Progrès vers la synthèse totale de l'hodgsonox

Ce mémoire présente une poursuite de l’étude vers la synthèse de l’hodgsonox, un sesquiterpénoïde naturel possédant des propriétés insecticides contre la mouche verte d’Australie, Lucilia cuprina. L’hodgsonox comporte six centres stéréogènes et trois cycles : un époxyde fusionné à un cycle à cinq chaînons et une fonction éther cyclique à six chaînons doublement allylique. La stratégie de synthèse de l’hodgsonox proposée comporte dix-neuf étapes linéaires. Elle s’appuie sur les travaux préliminaires de Lise Bréthous, étudiante au doctorat, de Nicolas Lévaray, étudiant à la maîtrise, ainsi que du Dr. Ying Dong Lu et de la Dr. Sonia Diab, qui ont tous travaillé précédemment dans le groupe de la Pr. Lebel. La première étape de cette synthèse consiste en une hydrogénation cinétique dynamique de Noyori permettant d’obtenir un seul diastéréoisomère à partir de l’α-acétylbutyrolactone. Une séquence de six étapes linéaires supplémentaires, comprenant l’ouverture de la lactone ainsi qu’une métathèse d’oléfine, permet d’obtenir le cycle à cinq chaînons avec un rendement global de 37%. L’unité isopropyle est par la suite installée par une addition conjuguée pour former un éther d’énol silylé, qui est directement oxydé en la cétone correspondante avec l’acétate de palladium(II). Une réaction d’hydrosilylation subséquente permet d’obtenir la stéréochimie syn attendue de l’unité isopropyle. Par la suite, la carbonylation d’un intermédiaire triflate permet d’obtenir le squelette de base pour la formation de l’éther cyclique. Enfin, le cycle à six chaînons est formé par insertion O−H intramoléculaire d’un diazo avec un rendement global de 2% sur 17 étapes. Les travaux spécifiques de l’auteure comprennent l’évaluation de conditions catalytiques pour l’oxydation de Saegusa de l’éther d’énol silylé. Les trois dernières étapes ont également été explorées par l’auteure. Il s’agit de l’époxydation de la double liaison endocyclique, de l’insertion dans un lien O−H catalysée par un dimère de rhodium, et de la méthylénation. Enfin, l’exploration d’une voie alternative a été entamée. Cette nouvelle voie consiste à former l’éther cyclique par une substitution nucléophile sur un époxyde. La double liaison exo-cyclique serait installée par une simple réaction de déshydratation.

Compact amplifier integrated microstrip antenna

compact microstrip antenna integrated with an amplifier having an area reduction of 70%, compared to the standard circular microstrip patch antenna, is presented. The antenna also provides an enhanced gain of 10-dB more than its passive counter part. The measured 2:1 VSWR band width is -4% at 790 MHz, which is 2.5 times larger than that of the passive microstrip antenna

Efficiency in Central Public Sector Enterprises in Kerala

For the analysis of productivity, capacity utilisation and profitability the data relating to the manufacturing central public sector enterprises in Kerala have been collected from the published annual reports of the companies, public enterprises surveys of Bureau of Public Enterprises (BPE), Economic Review of State Planning Board (SPB) and statistical review of central government enterprises by Centre for Monitoring Indian Economy (CMIE). Primary data have been collected by conducting personal interview with the high and middle level executives.

Low power optical phase conjugation in dyes embedded in polyvinyl alcohol films

Low power optical phase conjugation in polyvinyl alcohol films embedded with saturable dyes is reported. Phase conjugate reflectivity achieved is higher than that obtained in the case of similar gelatin films.

Offline Handwritten Malayalam Character Recognition Based on Chain Code Histogram

Optical Character Recognition plays an important role in Digital Image Processing and Pattern Recognition. Even though ambient study had been performed on foreign languages like Chinese and Japanese, effort on Indian script is still immature. OCR in Malayalam language is more complex as it is enriched with largest number of characters among all Indian languages. The challenge of recognition of characters is even high in handwritten domain, due to the varying writing style of each individual. In this paper we propose a system for recognition of offline handwritten Malayalam vowels. The proposed method uses Chain code and Image Centroid for the purpose of extracting features and a two layer feed forward network with scaled conjugate gradient for classification

Form-invariant bivariate weighted models

In this paper the class of continuous bivariate distributions that has form-invariant weighted distribution with weight function w(x1, x2) ¼ xa1 1 xa2 2 is identified. It is shown that the class includes some well known bivariate models. Bayesian inference on the parameters of the class is considered and it is shown that there exist natural conjugate priors for the parameters

Design and study of self-assembled functional organic and hybrid systems for biological applications

The focus of self-assembly as a strategy for the synthesis has been confined largely to molecules, because of the importance of manipulating the structure of matter at the molecular scale. We have investigated the influence of temperature and pH, in addition to the concentration of the capping agent used for the formation of the nano-bio conjugates. For example, the formation of the narrower size distribution of the nanoparticles was observed with the increase in the concentration of the protein, which supports the fact that γ-globulin acts both as a controller of nucleation as well as stabiliser. As analyzed through various photophysical, biophysical and microscopic techniques such as TEM, AFM, C-AFM, SEM, DLS, OPM, CD and FTIR, we observed that the initial photoactivation of γ-globulin at pH 12 for 3 h resulted in small protein fibres of ca. Further irradiation for 24 h, led to the formation of selfassembled long fibres of the protein of ca. 5-6 nm and observation of surface plasmon resonance band at around 520 nm with the concomitant quenching of luminescence intensity at 680 nm. The observation of light triggered self-assembly of the protein and its effect on controlling the fate of the anchored nanoparticles can be compared with the naturally occurring process such as photomorphogenesis.Furthermore,our approach offers a way to understand the role played by the self-assembly of the protein in ordering and knock out of the metal nanoparticles and also in the design of nano-biohybrid materials for medicinal and optoelectronic applications. Investigation of the potential applications of NIR absorbing and water soluble squaraine dyes 1-3 for protein labeling and anti-amyloid agents forms the subject matter of the third chapter of the thesis. The study of their interactions with various proteins revealed that 1-3 showed unique interactions towards serum albumins as well as lysozyme. 69%, 71% and 49% in the absorption spectra as well as significant quenching in the fluorescence intensity of the dyes 1-3, respectively. Half-reciprocal analysis of the absorption data and isothermal titration calorimetric (ITC) analysis of the titration experiments gave a 1:1 stoichiometry for the complexes formed between the lysozyme and squaraine dyes with association constants (Kass) in the range 104-105 M-1. We have determined the changes in the free energy (ΔG) for the complex formation and the values are found to be -30.78, -32.31 and -28.58 kJmol-1, respectively for the dyes 1, 2 and 3. Furthermore, we have observed a strong induced CD (ICD) signal corresponding to the squaraine chromophore in the case of the halogenated squaraine dyes 2 and 3 at 636 and 637 nm confirming the complex formation in these cases. To understand the nature of interaction of the squaraine dyes 1-3 with lysozyme, we have investigated the interaction of dyes 1-3 with different amino acids. These results indicated that the dyes 1-3 showed significant interactions with cysteine and glutamic acid which are present in the side chains of lysozyme. In addition the temperature dependent studies have revealed that the interaction of the dye and the lysozyme are irreversible. Furthermore, we have investigated the interactions of these NIR dyes 1-3 with β- amyloid fibres derived from lysozyme to evaluate their potential as inhibitors of this biologically important protein aggregation. These β-amyloid fibrils were insoluble protein aggregates that have been associated with a range of neurodegenerative diseases, including Huntington, Alzheimer’s, Parkinson’s, and Creutzfeldt-Jakob diseases. We have synthesized amyloid fibres from lysozyme through its incubation in acidic solution below pH 4 and by allowing to form amyloid fibres at elevated temperature. To quantify the binding affinities of the squaraine dyes 1-3 with β-amyloids, we have carried out the isothermal titration calorimetric (ITC) measurements. The association constants were determined and are found to be 1.2 × 105, 3.6× 105 and 3.2 × 105 M-1 for the dyes, 1-3, respectively. To gain more insights into the amyloid inhibiting nature of the squaraine dyes under investigations, we have carried out thioflavin assay, CD, isothermal titration calorimetry and microscopic analysis. The addition of the dyes 1-3 (5μM) led to the complete quenching in the apparent thioflavin fluorescence, thereby indicating the destabilization of β-amyloid fibres in the presence of the squaraine dyes. Further, the inhibition of the amyloid fibres by the squaraine dyes 1-3, has been evidenced though the DLS, TEM AFM and SAED, wherein we observed the complete destabilization of the amyloid fibre and transformation of the fibre into spherical particles of ca. These results demonstrate the fact that the squaraine dyes 1-3 can act as protein labeling agents as well as the inhibitors of the protein amyloidogenesis. The last chapter of the thesis describes the synthesis and investigation of selfassembly as well as bio-imaging aspects of a few novel tetraphenylethene conjugates 4-6.Expectedly, these conjugates showed significant solvatochromism and exhibited a hypsochromic shift (negative solvatochromism) as the solvent polarity increased, and these observations were justified though theoretical studies employing the B3LYP/6-31g method. We have investigated the self-assembly properties of these D-A conjugates though variation in the percentage of water in acetonitrile solution due to the formation of nanoaggregates. Further the contour map of the observed fluorescence intensity as a function of the fluorescence excitation and emission wavelength confirmed the formation of J-type aggregates in these cases. To have a better understanding of the type of self-assemblies formed from the TPE conjugates 4-6, we have carried out the morphological analysis through various microscopic techniques such as DLS, SEM and TEM. 70%, we observed rod shape architectures having ~ 780 nm in diameter and ~ 12 μM in length as evidenced through TEM and SEM analysis. We have made similar observations with the dodecyl conjugate 5 at ca. 70% and 50% water/acetonitrile mixtures, the aggregates formed from 4 and 5 were found to be highly crystalline and such structures were transformed to amorphous nature as the water fraction was increased to 99%. To evaluate the potential of the conjugate as bio-imaging agents, we have carried out their in vitro cytotoxicity and cellular uptake studies though MTT assay, flow cytometric and confocal laser scanning microscopic techniques. Thus nanoparticle of these conjugates which exhibited efficient emission, large stoke shift, good stability, biocompatibility and excellent cellular imaging properties can have potential applications for tracking cells as well as in cell-based therapies. In summary we have synthesized novel functional organic chromophores and have studied systematic investigation of self-assembly of these synthetic and biological building blocks under a variety of conditions. The investigation of interaction of water soluble NIR squaraine dyes with lysozyme indicates that these dyes can act as the protein labeling agents and the efficiency of inhibition of β-amyloid indicate, thereby their potential as anti-amyloid agents.

Entwurf und Betrieb von Regelungs- und Monitoringsystemen für dezentrale Energiesysteme auf der Basis von verteilten Embedded Systems

Nach einem einleitenden ersten Kapitel wird im zweiten Kapitel der Stand der Technik für Regelungs- und Monitoringsysteme mit vernetzten Systemen dargestellt. Daraus wird die Motivation zur Entwicklung neuer, kostengünstiger Systeme abgeleitet. Im dritten Kapitel folgt eine Darstellung der verschiedenen Arten marktverfügbarer Embedded Systems und dafür geeigneter Betriebs­systeme. Anforderungen an verteilte Regelungssysteme, unterschiedliche Strukturen dieser Systeme und deren Vor- und Nachteile sind Gegenstand des vierten Kapitels. Anhand von Beispielen aus den Bereichen Erzeugungsmanagement für den Betrieb von KWK-Anlagen, Energieverbrauchsmonitoring und Smart-Metering wird der Einsatz von verteilten Regelungs- und Monitoringsystemen im fünften Kapitel dargestellt. Im folgenden sechsten Kapitel wird die Bedeutung normierter Kommunikation für den Einsatz in verteilten Systemen sowie dafür vorhandene Standards aus der elektrischen Energieversorgungstechnik und der Automatisierungstechnik behandelt. Der Stand der Internet-Technik für verteilte Systeme ist Gegenstand des siebten Kapitels. Dabei werden zunächst die verschiedenen drahtlosen und drahtgebundenen Kommunikationsmedien vorgestellt und ihre Eigenschaften und die Rand­bedingungen für ihren Einsatz erörtert. Ebenso werden technische Probleme beim Einsatz der Internet-Technik aufgezeigt und Lösungsmöglichkeiten für diese Probleme dargestellt. Es folgt eine Übersicht von Netzwerkdiensten, die für den Betrieb von verteilten Systemen notwendig sind. Außerdem werden Techniken zur Überwachung von verteilten Systemen behandelt. Kapitel acht zeigt Sicherheitsrisiken bei der Nutzung des Internets auf und bewertet verschiedene Techniken zur Absicherung des Netzwerkverkehrs. Kapitel neun stellt ein Internet-basiertes Client-Server-System zur Online-Visualisierung von Anlagendaten im Webbrowser mit Hilfe von Java-Applets und XML-RPC vor. Die Visualisierung von Anlagendaten auf Mobiltelefonen mit Hilfe des Wireless Application Protocol sowie die dafür notwendige Software und Infrastruktur ist Gegenstand des zehnten Kapitels. Im elften Kapitel wird eine neuartige Software für die Simulation von dezentralen Energiesystemen und deren Regelungs­systemen auf Basis von virtuellen Maschinen, virtuellen Netzwerken und einer thermischen Simulationsumgebung vorgestellt sowie deren Anwendung für die Reglerentwicklung erklärt. Verschiedene Techniken für die Installation von Betriebssystemen und Software für die Embedded Systems eines verteilten Systems werden im Kapitel zwölf untersucht. Im Kapitel 13 werden verschiedene Technologien zur Konfiguration und Parametrierung von Regelungssystemen in der industriellen Prozess- und Fertigungs­automatisierung hinsichtlich ihrer Eignung für dezentrale Energiesysteme analysiert. Anschließend wird eine Software zur Installation und Parametrierung von Monitoringsystemen sowie der dazugehörigen Infrastruktur vorgestellt. Kapitel 14 beschäftigt sich mit Anforderungen an die Hardware für verteilte Systeme und mit Maßnahmen zur Erhöhung der Betriebs- und der Datensicherheit. Im 15. Kapitel werden die in den bisherigen Kapiteln vorgestellten Techniken anhand eines großen verteilten Monitoringsystems und anhand eines Power Flow and Power Quality Management Systems auf Basis von verteilten Embedded Systems evaluiert. Kapitel 16 fasst die Ergebnisse der Arbeit zusammen und enthält einen Ausblick auf zukünftige Entwicklungen.

Targeted Stimuli-Responsive Dextran Conjugates for Doxorubicin Delivery to Hepatocytes

A targeted, stimuli-responsive, polymeric drug delivery vehicle is being developed in our lab to help alleviate severe side-effects caused by narrow therapeutic window drugs. Targeting specific cell types or organs via proteins, specifically, lectin-mediated targeting holds potential due to the high specificity and affinity of receptor-ligand interactions, rapid internalization, and relative ease of processing. Dextran, a commercially available, biodegradable polymer has been conjugated to doxorubicin and galactosamine to target hepatocytes in a three-step, one-pot synthesis. The loading of doxorubicin and galactose on the conjugates was determined by absorbance at 485 nm and elemental analysis, respectively. Conjugation efficiency based on the amount loaded of each reactant varies from 20% to 50% for doxorubicin and from 2% to 20% for galactosamine. Doxorubicin has also been attached to dextran through an acid-labile hydrazide bond. Doxorubicin acts by intercalating with DNA in the nuclei of cells. The fluorescence of doxorubicin is quenched when it binds to DNA. This allows a fluorescence-based cell-free assay to evaluate the efficacy of the polymer conjugates where we measure the fluorescence of doxorubicin and the conjugates in increasing concentrations of calf thymus DNA. Fluorescence quenching indicates that our conjugates can bind to DNA. The degree of binding increases with polymer molecular weight and substitution of doxorubicin. In cell culture experiments with hepatocytes, the relative uptake of polymer conjugates was evaluated using flow cytometry, and the killing efficiency was determined using the MTT cell proliferation assay. We have found that conjugate uptake is much lower than that of free doxorubicin. Lower uptake of conjugates may increase the maximum dose of drug tolerated by the body. Also, non-galactosylated conjugate uptake is lower than that of the galactosylated conjugate. Microscopy indicates that doxorubicin localizes almost exclusively at the nucleus, whereas the conjugates are present throughout the cell. Doxorubicin linked to dextran through a hydrazide bond was used to achieve improved killing efficiency. Following uptake, the doxorubicin dissociates from the polymer in an endosomal compartment and diffuses to the nucleus. The LC₅₀ of covalently linked doxorubicin is 7.4 μg/mL, whereas that of hydrazide linked doxorubicin is 4.4 μg/mL.

Paroxysmal upgaze deviation: case report

The paroxysmal upgaze deviation is a syndrome that described in infants for first time in 1988; there are just about 50 case reports worldwide ever since. Its etiology is unclear and though it prognosis is variable; most case reports indicate that during growth the episodes tend to decrease in frequency and duration until they disappear. It describes a 16-months old male child who since 11-months old presented many episodes of variable conjugate upward deviation of the eyes, compensatory neck flexion and down-beat saccades in attempted downgaze. These events are predominantly diurnal, and are exacerbated by stressful situations such as fasting or insomnia, however and improve with sleep. They have normal neurologic and ophthalmologic examination, and neuroimaging and EEG findings are not relevant.

Análisis estructural de sectores estratégicos

    This document is a reflextion on a proposal that is called: “Structural analysis of strategic sectors”, the analysis that will be explained on manages to conjugate a series of data originating from different sectorial fronts, for to be utilized to discretion by the analysts, and its result should be understood as a perception, but not like a diagnosis. The analysis is comprised of sev eral test whose study should be done carefully, trying to integrate the individual results of each one of the components to translate them in a result that I call: Perception on the environment of the organization. The tests that are proposed are the following: Analysis of the forces of the market, Lifting of the competitive panorama, Analysis of supposed and capacities of the competence, Analysis of profit value, employment, certifications and foreign trade. 

Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

La butirilcolinesterasa humana (BChE; EC 3.1.1.8) es una enzima polimórfica sintetizada en el hígado y en el tejido adiposo, ampliamente distribuida en el organismo y encargada de hidrolizar algunos ésteres de colina como la procaína, ésteres alifáticos como el ácido acetilsalicílico, fármacos como la metilprednisolona, el mivacurium y la succinilcolina y drogas de uso y/o abuso como la heroína y la cocaína. Es codificada por el gen BCHE (OMIM 177400), habiéndose identificado más de 100 variantes, algunas no estudiadas plenamente, además de la forma más frecuente, llamada usual o silvestre. Diferentes polimorfismos del gen BCHE se han relacionado con la síntesis de enzimas con niveles variados de actividad catalítica. Las bases moleculares de algunas de esas variantes genéticas han sido reportadas, entre las que se encuentra las variantes Atípica (A), fluoruro-resistente del tipo 1 y 2 (F-1 y F-2), silente (S), Kalow (K), James (J) y Hammersmith (H). En este estudio, en un grupo de pacientes se aplicó el instrumento validado Lifetime Severity Index for Cocaine Use Disorder (LSI-C) para evaluar la gravedad del consumo de “cocaína” a lo largo de la vida. Además, se determinaron Polimorfismos de Nucleótido Simple (SNPs) en el gen BCHE conocidos como responsables de reacciones adversas en pacientes consumidores de “cocaína” mediante secuenciación del gen y se predijo el efecto delos SNPs sobre la función y la estructura de la proteína, mediante el uso de herramientas bio-informáticas. El instrumento LSI-C ofreció resultados en cuatro dimensiones: consumo a lo largo de la vida, consumo reciente, dependencia psicológica e intento de abandono del consumo. Los estudios de análisis molecular permitieron observar dos SNPs codificantes (cSNPs) no sinónimos en el 27.3% de la muestra, c.293A>G (p.Asp98Gly) y c.1699G>A (p.Ala567Thr), localizados en los exones 2 y 4, que corresponden, desde el punto de vista funcional, a la variante Atípica (A) [dbSNP: rs1799807] y a la variante Kalow (K) [dbSNP: rs1803274] de la enzima BChE, respectivamente. Los estudios de predicción In silico establecieron para el SNP p.Asp98Gly un carácter patogénico, mientras que para el SNP p.Ala567Thr, mostraron un comportamiento neutro. El análisis de los resultados permite proponer la existencia de una relación entre polimorfismos o variantes genéticas responsables de una baja actividad catalítica y/o baja concentración plasmática de la enzima BChE y algunas de las reacciones adversas ocurridas en pacientes consumidores de cocaína.

Estudio de factibilidad para la exportación de pitahaya amarilla al mercado de Japón, como uno de los países líderes de la cuenca del Pacífico

A través de la elaboración de un análisis de mercado, de la situación actual del producto a exportar a nivel mundial y del sector agrícola tanto Colombiano como Japonés, y tomando como referente las diversas teorías de comercio internacional, se logra establecer un plan de negocio viable, en donde se define la forma correcta y factible de llevar a cabo el proceso de exportación, y de esta manera lograr el posicionamiento de un fruto exótico colombiano en el exterior. A partir del análisis realizado al sector agrícola Colombiano y Japonés, y teniendo en cuenta la situación actual de la pitahaya amarilla a nivel mundial, se logró identificar el comportamiento de la oferta y la demanda de este fruto, y la frecuencia con la que se realizan las exportaciones, con el fin de establecer las necesidades del mercado de Japón y aprovechar la ventaja comparativa que Colombia tiene frente a este país para poder suplir el mercado. Ante la indiscutible escasez de frutos exóticos como lo es la pitahaya amarilla en un país como Japón, dadas las condiciones geográficas con las que cuenta, y al ser este uno de los productos más apetecidos en esta sociedad, fue el motivo por el cual este país se escogió como destino para realizar el proceso de exportación. Adicional a esto, la ubicación geográfica de ambos países, y sus regulaciones y normas internacionales, hacen posible y viable la ejecución del presente estudio.

Análisis económico de las vacunas 10-valente y 13-valente contra neumococo: revisión sistemática

Introducción: Las vacunas clásicamente han representado un método económico y eficaz para el control y prevención de múltiples enfermedades infecciosas. En los últimos años se han introducido nuevas vacunas contra neumococo a precios elevados, y los diferentes análisis económicos a nivel mundial de estas vacunas no muestran tendencias. El objetivo de este trabajo era resumir la evidencia existente a través de los diferentes estudios económicos evaluando las dos vacunas de segunda generación contra neumococo en la población a riesgo. Metodología: En este trabajo se realizo una revisión sistemática de la literatura en 8 bases de datos localizadas en diferentes partes del mundo y también que tuvieran literatura gris. Los artículos fueron inicialmente evaluados acorde a su titulo y resumen, posteriormente los elegidos se analizaron en su totalidad. Resultados: Se encontraron 404 artículos, de los cuales 20 fueron incluidos en el análisis final. Se encontró que la mayoría de los estudios se realizaron en áreas donde la enfermedad tiene una carga baja, como es Norte América y Europa, mientras que en los lugares del mundo donde la carga es mas alta, se realizaron pocos estudios. De igual manera se observo que la mayoría de los estudios mostraron por los menos ser costo efectivos respecto a la no vacunación, y en su totalidad las dos vacunas de segunda generación mostraron costo efectividad respecto a la vacunación con PCV-7. Los resultados de los estudios son muy heterogéneos, hasta dentro del mismo país, señalando la necesidad de guías para la conducción de este tipo de estudios. De igual manera, la mayoría de los estudios fueron financiados por farmacéuticas, mientras en un numero muy reducido por entes gubernamentales. Conclusiones: La mayoría de los estudios económicos sobre las vacunas de segunda generación contra neumococo han sido realizados en países con un alto índice de desarrollo económico y patrocinados por farmacéuticas. Dado que la mayoría de la carga de la enfermedad se encuentran en regiones con un menor nivel de desarrollo económico se deberían realizar mas en estas zonas. De igual manera, al ser la vacunación un asunto de salud publica y con un importante impacto económico los gobiernos deberían estar mas involucrados en los mismos.

Usos del weblog en la universidad para la gestión de conocimientos y trabajo en red.

Resumen basado en el de la publicación