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Fourth Step (fourth + step)
Selected AbstractsPortfolio selection on the Madrid Exchange: a compromise programming modelINTERNATIONAL TRANSACTIONS IN OPERATIONAL RESEARCH, Issue 1 2003E. Ballestero As a contribution to portfolio selection analysis, we develop a compromise programming approach to the investor's utility optimum on the Madrid Online Market. This approach derives from linkages between utility functions under incomplete information, Yu's compromise set, and certain biased sets of portfolios on the efficient frontier. These linkages rely on recent theorems in multi,criteria literature, which allow us to approximate the investor's utility optimum between bounds which are determined either by linear programming models or graphic techniques. Returns on 104 stocks are computed from capital gains and cash,flows, including dividends and rights offerings, over the period 1992,1997. The first step consists in normalizing the mean,variance efficient frontier, which is defined in terms of two indexes, profitability and safety. In the second step, interactive dialogues to elicit the investor's preferences for profitability and safety are described. In the third step, the utility optimum for each particular investor who pursues a buy,&,hold policy is bounded on the efficient frontier. From this step, a number of portfolios close to the investor's utility optimum are obtained. In the fourth step, compromise programming is used again to select one ,satisficing' portfolio from the set already bounded for each investor. This step is new with respect to previous papers in which compromise/utility models are employed. Computing processes are detailed in tables and figures which also display the numerical results. Extensions to active management policies are suggested. [source] Ortho Effects in Quantitative Structure Activity Relationships for Lipase Inhibition by Aryl CarbamatesMOLECULAR INFORMATICS, Issue 8 2003Gialih Lin Abstract Ortho -substituted phenyl- N -butyl carbamates (1,11) are synthesized and evaluated for their inhibition effects on Pseudomonas species lipase. Carbamates 1,11 are characterized as pseudo-substrate inhibitors of the enzyme. The logarithms of dissociation constant (Ki), carbamylation constant (k2), and bimolecular inhibition constant (ki) multiply linearly correlate with Hammett substituent constant (,), Taft-Kutter-Hansch ortho steric constant (ES), and Swan-Lupton field constant (F). For ,logKi -, logk2 -, and logki -correlations, values of ,, ,, f, ,XR are 0.2, ,0.06, ,1.7, 0.8; 0.0, 0.0, 1.0, ,0.07; and ,1.8, 7, 0.6, 5; respectively. The enzyme inhibition mechanism is composed of four steps: 1) the first step which is protonation of carbamates 1,11, 2) the second step (Ki1) which involves in the proton 1,3-shift of protonated carbamates 1,11 then the pseudo- trans to cis conformational change, 3) the third step (Ki2) which is formation of a negative charged enzyme-inhibitor tetrahedral intermediate, and 4) the fourth step (k2) which is the carbamylation step. The former three steps are likely composed of the Ki step. There is little ortho steric enhancement effect in the Ki step. From cross-interaction correlations, distance between carbamate and phenyl substituents in transition state for the Ki step is relatively short due to a large ,XR value of 7. The k2 step is insensitive to ortho steric effect. The k2 step involves in departure of leaving group, substituted phenol in which is protonated from the proton 1,3-shift but not from the active site histidine of the enzyme. From cross-interaction correlations, the distance between carbamate and phenyl substituents in transition state for the k2 step is relatively long due to a small ,XR value of 0.6. [source] Evidence that WbpD is an N -acetyltransferase belonging to the hexapeptide acyltransferase superfamily and an important protein for O-antigen biosynthesis in Pseudomonas aeruginosa PAO1MOLECULAR MICROBIOLOGY, Issue 5 2005Cory Q. Wenzel Summary Di- N -acetylated uronic acid residues are unique sugar moieties observed in the lipopolysaccharides (LPS) of respiratory pathogens including several serotypes of Pseudomonas aeruginosa and several species of Bordetella. WbpD of P. aeruginosa PAO1 (serotype O5) is a putative 3- N -acetyltransferase that has been implicated in the biosynthesis of UDP-2,3-diacetamido-2,3-dideoxy- d -mannuronic acid [UDP- d -Man(2NAc3NAc)A], a precursor for the d -Man(2NAc3NAc)A residues in the B-band O antigen of this bacterium. A chromosomal knockout mutant of wbpD is incapable of producing either long-chain B-band O antigen (, 2 repeating units) or semi-rough LPS (lipid A-core + one repeat). Adding wbpD in trans restored LPS production to the wild-type level; this indicates that wbpD is important for biosynthesis of individual B-band O-antigen repeating units. WbpD contains left-handed beta-helical (L,H) structure as observed by Conserved Domain analysis and in silico secondary and tertiary structure predictions. This feature suggested that WbpD belongs to the hexapeptide acyltransferase (HexAT) superfamily of enzymes. WbpD was overexpressed as an N-terminally histidine-tagged fusion protein (His6,WbpD) and purified to >,95% purity. The protein was subjected to Far-UV circular dichroism spectroscopy, and the data revealed that WbpD contains left-handed helical structure, which substantiated in silico predictions made earlier. Results from SDS-PAGE, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS), and gel filtration analyses indicated that His6 -WbpD has trimeric organization, consistent with the quaternary structure of HexATs. The binding of acetyl-CoA by WbpD was demonstrated by MALDI-TOF MS, suggesting that WbpD is an acetyltransferase that utilizes a direct-transfer reaction mechanism. Incubation of WbpD with acetyl-CoA significantly enhanced the stability of the protein and prevented precipitation over a course of 14 days. As a substrate for studying the enzymatic activity of WbpD is unavailable at present, a structure-based model for the L,H domain of WbpD was generated. Comparisons between this model and the L,H domains of known HexATs suggested that Lys136 plays a role in acetyl-CoA binding. A K136A site-directed mutant construct could only partially complement the wbpD knockout, and this mutation also reduced the stabilizing effects of acetyl-CoA, while a K136R mutation showed no discernible effect on complementation of the wbpD mutant or the stabilizing effects of acetyl-CoA on the purified mutant protein. A modified pathway was proposed for the biosynthesis of UDP- d -Man(2NAc3NAc)A, in which WbpD is involved in the catalysis of the fourth step by acting as a UDP-2-acetamido-3-amino-2,3-dideoxy- d -glucuronic acid 3- N -acetyltransferase. [source] Crystal structure of the yeast His6 enzyme suggests a reaction mechanismPROTEIN SCIENCE, Issue 6 2006Sophie Quevillon-Cheruel Abstract The Saccharomycescerevisiae His6 gene codes for the enzyme phosphoribosyl-5-amino-1-phosphoribosyl-4-imidazolecarboxamide isomerase, catalyzing the fourth step in histidine biosynthesis. To get an insight into the structure and function of this enzyme, we determined its X-ray structure at a resolution of 1.30 Å using the anomalous diffraction signal of the protein's sulphur atoms at 1.77 Å wavelength. His6 folds in an (,/,)8 barrel similar to HisA, which performs the same function in bacteria and archaea. We found a citrate molecule from the buffer bound in a pocket near the expected position of the active site and used it to model the open form of the substrate (phosphoribulosyl moiety), which is a reaction intermediate. This model enables us to identify catalytic residues and to propose a reaction mechanism where two aspartates act as acid/base catalysts: Asp134 as a proton donor for ring opening, and Asp9 as a proton acceptor and donor during enolization of the aminoaldose. Asp9 is conserved in yeast His6 and bacterial or archaeal HisA sequences, and Asp134 has equivalents in both HisA and TrpF, but they occur at a different position in the protein sequence. [source] Community-based Participatory Research: Development of an Emergency Department,based Youth Violence Intervention Using Concept MappingACADEMIC EMERGENCY MEDICINE, Issue 8 2010Carolyn E. Snider MD, FRCPC ACADEMIC EMERGENCY MEDICINE 2010; 17:1,9 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives:, Emergency departments (EDs) see a high number of youths injured by violence. In Ontario, the most common cause of injury for youths visiting EDs is assault. Secondary prevention strategies using the teachable moment (i.e., events that can lead individuals to make positive changes in their lives) are ideal for use by clinicians. An opportunity exists to take advantage of the teachable moment in the ED in an effort to prevent future occurrences of injury in at-risk youths. However, little is known about perceptions of youths, parents, and community organizations about such interventions in EDs. The aims of this study were to engage youths, parents, and frontline community workers in conceptualizing a hospital-based violence prevention intervention and to identify outcomes relevant to the community. Methods:, Concept mapping is an innovative, mixed-method research approach. It combines structured qualitative processes such as brainstorming and group sorting, with various statistical analyses such as multidimensional scaling and hierarchical clustering, to develop a conceptual framework, and allows for an objective presentation of qualitative data. Concept mapping involves multiple structured steps: 1) brainstorming, 2) sorting, 3) rating, and 4) interpretation. For this study, the first three steps occurred online, and the fourth step occurred during a community meeting. Results:, Over 90 participants were involved, including youths, parents, and community youth workers. A two-dimensional point map was created and clusters formed to create a visual display of participant ideas on an ED-based youth violence prevention intervention. Issues related to youth violence prevention that were rated of highest importance and most realistic for hospital involvement included mentorship, the development of youth support groups in the hospital, training doctors and nurses to ask questions about the violent event, and treating youth with respect. Small-group discussions on the various clusters developed job descriptions, a list of essential services, and suggestions on ways to create a more youth-friendly environment in the hospital. A large-group discussion revealed outcomes that participants felt should be measured to determine the success of an intervention program. Conclusions:, This study has been the springboard for the development of an ED-based youth violence intervention that is supported by the community and affected youth. Using information generated by youth that is grounded in their experience through participatory research methods is feasible for the development of successful and meaningful youth violence prevention interventions. [source] Expression, purification and crystallization of Trypanosoma cruzi dihydroorotate dehydrogenase complexed with orotateACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 10 2005Daniel Ken Inaoka Dihydroorotate dehydrogenase (DHOD) catalyzes the oxidation of dihydroorotate to orotate, the fourth step and the only redox reaction in the de novo biosynthesis of pyrimidine. DHOD from Trypanosoma cruzi (TcDHOD) has been expressed as a recombinant protein in Escherichia coli and purified to homogeneity. Crystals of the TcDHOD,orotate complex were grown at 277,K by the sitting-drop vapour-diffusion technique using polyethylene glycol 3350 as a precipitant. The crystals diffract to better than 1.8,Å resolution using synchrotron radiation (, = 0.900,Å). X-ray diffraction data were collected at 100,K and processed to 1.9,Å resolution with 98.2% completeness and an overall Rmerge of 7.8%. The TcDHOD crystals belong to the orthorhombic space group P212121, with unit-cell parameters a = 67.87, b = 71.89, c = 123.27,Å. The presence of two molecules in the asymmetric unit (2 × 34,kDa) gives a crystal volume per protein weight (VM) of 2.2,Å3,Da,1 and a solvent content of 44%. [source] | ||||||||||