Analytical characteristics and discrimination of Brazilian commercial grape juice, nectar, and beverage

The production and commercialization of Brazilian grape juice is increasing annually, mainly due to its typicality, quality, and nutritional value. The present research was carried out in view of the great significance of Brazilian grape juice for the grape and wine industry. The purpose of this study, therefore, was to assess its composition as well as the discrimination between grape juice and other beverages. Twenty four samples of whole, sweetened, and reprocessed grape juices, grape nectar, and grape beverage were evaluated. Classical variables were analyzed by means of physicochemical methods; tartaric and malic acids, by HPLC; methanol, by gas chromatography; minerals, by atomic absorption spectrophotometry. These products were discriminated by the Principal Component Analysis (PCA). Results show that whole and sweetened grape juices were discriminated from other grape products because they featured higher values of total soluble solids, tartaric and malic acids, most minerals, phenolic compounds, and K/Na ratio, whereas grape nectar and grape beverage presented higher values of ºBrix/titratable acidity ratio. Reprocessed juice was discriminated due to its higher concentrations of Li and Na and lower hue.

Study of the enthalpy-entropy mechanism from water sorption of orange seeds (C. sinensis cv. Brazilian) for the use of agro-industrial residues as a possible source of vegetable oil production

Orange seeds are a promising agroindustry-waste which can be implemented in the extraction and production of vegetable oil. The relationship between moisture content and water activity provides useful information for the processing and storage of this waste item. The aim of this study was to determine the mechanism of water sorption enthalpy-entropy of orange seeds (C. sinensis cv. Brazilians) according to the moisture content. Therefore, desorption isotherms were determined at five different temperature (30, 40, 50, 60, and 70 ºC) under a wide range of moisture content (0.005-0.057 kg kg-1 d.b.) and water activity (0.02-0.756). Theoretical and empirical models were used for modeling the desorption isotherms. An analytical solution of the Clausius-Clapeyron equation was proposed to compute the isosteric heat of sorption, the differential entropy, and Gibbs free energy using the Oswin model when the effect of temperature on the hygroscopic equilibrium was considered.

Blue and Uv-Emitting Upconversion Nanoparticles: Synthesis and (Bio) Analytical Applications.

Rare-earth based upconverting nanoparticles (UCNPs) have attracted much attention due to their unique luminescent properties. The ability to convert multiple photons of lower energy to ones with higher energy through an upconversion (UC) process offers a wide range of applications for UCNPs. The emission intensities and wavelengths of UCNPs are important performance characteristics, which determine the appropriate applications. However, insufficient intensities still limit the use of UCNPs; especially the efficient emission of blue and ultraviolet (UV) light via upconversion remains challenging, as these events require three or more near-infrared (NIR) photons. The aim of the study was to enhance the blue and UV upconversion emission intensities of Tm3+ doped NaYF4 nanoparticles and to demonstrate their utility in in vitro diagnostics. As the distance between the sensitizer and the activator significantly affect the energy transfer efficiency, different strategies were explored to change the local symmetry around the doped lanthanides. One important strategy is the intentional co-doping of active (participate in energy transfer) or passive (do not participate in energy transfer) impurities into the host matrix. The roles of doped passive impurities (K+ and Sc3+) in enhancing the blue and UV upconversions, as well as in influencing the intense UV upconversion emission through excess sensitization (active impurity) were studied. Additionally, the effects of both active and passive impurity doping on the morphological and optical performance of UCNPs were investigated. The applicability of UV emitting UCNPs as an internal light source for glucose sensing in a dry chemistry test strip was demonstrated. The measurements were in agreement with the traditional method based on reflectance measurements using an external UV light source. The use of UCNPs in the glucose test strip offers an alternative detection method with advantages such as control signals for minimizing errors and high penetration of the NIR excitation through the blood sample, which gives more freedom for designing the optical setup. In bioimaging, the excitation of the UCNPs in the transparent IR region of the tissue permits measurements, which are free of background fluorescence and have a high signal-to-background ratio. In addition, the narrow emission bandwidth of the UCNPs enables multiplexed detections. An array-in-well immunoassay was developed using two different UC emission colours. The differentiation between different viral infections and the classification of antibody responses were achieved based on both the position and colour of the signal. The study demonstrates the potential of spectral and spatial multiplexing in the imaging based array-in-well assays.

Detecting Deceit – Guessing or Assessing? Study on the Applicability of Veracity Assessment Methods in Human Intelligence

Intelligence from a human source, that is falsely thought to be true, is potentially more harmful than a total lack of it. The veracity assessment of the gathered intelligence is one of the most important phases of the intelligence process. Lie detection and veracity assessment methods have been studied widely but a comprehensive analysis of these methods’ applicability is lacking. There are some problems related to the efficacy of lie detection and veracity assessment. According to a conventional belief an almighty lie detection method, that is almost 100% accurate and suitable for any social encounter, exists. However, scientific studies have shown that this is not the case, and popular approaches are often over simplified. The main research question of this study was: What is the applicability of veracity assessment methods, which are reliable and are based on scientific proof, in terms of the following criteria? o Accuracy, i.e. probability of detecting deception successfully o Ease of Use, i.e. easiness to apply the method correctly o Time Required to apply the method reliably o No Need for Special Equipment o Unobtrusiveness of the method In order to get an answer to the main research question, the following supporting research questions were answered first: What kinds of interviewing and interrogation techniques exist and how could they be used in the intelligence interview context, what kinds of lie detection and veracity assessment methods exist that are reliable and are based on scientific proof and what kind of uncertainty and other limitations are included in these methods? Two major databases, Google Scholar and Science Direct, were used to search and collect existing topic related studies and other papers. After the search phase, the understanding of the existing lie detection and veracity assessment methods was established through a meta-analysis. Multi Criteria Analysis utilizing Analytic Hierarchy Process was conducted to compare scientifically valid lie detection and veracity assessment methods in terms of the assessment criteria. In addition, a field study was arranged to get a firsthand experience of the applicability of different lie detection and veracity assessment methods. The Studied Features of Discourse and the Studied Features of Nonverbal Communication gained the highest ranking in overall applicability. They were assessed to be the easiest and fastest to apply, and to have required temporal and contextual sensitivity. The Plausibility and Inner Logic of the Statement, the Method for Assessing the Credibility of Evidence and the Criteria Based Content Analysis were also found to be useful, but with some limitations. The Discourse Analysis and the Polygraph were assessed to be the least applicable. Results from the field study support these findings. However, it was also discovered that the most applicable methods are not entirely troublefree either. In addition, this study highlighted that three channels of information, Content, Discourse and Nonverbal Communication, can be subjected to veracity assessment methods that are scientifically defensible. There is at least one reliable and applicable veracity assessment method for each of the three channels. All of the methods require disciplined application and a scientific working approach. There are no quick gains if high accuracy and reliability is desired. Since most of the current lie detection studies are concentrated around a scenario, where roughly half of the assessed people are totally truthful and the other half are liars who present a well prepared cover story, it is proposed that in future studies lie detection and veracity assessment methods are tested against partially truthful human sources. This kind of test setup would highlight new challenges and opportunities for the use of existing and widely studied lie detection methods, as well as for the modern ones that are still under development.

Cognitive coaching : a multiple case study /

The purpose of this qualitative study was to investigate the application of Cognitive Coaching as a school-based professional development program to improve instructional thought and decision making as well as to enhance staff perceptions, coUegiality and school culture. This topic emerged from personal and professional issues related to the role ofthe reflective practitioner in improving the quality of education, yet cognizant of the fact that little professional development was available to train teachers to become reflective. This case study, positioned within the interpretive sciences, focused on three teachers and how their experiences with cognitive coaching affected their teaching practices. Their knowledge, understanding and use of the four stages of instructional thought (preactive, interactive, reflective and projective) were tested before and at the end of eight coaching cycles, and again after two months to determine whether they had continued to use the reflective process. They were also assessed on whether their attitude towards peer coaching had changed, whether their feelings about teaching had become more positive and whether their professional dialogue had increased. Three methods of data collection were selected to assess growth: interviews, observations and joumaling. Analysis primarily consisted of coding and organizing data according to emerging themes. Although the professed aim of cognitive coaching was to teach the process in order that the teachers would become self-analytical and self-modifying, this study found that the value of the coaching, after trust had been established in both the coach and the process, was in the dialoguing and the time set aside to do it. Once the coaching stopped providing the time to dialogue, to examine one's meanings and beliefs, so did the critical self-reflection. As a result ofthe cognitive coaching experience though, all participants grew in their feelings of efficacy, craftsmanship, flexibility, consciousness and interdependence. The actual and potential significance ofthis study was discussed according to implications for teacher supervision, professional development, school culture, further areas of research and to my personal growth and development.

Orientation of Non-Native 2-Monosubstituted and 2,3-Disubstituted 1,4-Naphthoquinones in the A1 binding site of PSI and the effect on the rate of electron transfer : an electron paramagnetic resonance spectroscopy study

The proce-ss ofoxygenic photosynthesis is vital to life on Earth. the central event in photosynthesis is light induced electron transfer that converts light into energy for growth. Ofparticular significance is the membrane bound multisubunit protein known as Photosystem I (PSI). PSI is a reaction centre that is responsible for the transfer of electrons across the membrane to reduce NADP+ to NADPH. The recent publication ofa high resolution X-ray structure of PSI has shown new information about the structure, in particular the electron transfer cofactors, which allows us to study it in more detail. In PSI, the secondary acceptor is crucial for forward electron transfer. In this thesis, the effect of removing the native acceptor phylloquinone and replacing it with a series of structurally related quinones was investigated via transient electron paramagnetic resonance (EPR) experiments. The orientation of non native quinones in the binding site and their ability to function in the electron transfer process was determined. It was found that PSI will readily accept alkyl naphthoquinones and anthraquinone. Q band EPR experiments revealed that the non-native quinones are incorporated into the binding site with the same orientation of the headgroup as in the native system. X band EPR spectra and deuteration experiments indicate that monosubstituted naphthoquinones are bound to the Al site with their side group in the position occupied by the methyl group in native PSI (meta to the hydrogen bonded carbonyl oxygen). X band EPR experiments show that 2, 3- disubstituted methyl naphthoquinones are also incorporated into the Al site in the same orientation as phylloquinone, even with the presence of a halogen- or sulfur-containing side chain in the position normally occupied by the phytyl tail ofphylloquinone. The exception to this is 2-bromo-3-methyl --.- _. -. - -- - - 4 _._ _ _ - _ _ naphthoquinone which has a poorly resolved spectrum, making determination of the orientation difficuh. All of the non-native quinones studied act as efficient electron acceptors. However, forward electron transfer past the quinone could only be demonstrated for anthraquinone, which has a more negative midpoint potential than phylloquinone. In the case of anthraquinone, an increased rate of forward electron transfer compared to native PSI was found. From these results we can conclude that the rate ofelectron transfer from Al to Fx in native PSI lies in the normal region ofthe Marcus Curve.

Perceptions of intergroup bias : the roles of social projection and meta-stereotypes

Underlying intergroup perceptions include processes of social projection (perceiving personal traitslbeliefs in others, see Krueger 1998) and meta-stereotyping (thinking about other groups' perceptions of one's own group, see Vorauer et aI., 1998). Two studies were conducted to investigate social projection and meta-stereotypes in the domain of White-Black racial relations. Study 1, a correlational study, examined the social projection of prejudice and 'prejudiced' meta-stereotypes among Whites. Results revealed that (a) Whites socially projected their intergroup attitudes onto other Whites (and Blacks) [i.e., Whites higher in prejudice against Blacks believed a large percentage of Whites (Blacks) are prejudiced against Blacks (Whites), whereas Whites low in prejudice believed a smaller percentage of Whites (Blacks) are prejudiced]; (b) Whites held the meta:..stereotype that their group (Whites) is viewed by Blacks to be prejudiced; and (c) prejudiced meta-stereotypes may be formed through the social projection of intergroup attitudes (result of path-model tests). Further, several correlates of social projection and meta-stereotypes were identified, including the finding that feeling negatively stereotyped by an outgroup predicted outgroup avoidance through heightened intergroup anxiety. Study 2 replicated and extended these findings, investigating the social projection of ingroup favouritism and meta- and other-stereotypes about ingroup favouritism. These processes were examined experimentally using an anticipated intergroup contact paradigm. The goal was to understand the experimental conditions under which people would display the strongest social projection of intergroup attitudes, and when experimentally induced meta-stereotypes (vs. other-stereotypes; beliefs about the group 11 preferences of one's outgroup) would be most damaging to intergroup contact. White participants were randomly assigned to one of six conditions and received (alleged) feedback from a previously completed computer-based test. Depending on condition, this information suggested that: (a) the participant favoured Whites over Blacks; (b) previous White participants favoured Whites over Blacks; (c) the participant's Black partner favoured Blacks over Whites; (d) previous Black participants favoured Blacks over Whites; (e) the participant's Black partner viewed the participant to favour Whites over Blacks; or (£) Black participants previously participating viewed Whites to favour Whites over Blacks. In a defensive reaction, Whites exhibited enhanced social projection of personal intergroup attitudes onto their ingroup under experimental manipulations characterized by self-concept threat (i.e., when the computer revealed that the participant favoured the ingroup or was viewed to favour the ingroup). Manipulated meta- and otherstereotype information that introduced intergroup contact threat, on the other hand, each exerted a strong negative impact on intergroup contact expectations (e.g., anxiety). Personal meta-stereotype manipulations (i.e., when the participant was informed that her/ his partner thinks s/he favours the ingroup) exerted an especially negative impact on intergroup behaviour, evidenced by increased avoidance of the upcoming interracial interaction. In contrast, personal self-stereotype manipulations (i.e., computer revealed that one favoured the ingroup) ironically improved upcoming intergroup contact expectations and intentions, likely due to an attempt to reduce the discomfort of holding negative intergroup attitudes. Implications and directions for future research are considered.

Développement de techniques analytiques pour la détermination des agents anti-infectieux dans les eaux environnementales

Les agents anti-infectieux sont utilisés pour traiter ou prévenir les infections chez les humains, les animaux, les insectes et les plantes. L’apparition de traces de ces substances dans les eaux usées, les eaux naturelles et même l’eau potable dans plusieurs pays du monde soulève l’inquiétude de la communauté scientifique surtout à cause de leur activité biologique. Le but de ces travaux de recherche a été d’étudier la présence d’anti-infectieux dans les eaux environnementales contaminées (c.-à-d. eaux usées, eaux naturelles et eau potable) ainsi que de développer de nouvelles méthodes analytiques capables de quantifier et confirmer leur présence dans ces matrices. Une méta-analyse sur l’occurrence des anti-infectieux dans les eaux environnementales contaminées a démontré qu’au moins 68 composés et 10 de leurs produits de transformation ont été quantifiés à ce jour. Les concentrations environnementales varient entre 0.1 ng/L et 1 mg/L, selon le composé, la matrice et la source de contamination. D’après cette étude, les effets nuisibles des anti-infectieux sur le biote aquatique sont possibles et ces substances peuvent aussi avoir un effet indirect sur la santé humaine à cause de sa possible contribution à la dissémination de la résistance aux anti-infecteiux chez les bactéries. Les premiers tests préliminaires de développement d’une méthode de détermination des anti-infectieux dans les eaux usées ont montré les difficultés à surmonter lors de l’extraction sur phase solide (SPE) ainsi que l’importance de la sélectivité du détecteur. On a décrit une nouvelle méthode de quantification des anti-infectieux utilisant la SPE en tandem dans le mode manuel et la chromatographie liquide couplée à la spectrométrie de masse en tandem (LC-MS/MS). Les six anti-infectieux ciblés (sulfaméthoxazole, triméthoprime, ciprofloxacin, levofloxacin, clarithromycin et azithromycin) ont été quantifiés à des concentrations entre 39 et 276 ng/L dans les échantillons d’affluent et d’effluent provenant d’une station d’épuration appliquant un traitement primaire et physico- chimique. Les concentrations retrouvées dans les effluents indiquent que la masse moyenne totale de ces substances, déversées hebdomadairement dans le fleuve St. Laurent, était de ~ 2 kg. En vue de réduire le temps total d’analyse et simplifier les manipulations, on a travaillé sur une nouvelle méthode de SPE couplée-LC-MS/MS. Cette méthode a utilisé une technique de permutation de colonnes pour préconcentrer 1.00 mL d’échantillon dans une colonne de SPE couplée. La performance analytique de la méthode a permis la quantification des six anti-infectieux dans les eaux usées municipales et les limites de détection étaient du même ordre de grandeur (13-60 ng/L) que les méthodes basées sur la SPE manuelle. Ensuite, l’application des colonnes de SPE couplée de chromatographie à débit turbulent pour la préconcentration de six anti-infectieux dans les eaux usées a été explorée pour diminuer les effets de matrice. Les résultats obtenus ont indiqué que ces colonnes sont une solution de réchange intéressante aux colonnes de SPE couplée traditionnelles. Finalement, en vue de permettre l’analyse des anti-infectieux dans les eaux de surface et l’eau potable, une méthode SPE couplée-LC-MS/MS utilisant des injections de grand volume (10 mL) a été développée. Le volume de fuite de plusieurs colonnes de SPE couplée a été estimé et la colonne ayant la meilleure rétention a été choisie. Les limites de détection et de confirmation de la méthode ont été entre 1 à 6 ng/L. L’analyse des échantillons réels a démontré que la concentration des trois anti-infectieux ciblés (sulfaméthoxazole, triméthoprime et clarithromycine) était au dessous de la limite de détection de la méthode. La mesure des masses exactes par spectrométrie de masse à temps d’envol et les spectres des ions produits utilisant une pente d’énergie de collision inverse dans un spectromètre de masse à triple quadripôle ont été explorés comme des méthodes de confirmation possibles.

A study of chymotrypsin immobilization conditions for improved peptide mapping

La cartographie peptidique est une technique de grande importance utilisée lors de l’identification des protéines et la caractérisation des modifications post-traductionnelles des protéines. Deux méthodes sont utilisées afin de couper les protéines en peptides pour la cartographie : les méthodes chimiques et les méthodes enzymatiques. Dans ce projet, l’enzyme chymotrypsine a été utilisée pour l’hydrolyse (la digestion) des liens peptidiques. Cependant, l’autoprotéolyse des enzymes peut augmenter la complexité des échantillons, rendant ainsi ardue l’obtention de pics résolus suite à l’apparition de pics non-désirés dans la carte peptidique. Par conséquent, nous avons utilisé la réticulation des enzymes protéolytiques par réaction avec le glutaraldéhyde (GA) donnant une enzyme insoluble afin de réduire l’autoprotéolyse. L’immobilisation de la chymotrypsine par GA a été effectuée selon une méthode rapportée précédemment par le groupe Waldron. L’électrophorèse capillaire (CE) couplée à l’absorption UV-visible a été utilisée pour la séparation et la détection de peptides et pour obtenir ainsi une cartographie peptidique. Deux tampons différents ont été évalués afin d’obtenir les meilleures conditions pour la digestion de substrats protéiques par la chymotrypsine libre (soluble) ou la GAchymotrypsine et l’analyse par CE. Les cartes des peptides autoprotéolytiques ont été comparées entre les deux formats de chymotrypsine. Afin d’améliorer la cartographie peptidique, nous avons évalué trois méthodes de conditionnement du capillaire CE et deux méthodes pour stopper la digestion. Le bicarbonate d’ammonium s’est avéré être le tampon optimal pour la digestion en solution et l’utilisation d’un bain d’acétone et de glace sèche s’est avérée être la méthode optimale pour stopper la digestion. Une solution de SDS, 25 mM, dans l’étape de rinçage a été utilisée après chaque analyse CE et a permis d’améliorer la résolution des cartes peptidiques. La comparaison entre l’autoprotéolyse de la chymotrypsine libre et de celle immobilisé par GA a été effectuée par des tests utilisant une gamme de six différentes combinaisons de conditions afin d’évaluer le temps (30 et 240 min) et la température de digestion (4, 24 et 37°C). Dans ces conditions, nos résultats ont confirmé que le GA-chymotrypsine réduit l’autoprotéolyse par rapport à l’enzyme libre. La digestion (à 37°C/240 min) de deux substrats modèles par la chymotrypsine libre et immobilisée en fonction de la température de dénaturation du substrat a été étudiée. iii Avant la digestion, les substrats (l’albumine de sérum bovine, BSA, et la myoglobine) ont été dénaturés par chauffage pendant 45 min à trois températures différentes (60, 75 et 90°C). Les résultats ont démontré que la dénaturation par chauffage du BSA et de la myoglobine n’a pas amélioré la cartographie peptidique pour la GA-chymotrypsine, tandis que la digestion de ceux-ci en présence de la chymotrypsine libre a amélioré de façon quantifiable à des températures élevées. Ainsi, le chauffage du substrat à 90°C avec l’enzyme soluble facilite le dépliement partiel du substrat et sa digestion limitée, ce qui a été mieux pour la myoglobine que pour la BSA.

Meta-heuristic Solution Methods for Rich Vehicle Routing Problems

Le problème de tournées de véhicules (VRP), introduit par Dantzig and Ramser en 1959, est devenu l'un des problèmes les plus étudiés en recherche opérationnelle, et ce, en raison de son intérêt méthodologique et de ses retombées pratiques dans de nombreux domaines tels que le transport, la logistique, les télécommunications et la production. L'objectif général du VRP est d'optimiser l'utilisation des ressources de transport afin de répondre aux besoins des clients tout en respectant les contraintes découlant des exigences du contexte d’application. Les applications réelles du VRP doivent tenir compte d’une grande variété de contraintes et plus ces contraintes sont nombreuse, plus le problème est difficile à résoudre. Les VRPs qui tiennent compte de l’ensemble de ces contraintes rencontrées en pratique et qui se rapprochent des applications réelles forment la classe des problèmes ‘riches’ de tournées de véhicules. Résoudre ces problèmes de manière efficiente pose des défis considérables pour la communauté de chercheurs qui se penchent sur les VRPs. Cette thèse, composée de deux parties, explore certaines extensions du VRP vers ces problèmes. La première partie de cette thèse porte sur le VRP périodique avec des contraintes de fenêtres de temps (PVRPTW). Celui-ci est une extension du VRP classique avec fenêtres de temps (VRPTW) puisqu’il considère un horizon de planification de plusieurs jours pendant lesquels les clients n'ont généralement pas besoin d’être desservi à tous les jours, mais plutôt peuvent être visités selon un certain nombre de combinaisons possibles de jours de livraison. Cette généralisation étend l'éventail d'applications de ce problème à diverses activités de distributions commerciales, telle la collecte des déchets, le balayage des rues, la distribution de produits alimentaires, la livraison du courrier, etc. La principale contribution scientifique de la première partie de cette thèse est le développement d'une méta-heuristique hybride dans la quelle un ensemble de procédures de recherche locales et de méta-heuristiques basées sur les principes de voisinages coopèrent avec un algorithme génétique afin d’améliorer la qualité des solutions et de promouvoir la diversité de la population. Les résultats obtenus montrent que la méthode proposée est très performante et donne de nouvelles meilleures solutions pour certains grands exemplaires du problème. La deuxième partie de cette étude a pour but de présenter, modéliser et résoudre deux problèmes riches de tournées de véhicules, qui sont des extensions du VRPTW en ce sens qu'ils incluent des demandes dépendantes du temps de ramassage et de livraison avec des restrictions au niveau de la synchronization temporelle. Ces problèmes sont connus respectivement sous le nom de Time-dependent Multi-zone Multi-Trip Vehicle Routing Problem with Time Windows (TMZT-VRPTW) et de Multi-zone Mult-Trip Pickup and Delivery Problem with Time Windows and Synchronization (MZT-PDTWS). Ces deux problèmes proviennent de la planification des opérations de systèmes logistiques urbains à deux niveaux. La difficulté de ces problèmes réside dans la manipulation de deux ensembles entrelacés de décisions: la composante des tournées de véhicules qui vise à déterminer les séquences de clients visités par chaque véhicule, et la composante de planification qui vise à faciliter l'arrivée des véhicules selon des restrictions au niveau de la synchronisation temporelle. Auparavant, ces questions ont été abordées séparément. La combinaison de ces types de décisions dans une seule formulation mathématique et dans une même méthode de résolution devrait donc donner de meilleurs résultats que de considérer ces décisions séparément. Dans cette étude, nous proposons des solutions heuristiques qui tiennent compte de ces deux types de décisions simultanément, et ce, d'une manière complète et efficace. Les résultats de tests expérimentaux confirment la performance de la méthode proposée lorsqu’on la compare aux autres méthodes présentées dans la littérature. En effet, la méthode développée propose des solutions nécessitant moins de véhicules et engendrant de moindres frais de déplacement pour effectuer efficacement la même quantité de travail. Dans le contexte des systèmes logistiques urbains, nos résultats impliquent une réduction de la présence de véhicules dans les rues de la ville et, par conséquent, de leur impact négatif sur la congestion et sur l’environnement.

In Vitro Ketamine CYP3A Mediated Metabolism Study using Mammalian Liver S9 Fractions, cDNA Expressed Enzymes and Liquid Chromatography Tandem Mass Spectrometry

Ketamine is widely used in medicine in combination with several benzodiazepines including midazolam. The objectives of this study were to develop a novel HPLC-MS/SRM method capable of quantifying ketamine and norketamine using an isotopic dilution strategy in biological matrices and study the formation of norketamine, the principal metabolite of ketamine with and without the presence of midazolam, a well-known CYP3A substrate. The chromatographic separation was achieved using a Thermo Betasil Phenyl 100 x 2 mm column combined with an isocratic mobile phase composed of acetonitrile, methanol, water and formic acid (60:20:20:0.4) at a flow rate of 300 μL/min. The mass spectrometer was operating in selected reaction monitoring mode and the analytical range was set at 0.05–50 μM. The precision (%CV) and accuracy (%NOM) observed were ranging from 3.9–7.8 and 95.9.2–111.1% respectively. The initial rate of formation of norketamine was determined using various ketamine concentration and Km values of 18.4 μM, 13.8 μM and 30.8 μM for rat, dog and human liver S9 fractions were observed respectively. The metabolic stability of ketamine on liver S9 fractions was significantly higher in human (T1/2 = 159.4 min) compared with rat (T1/2 = 12.6 min) and dog (T1/2 = 7.3 min) liver S9 fractions. Moreover significantly lower IC50 and Ki values observed in human compared with rat and dog liver S9 fractions. Experiments with cDNA expressed CYP3A enzymes showed the formation of norketamine is mediated by CYP3A but results suggest an important contribution from others isoenzymes, most likely CYP2C particularly in rat.

Nature, culture et progrès : histoire comparative du concept de transition entre paléolithiques moyen et supérieur en archéologie préhistorique

Doctorat effectué en cotutelle Pour le département d'histoire de l'Université de Montréal, M.M. Jacques G. Ruelland et Othmar Keel, Pour le laboratoire P.A.C.E.A.– U.M.R. 5199. C.N.R.S., de l'École doctorale des sciences Terre-Mer, directeurs successifs, M. P.-Y. Demars, puis M. Michel Lenoir. Thèse soutenue à Bordeaux le 6 juin 2012.

Analytical Investigations 0n Collapse of Cylindrical Submarine Shells

Submarine hull structure is a watertight envelope, under hydrostatic pressure when in operation. Stiffened cylindrical shells constitute the major portion of these submarine hulls and these thin shells under compression are susceptible to buckling failure. Normally loss of stability occurs at the limit point rather than at the bifurcation point and the stability analysis has to consider the change in geometry at each load step. Hence geometric nonlinear analysis of the shell forms becomes. a necessity. External hydrostatic pressure will follow the deformed configuration of the shell and hence follower force effect has to be accounted for. Computer codes have been developed based on all-cubic axisymmetric cylindrical shell finite element and discrete ring stiffener element for linear elastic, linear buckling and geometric nonIinear analysis of stiffened cylindrical shells. These analysis programs have the capability to treat hydrostatic pressure as a radial load and as a follower force. Analytical investigations are carried out on two attack submarine cylindrical hull models besides standard benchmark problems. In each case, the analysis has been carried out for interstiffener, interdeepframe and interbulkhead configurations. The shell stiffener attachment in each of this configuration has been represented by the simply supported-simply supported, clamped-clamped and fixed-fixed boundary conditions in this study. The results of the analytical investigations have been discussed and the observations and conclusions are described. Rotation restraint at the ends is influential for interstiffener and interbulkhead configurations and the significance of axial restraint becomes predominant in the interbulkhead configuration. The follower force effect of hydrostatic pressure is not significant in interstiffener and interdeepframe configurations where as it has very high detrimental effect on buckling pressure on interbulkhead configuration. The geometric nonlinear interbulkhead analysis incorporating follower force effect gives the critical value of buckling pressure and this analysis is recommended for the determination of collapse pressure of stiffened cylindrical submarine shells.

Study of Capital Structure in Major Industrial Concerns in Kerala

To make an analytical description of the considerations for the capital structure decision and to explain the patterns of capital structure prevailing in the state, private and central sector manufacturing concerns in Kerala. To evaluate the capital structure highlighting the effect of financial leverage in an EBIT-EPS tangle. To find out the effect of capital structure on the returns and liquidity and solvency of the firms.

Analytical Studies on Diffusion and lntermittency in Chaotic Maps

The study of simple chaotic maps for non-equilibrium processes in statistical physics has been one of the central themes in the theory of chaotic dynamical systems. Recently, many works have been carried out on deterministic diffusion in spatially extended one-dimensional maps This can be related to real physical systems such as Josephson junctions in the presence of microwave radiation and parametrically driven oscillators. Transport due to chaos is an important problem in Hamiltonian dynamics also. A recent approach is to evaluate the exact diffusion coefficient in terms of the periodic orbits of the system in the form of cycle expansions. But the fact is that the chaotic motion in such spatially extended maps has two complementary aspects- - diffusion and interrnittency. These are related to the time evolution of the probability density function which is approximately Gaussian by central limit theorem. It is noticed that the characteristic function method introduced by Fujisaka and his co-workers is a very powerful tool for analysing both these aspects of chaotic motion. The theory based on characteristic function actually provides a thermodynamic formalism for chaotic systems It can be applied to other types of chaos-induced diffusion also, such as the one arising in statistics of trajectory separation. It was noted that there is a close connection between cycle expansion technique and characteristic function method. It was found that this connection can be exploited to enhance the applicability of the cycle expansion technique. In this way, we found that cycle expansion can be used to analyse the probability density function in chaotic maps. In our research studies we have successfully applied the characteristic function method and cycle expansion technique for analysing some chaotic maps. We introduced in this connection, two classes of chaotic maps with variable shape by generalizing two types of maps well known in literature.