Algorithm for entropy monitor.
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Algorithms↗
Biomedical subjects
D Duncan
Publications and source records attributed to D Duncan.
Meeting everyday water needs--a company's contribution.
As a packaged consumer goods company serving mass markets around the world for household and personal hygiene products, laundry detergents and foods, Unilever's business is inextricably linked with consumers' interest in meeting their everyday water needs. Once the basic need for drinking water is met, almost all other "everyday" water needs derive from consumption associated with the type of products Unilever sells. Use of some of these products, such as basic toilet soap, involve "actual" water consumption; others, such as margarine, concern "virtual" water consumption through agricultural production. Global scenarios for water and sanitation present a major challenge to long-term business strategies that assume sustained economic growth particularly in emerging and developing markets. Responsibility for finding and delivering solutions lies with all major actors in society. For companies such as Unilever, a priority is to help break the link between economic development on the one hand, and increased water use and water degradation on the other. Water catchment level perspectives are central to realising this vision. Unilever uses such a framework, building an experience-based model that demonstrates how a "consumer" company can engage in meeting everyday water needs with a sustained positive impact.
Activities of Daily Living↗
A concise synthesis of turneforcidine via a metalloiminium ion cyclization terminated by the 2-(methylthio)-3-(trimethylsilyl)-1-propenyl moiety.
A concise synthetic route to racemic turneforcidine (1) is described that relies on the stereocontrolled cyclization of the 2-(methylthio)-3-(trimethylsilyl)-1-propenyl bearing imine 5 in the presence of TiCl(4). Reaction: see text.
Imines↗
Intramolecular cyclizations of imines bearing the 2-(thiomethyl)-3-trimethylsilyl-1-propenyl terminator. An efficient new procedure for the stereocontrolled synthesis of functionalized pyrrolidine derivatives.
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Cyclization↗
Drug use and mental well being among a sample of undergraduate and graduate college students.
Stress related disorders in college students are widespread and largely preventable. Students do not have the preventative skills necessary to manage stress in their lives and, because of the inability to cope, students may turn to alcohol and drugs to alleviate the pressures they are experiencing. The purpose of this study was to describe the association between stress and alcohol and drug use. A total of 772 undergraduate and graduate students from a small, elite, private university were randomly selected from 4000 students to complete two anonymous questionnaires. The Core Alcohol and Drug Survey identified the frequency and consequences of alcohol and drug use, and the General-Well Being Schedule was used to assess subjective well being and mental health status. The results of this study revealed that, for this sample of students, health behaviors such as using drugs recreationally and drinking alcohol played an associative role with general well being. A significant relationship was also found between student participation in intramural or club sports and positive mental well being.
Adaptation, Psychological↗
Parents who report using illicit drugs: findings and implications from the DRUGNET study.
In recent years, a national discussion has emerged concerning what parents should tell their children about their own past drug use. DRUGNET is an ongoing, on-line survey of successful, healthy, adults who occasionally use illicit drugs. This paper reviews data from a subset of this survey, namely, those respondents who were parents with self-reported use of at least one illicit drug. The sample (n = 325) was predominantly white men who reported having above average education and household incomes. Their mental health as measured by the General Well-being Schedule was similar to the national norm. Respondents reported using drugs to manage parental stress and expressed concerns over how to communicate with their children and legal risks related to their own drug use. The limitations and the implications of these data are discussed.
Adolescent↗
The general well-being of recreational drug users: a survey on the WWW.
American drug policy is predicated upon a dichotomy between legal drugs and illegal drugs - good drugs that enhance health and bad drugs which damage health. The fact of psychiatric co-morbidity between substance misuse disorders and other mental disorders is commonly taken to mean that drug use is damaging to mental health. The purpose of this study was to examine the mental well-being of a sample of occasional, recreational drug users. DRUGNET was an on-line survey of recreational drug use by non-deviant adults via the WWW. Volunteer subjects (n=906) completed the survey over the internet between March and September 1997. Mental health was assessed utilizing the General Well-being Schedule (GWBS). A complete demographic profile of the sample was taken. The GWBS correlated with frequency of use, intoxication levels and types of drugs consumed. This study demonstrates the existence of healthy, normally functioning adults who occasionally use psychoactive drugs.
Journal Article↗
Characterization of active-site mutants of Schizosaccharomyces pombe phosphoglycerate mutase. Elucidation of the roles of amino acids involved in substrate binding and catalysis.
The roles of a number of amino acids present at the active site of the monomeric phosphoglycerate mutase from the fission yeast Schizosaccharomyces pombe have been explored by site-directed mutagenesis. The amino acids examined could be divided broadly into those presumed from previous related structural studies to be important in the catalytic process (R14, S62 and E93) and those thought to be important in substrate binding (R94, R120 and R121). Most of these residues have not previously been studied by site-directed mutagenesis. All the mutants except R14 were expressed in an engineered null strain of Saccharomyces cerevisiae (S150-gpm:HIS) in good yield. The R14Q mutant was expressed in good yield in the transformed AH22 strain of S. cerevisiae. The S62A mutant was markedly unstable, preventing purification. The various mutants were purified to homogeneity and characterized in terms of kinetic parameters, CD and fluorescence spectra, stability towards denaturation by guanidinium chloride, and stability of phosphorylated enzyme intermediate. In addition, the binding of substrate (3-phosphoglycerate) to wild-type, E93D and R120,121Q enzymes was measured by isothermal titration calorimetry. The results provide evidence for the proposed roles of each of these amino acids in the catalytic cycle and in substrate binding, and will support the current investigation of the structure and dynamics of the enzyme using multidimensional NMR techniques.
Amino Acid Sequence↗
Organization of orthopaedic trauma services: a survey of the Orthopaedic Trauma Association.
OBJECTIVES: This study was undertaken to collect information about the organization of orthopaedic trauma services in different types of hospitals, with particular emphasis on hospital support arrangements in different practice situations. DESIGN: A survey was sent to all members of the Orthopaedic Trauma Association (OTA) as part of the organization's newsletter. Fractoids. In addition, the survey was distributed by the OTA's E-mail discussion list, ORT-1. MAIN OUTCOME MEASUREMENTS: The survey included questions about the size and nature of the hospital, resident involvement, academic affiliation, number of orthopaedic physician staff, training of the staff, presence of an organized orthopaedic trauma service, distribution of call and patients, and hospital support. RESULTS: Fifty-seven responses were received from North American centers, of which six were duplications. Responses came from institutions of all types and sizes, although most came from urban, Level 1 trauma centers with academic affiliation. Twenty-nine hospitals had a designated orthopaedic trauma service, and twenty-six had a director. Eighteen institutions had ancillary staff (nurses, physician's assistants, etc.) assigned to the orthopaedic trauma service. Hospitals with an academic affiliation were statistically more likely to have a designated orthopaedic trauma service and to distribute trauma patients by subspecialty expertise. In hospitals with a designated orthopaedic trauma service or director, it was more common to have ancillary support staff and to have it funded by the hospital, although the differences did not rise to statistical significance. CONCLUSIONS: There are differences in organization of orthopaedic trauma care between hospitals, which may be related to hospital size, academic affiliation, and orthopaedic department organization. Further study is necessary to determine whether organizational differences translate into differences in patient outcome after trauma.
Benchmarking↗
The folding and assembly of the dodecameric type II dehydroquinases.
The dodecameric type II dehydroquinases (DHQases) have an unusual quaternary structure in which four trimeric units are arranged with cubic 23 symmetry. The unfolding and refolding behaviour of the enzymes from Streptomyces coelicolor and Mycobacterium tuberculosis have been studied. Gel-permeation studies show that, at low concentrations (0.5 M) of guanidinium chloride (GdmCl), both enzymes dissociate into trimeric units, with little or no change in the secondary or tertiary structure and with a 15% loss (S. coelicolor) or a 55% increase (M. tuberculosis) in activity. At higher concentrations of GdmCl, both enzymes undergo sharp unfolding transitions over narrow ranges of the denaturant concentration, consistent with co-operative unfolding of the subunits. When the concentration of GdmCl is lowered by dilution from 6 M to 0.55 M, the enzyme from S. coelicolor refolds in an efficient manner to form trimeric units, with more than 75% regain of activity. Using a similar approach the M. tuberculosis enzyme regains less than 35% activity. From the time courses of the changes in CD, fluorescence and activity of the S. coelicolor enzyme, an outline model for the refolding of the enzyme has been proposed. The model involves a rapid refolding event in which approximately half the secondary structure is regained. A slower folding process follows within the monomer, resulting in acquisition of the full secondary structure. The major changes in fluorescence occur in a second-order process which involves the association of two folded monomers. Regain of activity is dependent on a further associative event, showing that the minimum active unit must be at least trimeric. Reassembly of the dodecameric S. coelicolor enzyme and essentially complete regain of activity can be accomplished if the denatured enzyme is dialysed extensively to remove GdmCl. These results are discussed in terms of the recently solved X-ray structures of type II DHQases from these sources.
Bacterial Proteins↗
The role of the C-terminal region in phosphoglycerate mutase.
Removal of the C-terminal seven residues from phosphoglycerate mutase from Saccharomyces cerevisiae by limited proteolysis is associated with loss of mutase activity, but no change in phosphatase activity. The presence of the cofactor 2, 3-bisphosphoglycerate, or of the cofactor and substrate 3-phosphoglycerate together, confers protection against proteolysis. The substrate alone offers no protection. Replacement of either or both of the two lysines at the C-terminus by glycines has only limited effects on the kinetic properties of phosphoglycerate mutase, indicating that these residues are unlikely to be involved in crucial electrostatic interactions with the substrate, intermediate or product in the reaction. However, the double-mutant form of the enzyme is more sensitive to proteolysis and is no longer protected against proteolysis by the presence of cofactor. The proteolysed wild-type and two of the mutated forms of the enzyme show a reduced response to 2-phosphoglycollate, which enhances the instability of the phospho form of the native enzyme. The phosphoglycerate mutase from Schizosaccharomyces pombe, which lacks the analogous C-terminal tail, has an inherently lower mutase activity and is also less responsive to stimulation by 2-phosphoglycollate. It is proposed that the C-terminal region of phosphoglycerate mutase helps to maintain the enzyme in its active phosphorylated form and assists in the retention of the bisphosphoglycerate intermediate at the active site. However, its role seems not to be to contribute directly to ligand binding, but rather to exert indirect effects on the transfer of the phospho group between substrate, enzyme, intermediate and product.
Amino Acid Sequence↗
The spineless-aristapedia and tango bHLH-PAS proteins interact to control antennal and tarsal development in Drosophila.
The Drosophila spineless (ss) gene encodes a basic-helix-loop-helix-PAS transcription factor that is required for proper specification of distal antennal identity, establishment of the tarsal regions of the legs, and normal bristle growth. ss is the closest known homolog of the mammalian aryl hydrocarbon receptor (Ahr), also known as the dioxin receptor. Dioxin and other aryl hydrocarbons bind to the PAS domain of Ahr, causing Ahr to translocate to the nucleus, where it dimerizes with another bHLH-PAS protein, the aryl hydrocarbon receptor nuclear translocator (Arnt). Ahr:Arnt heterodimers then activate transcription of target genes that encode enzymes involved in metabolizing aryl hydrocarbons. In this report, we present evidence that Ss functions as a heterodimer with the Drosophila ortholog of Arnt, Tango (Tgo). We show that the ss and tgo genes have a close functional relationship: loss-of-function alleles of tgo were recovered as dominant enhancers of a ss mutation, and tgo-mutant somatic clones show antennal, leg, and bristle defects almost identical to those caused by ss(-) mutations. The results of yeast two-hybrid assays indicate that the Ss and Tgo proteins interact directly, presumably by forming heterodimers. Coexpression of Ss and Tgo in Drosophila SL2 cells causes transcriptional activation of reporters containing mammalian Ahr:Arnt response elements, indicating that Ss:Tgo heterodimers are very similar to Ahr:Arnt heterodimers in DNA-binding specificity and transcriptional activation ability. During embryogenesis, Tgo is localized to the nucleus at sites of ss expression. This localization is lost in a ss null mutant, suggesting that Tgo requires heterodimerization for translocation to the nucleus. Ectopic expression of ss causes coincident ectopic nuclear localization of Tgo, independent of cell type or developmental stage. This suggests that the interaction of Ss and Tgo does not require additional signals, unlike the ligand-dependent interaction of Ahr and Arnt. Despite the very different biological roles of Ahr and Arnt in insects and mammals, the molecular mechanisms by which these proteins function appear to be largely conserved.
Alleles↗
Purification and characterization of pyruvate kinase from Schizosaccharomyces pombe: evidence for an unusual quaternary structure.
Earlier attempts to purify and characterize nonrecombinant pyruvate kinase from Schizosaccharomyces pombe proved difficult due to problems associated with the instability of the protein. The enzyme has been overexpressed in Saccharomyces cerevisiae strain AH22, permitting studies to determine the conditions required to stabilize the enzyme during purification. Recombinant S. pombe pyruvate kinase was purified by a combination of ion-exchange chromatography and gel filtration. The purified enzyme showed sigmoidal kinetics with respect to PEP; in the presence of FBP, the kinetics were restored to Michaelis-Menten behavior. With respect to ADP, the Hill coefficient was not affected by FBP. Determination of the molecular mass of the purified enzyme by ultracentrifugation showed that it behaved as a dimer-tetramer system with a Kd of approximately 1 microM.
Adenosine Diphosphate↗
Structure of the Shigella dysenteriae haem transport locus and its phylogenetic distribution in enteric bacteria.
The ability to transport and use haemin as an iron source is frequently observed in clinical isolates of Shigella spp. and pathogenic Escherichia coli. We found that many of these haem-utilizing E. coli strains contain a gene that hybridizes at high stringency to the S. dysenteriae type 1 haem receptor gene, shuA. These shuA-positive strains belong to multiple phylogenetic groups and include clinical isolates from enteric, urinary tract and systemic infections. The distribution of shuA in these strains suggests horizontal transfer of the haem transport locus. Some haem-utilizing pathogenic E. coli strains did not hybridize with shuA, so at least one other haem transport system is present in this group. We also characterized the chromosomal region containing shuA in S. dysenteriae. The shuA gene is present in a discrete locus, designated the haem transport locus, containing eight open reading frames. Several of the proteins encoded in this locus participate with ShuA in haem transport, as a Salmonella typhimurium strain containing the entire haem transport locus used haem much more efficiently than the same strain containing only shuA. The haem transport locus is not present in E. coli K-12 strains, but the sequences flanking the haem transport locus in S. dysenteriae matched those at the 78.7 minute region of E. coli K-12. The junctions and flanking sequences in the shuA-positive pathogenic E. coli strains tested were nearly identical to those in S. dysenteriae, indicating that, in these strains, the haem transport locus has an organization similar to that in S. dysenteriae, and it is located in the same relative position on the chromosome.
Bacterial Outer Membrane Proteins↗
Antidepressant interactions with warfarin.
The interactions between warfarin and antidepressants can have potentially serious consequences resulting from enhanced or reduced anticoagulant activity. Information about such interactions was obtained from a Medline and hand search of the published literature, and by directly contacting manufacturers. The different classes of antidepressants are discussed in turn. The possible mechanisms are considered with particular reference to the cytochrome p450 system. From currently available data on the newer antidepressants our conclusions are that citalopram, nefazodone and sertraline may be relatively less likely to interact with warfarin. Fluoxetine, fluvoxamine, paroxetine and moclobemide appear to have the highest potential of the antidepressants for interactions. There is insufficient data on venlafaxine to make a prediction. The clinical implications of these findings are discussed and specific recommendations for International Normalized Ratio monitoring are suggested.
Animals↗
Alcoholic patients' experience and attitudes on pharmacotherapy for alcoholism.
Clinical studies have demonstrated that pharmacotherapies may improve alcoholism treatment, when combined with traditional psychosocial therapies. Recently, the opioid antagonist, naltrexone, has been approved as an adjunct in alcoholism treatment, and several other pharmacotherapies for alcoholism are under development. Because of the abstinence orientation of many patients, we assessed attitudes regarding medications, and explored whether alcoholic patients would consider taking medication as part of their alcoholism treatment. Active patients (n = 127) in three alcohol treatment settings were surveyed with an anonymous questionnaire which asked demographics, personal alcoholism history and questions about medication use. They were asked whether they felt disulfiram and naltrexone were helpful for alcoholics and whether they would take the medications. The findings indicate that the patients were divided about the use of pharmacotherapy for the treatment of alcoholism. The strongest predictor of willingness to take medication was a belief that the medication would be helpful.
Adult↗
Recognition of intussusception around gastrojejunostomy tubes in children.
OBJECTIVE: We describe antegrade intussusceptions of duodenum and jejunum around gastrojejunostomy tubes seen on sonography and fluoroscopic contrast tube studies. Reduction of the intussusception was achieved by bolus injection of air or contrast medium through the tube or exchange over a wire. CONCLUSION: Sonography and fluoroscopic contrast tube studies permit diagnosis of intussusception around gastrojejunostomy tubes.
Child, Preschool↗
Dietary energy sources and colon cancer risk.
Because energy-contributing nutrients are highly correlated with total energy, the association with colon cancer from energy versus other components of energy-providing nutrients is often not clear. Dietary data from a population-based case-control study of colon cancer were analyzed in subjects from California, Utah, and Minnesota in 1991-1994 to assess the colon cancer risk associated with consumption of energy, fat, protein, and carbohydrate. After adjustment for long-term physical activity, total energy intake increased risk of colon cancer in men (odds ratio = 1.74, 95% confidence interval 1.14-2.67 for highest vs. lowest quartile) and in women (odds ratio = 1.70, 95% confidence interval 1.07-2.70). Various methods of analysis suggested that intakes of individual sources of energy (dietary fat, protein, and carbohydrate) were not associated with colon cancer risk after total energy intake was taken into account. People who consumed a high-calorie diet that was dense in fiber and calcium appeared to be at lower risk than people with the same caloric intake who consumed smaller amounts of dietary fiber and calcium. Individuals with a first-degree relative with colorectal cancer, especially those diagnosed at a younger age, were at a greater risk from a diet high in energy than were individuals without a family history of colorectal cancer.
Adult↗