Human diseases related to aluminium overload

Abstract  

In this paper attention is devoted to the role of aluminium in osteodistrophy and dialysis dementia. In fact, these diseases, in spite of the actions that have drastically reduced their occurrence, have so far constituted a cause of great medical concern. As a preliminary point, some aspects concerning the solution chemistry of aluminium are considered, then the medical problems are described and finally the chelation therapy of aluminium overload, giving some insight on the chelators recently proposed.     

Development and validation of an integrated computational approach for the study of ionic species in solution by means of effective two-body potentials. The case of Zn2+, Ni2+, and Co2+ in aqueous solutions

In this paper we have developed an effective computational procedure for the structural and dynamical investigation of ions in aqueous solutions. Quantum mechanical potential energy surfaces for the interaction of a transition metal ion with a water molecule have been calculated taking into account the effect of bulk solvent by the polarizable continuum model (PCM). The effective ion-water interactions have been fitted by suitable analytical potentials, and have been utilized in molecular dynamics (MD) simulations to obtain structural and dynamical properties of the ionic aqueous solutions. This procedure has been successfully applied to the Co2+-H2O open-shell system and, for the first time, Co-oxygen and Co-hydrogen pair potential functions have been determined and employed in MD simulations. The reliability of the whole procedure has been assessed by applying it also to the Zn2+ and Ni2+ aqueous solutions, and the structural and dynamical properties of the three systems have been calculated by means of MD simulations and have been found to be in very good agreement with experimental results. The structural parameters of the first solvation shells issuing from the MD simulations provide an effective complement to extended X-ray absorption fine structure (EXAFS) experiments.     

High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors

Selective protein kinase inhibitors have only been developed against a small number of kinase targets. Here we demonstrate that "high-throughput kinase profiling" is an efficient method for the discovery of lead compounds for established as well as unexplored kinase targets. We screened a library of 118 compounds constituting two distinct scaffolds (furan-thiazolidinediones and pyrimido-diazepines) against a panel of 353 kinases. A distinct kinase selectivity profile was observed for each scaffold. Selective inhibitors were identified with submicromolar cellular activity against PIM1, ERK5, ACK1, MPS1, PLK1-3, and Aurora A,B kinases. In addition, we identified potent inhibitors for so far unexplored kinases such as DRAK1, HIPK2, and DCAMKL1 that await further evaluation. This inhibitor-centric approach permits comprehensive assessment of a scaffold of interest and represents an efficient and general strategy for identifying new selective kinase inhibitors.     

A control method for speeding up response of hydroelectric station power canals

A control method which, through the suitable servo-operation of the check gates, attains a consistent improvement in the speed of response of hydroelectric power canals is presented. Its application allows the size of the canal headpond to be reduced at the design stage of the power station as well. The proposed method is based on the constant volume control concept and uses a mathematical model of the power canal derived from linearization of the Saint-Venant equations. The results of the computer simulation of a controlled real system's dynamic behavior obtained through the use of the method of characteristics are presented.     

Sub-optimal constant-volume control for open channel networks

A state variable mathematical model for use in the synthesis of automatic control systems for open-channel networks is presented. The system considered here consists of n-cascaded reaches joined by control gates.The linear time invariant model consists of a controllable and observable representation where the state variables are the stored water volume variations in each reach and the control signals are the variations of the control gates opening sections. The model derives, through appropriate simplifications, from a more complex one in terms of transfer functions which was derived by linearizing the Saint-Venant equations.The problem of a linear quadratic optimal regulator is formulated in classical terms for the canal system and the constant-volume control laws obtained for the simplified model have been imposed on the complex one: such a control is therefore to be considered sub-optimal.The results of a digital simulation of the controlled system behaviour indicate that the system operates with practically constant stored water volumes in each reach and that such behaviour is fairly close to that of a pressure-water pipe system.     

The marked influence of steric and electronic properties of ancillary pyridylthioether ligands on the rate of allene insertion into the palladium–carbon bond

Neutral methyl- and acyl-palladium chloro complexes containing pyridylthioether ancillary ligands (R′N---SR) (R′=H, Me, Cl; R=Me, Et, i-Pr, t-Bu, Ph) have been synthesised and characterised by elemental analysis and spectroscopic methods. The reactivity of these complexes toward allene (allene=DMA=1,1-dimethylpropadiene; TMA=1,1,3,3-tetramethylpropadiene) insertion into the palladium–carbon bond has been studied by ¹H-NMR and UV–vis techniques. The rate of reaction appears to be strongly influenced by the steric and electronic properties of the ancillary ligand. The distortion induced by the substituent R′ in position 6 of the pyridine ring on the main coordination plane of the substrate (allowed by sulphur sp³ hybridisation) renders the substrate itself more prone to nucleophilic attack by the allene. The rate of allene insertion can further be enhanced by lowering the basicity of the chelating atoms in the N---S moiety which results in an increase of electrophilicity of the palladium core, so that the rate constants measured in the case of the complexes containing the ligand 6-chloro-2-phenylthiomethylpyridine (ClN---SPh) are by far the greatest observed so far for similar reactions. Furthermore, on the basis of the indications emerging from the exhaustive study on the behaviour of all the related pyridylthioether methyl complexes, an associative asynchronous bond making mechanism for the rate determining nucleophilic attack by allene is proposed.     

Low-energy electron scattering by cubane: resonant states and Ramsauer-Townsend features from quantum calculations in the gas phase

Calculations are carried out, using a nonempirical modeling of the interaction potential and solving the quantum scattering coupled channel equations, for low energy electron scattering from cubane (C8H8) molecules in the gas phase. Total integral cross sections are obtained and partial contributions are analyzed for the most important irreducible representations that describe the continuum electron in the Oh molecular symmetry. Several trapping resonances are found and analyzed in terms of the molecular-type features of the resonant electron states associated with them. A Ramsauer-Townsend minimum is also found and its possible behavior related to features of the scattering length as k --> 0.     

Controllability method for acoustic scattering with spectral elements

We formulate the Helmholtz equation as an exact controllability problem for the time-dependent wave equation. The problem is then discretized in time domain with central finite difference scheme and in space domain with spectral elements. This approach leads to high accuracy in spatial discretization. Moreover, the spectral element method results in diagonal mass matrices, which makes the time integration of the wave equation highly efficient. After discretization, the exact controllability problem is reformulated as a least-squares problem, which is solved by the conjugate gradient method. We illustrate the method with some numerical experiments, which demonstrate the significant improvements in efficiency due to the higher order spectral elements. For a given accuracy, the controllability technique with spectral element method requires fewer computational operations than with conventional finite element method. In addition, by using higher order polynomial basis the influence of the pollution effect is reduced.     

On binary linear <Emphasis Type="Italic">r</Emphasis>-identifying codes

A subspace C of the binary Hamming space F ⁿ of length n is called a linear r-identifying code if for all vectors of F ⁿ the intersections of C and closed r-radius neighbourhoods are nonempty and different. In this paper, we give lower bounds for such linear codes. For radius r =  2, we give some general constructions. We give many (optimal) constructions which were found by a computer search. New constructions improve some previously known upper bounds for r-identifying codes in the case where linearity is not assumed.     

Superconductivity in doped polyethylene at high pressure

In this work we study the pressure-dependent phase diagram of polyethylene (H₂C)_x from 50 to 200 GPa. Low-symmetry, organic polymeric phases, that are dynamically stable and thermodynamically competitive with elemental decomposition, are reported. Electronic structure calculations reveal that the band gap of the lowest energy polymeric phase decreases from 5.5 to 4.5 eV in the 50–200 GPa range, but metalization occurs only for pressures well above 500 GPa. The possibility of metalization via doping was also investigated, observing that it can be achieved through boron substitution at carbon sites. We report a sizable electron-phonon coupling (λ ? 0.79) in this metallic phase, with an estimated superconducting transition temperature of about 35 K. However, a rather narrow domain of stability is found; most of the dopant elements render the polymeric phases unstable and induce amorphization. This suggests that doping under pressure, though presenting an alternative route to find high temperature superconductors, would be challenging to achieve experimentally.