Solution- and crystal-phase covalent modification of lysozyme by a purpose-designed organoruthenium complex. A MALDI-TOF MS study of its metal binding sites

Study of the reaction between the transition organometallic complex 4-ruthenocenyl 2,6-dimethylpyrylium tetrafluoroborate and the enzyme hen egg white lysozyme (HEWL) in solution and by diffusion in crystals was performed by use of a combination of spectroscopic and chromatographic methods. Conjugation involving the lysine residues of lysozyme appeared to occur readily, yielding very stable ruthenocenyl pyridinium adducts with average degrees of incorporation ranging from 0.2 to 1.8 metal complexes per protein molecule, depending on reaction conditions. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that the protein conjugates were in fact mixtures of unmodified, mono-, di- and sometimes tripyridinium adducts. In combination with reversed-phased HPLC, we were able to show that six different monoruthenocenyl pyridinium adducts were formed in solution. This result was confirmed by trypsin digestion of a ruthenocenyl pyridinium conjugate and MALDI-TOF MS analysis of the peptide mixture, which showed that lysines 1, 13, 33, 96, 97 and 116 were involved in the reaction with the pyrylium complex, lysines 13, 33 and 116 being the major binding sites. In the tetragonal crystal state, no binding of the ruthenium complex was shown to occur at lysine 116, owing to steric hindrance at this particular position.     

Performance Analysis of Multiuser Detectors for Uplink Quasi-synchronous MC-CDMA Systems

This paper analyses and compares the average bit error rate (BER) of different multiuser detectors (MUD) in the uplink of a multicarrier code- division multiple access (MC-CDMA) system. In particular, maximum likelihood, zero-forcing, minimum mean-square error and interference cancellation-based multiuser detectors have been analysed for the special case of uncorrelated subcarriers. The derived BER expressions are based upon previous results on diversity combining and also on recent findings on multiple input multiple output (MIMO) architectures. The subcarrier correlation is considered in the context of physical parameters currently under discussion for future wireless systems to give an indication up to what extent the assumption of uncorrelated subcarrier fading is plausible.     

A SOCIOLOGICAL PERSPECTIVE ON THE REORDERING PROBLEM IN MULTIPATH ROUTING

The term multipath routing means using multiple paths concurrently to transport data over network. The main problem of this routing scheme is the difference among the delays of selected paths, which causes reordering of a single flow's packets. In this paper, this problem is analyzed through a sociological perspective. We show that reordering problem is not inherently related to multipath routing, rather caused by the dominant capitalist view of the problem. then, the problem is addressed through a Marxism perspective. We theoretically prove that by this perspective, there exists a routing scheme that minimizes latency and also the requirement of buffering at receiver.     

A GRASP with path-relinking heuristic for the survivable IP/MPLS-over-WSON multi-layer network optimization problem

In this paper we deal with the survivable internet protocol (IP)/multi-protocol label switching (MPLS)-over-wavelength switched optical network (WSON) multi-layer network optimization problem (SIMNO). This problem entails planning an IP/MPLS network layer over a photonic mesh infrastructure whilst, at the same time, ensuring the highest availability of services and minimizing the capital expenditures (CAPEX) investments. Such a problem is currently identified as an open issue among network operators, and hence, its solution is of great interest. To tackle SIMNO, we first provide an integer linear programming (ILP) formulation which provides an insight into the complexity of its managing. Then, a greedy randomized adaptive search procedure (GRASP) with path-relinking (PR) together with a biased random-key genetic algorithm (BRKGA) are specifically developed to help solve the problem. The performance of both heuristics is exhaustively tested and compared making use of various network and traffic instances. Numerical experiments show the benefits of using GRASP instead of BRKGA when dealing with highly complex network scenarios. Moreover, we verified that the use of GRASP with PR remarkably improves the basic GRASP algorithm, particularly in real-sized, complex scenarios such as those proposed in this paper.     

Background voltage distortion influence on power electric systems in the presence of the Steinmetz circuit

In traction systems, it is usual to connect reactances in delta configuration with single-phase loads to reduce voltage unbalances and avoid electric system operation problems. This set is known as Steinmetz circuit. Parallel and series resonances can occur due to the capacitive reactance of the Steinmetz circuit and affect power quality. In this paper, the series resonance “observed” from the supply system is numerically located. The study of this resonance is important to avoid problems due to background voltage distortion. Experimental measurements are also presented to validate the obtained numerical results.     

New chemosensors based on thiomacrocycle-containing coumarin-343 fluoroionophor: X-ray structures and previous results on the effect of cation binding on the photophysical properties

Two new emissive chemosensors based on coumarin-343 have been synthesized, and their photophysical studies conducted. L1 contains an aza-thio macrocycle ring as the chelating unit, which has great affinity for soft metal ions, whereas L2 is a parent species without macrocyclic unit. Both compounds were separated by column chromatography and characterized by elemental analysis, ¹H,¹³C NMR, UV–vis and FAB mass spectroscopy. The X-ray structures of L1 and L2 and the supramolecular interactions in the solid state are discussed. Preliminary results on the metal–ion sensing effects of the ligands are presented. Titrations with Ag⁺, Pd²⁺ and Ni²⁺ have been studied by UV–vis absorption and fluorescence spectroscopy.     

Entrapment of Phenytoin into Microspheres of Oleaginous Materials: Process Development and in Vitro Evaluation of Drug Release

A novel multiparticulate preparation of the antiepileptic agent phenytoin (1) was developed and evaluated in vitro. The preparation consists of gastroresistant microparticulate drug delivery system formulated with oleaginous material (lipospheres) to minimize unwanted effects of l on gastric apparatus. The drug was dispersed in a spherical micromatrix consisting of a mixture of stearyl alcohol and glycerol esters of various fatty acids. The best mixture to obtain discrete, reproducible, free-flowing lipospheres consisted of glyceryl monostearate dilaurate and stearyl alcohol (ratio 3: 17). The lipospheres were obtained by a technique involving melting and dispersion of drug-containing oleaginous material in aqueous medium. The oily droplets of the resulting emulsion after cooling under rapid stirring were transformed into solid. About 99% of the lipospheres were of particle size range 100-800 pm. The lipospheres were analyzed to determine the drug content in various particle sizes and to characterize the in vitro release profile. The average drug content was 23.8% w/w. Drug encapsulation efficiency was about 93.6% and the yield of production ranged from 94 to 98%. The drug discharge pattern from the microparticulate system in the intestinal environment was evaluated. Kinetic results were analyzed to distinguish between various release models. The matrix diffusion-controlled equation was the most appropriate one in describing drug release.     

Structural Determinants of the Selectivity of 3‐Benzyluracil‐1‐acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10

The human enzymes aldose reductase (AR) and AKR1B10 have been thoroughly explored in terms of their roles in diabetes, inflammatory disorders, and cancer. In this study we identified two new lead compounds, 2‐(3‐(4‐chloro‐3‐nitrobenzyl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0048, 3 ) and 2‐(2,4‐dioxo‐3‐(2,3,4,5‐tetrabromo‐6‐methoxybenzyl)‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0049, 4 ), which selectively target these enzymes. Although 3 and 4 share the 3‐benzyluracil‐1‐acetic acid scaffold, they have different substituents in their aryl moieties. Inhibition studies along with thermodynamic and structural characterizations of both enzymes revealed that the chloronitrobenzyl moiety of compound 3 can open the AR specificity pocket but not that of the AKR1B10 cognate. In contrast, the larger atoms at the ortho and/or meta positions of compound 4 prevent the AR specificity pocket from opening due to steric hindrance and provide a tighter fit to the AKR1B10 inhibitor binding pocket, probably enhanced by the displacement of a disordered water molecule trapped in a hydrophobic subpocket, creating an enthalpic signature. Furthermore, this selectivity also occurs in the cell, which enables the development of a more efficient drug design strategy: compound 3 prevents sorbitol accumulation in human retinal ARPE‐19 cells, whereas 4 stops proliferation in human lung cancer NCI‐H460 cells.