A novel and rational approach towards designing aluminium chelators

Aluminium (Al) is known to be neurotoxic and has been associated with the aetiology of Alzheimer's Disease. To date, only desferrioxamine (DFO), a trihydroxamic acid siderophore has been used in the clinical environment for the removal of Al from the body. However, this drug is expensive, orally inactive and is associated with many side effects. These studies employed a theoretical approach, with the use of quantum mechanics (QM) via semi-empirical molecular orbital (MO) calculations, and a practical approach using U87-MG glioblastoma cells as a model for evaluating the influence of potential chelators on the passage of aluminium into cells. Preliminary studies involving the Cambridge Structural Database (CSD) identified that Al prefers binding to bidentate ligands in a 3:1 manner, whereby oxygen was the exclusive donating atom. Statistically significant differences in M-O bond lengths when compared to other trivalent metal ions such as Fe3+ were established and used as an acceptance criterion for subsequent MO calculations. Of the semi-empirical methods parameterised for Al, the PM3 Hamiltonian was found to give the most reliable final optimised geometries of simple 3:1 Al complexes. Consequently the PM3 Hamiltonian was used for evaluating the Hf of 3:1 complexes with more complicated ligands. No correlation exists between published stability constants and individual parameters calculated via PM3 optimisations, although investigation of the dicarboxylates reveals a correlation of 0.961 showing promise for affinity prediction of closely related ligands. A simple and inexpensive morin spectrofluorescence assay has been developed and optimised producing results comparable to atomic absorption spectroscopy methods for the quantitative analysis of Al. This assay was used in subsequent in vitro models, initially on E. coli, which indicated that Al inhibits the antimicrobial action of ciprofloxacin, a potent quinolone antibiotic. Ensuing studies using the second model, U87-MG cells, investigated the influence of chelators on the transmembrane transport of Al, identifying 1,2-diethylhydroxypyridin-4-one as a ligand showing greatest potential for chelating Al in the clinical situation. In conclusion, these studies have explored semi-empirical MO Hamiltonians and an in-vitro U87-MG cell line, both as possible methods for predicting effective chelators of Al.

The rational design of vaccines

This review provides an insight into the various opportunities for vaccine intervention, analysis of strategies for vaccine development, vaccine ability to modulate immune responses and resultant rational vaccine design. In addition, wider aspects are considered, such as biotechnological advances, advances in immunological understanding and host-pathogen interactions. The key question addressed here is, with all our research and understanding, have we reached a new echelon in vaccine development, that of rational design? ©2005 Elsevier Ltd. All rights reserved.

Rational design of heterogeneous catalysts for biodiesel synthesis

Dwindling oil reserves and growing concerns over carbon dioxide emissions and associated climate change are driving the utilisation of renewable feedstocks as alternative, sustainable fuel sources. Catalysis has a rich history of facilitating energy efficient, selective molecular transformations, and contributes to 90% of current chemical manufacturing processes. In a post-petroleum era, catalysis will be pivotal in overcoming the scientific and engineering barriers to economically feasible bio-fuels. This perspective highlights some recent developments in heterogeneous catalysts for the synthesis of biodiesel from renewable resources, derived from plant and aquatic oil sources. Particular attention will be paid to the importance of catalyst pore architecture, surface polarity and acid and base properties, in meeting the challenge of transforming highly polar and viscous bio-based reactants. © 2012 The Royal Society of Chemistry.

Optimization of Rational Approximations by Continued Fractions

The paper has been presented at the 12th International Conference on Applications of Computer Algebra, Varna, Bulgaria, June, 2006.

Projectively Normal Line Bundles on K-Gonal Curves and Rational Surfaces

2000 Mathematics Subject Classification: 14H50.

A racionális kisvállalati gazdálkodás tényezői, 2006-2010 (Factors in rational operation of small business, 2006-2010)

A tanulmány a hazai kis- és középvállalati szektorban 2006-ban elvégzett, majd 2010-ben megismételt kérdőíves felmérések eredményei alapján igyekszik bemutatni a racionális vállalati gazdálkodás sajátosságait. Vizsgálatunk fő kérdése, hogy e szektor vállalkozásainak gazdálkodását milyen tényezők teszik ésszerűvé, s hogy a 2006-2010 között eltelt időszakban milyen változások figyelhetők meg a gazdálkodói magatartásuk alakulásában. Eredményeink alapján megállapíthatjuk, hogy a mai napig megtalálhatók a kisvállalkozói - háztartási szemléletű, megélhetésorientált - gazdálkodás nyomai, de a racionális gazdálkodás általunk használt mutatói szerint e vállalkozások körében szakszerűbbé vált a gazdálkodás. Ebben a folyamatban szerepet játszott a gazdasági válság, amely által előidézett helyzethez kénytelenek voltak alkalmazkodni a kis- és közepes vállalkozások: felismerték, hogy célravezetőbb a hatékonyság és a költségek szempontjából a racionális pénzpiaci magatartás követése, s ezzel összhangban a válság miatti zavarok elhárítására kiadáscsökkentő eszközök alkalmazása. A kis- és közepes vállalkozások gazdálkodásával kapcsolatos racionális döntések előmozdításában elsősorban a korszerű pénzügyi ismereteknek és a szakmai tudásnak van szerepe. / === / The study seeks to identify the attributes of rational business operation, using a questionnaire survey of small and medium-sized firms made in 2006 and a repeat of it in 2010. The main questions addressed are what factors contribute to rational operation in the firms in the sector and what changes over the 2006-10 period can be discerned in business behaviour. The findings show that traces of small business-style operation (a household or livelihood orientation) could still be found, but the indicators of rationality employed in the survey show that the operation of the firms became more rational. A role in the process was played by the economic crisis, which forced small and medium-sized businesses to adapt: they recognized that it was better from the point of view of efficiency and costs to follow rational money-market behaviour, and in line with that, use spending-reduction tools to evade the disturbances of the crisis. The main factors behind the shift towards rational decision-making in the running of small and medium-sized firms are up-to-date financial information and professional expertise.

An autoregressive conditional filtering process to remove intraday seasonal volatility and its application to testing the noisy rational expectations model

We develop a new autoregressive conditional process to capture both the changes and the persistency of the intraday seasonal (U-shape) pattern of volatility in essay 1. Unlike other procedures, this approach allows for the intraday volatility pattern to change over time without the filtering process injecting a spurious pattern of noise into the filtered series. We show that prior deterministic filtering procedures are special cases of the autoregressive conditional filtering process presented here. Lagrange multiplier tests prove that the stochastic seasonal variance component is statistically significant. Specification tests using the correlogram and cross-spectral analyses prove the reliability of the autoregressive conditional filtering process. In essay 2 we develop a new methodology to decompose return variance in order to examine the informativeness embedded in the return series. The variance is decomposed into the information arrival component and the noise factor component. This decomposition methodology differs from previous studies in that both the informational variance and the noise variance are time-varying. Furthermore, the covariance of the informational component and the noisy component is no longer restricted to be zero. The resultant measure of price informativeness is defined as the informational variance divided by the total variance of the returns. The noisy rational expectations model predicts that uninformed traders react to price changes more than informed traders, since uninformed traders cannot distinguish between price changes caused by information arrivals and price changes caused by noise. This hypothesis is tested in essay 3 using intraday data with the intraday seasonal volatility component removed, as based on the procedure in the first essay. The resultant seasonally adjusted variance series is decomposed into components caused by unexpected information arrivals and by noise in order to examine informativeness.

An Autoregressive Conditional Filtering Process to remove Intraday Seasonal Volatility and its Application to Testing the Noisy Rational Expectations Model

We develop a new autoregressive conditional process to capture both the changes and the persistency of the intraday seasonal (U-shape) pattern of volatility in essay 1. Unlike other procedures, this approach allows for the intraday volatility pattern to change over time without the filtering process injecting a spurious pattern of noise into the filtered series. We show that prior deterministic filtering procedures are special cases of the autoregressive conditional filtering process presented here. Lagrange multiplier tests prove that the stochastic seasonal variance component is statistically significant. Specification tests using the correlogram and cross-spectral analyses prove the reliability of the autoregressive conditional filtering process. In essay 2 we develop a new methodology to decompose return variance in order to examine the informativeness embedded in the return series. The variance is decomposed into the information arrival component and the noise factor component. This decomposition methodology differs from previous studies in that both the informational variance and the noise variance are time-varying. Furthermore, the covariance of the informational component and the noisy component is no longer restricted to be zero. The resultant measure of price informativeness is defined as the informational variance divided by the total variance of the returns. The noisy rational expectations model predicts that uninformed traders react to price changes more than informed traders, since uninformed traders cannot distinguish between price changes caused by information arrivals and price changes caused by noise. This hypothesis is tested in essay 3 using intraday data with the intraday seasonal volatility component removed, as based on the procedure in the first essay. The resultant seasonally adjusted variance series is decomposed into components caused by unexpected information arrivals and by noise in order to examine informativeness.

Elaine Noble, Boston Legislator at Gay Delegates press conference

General note: Title and date provided by Bettye Lane.

Elaine Noble, Boston Legislator at Gay Delegates press conference

General note: Title and date provided by Bettye Lane.

Boston Legislator Elaine Noble at Gay Delegates press conference

General note: Title and date provided by Bettye Lane.

Classifying Rational G-Spectra for Finite G

We give a new proof that for a finite group G, the category of rational G-equivariant spectra is Quillen equivalent to the product of the model categories of chain complexes of modules over the rational group ring of the Weyl group of H in G, as H runs over the conjugacy classes of subgroups of G. Furthermore, the Quillen equivalences of our proof are all symmetric monoidal. Thus we can understand categories of algebras or modules over a ring spectrum in terms of the algebraic model.