Scale factor local search in differential evolution

This paper proposes the scale factor local search differential evolution (SFLSDE). The SFLSDE is a differential evolution (DE) based memetic algorithm which employs, within a self-adaptive scheme, two local search algorithms. These local search algorithms aim at detecting a value of the scale factor corresponding to an offspring with a high performance, while the generation is executed. The local search algorithms thus assist in the global search and generate offspring with high performance which are subsequently supposed to promote the generation of enhanced solutions within the evolutionary framework. Despite its simplicity, the proposed algorithm seems to have very good performance on various test problems. Numerical results are shown in order to justify the use of a double local search instead of a single search. In addition, the SFLSDE has been compared with a standard DE and three other modern DE based metaheuristic for a large and varied set of test problems. Numerical results are given for relatively low and high dimensional cases. A statistical analysis of the optimization results has been included in order to compare the results in terms of final solution detected and convergence speed. The efficiency of the proposed algorithm seems to be very high especially for large scale problems and complex fitness landscapes.     

Enhanced mass resolution method development, validation and assay application to support preclinical studies of a new drug candidate

A very highly sensitive and highly selective liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method was developed to evaluate and quantify a new drug candidate in different biological matrices. Following a simple plasma protein precipitation using acetonitrile, the post-treatment samples were analyzed on a C18 column interfaced with a new generation of triple-quadrupole mass spectrometer. The recently introduced triple-quadrupole mass spectrometer, the TSQ Quantum Ultra, with enhanced mass-resolution capability, demonstrated improved sensitivity (0.05 ng/mL), coupled with suitable accuracy and precision, over a broad linear dynamic range (0.05-1000 ng/mL). A comparison of the assay performance data (dynamic range, calibration curve equation, precision and accuracy) of the enhanced resolution method against a unit resolution method under optimized conditions showed the performance improvement of the enhanced mass resolution method for bioanalytical high-throughput applications. The enhanced mass resolution method herein described was successfully applied to the evaluation of the pharmacokinetic profile of a new drug candidate in rat, rabbit and dog plasma samples.     

An intramolecularly self-templated synthesis of macrocycles: self-filling effects on the formation of prismarenes

Ethyl- and propyl-prism[6]arenes are obtained in high yields and in short reaction times, independent of the nature and size of the solvent, in the cyclization of 2,6-dialkoxynaphthalene with paraformaldehyde. PrS[6]Et or PrS[6]nPr adopt, both in solution and in the solid state, a folded cuboid-shaped conformation, in which four inward oriented alkyl chains fill the cavity of the macrocycle. On these bases, we proposed that the cyclization of PrS[6]Et or PrS[6]nPr occurs through an intramolecular thermodynamic self-templating effect. In other words, the self-filling of the internal cavity of PrS[6]Et or PrS[6]nPr stabilizes their cuboid structure, driving the equilibrium toward their formation. Molecular recognition studies, both in solution and in the solid state, show that the introduction of guests into the macrocycle cavity forces the cuboid scaffold to open, through an induced-fit mechanism. An analogous conformational change from a closed to an open state occurs during the endo-cavity complexation process of the pentamer, PrS[5]. These results represent a rare example of a thermodynamically controlled cyclization process driven through an intramolecular self-template effect, which could be exploited in the synthesis of novel macrocycles.

Ethyl- and propyl-prism[6]arenes are obtained by an intramolecular thermodynamic self-template effect: the self-filling of the internal cavity stabilizes their cuboid structure, driving the equilibrium toward their formation.     

Two general methods for the isolation of enzyme activities by colony filter screening

We describe two general methodologies, based on filter-sandwich assays, for isolating enzymatic activities from a large repertoire of protein variants expressed in the cytoplasm of E. coli cells. The enzymes are released by the freezing and thawing of bacterial colonies grown on a porous master filter and diffuse to a second "reaction" filter that closely contacts the master filter. Reaction substrates can be immobilized either on the filter or on the enzyme itself (which is then, in turn, captured on the reaction filter). The resulting products are detected with suitable affinity reagents. We used biotin ligase as a model enzyme to assess the performance of the two methodologies. Active enzymes were released by the bacteria, locally biotinylated the immobilized target substrate peptide, and allowed the sensitive and specific detection of individual catalytically active colonies.     

Charm mixing from BABAR

We present recent results from BABAR experiment for D0-D0 mixing measurements. Mixing parameters can be measured in different ways using different D0 decay modes, here we discuss the most sensitive analyses such as DO→K+π- where we had the first evidence of charm mixing, the measurement of the ratio of lifetimes of the decays DO→K+K-and DO→π- relative to D0→K-π+, the time dependent Dalitz plot analysis of D0→K+π-π0.New limits on CP-violating time-integrated asymmetries in D0→K+K- and D0→π+π- are also discussed. The analyses presented are based on 384 fb-1 data collected with the BABAR detector at the PEP-Ⅱ asymmetric B Factory.     

Fluorinated PLGA Nanoparticles for Enhanced Drug Encapsulation and 19F NMR Detection

In the continuous search for multimodal systems with combined diagnostic and therapeutic functions, several efforts have been made to develop multifunctional drug delivery systems. In this work, through a covalent approach, a new class of fluorinated poly(lactic-co-glycolic acid) co-polymers (F-PLGA) were designed that contain an increasing number of magnetically equivalent fluorine atoms. In particular, two novel compounds, F₃-PLGA and F₉-PLGA, were synthesized and their chemical structure and thermal stability were analyzed by solution NMR, DSC, and TGA. The obtained F-PLGA compounds were proven to form in aqueous solution colloidal stable nanoparticles (NPs) displaying a strong ¹⁹F NMR signal. The fluorinated NPs also showed an enhanced ability to load hydrophobic drugs containing fluorine atoms compared to analogous pristine PLGA NPs. Preliminary in vitro studies showed high cell viability and the NP ability to intracellularly deliver and release a functioning drug.     

Errors associated with nonuniform concentrations upon rate constants using absorption techniques

Kinetic absorption spectroscopy is a commonly used technique in the experimental determination of rate constants. Here we consider the effect of nonuniform reactant concentrations upon the measured results and the errors associated with the final determination of second-order rate constants in particular. We conclude that the errors associated with nonuniformity of reactant, while significant, are comparable or less than other common systematic or random errors. © 1993 John Wiley & Sons, Inc.     

Ion-exchange chromatographic assay of peptidases acting on the C-terminal hexapeptide sequence of substance P

A rapid and sensitive assay for peptidases acting on the C-terminal hexapeptide sequence of the neuropeptide substance P is described. The radiolabelled substrate, N alpha-[125I]desaminotyrosyl-substance P (6-11) is easily prepared by coupling commercially available radioiodinated Bolton-Hunter reagent with substance P (6-11). Peptidase activity is determined by quantitative separation of the degradation products from the intact substrate on small QAE-Sephadex columns. The assay has been used to measure degradation of the substrate by rat parotid and diencephalon slices. The peptidase activity in the latter system was inhibited by substance P and substance P fragments and was sensitive to metal chelators and thiol reagents.