Design, development and construction of an outdoor testing facility for semi-transparent photovoltaic modules

Building-integrated Photovoltaics (BIPV) is one of the most promising technologies enabling buildings to generate on-site part of their electricity needs while performing architectural functionalities. A clear example of BIPV products consists of semi-transparent photovoltaic modules (STPV), designed to replace the conventional glazing solutions in building façades. Accordingly, the active building envelope is required to perform multiple requirements such as provide solar shading to avoid overheating, supply solar gains and thermal insulation to reduce heat loads and improve daylight utilization. To date, various studies into STPV systems have focused on their energy performance based on existing simulation programs, or on the modelling, normally validated by limited experimental data, of the STPV modules thermal behaviour. Taking into account that very limited experimental research has been conducted on the energy performance of STPV elements and that the characterization in real operation conditions is necessary to promote an energetically efficient integration of this technology in the building envelope, an outdoor testing facility has been designed, developed and built at the Solar Energy Institute of the Technical University of Madrid. In this work, the methodology used in the definition of the testing facility, its capability and limitations are presented and discussed.

High power beam dump project for the accelerator prototype LIPAc: Cooling design and analysis

En el campo de la fusión nuclear y desarrollándose en paralelo a ITER (International Thermonuclear Experimental Reactor), el proyecto IFMIF (International Fusion Material Irradiation Facility) se enmarca dentro de las actividades complementarias encaminadas a solucionar las barreras tecnológicas que aún plantea la fusión. En concreto IFMIF es una instalación de irradiación cuya misión es caracterizar materiales resistentes a condiciones extremas como las esperadas en los futuros reactores de fusión como DEMO (DEMOnstration power plant). Consiste de dos aceleradores de deuterones que proporcionan un haz de 125 mA y 40 MeV cada uno, que al colisionar con un blanco de litio producen un flujo neutrónico intenso (1017 neutrones/s) con un espectro similar al de los neutrones de fusión [1], [2]. Dicho flujo neutrónico es empleado para irradiar los diferentes materiales candidatos a ser empleados en reactores de fusión, y las muestras son posteriormente examinadas en la llamada instalación de post-irradiación. Como primer paso en tan ambicioso proyecto, una fase de validación y diseño llamada IFMIFEVEDA (Engineering Validation and Engineering Design Activities) se encuentra actualmente en desarrollo. Una de las actividades contempladas en esta fase es la construcción y operación de una acelarador prototipo llamado LIPAc (Linear IFMIF Prototype Accelerator). Se trata de un acelerador de deuterones de alta intensidad idéntico a la parte de baja energía de los aceleradores de IFMIF. Los componentes del LIPAc, que será instalado en Japón, son suministrados por diferentes países europeos. El acelerador proporcionará un haz continuo de deuterones de 9 MeV con una potencia de 1.125 MW que tras ser caracterizado con diversos instrumentos deberá pararse de forma segura. Para ello se requiere un sistema denominado bloque de parada (Beam Dump en inglés) que absorba la energía del haz y la transfiera a un sumidero de calor. España tiene el compromiso de suministrar este componente y CIEMAT (Centro de Investigaciones Energéticas Medioambientales y Tecnológicas) es responsable de dicha tarea. La pieza central del bloque de parada, donde se para el haz de iones, es un cono de cobre con un ángulo de 3.5o, 2.5 m de longitud y 5 mm de espesor. Dicha pieza está refrigerada por agua que fluye en su superficie externa por el canal que se forma entre el cono de cobre y otra pieza concéntrica con éste. Este es el marco en que se desarrolla la presente tesis, cuyo objeto es el diseño del sistema de refrigeración del bloque de parada del LIPAc. El diseño se ha realizado utilizando un modelo simplificado unidimensional. Se han obtenido los parámetros del agua (presión, caudal, pérdida de carga) y la geometría requerida en el canal de refrigeración (anchura, rugosidad) para garantizar la correcta refrigeración del bloque de parada. Se ha comprobado que el diseño permite variaciones del haz respecto a la situación nominal siendo el flujo crítico calorífico al menos 2 veces superior al nominal. Se han realizado asimismo simulaciones fluidodinámicas 3D con ANSYS-CFX en aquellas zonas del canal de refrigeración que lo requieren. El bloque de parada se activará como consecuencia de la interacción del haz de partículas lo que impide cualquier cambio o reparación una vez comenzada la operación del acelerador. Por ello el diseño ha de ser muy robusto y todas las hipótesis utilizadas en la realización de éste deben ser cuidadosamente comprobadas. Gran parte del esfuerzo de la tesis se centra en la estimación del coeficiente de transferencia de calor que es determinante en los resultados obtenidos, y que se emplea además como condición de contorno en los cálculos mecánicos. Para ello por un lado se han buscado correlaciones cuyo rango de aplicabilidad sea adecuado para las condiciones del bloque de parada (canal anular, diferencias de temperatura agua-pared de decenas de grados). En un segundo paso se han comparado los coeficientes de película obtenidos a partir de la correlación seleccionada (Petukhov-Gnielinski) con los que se deducen de simulaciones fluidodinámicas, obteniendo resultados satisfactorios. Por último se ha realizado una validación experimental utilizando un prototipo y un circuito hidráulico que proporciona un flujo de agua con los parámetros requeridos en el bloque de parada. Tras varios intentos y mejoras en el experimento se han obtenido los coeficientes de película para distintos caudales y potencias de calentamiento. Teniendo en cuenta la incertidumbre de las medidas, los valores experimentales concuerdan razonablemente bien (en el rango de 15%) con los deducidos de las correlaciones. Por motivos radiológicos es necesario controlar la calidad del agua de refrigeración y minimizar la corrosión del cobre. Tras un estudio bibliográfico se identificaron los parámetros del agua más adecuados (conductividad, pH y concentración de oxígeno disuelto). Como parte de la tesis se ha realizado asimismo un estudio de la corrosión del circuito de refrigeración del bloque de parada con el doble fin de determinar si puede poner en riesgo la integridad del componente, y de obtener una estimación de la velocidad de corrosión para dimensionar el sistema de purificación del agua. Se ha utilizado el código TRACT (TRansport and ACTivation code) adaptándalo al caso del bloque de parada, para lo cual se trabajó con el responsable (Panos Karditsas) del código en Culham (UKAEA). Los resultados confirman que la corrosión del cobre en las condiciones seleccionadas no supone un problema. La Tesis se encuentra estructurada de la siguiente manera: En el primer capítulo se realiza una introducción de los proyectos IFMIF y LIPAc dentro de los cuales se enmarca esta Tesis. Además se describe el bloque de parada, siendo el diseño del sistema de rerigeración de éste el principal objetivo de la Tesis. En el segundo y tercer capítulo se realiza un resumen de la base teórica así como de las diferentes herramientas empleadas en el diseño del sistema de refrigeración. El capítulo cuarto presenta los resultados del relativos al sistema de refrigeración. Tanto los obtenidos del estudio unidimensional, como los obtenidos de las simulaciones fluidodinámicas 3D mediante el empleo del código ANSYS-CFX. En el quinto capítulo se presentan los resultados referentes al análisis de corrosión del circuito de refrigeración del bloque de parada. El capítulo seis se centra en la descripción del montaje experimental para la obtención de los valores de pérdida de carga y coeficiente de transferencia del calor. Asimismo se presentan los resultados obtenidos en dichos experimentos. Finalmente encontramos un capítulo de apéndices en el que se describen una serie de experimentos llevados a cabo como pasos intermedios en la obtención del resultado experimental del coeficiente de película. También se presenta el código informático empleado para el análisis unidimensional del sistema de refrigeración del bloque de parada llamado CHICA (Cooling and Heating Interaction and Corrosion Analysis). ABSTRACT In the nuclear fusion field running in parallel to ITER (International Thermonuclear Experimental Reactor) as one of the complementary activities headed towards solving the technological barriers, IFMIF (International Fusion Material Irradiation Facility) project aims to provide an irradiation facility to qualify advanced materials resistant to extreme conditions like the ones expected in future fusion reactors like DEMO (DEMOnstration Power Plant). IFMIF consists of two constant wave deuteron accelerators delivering a 125 mA and 40 MeV beam each that will collide on a lithium target producing an intense neutron fluence (1017 neutrons/s) with a similar spectra to that of fusion neutrons [1], [2]. This neutron flux is employed to irradiate the different material candidates to be employed in the future fusion reactors, and the samples examined after irradiation at the so called post-irradiative facilities. As a first step in such an ambitious project, an engineering validation and engineering design activity phase called IFMIF-EVEDA (Engineering Validation and Engineering Design Activities) is presently going on. One of the activities consists on the construction and operation of an accelerator prototype named LIPAc (Linear IFMIF Prototype Accelerator). It is a high intensity deuteron accelerator identical to the low energy part of the IFMIF accelerators. The LIPAc components, which will be installed in Japan, are delivered by different european countries. The accelerator supplies a 9 MeV constant wave beam of deuterons with a power of 1.125 MW, which after being characterized by different instruments has to be stopped safely. For such task a beam dump to absorb the beam energy and take it to a heat sink is needed. Spain has the compromise of delivering such device and CIEMAT (Centro de Investigaciones Energéticas Medioambientales y Tecnológicas) is responsible for such task. The central piece of the beam dump, where the ion beam is stopped, is a copper cone with an angle of 3.5o, 2.5 m long and 5 mm width. This part is cooled by water flowing on its external surface through the channel formed between the copper cone and a concentric piece with the latter. The thesis is developed in this realm, and its objective is designing the LIPAc beam dump cooling system. The design has been performed employing a simplified one dimensional model. The water parameters (pressure, flow, pressure loss) and the required annular channel geometry (width, rugoisty) have been obtained guaranteeing the correct cooling of the beam dump. It has been checked that the cooling design allows variations of the the beam with respect to the nominal position, being the CHF (Critical Heat Flux) at least twice times higher than the nominal deposited heat flux. 3D fluid dynamic simulations employing ANSYS-CFX code in the beam dump cooling channel sections which require a more thorough study have also been performed. The beam dump will activateasaconsequenceofthe deuteron beam interaction, making impossible any change or maintenance task once the accelerator operation has started. Hence the design has to be very robust and all the hypotheses employed in the design mustbecarefully checked. Most of the work in the thesis is concentrated in estimating the heat transfer coefficient which is decisive in the obtained results, and is also employed as boundary condition in the mechanical analysis. For such task, correlations which applicability range is the adequate for the beam dump conditions (annular channel, water-surface temperature differences of tens of degrees) have been compiled. In a second step the heat transfer coefficients obtained from the selected correlation (Petukhov- Gnielinski) have been compared with the ones deduced from the 3D fluid dynamic simulations, obtaining satisfactory results. Finally an experimental validation has been performed employing a prototype and a hydraulic circuit that supplies a flow with the requested parameters in the beam dump. After several tries and improvements in the experiment, the heat transfer coefficients for different flows and heating powers have been obtained. Considering the uncertainty in the measurements the experimental values agree reasonably well (in the order of 15%) with the ones obtained from the correlations. Due to radiological reasons the quality of the cooling water must be controlled, hence minimizing the copper corrosion. After performing a bibligraphic study the most adequate water parameters were identified (conductivity, pH and dissolved oxygen concentration). As part of this thesis a corrosion study of the beam dump cooling circuit has been performed with the double aim of determining if corrosion can pose a risk for the copper beam dump , and obtaining an estimation of the corrosion velocitytodimension the water purification system. TRACT code(TRansport and ACTivation) has been employed for such study adapting the code for the beam dump case. For such study a collaboration with the code responsible (Panos Karditsas) at Culham (UKAEA) was established. The work developed in this thesis has supposed the publication of three articles in JCR journals (”Journal of Nuclear Materials” y ”Fusion Engineering and Design”), as well as presentations in more than four conferences and relevant meetings.

Design and characterization of α-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination

α-Melanocyte stimulating hormone (α-MSH) analogs, cyclized through site-specific rhenium (Re) and technetium (Tc) metal coordination, were structurally characterized and analyzed for their abilities to bind α-MSH receptors present on melanoma cells and in tumor-bearing mice. Results from receptor-binding assays conducted with B16 F1 murine melanoma cells indicated that receptor-binding affinity was reduced to approximately 1% of its original levels after Re incorporation into the cyclic Cys4,10, d-Phe7–α-MSH4-13 analog. Structural analysis of the Re–peptide complex showed that the disulfide bond of the original peptide was replaced by thiolate–metal–thiolate cyclization. A comparison of the metal-bound and metal-free structures indicated that metal complexation dramatically altered the structure of the receptor-binding core sequence. Redesign of the metal binding site resulted in a second-generation Re–peptide complex (ReCCMSH) that displayed a receptor-binding affinity of 2.9 nM, 25-fold higher than the initial Re–α-MSH analog. Characterization of the second-generation Re–peptide complex indicated that the peptide was still cyclized through Re coordination, but the structure of the receptor-binding sequence was no longer constrained. The corresponding 99mTc- and 188ReCCMSH complexes were synthesized and shown to be stable in phosphate-buffered saline and to challenges from diethylenetriaminepentaacetic acid (DTPA) and free cysteine. In vivo, the 99mTcCCMSH complex exhibited significant tumor uptake and retention and was effective in imaging melanoma in a murine-tumor model system. Cyclization of α-MSH analogs via 99mTc and 188Re yields chemically stable and biologically active molecules with potential melanoma-imaging and therapeutic properties.

Oxide Semiconductors For Organic Opto-electronic Devices

Development of transparent oxide semiconductors (TOS) from Earth-abundant materials is of great interest for cost-effective thin film device applications, such as solar cells, light emitting diodes (LEDs), touch-sensitive displays, electronic paper, and transparent thin film transistors. The need of inexpensive or high performance electrode might be even greater for organic photovoltaic (OPV), with the goal to harvest renewable energy with inexpensive, lightweight, and cost competitive materials. The natural abundance of zinc and the wide bandgap ($sim$3.3 eV) of its oxide make it an ideal candidate. In this dissertation, I have introduced various concepts on the modulations of various surface, interface and bulk opto-electronic properties of ZnO based semiconductor for charge transport, charge selectivity and optimal device performance. I have categorized transparent semiconductors into two sub groups depending upon their role in a device. Electrodes, usually 200 to 500 nm thick, optimized for good transparency and transporting the charges to the external circuit. Here, the electrical conductivity in parallel direction to thin film, i.e bulk conductivity is important. And contacts, usually 5 to 50 nm thick, are optimized in case of solar cells for providing charge selectivity and asymmetry to manipulate the built in field inside the device for charge separation and collection. Whereas in Organic LEDs (OLEDs), contacts provide optimum energy level alignment at organic oxide interface for improved charge injections. For an optimal solar cell performance, transparent electrodes are designed with maximum transparency in the region of interest to maximize the light to pass through to the absorber layer for photo-generation, plus they are designed for minimum sheet resistance for efficient charge collection and transport. As such there is need for material with high conductivity and transparency. Doping ZnO with some common elements such as B, Al, Ga, In, Ge, Si, and F result in n-type doping with increase in carriers resulting in high conductivity electrode, with better or comparable opto-electronic properties compared to current industry-standard indium tin oxide (ITO). Furthermore, improvement in mobility due to improvement on crystallographic structure also provide alternative path for high conductivity ZnO TCOs. Implementing these two aspects, various studies were done on gallium doped zinc oxide (GZO) transparent electrode, a very promising indium free electrode. The dynamics of the superimposed RF and DC power sputtering was utilized to improve the microstructure during the thin films growth, resulting in GZO electrode with conductivity greater than 4000 S/cm and transparency greater than 90 %. Similarly, various studies on research and development of Indium Zinc Tin Oxide and Indium Zinc Oxide thin films which can be applied to flexible substrates for next generation solar cells application is presented. In these new TCO systems, understanding the role of crystallographic structure ranging from poly-crystalline to amorphous phase and the influence on the charge transport and optical transparency as well as important surface passivation and surface charge transport properties. Implementation of these electrode based on ZnO on opto-electronics devices such as OLED and OPV is complicated due to chemical interaction over time with the organic layer or with ambient. The problem of inefficient charge collection/injection due to poor understanding of interface and/or bulk property of oxide electrode exists at several oxide-organic interfaces. The surface conductivity, the work function, the formation of dipoles and the band-bending at the interfacial sites can positively or negatively impact the device performance. Detailed characterization of the surface composition both before and after various chemicals treatment of various oxide electrode can therefore provide insight into optimization of device performance. Some of the work related to controlling the interfacial chemistry associated with charge transport of transparent electrodes are discussed. Thus, the role of various pre-treatment on poly-crystalline GZO electrode and amorphous indium zinc oxide (IZO) electrode is compared and contrasted. From the study, we have found that removal of defects and self passivating defects caused by accumulation of hydroxides in the surface of both poly-crystalline GZO and amorphous IZO, are critical for improving the surface conductivity and charge transport. Further insight on how these insulating and self-passivating defects cause charge accumulation and recombination in an device is discussed. With recent rapid development of bulk-heterojunction organic photovoltaics active materials, devices employing ZnO and ZnO based electrode provide air stable and cost-competitive alternatives to traditional inorganic photovoltaics. The organic light emitting diodes (OLEDs) have already been commercialized, thus to follow in the footsteps of this technology, OPV devices need further improvement in power conversion efficiency and stable materials resulting in long device lifetimes. Use of low work function metals such as Ca/Al in standard geometry do provide good electrode for electron collection, but serious problems using low work-function metal electrodes originates from the formation of non-conductive metal oxide due to oxidation resulting in rapid device failure. Hence, using low work-function, air stable, conductive metal oxides such as ZnO as electrons collecting electrode and high work-function, air stable metals such as silver for harvesting holes, has been on the rise. Devices with degenerately doped ZnO functioning as transparent conductive electrode, or as charge selective layer in a polymer/fullerene based heterojunction, present useful device structures for investigating the functional mechanisms within OPV devices and a possible pathway towards improved air-stable high efficiency devices. Furthermore, analysis of the physical properties of the ZnO layers with varying thickness, crystallographic structure, surface chemistry and grain size deposited via various techniques such as atomic layer deposition, sputtering and solution-processed ZnO with their respective OPV device performance is discussed. We find similarity and differences in electrode property for good charge injection in OLEDs and good charge collection in OPV devices very insightful in understanding physics behind device failures and successes. In general, self-passivating surface of amorphous TCOs IZO, ZTO and IZTO forms insulating layer that hinders the charge collection. Similarly, we find modulation of the carrier concentration and the mobility in electron transport layer, namely zinc oxide thin films, very important for optimizing device performance.

Controversy between curriculum design and curriculum development of online "highly specialized" education in the field of construction

Nowadays, on a global level, the Higher Education System has a complex and broad horizon of curricular tools to use in the teaching and learning process. In addition to these new educational instruments, full of possibilities, we face specific socio-economic conditions that affect in a significantly way the Curriculum Development in certain knowledge areas (areas traditionally built on a methodology based on a physical presence of students in the classroom). Some areas such as Restoration, Rehabilitation or Construction Pathologies, and the construction sector in general, require very defined and particular knowledge that only a small number of experts claim as specialized training. All these aspects condition the teaching methodology performed in a physical classroom at a university campus (the only option used until recent years) and made us consider the integration of online teaching in these areas too. The present work shows the teaching methodology used for the development of two online courses, where we offer distance learning for "highly specialized" formation in the Edification area (an area where traditionally there was only classroom training). At the beginning, both courses were designed by classroom training, but got a really small number of applications due to the specialized topic proposed. Later, we proposed a "Curriculum Redesign" of the contents, offering an online modality, which implied a significant demand both within and outside the university area. A notable feature of this educational experience is the great spectrum opened for attendees of both courses in the online version. This situation improved significantly the "Curriculum Development" for the student and implied an interesting new proposal on the offered contents and materials (what would have been really difficult to get in a face to face classroom). In conclusion, the absence of certain types of specialized contents in the academic university curricula makes essential to raise new methodologies to save the gap in this area through additional training courses as those analyzed in this paper. Thus, our experience opens a debate on the appropriateness of implementing online training in relation to the face to face training in constructive content subjects and, especially, presents a new scheme, not without controversy, for the curriculum design.

Design and synthesis of constrained azacyclic pyrrolidine analogues of FTY720 as anticancer agents & metal coordination-controlled and bifunctional catalysis toward tertiary β-Ketols

Cette thèse se compose en deux parties: Première Partie: La conception et la synthèse d’analogues pyrrolidiniques, utilisés comme agents anticancéreux, dérivés du FTY720. FTY720 est actuellement commercialisé comme médicament (GilenyaTM) pour le traitement de la sclérose en plaques rémittente-récurrente. Il agit comme immunosuppresseur en raison de son effet sur les récepteurs de la sphingosine-1-phosphate. A fortes doses, FTY720 présente un effet antinéoplasique. Cependant, à de telles doses, un des effets secondaires observé est la bradycardie dû à l’activation des récepteurs S1P1 et S1P3. Ceci limite son potentiel d’utilisation lors de chimiothérapie. Nos précédentes études ont montré que des analogues pyrrolidiniques dérivés du FTY720 présentaient une activité anticancéreuse mais aucune sur les récepteurs S1P1 et S1P3. Nous avons soumis l’idée qu’une étude relation structure-activité (SARs) pourrait nous conduire à la découverte de nouveaux agents anti tumoraux. Ainsi, deux séries de composés pyrrolidiniques (O-arylmethyl substitué et C-arylmethyl substitué) ont pu être envisagés et synthétisés (Chapitre 1). Ces analogues ont montré d’excellentes activités cytotoxiques contre diverses cellules cancéreuses humaines (prostate, colon, sein, pancréas et leucémie), plus particulièrement les analogues actifs qui ne peuvent pas être phosphorylés par SphK, présentent un plus grand potentiel pour le traitement du cancer sans effet secondaire comme la bradycardie. Les études mécanistiques suggèrent que ces analogues de déclencheurs de régulation négative sur les transporteurs de nutriments induisent une crise bioénergétique en affamant les cellules cancéreuses. Afin d’approfondir nos connaissances sur les récepteurs cibles, nous avons conçu et synthétisé des sondes diazirine basées sur le marquage d’affinité aux photons (méthode PAL: Photo-Affinity Labeling) (Chapitre 2). En s’appuyant sur la méthode PAL, il est possible de récolter des informations sur les récepteurs cibles à travers l’analyse LC/MS/MS de la protéine. Ces tests sont en cours et les résultats sont prometteurs. Deuxième partie: Coordination métallique et catalyse di fonctionnelle de dérivés β-hydroxy cétones tertiaires. Les réactions de Barbier et de Grignard sont des méthodes classiques pour former des liaisons carbone-carbone, et généralement utilisées pour la préparation d’alcools secondaires et tertiaires. En vue d’améliorer la réaction de Grignard avec le 1-iodobutane dans les conditions « one-pot » de Barbier, nous avons obtenu comme produit majoritaire la β-hydroxy cétone provenant de l’auto aldolisation de la 5-hexen-2-one, plutôt que le produit attendu d’addition de l’alcool (Chapitre 3). La formation inattendue de la β-hydroxy cétone a également été observée en utilisant d’autres dérivés méthyl cétone. Étonnement dans la réaction intramoléculaire d’une tricétone, connue pour former la cétone Hajos-Parrish, le produit majoritaire est rarement la β-hydroxy cétone présentant la fonction alcool en position axiale. Intrigué par ces résultats et après l’étude systématique des conditions de réaction, nous avons développé deux nouvelles méthodes à travers la synthèse sélective et catalytique de β-hydroxy cétones spécifiques par cyclisation intramoléculaire avec des rendements élevés (Chapitre 4). La réaction peut être catalysée soit par une base adaptée et du bromure de lithium comme additif en passant par un état de transition coordonné au lithium, ou bien soit à l’aide d’un catalyseur TBD di fonctionnel, via un état de transition médiée par une coordination bidenté au TBD. Les mécanismes proposés ont été corroborés par calcul DFT. Ces réactions catalytiques ont également été appliquées à d’autres substrats comme les tricétones et les dicétones. Bien que les efforts préliminaires afin d’obtenir une enantioselectivité se sont révélés sans succès, la synthèse et la recherche de nouveaux catalyseurs chiraux sont en cours.

Design and synthesis of constrained azacyclic pyrrolidine analogues of FTY720 as anticancer agents & metal coordination-controlled and bifunctional catalysis toward tertiary β-Ketols

Cette thèse se compose en deux parties: Première Partie: La conception et la synthèse d’analogues pyrrolidiniques, utilisés comme agents anticancéreux, dérivés du FTY720. FTY720 est actuellement commercialisé comme médicament (GilenyaTM) pour le traitement de la sclérose en plaques rémittente-récurrente. Il agit comme immunosuppresseur en raison de son effet sur les récepteurs de la sphingosine-1-phosphate. A fortes doses, FTY720 présente un effet antinéoplasique. Cependant, à de telles doses, un des effets secondaires observé est la bradycardie dû à l’activation des récepteurs S1P1 et S1P3. Ceci limite son potentiel d’utilisation lors de chimiothérapie. Nos précédentes études ont montré que des analogues pyrrolidiniques dérivés du FTY720 présentaient une activité anticancéreuse mais aucune sur les récepteurs S1P1 et S1P3. Nous avons soumis l’idée qu’une étude relation structure-activité (SARs) pourrait nous conduire à la découverte de nouveaux agents anti tumoraux. Ainsi, deux séries de composés pyrrolidiniques (O-arylmethyl substitué et C-arylmethyl substitué) ont pu être envisagés et synthétisés (Chapitre 1). Ces analogues ont montré d’excellentes activités cytotoxiques contre diverses cellules cancéreuses humaines (prostate, colon, sein, pancréas et leucémie), plus particulièrement les analogues actifs qui ne peuvent pas être phosphorylés par SphK, présentent un plus grand potentiel pour le traitement du cancer sans effet secondaire comme la bradycardie. Les études mécanistiques suggèrent que ces analogues de déclencheurs de régulation négative sur les transporteurs de nutriments induisent une crise bioénergétique en affamant les cellules cancéreuses. Afin d’approfondir nos connaissances sur les récepteurs cibles, nous avons conçu et synthétisé des sondes diazirine basées sur le marquage d’affinité aux photons (méthode PAL: Photo-Affinity Labeling) (Chapitre 2). En s’appuyant sur la méthode PAL, il est possible de récolter des informations sur les récepteurs cibles à travers l’analyse LC/MS/MS de la protéine. Ces tests sont en cours et les résultats sont prometteurs. Deuxième partie: Coordination métallique et catalyse di fonctionnelle de dérivés β-hydroxy cétones tertiaires. Les réactions de Barbier et de Grignard sont des méthodes classiques pour former des liaisons carbone-carbone, et généralement utilisées pour la préparation d’alcools secondaires et tertiaires. En vue d’améliorer la réaction de Grignard avec le 1-iodobutane dans les conditions « one-pot » de Barbier, nous avons obtenu comme produit majoritaire la β-hydroxy cétone provenant de l’auto aldolisation de la 5-hexen-2-one, plutôt que le produit attendu d’addition de l’alcool (Chapitre 3). La formation inattendue de la β-hydroxy cétone a également été observée en utilisant d’autres dérivés méthyl cétone. Étonnement dans la réaction intramoléculaire d’une tricétone, connue pour former la cétone Hajos-Parrish, le produit majoritaire est rarement la β-hydroxy cétone présentant la fonction alcool en position axiale. Intrigué par ces résultats et après l’étude systématique des conditions de réaction, nous avons développé deux nouvelles méthodes à travers la synthèse sélective et catalytique de β-hydroxy cétones spécifiques par cyclisation intramoléculaire avec des rendements élevés (Chapitre 4). La réaction peut être catalysée soit par une base adaptée et du bromure de lithium comme additif en passant par un état de transition coordonné au lithium, ou bien soit à l’aide d’un catalyseur TBD di fonctionnel, via un état de transition médiée par une coordination bidenté au TBD. Les mécanismes proposés ont été corroborés par calcul DFT. Ces réactions catalytiques ont également été appliquées à d’autres substrats comme les tricétones et les dicétones. Bien que les efforts préliminaires afin d’obtenir une enantioselectivité se sont révélés sans succès, la synthèse et la recherche de nouveaux catalyseurs chiraux sont en cours.

Site planning. : Instructions and information for architect-engineers engaged under cost-plus-a-fixed-fee contracts for design and supervision of emergency defense construction projects.

Apr. 14, 1941.

Design and analysis of a metal bridge railing

"Final report for U.S. Department of Commerce, Bureau of Public Works. contract no. CPR 11-7987."

The half-timber house; its origin, design, modern plan, and construction;

Mode of access: Internet.

Metrication in building design, production, and construction : a compendium of 10 papers /

Includes index.

Practical shipbuilding; a treatise on the structural design and building of modern steel vessels; the work of construction, from the making of the raw material to the equipped vessel, including subsquent up-keep and repairs.

I. Text.--II. Diagrams and illustrations.

The Dutch colonial house; its origin, design, modern plan and construction;

Mode of access: Internet.

Building the half-timber house; its origin, design, modern plan, and construction,

Previously published under title: The half-timber house... New York, McBride, Nast & company, 1912.