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Extended pharmacological profiles of rat P2Y2 and rat P2Y4 receptors and their sensitivity to extracellular H+ and Zn2+ ions
Get PDF1. Two molecularly distinct rat P2Y receptors activated equally by adenosine-5'-triphosphate (ATP) and uridine-5'-triphosphate (UTP) (rP2Y2 and rP2Y4 receptors) were expressed in Xenopus oocytes and studied extensively to find ways to pharmacologically distinguish one from the other. 2. Both P2Y subtypes were activated fully by a number of nucleotides. Tested nucleotides were equipotent at rP2Y4 (ATP=UTP=CTP=GTP=ITP), but not at rP2Y2 (ATP=UTP>CTP>GTP>ITP). For dinucleotides (ApnA, n=2-6), rP2Y4 was only fully activated by Ap4A, which was as potent as ATP. All tested dinucleotides, except for Ap2A, fully activated rP2Y2, but none were as potent as ATP. ATP gamma S and BzATP fully activated rP2Y2, whereas ATP gamma S was a weak agonist and BzATP was inactive (as an agonist) at rP2Y4 receptors. 3. Each P2Y subtype showed different sensitivities to known P2 receptor antagonists. For rP2Y2, the potency order was suramin>>PPADS= RB-2>TNP-ATP and suramin was a competitive antagonist (pA2, 5.40). For rP2Y4, the order was RB-2>>suramin>PPADS> TNP-ATP and RB-2 was a competitive antagonist (pA2, 6.43). Also, BzATP was an antagonist at rP2Y4 receptors. 4. Extracellular acidification (from pH 8.0 to pH 5.5) enhanced the potency of ATP and UTP by 8-10-fold at rP2Y4 but did not affect agonist responses at rP2Y2 receptors. 5. Extracellular Zn2+ ions (0.1-300 microM) coapplied with ATP inhibited agonist responses at rP2Y4 but not at rP2Y2 receptors. 6. These two P2Y receptors differ significantly in terms of agonist and antagonist profiles, and the modulatory activities of extracellular H+ and Zn2+ ions. These pharmacological differences will help to distinguish between rP2Y2 and rP2Y4 receptors, in vivo
Modeling the framework stability and catalytic activity of pure and transition metal-doped zeotypes
Get PDFWe present a thorough computational study of transition metal-doped zeolite and aluminophosphate (AlPO) frameworks. The
structural and electronic chemistry of the dopants is examined with ab initio quantum mechanical calculations, and the results correlated with the Br^nsted and Lewis acid strength, and with the redox potential of the dopant ions in the framework. The energetics of doping is provided, and is employed to analyze the mode of dopant incorporation, and its site ordering in the microporous framework. In total, 23 dopant ions are examined in the isostructural framework of chabasite and AlPO-34. These cover most of the isomorphous framework replacements known to occur experimentally, but also framework replacements that have not yet been achieved. In this case, ab initio modeling techniques are employed in a predictive way. Finally, we present a computational study of the alkene epoxidation on titanosilicates, that covers the whole catalytic cycle
Advances in Tool Management Systems
Get PDFThe current work, carried out in conjunction with the University of Hull, UK, addresses the need for better control of machining processes with the objective of increased operating efficiency based on reduced scrap, rework and lower tool inventory. The work reported here is primarily concerned with the application of intelligent systems to tool management and is based on the use of laser scattering techniques to detect and characterize edge defects in milling cutters
On the structure and coordination of the oxygen-donating species in Ti↑ MCM-41/TBHP oxidation catalysts: a density functional theory and EXAFS study
Get PDFWe present a combined density functional theory and EXAFS investigation into the geometry and coordination of the oxygen-donating species in surface grafted, tert-butyl hydroperoxide (TBHP) exposed Ti"MCM-41 oxidation catalysts. The formation of a number of different Ti(Z2-peroxo) and Ti(Z1-peroxo) type species, including radical and anionic complexes, has been examined, arising from the attack of peroxide (where both hydrogen peroxide and TBHP have been studied) on a tetrahedral TiIV site, together with and without one molecule of water. BP86=DZVP calculations show that the Ti(Z1-OOtBu) complex is 33 kJ mol�1 lower in energy than the Ti(Z2-OOtBu) complex which is contrary to previous estimates in the literature and we propose that 6-coordinate Ti(Z1-OOR) complexes, where R is the peroxide substituent (i.e. R 1⁄4 H for H2O2 and R 1⁄4 tBu for TBHP), are the oxygen-donating species in peroxide=titanosilicate mixtures. X-ray absorption analysis is in good agreement with our DFT predictions that Ti–peroxo species in TBHP=Ti"MCM-41 systems are 6-coordinate. Furthermore, our DFT cluster calculations and X-ray absorption analysis collectively reveal the presence of 6-coordinate ‘ Ti(Z2-OOtBu)(OHR) ’ and ‘ Ti(Z1-OOtBu)(OHR)�H2O ’ complexes in TBHP=Ti"MCM-41 catalysts
Sensitization by Extracellular Ca2+ of Rat P2X5 Receptor and Its Pharmacological Properties Compared with Rat P2X1.
Get PDFThe recombinant rat P2X(5) (rP2X(5)) receptor, a poorly understood ATP-gated ion channel, was studied under voltage-clamp conditions and compared with the better understood homomeric rP2X(1) receptor with which it may coexist in vivo. Expressed in defolliculated Xenopus laevis oocytes, rP2X(5) responded to ATP with slowly desensitizing inward currents that, for successive responses, ran down in the presence of extracellular Ca(2+) (1.8 mM). Replacement of Ca(2+) with either Ba(2+) or Mg(2+) prevented rundown, although agonist responses were very small, whereas reintroduction of Ca(2+) for short periods of time ( 2',3'-O-(2,4,6-trinitrophenyl)ATP (TNP-ATP) > suramin > reactive blue 2 (RB-2) > diinosine pentaphosphate (Ip(5)I). In contrast, the potency order at rP2X(1) was TNP-ATP = Ip(5)I > PPADS > suramin = RB-2. Thus, the Ca(2+)-sensitized homomeric rP2X(5) receptor is similar in agonist profile to homomeric rP2X(1)-although it can be distinguished from the latter by GTP agonism, antagonist profile, and the modulatory effects of H(+) and Zn(2+) ions
The Internet as an Educational Tool for Effectively Understanding the Engineering Profession
Get PDFThe Internet as a tool for acquiring information from global sources has proved invaluable to engineering students worldwide as an aid to research in many areas of their study. Engineering departments, for their part, have responded by preparing courses that develop the skills of their students in using this technology.
The focus of this paper deals with the use of the internet in teaching students about the engineering profession. By the end of this course, students should have an understanding of the various engineering disciplines, an awareness of engineering ethics and have the ability to effectively evaluate a case representative of a well known engineering project. In addition, students with little or no prior knowledge of the Internet will have developed and honed their abilities in using it as an effective research tool.
Furthermore, the influences upon students to follow an engineering career, prior to freshman engineering is examined, as well as difficulties they encounter during the learning process in the Engineering Profession course. Course quality is discussed with a view to understanding accreditation needs and understanding the need for examining the learning outcomes of students
Catalytic processes in porous transition metal silicates
Get PDFQuantum mechanical cluster calculations on the mechanism of alkene epoxidations within peroxide saturated titanium molecular sieve catalysts are reported. This thesis addresses three major themes; the first is the nature of the titanium active sites, in dehydrated and hydrated titanium molecular sieves. Secondly the nature and formation mechanism of the oxygen-donating species for oxidation catalysis is presented. Finally, elucidation of the complete mechanistic catalytic cycle for the titanium molecular sieve mediated oxidation of alkenes to epoxides, in the presence of peroxide, is reported. A focal point of this work is the relationship between reaction energetics and the structure and electronic properties of varied ligands and alkenes.
Highlights include the elucidation of a new, stable oxygen-donating species, (=Si0)3Ti-r|’[0(H)0H](0H2), isolated for the first time by this work, which has a low activation barrier of formation (< 20 kJmof’) and shows favourable reaction energetics for the epoxidation of alkenes.
Furthermore, the first experimental evidence for the existence of two particular oxygen-donating structures in the catalyst, (=SiO)3Ti-ri^(OOR).H2 0 and (=Si0 )3Ti-T|’(0 0 R)(0 H2).H2 0 , which were predicted to exist by quantum mechanical calculations by this work, is reported. One of the oxidation agents is shown to provide an energetically favourable route to epoxide formation and the other is proposed as the oxygen-donor for diol formation, one of the major by products in epoxidation catalysis
‘What works in correctional industries? A comparative study of European, Canadian and US correctional industries, educational, and vocational training programs at the start of the 21st century.
Get PDF• Most European countries have had large increases in prison populations (except for Scandinavian countries);
• In spite of recessions in some countries (Germany), labor markets inside correctional industries are doing well in Europe in terms of providing adequate work for prisoners;
• About 25% of prisoners in European prisons are provided with ‘meaningful’ and industrial work which replicates the work environment outside;
• 20-25 % of workplaces remain unfilled (except for France);
• All European countries are dealing with different sizes and types of prison population (e.g. high unit costs in Germany and UK for large number of young offenders), resulting in high costs in the short term; but this ‘investment’ can pay off, in terms of prisoner rehabilitation and resettlement;
• Post-release work schemes and prisoner employment data bank: working-out schemes [day-release] with private companies (Germany; The Netherlands; Belgium; Canada), which can aid offenders’ rehabilitation and recidivism rate;
• Increased integration of correctional industries with education, psycholog, offending behavior programs, therapeutic communities etc. (Germany; England; Belgium)