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.

A novel concentration dependent amino acid ion pair strategy to mediate drug permeation using indomethacin as a model insoluble drug

Assessment of oral drug bioavailability is an important parameter for new chemical entities (NCEs) in drug development cycle. After evaluating the pharmacological response of these new molecules, the following critical stage is to investigate their in vitro permeability. Despite the great success achieved by prodrugs, covalent linking the drug molecule with a hydrophobic moiety might result in a new entity that might be toxic or ineffective. Therefore, an alternative that would improve the drug uptake without affecting the efficacy of the drug molecule would be advantageous. The aim of the current study is to investigate the effect of ion-pairing on the permeability profile of a model drug: indomethacin (IND) to understand the mechanism behind the permeability improvement across Caco-2 monolayers. Arginine and lysine formed ion-pairs with IND at various molar ratios 1:1, 1:2, 1:4 and 1:8 as reflected by the double reciprocal graphs. The partitioning capacities of the IND were evaluated using octanol/water partitioning studies and the apparent permeabilities (P app) were measured across Caco-2 monolayers for the different formulations. Partitioning studies reflected the high hydrophobicity of IND (Log P = 3) which dropped upon increasing the concentrations of arginine/lysine in the ion pairs. Nevertheless, the prepared ion pairs improved IND permeability especially after 60 min of the start of the experiment. Coupling partitioning and permeability results suggest a decrease in the passive transcellular uptake due to the drop in IND portioning capacities and a possible involvement of active carriers. Future work will investigate which transport gene might be involved in the absorption of the ion paired formulations using molecular biology technologies. © 2014 Elsevier B.V. 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.

Pair breaking and bound states in disordered superconductors

We study the effects of inhomogeneous pairing interactions and impurities in short-coherence-length superconductors. Within the Born approximation, the effects of pairing disorder and magnetic impurities are identical. The T-matrices for pairing disorder sites with and without an impurity give rise to bound states within the BCS (Bardeen-Cooper-Schrieffer) gap, consistent with scanning tunnelling microscopy results on Bi2Sr2CaCu2O8+δ with Zn or Ni impurities.

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.

Refractive index sensor based on a pair of hybrid 45° and 81° tilted fiber gratings

A hybrid structure comprising of a 45° and an 81° TFG based RI sensor has been demonstrated. The experiment results show a higher RI sensitivity, being around 180nm/RIU at RI=1.345 and 926nm/RIU at RI=1.412 region. © 2014 OSA.

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

2000 Mathematics Subject Classification: 14H50.

Chemical sensor using Mach-Zehnder interferometer based on a pair of largely tilted fiber gratings

We propose an in-fiber Mach-Zehnder interferometer formed by a pair of largely tilted fiber gratings. The interference spectral characteristics have been investigated. The experimental results using this device as a chemical sensor have a sensitivity as high as 719nm/RIU. © 2012 OSA.

Orthogonally polarized bright–dark pulse pair generation in mode-locked fiber laser with a large-angle tilted fiber grating

We report on the generation of orthogonally polarized bright–dark pulse pair in a passively mode-locked fiber laser with a large-angle tilted fiber grating (LA-TFG). The unique polarization properties of the LA-TFG, i.e., polarization-dependent loss and polarization-mode splitting, enable dual-wavelength mode-locking operation. Besides dual-wavelength bright pulses with uniform polarization at two different wavelengths, the bright–dark pulse pair has also been achieved. It is found that the bright–dark pulse pair is formed due to the nonlinear couplings between lights with two orthogonal polarizations and two different wavelengths. Furthermore, harmonic mode-locking of bright–dark pulse pair has been observed. The obtained bright–dark pulse pair could find potential use in secure communication system. It also paves the way to manipulate the generation of dark pulse in terms of wavelength and polarization, using specially designed fiber grating for mode-locking.

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.

Consistency of the decision-maker in pair-wise comparisons

Most authors assume that the natural behaviour of the decision-maker is being inconsistent. This paper investigates the main sources of inconsistency and analyses methods for reducing or eliminating inconsistency. Decision support systems can contain interactive modules for that purpose. In a system with consistency control, there are three stages. First, consistency should be checked: a consistency measure is needed. Secondly, approval or rejection has to be decided: a threshold value of inconsistency measure is needed. Finally, if inconsistency is ‘high’, corrections have to be made: an inconsistency reducing method is needed. This paper reviews the difficulties in all stages. An entirely different approach is to elaborate a decision support system in order to force the decision-maker to give consistent values in each step of answering pair-wise comparison questions. An interactive questioning procedure resulting in consistent (sub) matrices has been demonstrated.