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Selected AbstractsModeling the Inhibitor Activity and Relative Binding Affinities in Enzyme-Inhibitor-Protein Systems: Application to Developmental Regulation in a PG-PGIP SystemBIOTECHNOLOGY PROGRESS, Issue 3 2004Wayne W. Fish Within a number of classes of hydrolytic enzymes are certain enzymes whose activity is modulated by a specific inhibitor-protein that binds to the enzyme and forms an inactive complex. One unit of a specific inhibitor-protein activity is often defined as the amount necessary to inhibit one unit of its target enzyme by 50 %. No objective quantitative means is available to determine this point of 50 % inhibition in crude systems such as those encountered during purification. Two models were derived: the first model is based on an irreversible binding approximation, and the second, or equilibrium, model is based on reversible binding. The two models were validated using the inhibition data for the polygalacturonase-polygalacturonase-inhibiting protein (PG-PGIP) system. Theory and experimental results indicate that the first model can be used for inhibitor protein activity determination and the second model can be used for inhibitor protein activity determination as well as for comparison of association constants among enzymes and their inhibitor-proteins from multiple sources. The models were used to identify and further clarify the nature of a differential regulation of expression of polygalacturonase-inhibiting protein in developing cantaloupe fruit. These are the first relations that provide for an objective and quantitative determination of inhibitor-protein activity in both pure and crude systems. Application of these models should prove valuable in gaining insights into regulatory mechanisms and enzyme-inhibitor-protein interactions. [source] The mitochondrial genome of the wine yeast Hanseniaspora uvarum: a unique genome organization among yeast/fungal counterpartsFEMS YEAST RESEARCH, Issue 1 2006Paraskevi V. Pramateftaki Abstract The complete sequence of the apiculate wine yeast Hanseniaspora uvarum mtDNA has been determined and analysed. It is an extremely compact linear molecule containing the shortest functional region ever found in fungi (11 094 bp long), flanked by Type 2 telomeric inverted repeats. The latter contained a 2704-bp-long subterminal region and tandem repeats of 839-bp units. In consequence, a population of mtDNA molecules that differed at the number of their telomeric reiterations was detected. The functional region of the mitochondrial genome coded for 32 genes, which included seven subunits of respiratory complexes and ATP synthase (the genes encoding for NADH oxidoreductase subunits were absent), two rRNAs and 23 tRNA genes which recognized codons for all amino acids. A single intron interrupted the cytochrome oxidase subunit 1 gene. A number of reasons contributed towards its strikingly small size, namely: (1) the remarkable size reduction (by >40%) of the rns and rnl genes; (2) that most tRNA genes and five of the seven protein-coding genes were the shortest among known yeast homologs; and (3) that the noncoding regions were restricted to 5.1% of the genome. In addition, the genome showed multiple changes in the orientation of transcription and the gene order differed drastically from other yeasts. When all protein coding gene sequences were considered as one unit and were compared with the corresponding molecules from all other complete mtDNAs of yeasts, the phylogenetic trees constructed robustly supported its placement basal to the yeast species of the ,Saccharomyces complex', demonstrating the advantage of this approach over single-gene or multigene approaches of unlinked genes. [source] Reconstruction of activity areas at a formative household in northwest ArgentinaGEOARCHAEOLOGY: AN INTERNATIONAL JOURNAL, Issue 4 2005María Marta Sampietro This paper analyzes the spatial pattern of landscapes and domestic unit activity areas at an archaeological site in northwest Argentina. The site is on a cone glacis in the Tafí Valley on the east side of Aconquija Mountain. The archaeological structures are associated with one of the earliest permanent villages of the region and date to the Formative Period of the Tafí culture (2296 ± 70 yr B.P. to 1140 ± 50 yr B.P.). Using photointerpretation, we distinguished two main structure types: agricultural structures, such as stone terraces, and circular houses. Statistical analysis of the different types of circular structures indicates that simple units had a uniform distribution, which reflects the main function of the area. The patio of one unit was excavated, and three burial cists were found under a Formative Period floor. Archaeological artifacts, together with 107 soil samples from the floor, were collected to establish activity areas within the domestic space. By analyzing soil chemistry (pH, calcium, organic and inorganic phosphorous) and ceramic and animal bone distributions, three major activity areas (animal processing, plant storage, and burials) were identified. © 2005 Wiley Periodicals, Inc. [source] Shifts in the ecological behaviour of plant species between two distant regions: evidence from the base richness gradient in miresJOURNAL OF BIOGEOGRAPHY, Issue 2 2008Petra Hájková Abstract Aim, Water pH and conductivity are known to be major environmental factors controlling the species composition of nutrient-poor wetlands. Based on the analysis of two large data sets of species co-occurrence, sampled along the entire pH/calcium gradient, we explored whether species exhibit similar or different ecological behaviour in the two regions. Location, West Carpathians (central Europe) and Bulgaria (south-eastern Europe), situated 800 km apart. Bulgaria represents a range margin for many mire species. Methods, The probability of occurrence of the 41 most common species along the pH and conductivity gradients was assessed using logistic regression fitted by means of generalized additive models. The species optimum and amplitude were determined. To check the possible effect of competitive release, we estimated where the potential maximum number of species (maximum overlap in realized niches) occurs along the base richness gradient. Results, Most of the 41 frequently occurring species showed a significant response to water pH and ln-transformed conductivity (approximating total mineral richness) in both regions. Eight species showed a shift in pH optimum greater than one unit, while 12 species showed the same or a larger shift along the conductivity gradient. Nearly all these striking shifts were connected to an extension of species tolerance towards mineral-poor acid habitats in Bulgaria, which causes links between species and measured factors to be conspicuously weaker in Bulgaria than in the West Carpathians. Regarding ecological amplitude, 24 species exhibited a wider tolerance to water conductivity in the West Carpathians, whereas 17 species exhibited a wider tolerance in Bulgaria. Main conclusions, A distinctive variation in the realized niche was observed in a large portion of the species examined. Niche shifts between local populations of the same species were similar to those of closely related vicariant species. Ecotypic adaptation within species is a possible explanation for this pattern. Other possible explanations (competitive release, specific habitat conditions, compensation for climate) seem to be less justified. The local populations of rich-fen species may have adapted to mineral-poor acid conditions in the high crystalline mountains of Bulgaria during dry periods of pleniglacials. Nomenclature,Marhold & Hindák (1998); for Balkan elements not included in this source, Andreev et al. (1992). [source] Impact of maternal body mass index on obstetric outcomeJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2007Meenakshi T. Sahu Abstract Aim:, The purpose of the present study was to correlate effect of maternal body mass index (BMI) on obstetric outcome. The studies conducted so far are from Western developed countries and there is a paucity of data from developing countries. Methods:, A prospective evaluation was carried out of 380 women in one unit of a tertiary care teaching hospital in North India from May 2005 to June 2006 on the effect of maternal BMI on pregnancy outcome. BMI was calculated as weight (kg) divided by height (m2). BMI was used to characterize women as lean (BMI < 19.8 kg/m2), normal (BMI 19.9,24.9 kg/m2), overweight (BMI 25,29.9 kg/m2) or obese (,30 kg/m2). Results:, Forty-six women (12.1%) out of 380 were underweight, 99 (26.1%) were overweight, 30 (7.9%) were obese and the remaining 205 (53.9%) had normal BMI. Anemia (P = 0.02) and low birthweight (P = 0.008) was significantly present among lean women. Obese women had a significant risk for gestational diabetes (P = 0.0004), pre-eclampsia (P = 0.004), cesarean delivery (P = 0.01) and macrosomia (P = 0.02). Conclusion:, Both lean and obese women carry a risk for adverse pregnancy outcome, therefore pregnant women should maintain a normal BMI to achieve a healthy pregnancy outcome. [source] Achieving acceptable reliability in oral examinations: an analysis of the Royal College of General Practitioners membership examination's oral componentMEDICAL EDUCATION, Issue 2 2003Val Wass Background, The membership examination of the Royal College of General Practitioners (RCGP) uses structured oral examinations to assess candidates' decision making skills and professional values. Aim, To estimate three indices of reliability for these oral examinations. Methods, In summer 1998, a revised system was introduced for the oral examinations. Candidates took two 20-minute (five topic) oral examinations with two examiner pairs. Areas for oral topics had been identified. Examiners set their own topics in three competency areas (communication, professional values and personal development) and four contexts (patient, teamwork, personal, society). They worked in two pairs (a quartet) to preplan questions on 10 topics. The results were analysed in detail. Generalisability theory was used to estimate three indices of reliability: (A) intercase (B) pass/fail decision and (C) standard error of measurement (SEM). For each index, a benchmark requirement was preset at (A) 0·8 (B) 0·9 and (C) 0·5. Results, There were 896 candidates in total. Of these, 87 candidates (9·7%) failed. Total score variance was attributed to: 41% candidates, 32% oral content, 27% examiners and general error. Reliability coefficients were: (A) intercase 0·65; (B) pass/fail 0·85. The SEM was 0·52 (i.e. precise enough to distinguish within one unit on the rating scale). Extending testing time to four 20-minute oral examinations, each with two examiners, or five orals, each with one examiner, would improve intercase and pass/fail reliabilities to 0·78 and 0·94, respectively. Conclusion, Structured oral examinations can achieve reliabilities appropriate to high stakes examinations if sufficient resources are available. [source] Optimal control of a production-inventory system with both backorders and lost salesNAVAL RESEARCH LOGISTICS: AN INTERNATIONAL JOURNAL, Issue 3 2010Saif Benjaafar Abstract We consider the optimal control of a production inventory-system with a single product and two customer classes where items are produced one unit at a time. Upon arrival, customer orders can be fulfilled from existing inventory, if there is any, backordered, or rejected. The two classes are differentiated by their backorder and lost sales costs. At each decision epoch, we must determine whether or not to produce an item and if so, whether to use this item to increase inventory or to reduce backlog. At each decision epoch, we must also determine whether or not to satisfy demand from a particular class (should one arise), backorder it, or reject it. In doing so, we must balance inventory holding costs against the costs of backordering and lost sales. We formulate the problem as a Markov decision process and use it to characterize the structure of the optimal policy. We show that the optimal policy can be described by three state-dependent thresholds: a production base-stock level and two order-admission levels, one for each class. The production base-stock level determines when production takes place and how to allocate items that are produced. This base-stock level also determines when orders from the class with the lower shortage costs (Class 2) are backordered and not fulfilled from inventory. The order-admission levels determine when orders should be rejected. We show that the threshold levels are monotonic (either nonincreasing or nondecreasing) in the backorder level of Class 2. We also characterize analytically the sensitivity of these thresholds to the various cost parameters. Using numerical results, we compare the performance of the optimal policy against several heuristics and show that those that do not allow for the possibility of both backordering and rejecting orders can perform poorly.© 2010 Wiley Periodicals, Inc. Naval Research Logistics 2010 [source] Voltage-activated proton currents in human lymphocytesTHE JOURNAL OF PHYSIOLOGY, Issue 1 2002Tom Schilling Voltage-activated proton currents are reported for the first time in human peripheral blood T and B lymphocytes and in the human leukaemic T cell line Jurkat E6-1. The properties of H+ currents studied using tight-seal voltage-clamp recording techniques were similar in all cells. Changing the pH gradient by one unit caused a 47 mV shift in the reversal potential, demonstrating high selectivity of the channels for protons. H+ current activation upon membrane depolarisation had a sigmoidal time course that could be fitted by a single exponential function after a brief delay. Increasing pHo shifted the activation threshold to more negative potentials, and increased both the H+ current amplitude and the rate of activation. In lymphocytes studied at pHi 6.0, the activation threshold was more negative and the H+ current density was three times larger than at pHi 7.0. Increasing the intracellular Ca2+ concentration to 1 ,m did not change H+ current amplitude or kinetics detectably. Extracellularly applied Zn2+ and Cd2+ inhibited proton currents, slowing activation and shifting the voltage-activation curve to more positive potentials. The H+ current amplitude was 100 times larger in CD19+ B lymphocytes and in Jurkat E6-1 cells than in CD3+ T lymphocytes. Following stimulation with the phorbol ester PMA, the H+ current density in peripheral blood T lymphocytes and Jurkat T cells increased. In contrast, the H+ current density of phorbol ester (PMA)-stimulated B lymphocytes was reduced and activation became slower. The pattern of expression of H+ channels in lymphocytes appears well suited to their proposed role of charge compensation during the respiratory burst. [source] Peri-operative management of an adult patient with type 2N von Willebrand's disease scheduled for coronary artery bypass graftANAESTHESIA, Issue 4 2007V. Gerling Summary We describe a patient with type 2N von Willebrand's disease scheduled for elective coronary artery bypass graft for severe three-vessel coronary artery disease with involvement of the left main stem. He was given a pre-operative bolus of 3000 IU factor VIII/Willebrand factor concentrate (, 40 IU.kg,1), followed by a continuous infusion of 3 IU.h,1 (228 IU.h,1) before undergoing coronary surgery with full heparinisation and cardiopulmonary bypass. There were no intra-operative bleeding complications and only one unit of packed red blood cells was required postoperatively. Thromboprophylaxis with low-molecular weight heparin and aspirin was given and the infusion of factor VIII/von Willebrand factor concentrate continued for 2 days. As a result of haematological monitoring, heparin therapy was changed from prophylactic to therapeutic on day 5,6 and stopped on day 7. [source] A capped trigonal prismatic cadmium complex with tetra- and tridentate ligands: bis(triethanolamine)-,3N,O,O,;,4N,O,O,,O,,-cadmium(II) squarate monohydrateACTA CRYSTALLOGRAPHICA SECTION C, Issue 8 2004brahim Uçar In the crystal structure of the title compound, [Cd(C6H15NO3)2](C4O4)·H2O, a supramolecular structure is observed. The asymmetric unit consists of one unit of the cationic Cd complex, one water molecule and two half-squarate anions, each sitting on a crystallographic inversion center. The different coordinations of the two triethanolamine (TEA) ligands results in an unusual example of coordination number seven for the CdII ion. Both TEA ligands coordinate to the CdII ion, forming a distorted monocapped trigonal prismatic geometry with approximate C2v symmetry. One of the TEA ligands acts as an N,O,O,-tridentate ligand, whereas the other behaves as an N,O,O,,O,,-tetradentate donor. The anions and cations are linked to one another by hydrogen bonds between hydroxy H atoms of the TEA ligands and squarate O atoms. The crystal structure is stabilized by O,H,O hydrogen bonds between the unligated water molecule and a squarate O atom, together with a weak ,,ring interaction between the ethylene group of a TEA ligand and a squarate anion. [source] Crystallization and preliminary X-ray diffraction analysis of the complex of Kunitz-type tamarind trypsin inhibitor and porcine pancreatic trypsinACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 11 2009Sakshi Tomar The complex of Tamarindus indica Kunitz-type trypsin inhibitor and porcine trypsin has been crystallized by the sitting-drop vapour-diffusion method using ammonium acetate as precipitant and sodium acetate as buffer. The homogeneity of complex formation was checked by size-exclusion chromatography and further confirmed by reducing SDS,PAGE. The crystals diffracted to 2.0,Å resolution and belonged to the tetragonal space group P41, with unit-cell parameters a = b = 57.1, c = 120.1,Å. Preliminary X-ray diffraction analysis indicated the presence of one unit of inhibitor,trypsin complex per asymmetric unit, with a solvent content of 45%. [source] Double cord blood transplantation in patients with high risk bone marrow failure syndromesBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2008A. Ruggeri Summary Patients with bone marrow failure syndromes (BMFS) who reject a first allogeneic transplant or fail immunosuppressive therapy (IST) have an especially grim prognosis. We report 14 patients (eight adults, six children) transplanted with double cord blood transplantation (dUCBT) for BMFS. Neutrophil recovery was observed in eight patients, with full donor chimerism of one unit, and acute GVHD in 10. With a median follow-up of 23 months, the estimated 2 years overall survival was 80 ± 17% and 33 ± 16% for patients with acquired and inherited BMFS, respectively. Transplantation of two partially HLA-matched UCB thus enables salvage treatment of high-risk patients with BMFS. [source] Seven 3-methylidene-1H -indol-2(3H)-ones related to the multiple-receptor tyrosine kinase inhibitor sunitinibACTA CRYSTALLOGRAPHICA SECTION C, Issue 2 2010John Spencer The solid-state structures of a series of seven substituted 3-methylidene-1H -indol-2(3H)-one derivatives have been determined by single-crystal X-ray diffraction and are compared in detail. Six of the structures {(3Z)-3-(1H -pyrrol-2-ylmethylidene)-1H -indol-2(3H)-one, C13H10N2O, (2a); (3Z)-3-(2-thienylmethylidene)-1H -indol-2(3H)-one, C13H9NOS, (2b); (3E)-3-(2-furylmethylidene)-1H -indol-2(3H)-one monohydrate, C13H9NO2·H2O, (3a); 3-(1-methylethylidene)-1H -indol-2(3H)-one, C11H11NO, (4a); 3-cyclohexylidene-1H -indol-2(3H)-one, C14H15NO, (4c); and spiro[1,3-dioxane-2,3,-indolin]-2,-one, C11H11NO3, (5)} display, as expected, intermolecular hydrogen bonding (N,H...O=C) between the 1H -indol-2(3H)-one units. However, methyl 3-(1-methylethylidene)-2-oxo-2,3-dihydro-1H -indole-1-carboxylate, C13H13NO3, (4b), a carbamate analogue of (4a) lacking an N,H bond, displays no intermolecular hydrogen bonding. The structure of (4a) contains three molecules in the asymmetric unit, while (4b) and (4c) both contain two independent molecules. [source] | ||||||||||||||||