous antioxidant defenses (superoxide dismutases, H2O2-removing enzymes, metal binding proteins) are inadequate to prevent damage completely, so diet-derived antioxidants are important in maintaining health. Many dietary compounds have been suggested to be important antioxidants: The evidence for a key role of vitamins E and C is strong, but that for carotenoids and related plant pigments is weaker. Interest is also growing in the role of plant phenolics, especially flavonoids. Some antioxidants can exert prooxidant effects in vitro, but their physiological relevance is uncertain. Experimental approaches to the optimization of antioxidant nutrient intake are proposed.

Efficacy of Pamidronate in Reducing Skeletal Complications in Patients with Breast Cancer and Lytic Bone Metastases

Abstract: Background Bisphosphonates such as pamidronate disodium inhibit osteoclast-induced bone resorption associated with cancer that has metastasized to bone. Methods Women with stage IV breast cancer who were receiving cytotoxic chemotherapy and had at least one lytic bone lesion were given either placebo or pamidronate (90 mg) as a two-hour intravenous infusion monthly for 12 cycles. Skeletal complications, including pathologic fractures, the need for radiation to bone or bone surgery, spinal cord compression, and hypercalcemia (a serum calcium concentration above 12 mg per deciliter [3.0 mmol per liter] or elevated to any degree and requiring treatment), were assessed monthly. Bone pain, use of analgesic drugs, performance status, and quality of life were assessed throughout the trial. Results The efficacy of treatment was evaluated in 380 of 382 randomized patients, 185 receiving pamidronate and 195 receiving placebo. The median time to the occurrence of the first skeletal complication was greater in the pa...

Oxidative stress and the pathogenesis of Parkinson's disease

Abstract: Current concepts of the pathogenesis of Parkinson's disease (PD) center on the formation of reactive oxygen species and the onset of oxidative stress leading to oxidative damage to substantia nigra pars compacta. Extensive postmortem studies have provided evidence to support the involvement of oxidative stress in the pathogenesis of PD; in particular, these include alterations in brain iron content, impaired mitochondrial function, alterations in the antioxidant protective systems (most notably superoxide dismutase [SOD] and reduced glutathione [GSH]), and evidence of oxidative damage to lipids, proteins, and DNA. Iron can induce oxidative stress, and intranigral injections have been shown to induce a model of progressive parkinsonism. A loss of GSH is associated with incidental Lewy body disease and may represent the earliest biochemical marker of nigral cell loss. GSH depletion alone may not result in damage to nigral neurons but may increase susceptibility to subsequent toxic or free radical exposure. The nature of the free radical species responsible for cell death in PD remains unknown, but there is evidence of involvement of hydroxyl radical (OH.), peroxynitrite, and nitric oxide. Indeed, OH. and peroxynitrite formation may be critically dependent on nitric oxide formation. Central to many of the processes involved in oxidative stress and oxidative damage in PD are the actions of monoamine oxidase-B (MAO-B). MAO-B is essential for the activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to 1-methyl-4-phenylpyridinium ion, for a component of the enzymatic conversion of dopamine to hydrogen peroxide (H2O2), and for the activation of other potential toxins such as isoquinolines and beta-carbolines. Thus, the inhibition of MAO-B by drugs such as selegiline may protect against activation of some toxins and free radicals formed from the MAO-B oxidation of dopamine. In addition, selegiline may act through a mechanism unrelated to MAO-B to increase neurotrophic factor activity and upregulate molecules such as glutathione, SOD, catalase, and BCL-2 protein, which protect against oxidant stress and apoptosis. Consequently, selegiline may be advantageous in the long-term treatment of PD.

Pharmacological and biochemical actions of simple coumarins : Natural products with therapeutic potential

Abstract: 1. 1. More than 1300 coumarins have been identified from natural sources, especially green plants. The pharmacological and biochemical properties and therapeutic applications of simple coumarins depend upon the pattern of substitution. More complex related compounds based on the coumarin nucleus include the dicoumarol/warfarin anticoagulants, aflatoxins and the psoralens (photosensitizing agents). 2. 2. Coumarin itself (1,2-benzopyrone) has long-established efficacy in slow-onset long-term reduction of lymphoedema in man, as confirmed in recent double-blind trials against elephantiasis and postmastectomy swelling of the arm. The mechanism of action is uncertain, but may involve macrophage-induced proteolysis of oedema protein. However, coumarin has low absolute bioavailability in man (<5%), due to extensive first-pass hepatic conversion to 7-hydroxycoumarin followed by glucuronida. tion. It may, therefore, be a prodrug. 3. 3. Scoparone (6,7-dimethoxycoumarin) has been purified from the hypolipidaemic Chinese herb Artemisia scoparia and shown to reduce the proliferative responses of human peripheral mononuclear cells, to relax smooth muscle, to reduce total cholesterol and triglycerides and to retard the characteristic pathomorphological changes in hypercholesterolaemic diabetic rabbits. Various properties of scoparone were suggested to account for these findings, including ability to scavenge reactive oxygen species, inhibition of tyrosine kinases and potentiation of prostaglandin generation. 4. 4. Osthole (7-methoxy-8-[3-methylpent-2-enyl]coumarin) from Angelica pubescens, used also in Chinese medicine, causes hypotension in vivo, and inhibits platelet aggregation and smooth muscle contraction in vitro. It may interfere with calcium influx and with cyclic nucleotide phosphodiesterases. 5. 5. Cloricromene, a synthetic coumarin derivative, also possesses antithrombotic antiplatelet actions, inhibits PMN neutrophil function and causes vasodilatation. Some of these properties of cloricromene have been ascribed to inhibition of arachidonate release from membrane phospholipids. 6. 6. Simple coumarins possessing ortho-dihydroxy functions, such as fraxetin and 4-methyldaphnetin, are potent inhibitors (low micromolar) of lipid peroxidation and scavengers of superoxide anion radicals and of aqueous alkylperoxyl radicals, but may be pro-oxidant (enhancing generation of hydroxyl radicals) in the presence of free iron ions. These coumarins also inhibit the proinflammatory 5-lipoxygenase enzyme at micromolar concentrations. Another related coumarin, 5, 7-dihydroxy-4-methylcoumarin, is of special interest as it inhibits lipid peroxidation, and scavenges alkylperoxyl and superoxide radicals. Unlike most other simple coumarins studied, 5,7-dihydroxy-4-methylcoumarin also scavenges hypochlorous acid, and is a potent inhibitor of cyclo-oxygenase, but is not pro-oxidant. 7. 7. 5,7- and 6,7-dihydroxy-4-methylcoumarin both reduced the duration of ventricular fibrillation in postischaemic reperfused isolated perfused rat hearts (in which oxygen-derived free radicals are implicated), showing that these antioxidant coumarins possess beneficial properties in this pathophysiological model. 8. 8. In view of the established low toxicity, relative cheapness, presence in the diet and occurrence in various herbal remedies of coumarins, it appears prudent to evaluate their properties and applications further.

A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders

Abstract: The serotonin transporter (5-HTT) is a candidate locus for aetiological involvement in affective disorders. Biochemical studies in suicides and depressed patients suggest that 5-HT uptake function is frequently reduced in affective illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such as fluoxetine. We have performed an association study of a short variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional activity of the 5-HTT promoter leading to low functional expression of the 5-HTT, in 454 patients with bipolar or unipolar affective disorder and 570 controls, derived from three European Centres (London, Milan and Wurzburg). In all three centres, the frequency of the low activity allele was higher in patients than in controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Wurzburg). Although these differences were not individually significant, a stratified analysis of all three samples gave a significant overall odds ratio of 1.23 (95% confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low-activity genotype among the patients was even greater (odds ratio 1.53, 95% confidence interval 1.04-2.23, P = 0.02), suggesting partial recessively of the low-activity allele. Given the functional role of 5-HTT, our findings suggest that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential genetic susceptibility factor for affective disorders. If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.

Shortest paths algorithms: theory and experimental evaluation

Abstract: We conduct an extensive computational study of shortest paths algorithms, including some very recent algorithms. We also suggest new algorithms motivated by the experimental results and prove interesting theoretical results suggested by the experimental data. Our computational study is based on several natural problem classes which identify strengths and weaknesses of various algorithms. These problem classes and algorithm implementations form an environment for testing the performance of shortest paths algorithms. The interaction between the experimental evaluation of algorithm behavior and the theoretical analysis of algorithm performance plays an important role in our research.

Oxidative stress, nutrition and health. Experimental strategies for optimization of nutritional antioxidant intake in humans.

Abstract: Reactive oxygen species and reactive nitrogen species are formed in the human body. Endogenous antioxidant defences are inadequate to scavenge them completely, so that ongoing oxidative damage to DNA, lipids, proteins and other molecules can be demonstrated and may contribute to the development of cancer, cardiovascular disease and possibly neurodegenerative disease. Hence diet-derived antioxidants may be particularly important in protecting against these diseases. Some antioxidants (e.g. ascorbate, certain flavonoids) can exert pro-oxidant actions in vitro, often by interaction with transition metal ions. The physiological relevance of these effects is uncertain, as is the optimal intake of most diet-derived antioxidants. In principle, these questions could be addressed by examining the effects of dietary composition and/or antioxidant supplementation upon parameters of oxidative damage in vivo. The methods available for measuring steady-state damage (i.e. the balance between damage and repair or replacement of damaged molecules) and the actual rate of damage to DNA, proteins and lipids are reviewed, highlighting areas in which further methodological development is urgently required.

Psychological markers in the detection of autism in infancy in a large population.

Abstract: BACKGROUND Investigation to see if there are key psychological risk indicators for autism in a random population study of children at 18 months of age; and to assess how well these discriminate children who receive a diagnosis of autism from other forms of developmental delay. METHOD Sixteen thousand children in the southeast of England were screened for autism by their health visitor or GP, during their routine 18-month-old developmental check-up, using the CHAT (Checklist for Autism in Toddlers). From a previous high-risk study we predicted that children at 18 months of age who failed three items ('protodeclarative pointing', 'gaze-monitoring', and 'pretend play') would be at risk for receiving a diagnosis of autism. From other evidence, we further predicted that those 18-month-olds who failed one or two of the key items (either pretend play, or protodeclarative pointing and pretend play) would be at risk for developmental delay without autism. RESULTS Twelve children out of the total population of 16,000 consistently failed the three key items. Of these, 10 (83.3%) received a diagnosis of autism. Thus, the false positive rate was 16.6% (2 out of 12 cases), and even these 2 cases were not normal. When the 10 children with autism were reassessed at 3.5 years of age, their diagnosis remained the same. Thus the false positive rate among the cases diagnosed with autism was zero. In contrast, of 22 children who consistently failed either protodeclarative pointing and/or pretend play, none received a diagnosis of autism, but 15 (68.2%) received a diagnosis of language delay. CONCLUSIONS Consistent failure of the three key items from the CHAT at 18 months of age carries an 83.3% risk of autism; and this pattern of risk indicator is specific to autism when compared to other forms of developmental delay.

Vitamin C: antioxidant or pro-oxidant in vivo?

Abstract: Ascorbic acid has a multiplicity of antioxidant properties, but it can exert pro-oxidant effects in vitro, usually by interaction with transition metal ions. It is as yet uncertain that these pro-oxidant effects have any biological relevance: some of the available data are summarized.

Body dysmorphic disorder. A survey of fifty cases.

Abstract: BACKGROUND Body dysmorphic disorder (BDD) consists of a preoccupation with an 'imagined' defect in appearance which causes significant distress or impairment in functioning. There has been little previous research into BDD. This study replicates a survey from the USA in a UK population and evaluates specific measures of BDD. METHOD Cross-sectional interview survey of 50 patients who satisfied DSM-IV criteria for BDD as their primary disorder. RESULTS The average age at onset was late adolescence and a large proportion of patients were either single or divorced. Three-quarters of the sample were female. There was a high degree of comorbidity with the most common additional Axis l diagnosis being either a mood disorder (26%), social phobia (16%) or obsessive-compulsive disorder (6%). Twenty-four per cent had made a suicide attempt in the past. Personality disorders were present in 72% of patients, the most common being paranoid, avoidant and obsessive-compulsive. CONCLUSIONS BDD patients had a high associated comorbidity and previous suicide attempts. BDD is a chronic handicapping disorder and patients are not being adequately identified or treated by health professionals.

Meanings and Consequences: a basis for distinguishing formative and summative functions of assessment?

Abstract: The assessment process is characterised as a cycle involving elicitation of evidence, which when interpreted appropriately may lead to action, which in turn, can yield further evidence and so on. An assessment is defined as serving a formative function when it elicits evidence that yields construct-referenced interpretations that form the basis for successful action in improving performance, whereas summative functions prioritise the consistency of meanings across contexts and individuals. Aspects of the interplay of meanings and consequences are explored for each of the three phases, and it is suggested that this interplay may be fruitful in distinguishing the two functions. Tensions between summative and formative functions of assessment are illustrated in the context of the National Curriculum, and although it is shown that such tensions will always exist, it is suggested that the separation of the elicitation of evidence from its interpretation can mitigate that tension.

A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin

Abstract: Pain differs from other sensations in many respects. Primary pain-sensitive neurons respond to a wide variety of noxious stimuli, in contrast to the relatively specific responses characteristic of other sensory systems, and the response is often observed to sensitize on repeated presentation of a painful stimulus, while adaptation is typically observed in other sensory systems. In most cases the cellular mechanisms of transduction and sensitization in response to painful stimuli are not understood. We report here that application of pulses of noxious heat to a subpopulation of isolated primary sensory neurons rapidly activates an inward current. The ion channel activated by heat discriminates poorly among alkali cations. Calcium ions both carry current and partially suppress the current carried by other ions. The current is markedly increased by bradykinin, a potent algogenic nonapeptide that is known to be released in vivo by tissue damage. Phosphatase inhibitors prolong the sensitization caused by bradykinin, and a similar sensitization is caused by activators of protein kinase C. We conclude that bradykinin sensitizes the response to heat by activating protein kinase C.

School choice, social class and distinction: the realization of social advantage in education

Abstract: Parental choice is one of the keystones of current education policy in the UK. A combination of open enrolment, per‐capita funding and deregulated admission procedures is encouraging competition between schools for student enrolments (at least in areas where there are surplus places). Parents are encouraged to see themselves as consumers of education, and ‘good parenting’ is defined, at least in part, in relation to the ‘responsibilities’ of choice (The Parents Charter, Department of Education 1992). Within education policy choice is taken to be both neutral and individualistic. In this paper, we attempt to challenge that neutrality and to argue that choice in education is systematically related to social class differences and the reproduction of class inequalities.

Blood radicals: reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system.

Abstract: Free radicals, such as superoxide, hydroxyl and nitric oxide, and other "reactive species", such as hydrogen peroxide, hypochlorous acid and peroxynitrite, are formed in vivo. Some of these molecules, e.g. superoxide and nitric oxide, can be physiologically useful, but they can also cause damage under certain circumstances. Excess production of reactive oxygen or nitrogen species (ROS, RNS), their production in inappropriate relative amounts (especially superoxide and NO) or deficiencies in antioxidant defences may result in pathological stress to cells and tissues. This oxidative stress can have multiple effects. It can induce defence systems, and render tissues more resistant to subsequent insult. If oxidative stress is excessive or if defence and repair responses are inadequate, cell injury can be caused by such mechanisms as oxidative damage to essential proteins, lipid peroxidation, DNA strand breakage and base modification, and rises in the concentration of intracellular "free" Ca(2+). Considerable evidence supports the view that oxidative damage involving both ROS and RNS is an important contributor to the development of atherosclerosis. Peroxynitrite (derived by reaction of superoxide with nitric oxide) and transition metal ions (perhaps released by injury to the vessel wall) may contribute to lipid peroxidation in atherosclerotic lesions.

The Asymptotic Distribution of Eigenvalues of Partial Differential Operators

Abstract: Main results Oscillatory integrals Construction of the wave group Singularities of the wave group Proof of main results Mechanical applications Appendix A. Spectral problem on the half-line Appendix B. Fourier Tauberian theorems Appendix C. Stationary phase formula Appendix D. Hamiltonian billiards: proofs Appendix E. Factorization of smooth functions and Taylor-type formulae References Principal notation Index.

A multi-stage approach to the coding of data from open-ended questions.

Abstract: One of the criticisms of qualitative research is that the processes and procedures of data analysis tire often not made explicit ( 1 ). This criticism is particularly pertinent to the analysis of open-ended questions. This paper outlines an approach to analysing open-ended questions using content analysis, making explicit the processes and procedures involved. The paper will also describe how the challenge of ensuring rigour and maintaining the diversity and subtlety of responses, which can easily be lost when attempting to quantify qualitative data, can be overcome.

Nitric oxide, nitrite, and Fnr regulation of hmp (flavohemoglobin) gene expression in Escherichia coli K-12.

Abstract: Escherichia coli possesses a soluble flavohemoglobin, with an unknown function, encoded by the hmp gene. A monolysogen containing an hmp-lacZ operon fusion was constructed to determine how the hmp promoter is regulated in response to heme ligands (O2, NO) or the presence of anaerobically utilized electron acceptors (nitrate, nitrite). Expression of the phi (hmp-lacZ)1 fusion was similar during aerobic growth in minimal medium containing glucose, glycerol, maltose, or sorbitol as a carbon source. Mutations in cya (encoding adenylate cyclase) or changes in medium pH between 5 and 9 were without effect on aerobic expression. Levels of aerobic and anaerobic expression in glucose-containing minimal media were similar; both were unaffected by an arcA mutation. Anaerobic, but not aerobic, expression of phi (hmp-lacZ)1 was stimulated three- to four-fold by an fnr mutation; an apparent Fnr-binding site is present in the hmp promoter. Iron depletion of rich broth medium by the chelator 2'2'-dipyridyl (0.1 mM) enhanced hmp expression 40-fold under anaerobic conditions, tentatively attributed to effects on Fnr. At a higher chelator concentration (0.4 mM), hmp expression was also stimulated aerobically. Anaerobic expression was stimulated 6-fold by the presence of nitrate and 25-fold by the presence of nitrite. Induction by nitrate or nitrite was unaffected by narL and/or narP mutations, demonstrating regulation of hmp by these ions via mechanisms alternative to those implicated in the regulation of other respiratory genes. Nitric oxide (10 to 20 microM) stimulated aerobic phi (hmp-lacZ)1 activity by up to 19-fold; soxS and soxR mutations only slightly reduced the NO effect. We conclude that hmp expression is negatively regulated by Fnr under anaerobic conditions and that additional regulatory mechanisms are involved in the responses to oxygen, nitrogen compounds, and iron availability. Hmp is implicated in reactions with small nitrogen compounds.

Social Polarisation, Economic Restructuring and Welfare State Regimes:

Abstract: The central argument of this paper is that it is misconceived to view social polarisation of occupational structure and incomes in global cities as either inevitable or as a direct product of econo...

A combined analysis of D22S278 marker alleles in affected sib-pairs: Support for a susceptibility locus for schizophrenia at chromosome 22q12

Abstract: Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide. This marker was chosen because it showed maximum evidence for linkage in three independent datasets (Vallada et al., Am J Med Genet 60:139-146, 1995; Polymeropoulos et al., Neuropsychiatr Genet 54:93-99, 1994; Lasseter et al., Am J Med Genet, 60:172-173, 1995. Using the affected sib-pair method as implemented by the program ESPA, the combined dataset showed 252 alleles shared compared with 188 alleles not share (chi-square 9.31, 1df, P = 0.001) where parental genotype data was completely known. When sib-pairs for whom parental data was assigned according to probability were included the number of alleles shared was 514.1 compared with 437.8 not shared (chi-square 6.12, 1df, P = 0.006). Similar results were obtained when a likelihood ratio method for sib-pair analysis was used. These results indicate that may be a susceptibility locus for schizophrenia at 22q12.

A Handbook of Statistical Analyses using SAS

Abstract: Introduction to SAS Introduction User Interface SAS Language Reading Data-The Data Step Modifying SAS Data Proc Step Global Statements SAS Graphics ODS-The Output Delivery System Enhancing Output Some Tips for Preventing and Correcting Errors Data Description and Simple Inference: Mortality and Water Hardness in the United Kingdom Introduction Methods of Analysis Analysis Using SAS Simple Inference for Categorical Data: From Sandflies to Organic Particulates in the Air Introduction Methods of Analysis Analysis Using SAS Analysis of Variance I: Treating Hypertension Introduction Analysis of Variance Model Analysis Using SAS Analysis of Variance II: School Attendance among Australian Children Introduction Analysis of Variance Model Analysis Using SAS Simple Linear Regression: Alcohol Consumption and Cirrhosis Deaths and How Old Is the Universe? Introduction Simple Linear Regression Analysis Using SAS Multiple Regression: Determinants of the Crime Rate in States of the United States Introduction Multiple Regression Model Analysis Using SAS Logistic Regression: Psychiatric Screening, Plasma Proteins, Danish Do-It-Yourself, and Lower Back Pain Description of Data Logistic Regression Model Analysis Using SAS Generalized Linear Models: Polyposis and School Attendance among Australian School Children Description of Data Generalized Linear Models Analysis Using SAS Generalized Additive Models: Burning Rubber and Air Pollution in the United States Introduction Scatterplots and Generalized Additive Models Analysis Using SAS Analysis of Variance of Repeated Measures Visual Acuity Description of Data Repeated Measures Data Analysis of Variance for Repeated Measures Designs Analysis Using SAS Longitudinal Data I: Treatment of Postnatal Depression Description of Data Analyses of Longitudinal Data Analysis Using SAS Longitudinal Data II: Linear Mixed Models. Computerized Delivery of Cognitive Behavioral Therapy-Beat the Blues Introduction Linear Mixed Models for Longitudinal Data Analysis Using SAS Longitudinal Data III: Generalized Estimating Equations and Generalized Mixed Models: Treating Toenail Infection Introduction Methods for Analyzing Longitudinal Data Where the Response Variable Cannot Be Assumed to Have a Normal Distribution Analysis Using SAS Survival Analysis: Gastric Cancer, the Treatment of Heroin Addicts, and Heart Transplants Introduction Describing Survival Data Cox's Regression Analysis Using SAS Principal Components Analysis and Factor Analysis: Olympic Decathlon and Statements about Pain Introduction Principal Components Analysis and Factor Analysis Analysis Using SAS Cluster Analysis: Air Pollution in the United States Introduction Cluster Analysis Analysis Using SAS Discriminant Function Analysis: Classifying Tibetan Skulls Description of Data Discriminant Function Analysis Analysis Using SAS Correspondence Analysis: Smoking and Motherhood, Sex and the Single Girl, and European Stereotypes Description of Data Displaying Contingency Table Data Graphically Using Correspondence Analysis Analysis Using SAS Appendix References Index Exercises appear at the end of each chapter.

Structure-function Analysis of the Bacterial Aromatic Ring-hydroxylating Dioxygenases

Abstract: Publisher Summary The bacterial aromatic ring-hydroxylating dioxygenases represent a broad range of multi-component enzymes that possess many properties and mechanisms in common. This has enabled their classification based on structural properties. This classification has been supported by sequence comparisons based on nucleotide and primary amino-acid sequences. Comparison of the low homology sequences has also enabled the identification of highly conserved functional motifs—for example iron-sulphur ligation domains—whereas analysis of high homology sequences has allowed the characterization of amino acids involved in more specific functions, such as the control of substrate specificity. This combination of sequence analysis with structure-function studies proves to be invaluable for future protein engineering of improved enzymes for both biocatalysis and environmental remediation. The chapter focuses on the ring-hydroxylating dioxygenases, referring to ring-cleavage dioxygenases and other related systems, and also describes bacterial oxygenases and dioxygenases.