Copper(II) ion binding to cellular prion protein

Prion diseases are fatal neurodegenerative diseases thought to arise from the post-translational conversion of normal cellular prion protein to a scrapie isoform. Experimental data suggest a role for copper(II) ions in the process. An ab initio QM/MM approach and available experimental data were combined in order to identify and evaluate three potential copper(II) ion binding sites in the C-terminal portion of the normal cellular prion protein. Our results suggest that copper(II) ion binds to His 187 but not to His 140 and His 177 of the binding site in the cellular prion protein.     

Barycentric coordinates for Lagrange interpolation over lattices on a simplex

In this paper, a (d?+?1)-pencil lattice on a simplex in ${\mathbb{R}}^d$ is studied. The lattice points are explicitly given in barycentric coordinates. This enables the construction and the efficient evaluation of the Lagrange interpolating polynomial over a lattice on a simplex. Also, the barycentric representation, based on shape parameters, turns out to be appropriate for the lattice extension from a simplex to a simplicial partition.     

On geometric interpolation by planar parametric polynomial curves

In this paper the problem of geometric interpolation of planar data by parametric polynomial curves is revisited. The conjecture that a parametric polynomial curve of degree can interpolate given points in is confirmed for under certain natural restrictions. This conclusion also implies the optimal asymptotic approximation order. More generally, the optimal order can be achieved as soon as the interpolating curve exists.

     

Antiviral Activities of Halogenated Emodin Derivatives against Human Coronavirus NL63

The current COVID-19 outbreak has highlighted the need for the development of new vaccines and drugs to combat Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Recently, various drugs have been proposed as potentially effective against COVID-19, such as remdesivir, infliximab and imatinib. Natural plants have been used as an alternative source of drugs for thousands of years, and some of them are effective for the treatment of various viral diseases. Emodin (1,3,8-trihydroxy-6-methylanthracene-9,10-dione) is a biologically active anthraquinone with antiviral activity that is found in various plants. We studied the selectivity of electrophilic aromatic substitution reactions on an emodin core (halogenation, nitration and sulfonation), which resulted in a library of emodin derivatives. The main aim of this work was to carry out an initial evaluation of the potential to improve the activity of emodin against human coronavirus NL63 (HCoV-NL63) and also to generate a set of initial SAR guidelines. We have prepared emodin derivatives which displayed significant anti-HCoV-NL63 activity. We observed that halogenation of emodin can improve its antiviral activity. The most active compound in this study was the iodinated emodin analogue E_3I, whose anti-HCoV-NL63 activity was comparable to that of remdesivir. Evaluation of the emodin analogues also revealed some unwanted toxicity to Vero cells. Since new synthetic routes are now available that allow modification of the emodin structure, it is reasonable to expect that analogues with significantly improved anti-HCoV-NL63 activity and lowered toxicity may thus be generated.     

DESA: a new hybrid global optimization method and its application to analog integrated circuit sizing

This paper presents a new hybrid global optimization method referred to as DESA. The algorithm exploits random sampling and the metropolis criterion from simulated annealing to perform global search. The population of points and efficient search strategy of differential evolution are used to speed up the convergence. The algorithm is easy to implement and has only a few parameters. The theoretical global convergence is established for the hybrid method. Numerical experiments on 23 mathematical test functions have shown promising results. The method was also integrated into SPICE OPUS circuit simulator to evaluate its practical applicability in the area of analog integrated circuit sizing. Comparison was made with basic simulated annealing, differential evolution, and a multistart version of the constrained simplex method. The latter was already a part of SPICE OPUS and produced good results in past research.     

Production of vibrationally excited hydrogen molecules by atom recombination on Cu and W materials

We have measured vibrational population of H(2) and D(2) molecules produced by atom (H or D) recombination on tungsten and copper material. The vibrational spectroscopy, based on the properties of dissociative electron attachment to hydrogen molecule, was used. The vibrationally excited molecules were produced by atom recombination in a cell where the studied sample is exposed to hydrogen atoms, from hot tungsten filament. Vibrational populations were obtained for the studied materials, which can be well described by the Boltzmann distribution, with specific vibrational temperatures for each material. The experimentally obtained vibrational populations for copper approximately agree with the theoretical predictions, whereas the experimentally obtained vibrational temperature for tungsten is higher and thus showing a considerable overpopulation of highly excited vibrational states than predicted. We propose that the origin of this higher excitation is related to the existence of high hydrogen surface coverage on tungsten, where hydrogen is occupying binding sites with different desorption energies. In order to obtain an insight into the recombination mechanism with more than one binding site per unit cell, a Monte Carlo simulation was performed, where it was assumed that the main production of molecules proceeds through the hot-atom recombination with an adsorbed atom. The results show that the recombination proceeds mainly through the weak binding sites, once they are occupied.     

Dihaloiodates(I): synthesis with hydrogen peroxide and their halogenating activity

Tetraalkylammonium and pyridinium dichloro- and dibromoiodates(I) were efficiently prepared from iodine and tetralkylammonium chloride or pyridine by oxidation with hydrogen peroxide in the presence of an equimolar amount of a hydrogen halide. Their halogenating activity was tested on 1,3-dimethoxybenzene and styrene as model substrates. The results show that ICl₂^? salts acted as iodinating reagents, while IBr₂^? salts brominated both substrates.