Automation of Chemical Reaction Kinetics and Product Distribution Studies in Pharmaceutical Development

An automated instrument was designed and constructed to facilitate the performance of pharmaceutical degradation studies. A brief theoretical background on degradation kinetics is given to rationalize the design of the instrument and representative data are provided to illustrate its successful application. This system was found to be capable of conducting multiple simultaneous isothermal and nonisothermal kinetic studies with user-defined temperature profiles, sampling periods, and data logging.     

On some operations on strings suggested by gene assembly in ciliates

We define three operations on strings and languages suggested by the process of gene assembly in hypotrichous ciliates. This process is considered to be a prine example of DNA computing in vivo. This paper is devoted to some computational aspects of these operations from a formal language point of view. The closure of the classes of regular and context-free languages under these operations is settled. Then, we consider theld-macronuclear language of a given languageL, which consists of allld-macronuclear strings obtained from the strings ofL by iteratively applying the loop-direct repeat-excision. Finally, we discuss some open problems and further directions of research. Rudolf Freund: He received his master and doctor degree in computer science from the Vienna University of Technology, Austria, in 1980 and 1982, respectively. In 1986, he received his master degree in mathematics and physics from the University Vienna, Austria. In 1988 he joined the Vienna University of Technology in Austria, where he became an Associate Professor in September 1995. He has given various lectures in theoretical computer science, especially on formal languages and automata. His research interests include array and graph grammars, regulated rewritung, infinite words, syntactic pattern recognition, neural networks, and especially models and systems for biological computing. In these fields he is author of more than sixty scientific papers. Carlos Martín-Vide: He is Professor and Head of the Research Group on Mathematical Linguistics at Rovira i Virgili University, Tarragona, Spain. His specialities are formal language theory and mathematical linguistics. His last volume edited is Where Mathematics, Computer Science, Linguistics and Biology Meet (Kluwer, 2001, with V. Mitrana). He published 150 papers in conference proceedings and journals such as: Acta Informatica, BioSystems. Computational Linguistics, Computers and Artificial Intelligence, Information Processing Letters, Information Sciences, International Journal of Computer Mathematics, New Generation Computing, Publicationes Mathematicae Debrecen, and Theoretical Computer Science. He is the editor-in-chief of the journal Grammars (Kluwer), and the chairman of the 1st International PhD School in Formal Languages and Applications (2001–2003). Victor Mitrana, Ph.D.: He is Professor of Computer Science at the Faculty of Mathematics, University of Bucharest. He received his MSc and PhD from the University of Bucharest in 1986 and 1993, respectively. In 1999 he was awarded with the “Gheorghe Lazar” Prize for Mathematics of the Romanian Academy. His research interests include: formal language theory and applications, combinatorics on words, computational models inspired from biology, mathematical linguistics. In these areas, he published three books, more than 100 papers, and edited two books. He is an associate editor of “The Korean Journal of Computational and Applied Mathematics” and an editor of “Journal of Universal Computer Science”.     

Application of the triisobutylaluminum-promoted reductive rearrangement to sucrose-5-enes

Carbohydrate-based vinyl acetals (5-hex-enopyranosides) undergo reductive rearrangement with triisobutylaluminum (TIBAL) to afford highly functionalized cyclohexanes in which both the aglycon and anomeric stereochemistry are retained. Here, we report the first application of this process to the rearrangement of hex-5-enopyranosides of sucrose in which the interglycosidic oxygen atom of the vinyl acetal system links the anomeric centers of both monosaccharide units. The sucrose-derived 5-hex-enopyranoside 1 undergoes smooth reductive rearrangement with TIBAL to afford the (1 → 2′) ether-linked pseudo-disaccharide 2 in 34% yield. The rearrangement is accompanied by some loss of stereochemical integrity at C-2′ due to a competitive exo-cleavage of the interglycosidic (O-C2′) bond, hence diastereomers at C-2′ are also obtained in 12% yield. The 4-O-allyl-protected sucrose-5-ene 3 is similarly transformed into the corresponding (1 → 2′) ether-linked pseudo-disaccharide 4 , illustrating the compatibility of the allyl group with the TIBAL reaction conditions.      

Effect of heat treatment on the anodic oxidation of Ti–0.2 Pd alloys in chloride solutions

The effect of heat treatment of Ti and Ti–0.2 Pd alloys on their anodic oxidation was studied in deaerated 1% NaCl by means of anodic linear sweep voltammetry, SEM, TEM, EDS, optical microscopy and microhardness measurements. The specimens, as fabricated, consisted of -phase only. The -phase, intergranular or with a Widmansttäten type growth, was produced by heat treatment of the Ti–0.2 Pd alloys at the temperature range from 750 to 850 C. The -phase was transformed into the -phase during quenching. The current density against voltage curves for pure Ti and Ti–0.2 Pd, as fabricated or heat-treated, presented an initial plateau at about 1.5 V vs Ag/AgCl/KCl (3 M), an anodic peak at about 4.5 V and a current increase due to the pitting attack at about 10 V. The anodic peak was related to an oxide growth together with a solution electrolysis. Current spikes appeared at random from potentials about 8.3 V, which were related to film breakdown and repair events. The passive films of the alloys oxidized up to about 10 V presented oxidation bands parallel to the surface, with different oxygen content and microhardness, together with a structural transformation of the -phase under the titanium oxide layer. The similar behaviour of pure Ti and Ti–0.2 Pd alloys in front of pitting corrosion in chloride was due to such a structural transformation.     

Efficacy evaluation of the molasses supplementation in normal and depleted rats diet

Molasses, a sugar cane by-product, has been consumed in Brazil since colonial times. The efficacy of molasses added to the diet of normal and depleted laboratory animals on growth and hemoglobin was tested. Forty weaning males rats, of 21 days of age, were divided into four groups of ten animals: Control (casein diet with 10.14% protein); Molasses (casein diet with 10.14% protein and 12.50% molasses); Depleted Control and Depleted Molasses, the later two submitted to protein depletion for the first 7 days of the trial. Animals were weighed at weaning (initial weight) and at the end of the experiment (final weight) and were fed the experimental rations and water ad libitum for 28 days (normal animals) and 21 days (depleted animals). Consumption was registered in order to calculate the Food Efficiency Ratio. At the end, animals fasted for 10 hours, killed and blood was collected by cardiac puncture to determine hemoglobin levels. Weight gain in all groups did not show statistically significant differences. Molasses fed animals presented a small, but not significant increase in hemoglobin levels, compared to the control groups. Considering the possible deleterious effects of a high sugar diet, that can originate furfural during food processing, it is necessary to conduct more studies to evaluate the utilization of these products for human consumption.     

Proliferation/differentiation of osteoblastic human alveolar bone cell cultures in the presence of stainless steel corrosion products

Human osteoblastic alveolar bone cells were cultured for 28 days in control conditions and in the presence of three non-lethal concentrations of AISI 316L stainless steel (SS) corrosion products. Cells were exposed to SS corrosion products in two experimental situations: (i) in selected stages of the incubation time (during the first, second, third and fourth week of culture); and (ii) during the 28 days incubation period. Cultures were characterized for cell proliferation, total protein content, alkaline phosphatase activity (ALP) and ability to form mineralized deposits; culture media was analyzed for ionized calcium (Ca) and phosphorus (P) concentrations throughout the incubation period. The presence of SS corrosion products during the different stages of the incubation period did not significantly affect the cell proliferation; however, a significant dose-dependent deleterious effect was observed on the levels and pattern of ALP activity, concentration of ionized Ca and P in the culture medium and, also, ability to form mineralized deposits, especially in cultures exposed during the first and second week of culture (respectively, lag phase and exponential cell growth phase). Similar effects were observed in cultures exposed to the SS corrosion products during the 28 days incubation period. However, the presence of such products during the third week (when the mineralization process occurs) and, also, during the fourth week, resulted in little or no significant effects on the behavior of alveolar bone cells. Results suggested that SS corrosion products above certain non-lethal concentrations may disturb the proliferation/differentiation relationship of osteoblastic human alveolar bone cell cultures. ©©2000 Kluwer Academic Publishers     

Effects of sediment geochemical properties on the toxicity of copper-spiked sediments to the marine amphipod Gammarus locusta

The contribution of some sediment features, namely acid-volatile sulfide (AVS) and total organic carbon (TOC) in order to explain the toxicity of copper-spiked sediments was investigated. A 10-day assay with the marine amphipod Gammarus locusta was performed with three selected sediment types that consisted of different proportions of fine fractions (FF) and TOC (0.5% FF/1% TOC; 25% FF/2% TOC; and 75% FF/4% TOC). Copper toxic effects were observed for 0.5% FF/25% FF sediments when simultaneously extracted copper (SEM(Cu)) minus acid volatile sulfide (SEM(Cu) - AVS) were 0.3 and 3.4 micromol/g, respectively. However, no significant mortality was observed for 75% FF sediment even when the sulfide binding capacity was exceeded (1.1 micromol/g < or = SEM(Cu) - AVS < or = 8.9 micromol/g). These results indicate that mortality could not be described solely as a function of the SEM(Cu) - AVS, suggesting the presence of other binding phases in addition to AVS. Results of the normalized LC50 values to total organic carbon indicated that this component probably also interferes in the amphipod survival, although not completely. The estimated LC50 values were close (2 mg Cu/g C and 8 mg Cu/g C, respectively for 0% FF and 25% FF sediment) although there was still a fourfold difference between them. Considering that none of these sediment features by itself could fully explain copper toxicity, an attempt was made to describe G. locusta mortality as a function of simultaneous SEM(Cu) - AVS and copper concentrations normalized to TOC. Nevertheless, the limited set of data available from this study prevented an attempt to model toxicity as a function of both of these factors. These findings reinforce the need to develop integrated models that include more than one binding phase, sulfide and organic carbon, and also other compartments of the system (e.g. interstitial water) to improve current methodologies for predicting copper toxicity based on sediment geochemical features.     

Materials Behavior in Laser Welding of Hardmetals to Steel

Tool manufacturing industry faces the problem of permanently joining hardmetals to steel holders with high shear strength. The mostly used welding process still is brazing. However, brazed joints have poor lifetimes, mostly when high temperatures are achieved and often break in operation. In a previous study about the ability of CO₂ and Nd:YAG lasers to weld hardmetals to steels, it was found that Nd:YAG lasers, working in continuous wave mode, could be used especially for welding hardmetals with Co content around 12%. This article discusses the materials behavior under laser radiation and analyzes the microstructural features observed.     

Conditioned and unconditioned fear organized in the inferior colliculus are differentially sensitive to injections of muscimol into the basolateral nucleus of the amygdala.

Chemical stimulation of the inferior colliculus (IC) with semicarbazide--an inhibitor of the gamma aminobutyric acid synthesizing enzyme--functions as an unconditioned stimulus in the conditioned place aversion test (CPA), and electrolytic lesions of the basolateral amygdala (BLA) enhance the aversiveness of the IC stimulation. This study examined the effects of inactivation of the BLA with muscimol on the conditioned and unconditioned fear using semicarbazide injections into the IC of rats subjected to conditioned (CPA) or unconditioned (open field) fear tests. In both tests, the rats were injected with semicarbazide or saline into the IC and muscimol or saline into the BLA. Muscimol decreased the CPA and increased the unconditioned fear elicited by IC injections of semicarbazide. These findings indicate that distinct modulatory mechanisms in the BLA are recruited during the conditioned and unconditioned fear triggered by IC activation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Phenotypic and functional analysis of CD4+ NKRP1A+ human T lymphocytes. Direct evidence that the NKRP1A molecule is involved in transendothelial migration

In this report, we show that among human CD4+ T lymphocytes 5-20% express the C-type lectin molecule NKRP1A. This lymphocyte subset displays a slightly more limited T cell receptor V beta repertoire than the CD4+ NKRP1A- counterpart. CD4+ NKRP1A+ T lymphocytes are characterized by a high expression of beta 1 and beta 2 integrins, thus representing a T lymphocyte subset that can possibly adhere and migrate through vascular endothelium. Indeed, resting CD4+ NKRP1A+ lymphocytes, differently from the CD4+ NKRP1A- subset, migrated across endothelial cell monolayers in a Transwell chamber system. Pretreatment of CD4+ NKRP1A+ T lymphocytes with an anti-NKRP1A monoclonal antibody (mAb) strongly reduced transendothelial migration, suggesting the involvement of the NKRP1A molecule in the transmigration process. Furthermore, cells of the NKRP1A- Jurkat CD4+ T cell line stably transfected with NKRP1A cDNA migrated more rapidly and efficiently than either untransfected or mock-transfected Jurkat cells. Finally, mAb-mediated cross-linking of NKRP1A molecules in CD4+ T lymphocytes induced the up-regulation of the lymphocyte function-associated antigen 1 Mg(2+)-binding site as well as beta 1 and beta 2 integrin chains. Altogether, these findings suggest that the NKRP1A molecule is involved in transendothelial migration of resting CD4+ T lymphocytes.