Modelling and study of cyclosporin A and related compounds in complexes with a Trypanosoma cruzi cyclophilin

Cyclophilins (CyPs) are enzymes involved in protein folding, catalyzing the isomerisation of peptidyl prolyl bonds in proteins and peptides between the cis- and trans-conformations. They are also the major cellular target for the immunosuppressive drug Cyclosporin A (CsA). In Trypanosoma cruzi, the most abundantly expressed CyP is an isoform of 19 kDa, TcCyP19, in which the enzymatic activity is inhibited by CsA. Among a reported set of CsA analogues, two non-immunosuppressive compounds, H-7-94 and F-7-62, proved to be the best inhibitors of TcCyP19 enzymatic activity as well as the most efficient trypanocidal drugs. With the objective of analysing, at the molecular level, how the structural differences between the three above-mentioned inhibitors justify their different inhibitory activity on TcCyP19, three-dimensional molecular modelling structures were generated to computationally simulate behaviours and interactions. An energy-minimized model of each binary complex in water with ions was obtained. These models were then used as starting point for molecular dynamic simulations, performed with GROMOS96 program. With the resulting set of co-ordinates and energies, a comparison of the interaction between CsA and both CsA analogues in T. cruzi and human cyclophilins were performed. Within the different magnitudes analysed, the total potential complex energy exhibited the best correlation with the experimental data. The results obtained in this study support the use of this methodology when designing new lead inhibitor compounds.     

TSP Heuristics: Domination Analysis and Complexity

   Abstract. We show that the 2-Opt and 3-Opt heuristics for the traveling salesman problem (TSP) on the complete graph K _n produce a solution no worse than the average cost of a tour in K _n in a polynomial number of iterations. As a consequence, we get that the domination numbers of the 2- Opt , 3- Opt , Carlier—Villon, Shortest Path Ejection Chain, and Lin—Kernighan heuristics are all at least (n-2)! / 2 . The domination number of the Christofides heuristic is shown to be no more than

Blending and foaming thermoplastic starch with poly (lactic acid) by CO2-aided hot melt extrusion

Biomaterials are materials that can be biodegradable or obtained from renewable resources. Among them, poly (lactic acid) (PLA) and thermoplastic starch (TPS) represent an interesting alternative to replace petro-sourced thermoplastics. In this study, blends made by TPS addition to PLA were subjected to a foaming process using supercritical CO₂-aided extrusion. Extruder die temperature and CO₂ content were the most prominent parameters explaining the structure of the foams obtained. Both parameters were intimately linked since the CO₂ flow depends on the melt temperature, the lower the temperature, the higher the CO₂ solubility. Therefore, the die temperature was chosen to pilot the process. Whatever the experimental conditions, a 50/50 (in wt%) blend was poorly foamed due to the strong incompatibility between both biopolymers. However, the blend made of 80 wt% PLA and 20 wt% TPS gave evenly foamed samples. In terms of expansion and type of porosity this blend behaved like pure PLA with high porosity, up to 96%, and the presence of a threshold die temperature separating a close cell porosity at lowest temperatures and an open cell structure above the threshold. This temperature threshold was however significantly lower to that obtained with pure PLA.     

Immobilization of enzymes onto modified polyacrylonitrile membranes: Application of the acyl azide method

Chemical reactions toward acyl azide activated polyacrylonitrile (PAN) and conditions for membrane surface modifications are described. Ultrafiltration (UF) membranes were prepared from PAN homopolymer and copolymer with methyl acrylate. Besides hydrazide formation and nitrosation, a new method to introduce acyl azide groups into carboxyl modified PAN, using azido transfer with diphenyl phosphoryl azide, was developed. Chemical conversions were characterized, especially with Fourier transform infrared spectroscopy. The heterogeneous modifications are not chemically selective due to side reactions and/or incomplete conversion. The pore structure is altered predominately via modified polymer swelling causing changed UF fluxes and selectivities. However, for the modification via PAN reaction with hydroxyl amine, acid hydrolysis, and azido transfer, the initial membrane separations performance is qualitatively preserved. Using the acyl azide ḿethod, amylo-glucosidase (AG) (EC 3.2.1.3) was immobilized onto the modified PAN UF membranes, enabling hydrolysis of starch or maltose to glucose. Enzyme activity was assayed depending on previous chemical modification (azide content) and immobilization (pH) conditions as well as hydrolysis parameters (substrate, conversion during diffusion or UF). The best results (up to 600 mU/cm² at 40°C and pH 5.0) were obtained after modification of PAN membranes via carboxyl creation and azido transfer. AG convalently bound to PAN is not influenced much in its catalytic properties (K_m = 3.48 and 3.1 mmol/L for free and bound AG, respectively, with maltose at 40°C and pH 5.0). Under UF conditions, AG effective activity can be improved by the convective flow through the membrane. UF selectivity for the polymer starch determines effective substrate concentrations in the membrane, thus affecting observed activities and product purities in the filtrate. © 1996 John Wiley & Sons, Inc.     

Functional versus random test generation for sequential circuits

This article presents a test generation method for sequential circuits based on their synthesis specifications as finite state machines (FSM) and provides comparison with random test generation. The finite state machines are represented by their state transition graph (STG). The test generation method is performed in two phases. The first phase is functional. It generates a test sequence which is one of the shortest input sequences going through all the transitions of the state transition graph machine. This sequence provides a high fault coverage of stuck-at faults on the synthesized circuit compared to a randomly generated test sequence. This fault coverage is very close to the ones of other sequences derived by fault-oriented test generation approaches [9], [10], although these latter sequences are much longer.The trend of the fault coverage curve for different test sequences including progressively the transitions of the test sequence defined in the first phase is similar to the one of the fault coverage curve of a random sequence but for same lengths the first curve gives larger fault coverage. Both curves grow rapidly until a given ratio of faults is detected then continue to grow very slowly exhibiting low efficiency.The second phase of the test generation method is fault-oriented. It uses a fault simulation based approach in order to compute the test sequence for the remaining faults not detected by the first phase. At the end of this phase the test sequence for all the nonredundant faults is derived and, the combinationally redundant faults and the sequentially redundant faults are distinguished.     

Effects of anthocyanins and other phenolics of boysenberry and blackcurrant as inhibitors of oxidative stress and damage to cellular DNA in SH‐SY5Y and HL‐60 cells

There is growing interest both from consumers and researchers in the role that berries play in human health. The objective of this study was to investigate whether anthocyanins and other phenolics present in boysenberries and blackcurrants are effective in protecting cells against the oxidative damage induced by hydrogen peroxide (H₂O₂). The concentrations of polyphenols used were within the human physiological range. The data showed that SH‐SY5Y human neuroblastoma cells were protected against H₂O₂‐induced toxicity by the anthocyanins and phenolic fractions. The concurrent addition of either fractions of these berries with H₂O₂ significantly inhibited the increase in intracellular reactive oxygen species (ROS) production. Pre‐incubation of cells with the same concentrations had no effect on the ROS level—a result that may be due to the metabolic conversion to inactive compounds. Anthocyanins and phenolic fractions of blackcurrant were better at protecting DNA of HL‐60 human promyelocytic cells from damage than similar fractions from boysenberry. The phenolic extract of blackcurrant demonstrated the highest protective effect against H₂O₂‐induced neurotoxicity, oxidative stress and DNA damage and may be a good candidate for inclusion into a processed functional food. Copyright © 2006 Society of Chemical Industry     

Interactive lounge: an interdisciplinary approach to the design of a gestural interaction device

Among the many new opportunities that digital technologies are enabling are an increased capacity for viewers to interact not only with the program content, but with an increasingly wide array of other digital applications. Within this context this project has developed a new interaction device (incorporating gestural platform technology) and user interfaces to facilitate interactive access to digital media in a lounge room setting. This paper provides an overview of an interdisciplinary design process applied by Australasian CRC for Interaction Design (ACID) researchers—in order to develop the device and present in detail its unique features.     

Higher-order derivative spectrophotometry for studying and characterization of proteins and other native and synthetic macromolecules

Higher-order derivative spectrophotometry is very well adapted to the analytical chemistry of native and synthetic macromolecules. This is shown with the aid of some characteristic examples. The following ones have been described: The investigation of iso-forms of LDH, of myoglobins (whale and horse), of oligomer enzymes, the studying of the surroundings of the chromophores phe, tyr and trp in proteins, and of protein powder spectra; further spectra of nucleid acid, the quantitative estimation of monomers and additives in synthetic polymers, and the characterization of poly(vinyl pyrrolidons) of different molecular weights.     

Verbal processing deficits in schizophrenia.

The authors reported that a subgroup of schizophrenic patients performed well on a tone serial position task but was impaired on an auditory word serial position task (Wexler, Stevens, Bowers, Cerniak, & Goldman-Rakic, 1998). This study assessed 30 schizophrenic and 32 controls (matched for comparable tone discrimination) on 4 versions of the verbal serial position tasks and 2 tone serial position tasks. Patients performed poorly on all verbal tasks but performed comparably to controls when tones served as stimuli. Proactive interference and visual presentation further compounded the verbal deficits. Deficits persisted with pronounceable nonword stimuli. These findings provide evidence of specific deficits in language-related processing, although the authors could not rule out the possibility that the differential effects that were observed between the tone and word tasks, and particularly among the verbal tasks, may result from differing discriminating power of the different tests. (PsycINFO Database Record (c) 2010 APA, all rights reserved)