Synthesis and SAR of C12-C13-oxazoline derivatives of epothilone A

The SAR of a series of new epothilone A derivatives with a 2-substituted-1,3-oxazoline moiety trans-fused to the C12-C13 bond of the deoxy macrocycle have been investigated with regard to tubulin polymerization induction and cancer cell growth inhibition. Significant differences in antiproliferative activity were observed between different analogs, depending on the nature of the substituent at the 2-position of the oxazoline ring. The most potent compounds showed comparable activity with the natural product epothilone A. Modeling studies provide a preliminary rationale for the observed SAR.

Ensayos de laboratorio para la medida de la tasa de absorción específica (SAR) en dispositivos móviles

El proyecto trata del estudio de la tasa de absorción específica (SAR). En él se estudia la SAR que desprenden distintos dispositivos de comunicaciones inalámbricos. Se ha llevado a cabo en las instalaciones de la SETSI, en el laboratorio de radiofrecuencia situado en El Casar, Guadalajara, que pertenece al Ministerio de Industria Comercio y Turismo. La SAR es una relación entre la energía electromagnética acumulada en una masa de un material o tejido concreto. Por tanto, lo primero es definir la SAR, en la que se exponen sus parámetros. Además, se recogen los límites de exposición fijados por las normas internacionales IEC 62209-1 e IEC 62209-2 en relación a SAR. Posteriormente, acorde con las normas, se realiza una definición detallada de un banco de medidas de SAR, en donde se explica cada uno de los componentes del banco de manera detallada así como los sistemas que intervienen previamente a la realización de la medida, tipos de los sistemas para realizar las verificaciones pertinentes, y también las incertidumbres de ciertos parámetros. También se realiza un proceso completo de medida de SAR en el laboratorio de la SETSI, donde se realizan las comprobaciones necesarias para la realización de una serie de medidas sobre dispositivos de comunicaciones móviles. Éstas medidas se realizan primero sobre un teléfono móvil en las frecuencias de GSM, UMTS y WIFI, en las configuraciones estipuladas por la norma; “tocando” e “inclinada 15°” comparando los valores obtenidos con los límites marcados por las normas internacionales. Por último, en este apartado se realizan ciertas medidas con otras configuraciones que no están recogidas en la norma para intentar obtener los máximos valores de SAR posibles. Después se realiza una comparación entre dos dispositivos tipo “tablet”, para ello se realizan medidas en la banda de WIFI y se comentan los resultados obtenidos, relacionado con el diseño de cada uno de ellos. Posteriormente se realiza un presupuesto de un banco de SAR, donde se detallan todos los componentes que intervienen en la realización de las medidas de SAR, pero no se incluyen en él, los costes de mantenimiento o los costes relacionados con su uso. Por último se explican las conclusiones finales desprendidas de la realización de este proyecto de fin de carrera así como la bibliografía utilizada. ABTRACT This project consists on the study of the specific absorption rate (SAR).It studies the different SAR of several wireless communications devices. It has been held in SETSI’S facilities, in its radio frecuency laboratory located in El Casar, Guadalajara, which belongs to the Ministy of Industry, Trade and Tourism. The SAR is a ratio between the electromagnetic energy accumulated in a mass of concrete material or tissue. Therefore, the SAR is defined first, which sets its parameters. Also lists the exposure limits set by international standards IEC 62209-1 and IEC 62209-2 regarding SAR. Subsequently, according to the guidelines, performing a detailed definition of a SAR measures bench, which explains each of the components in detail of the bench and involved systems prior to the realization of the extent and types of systems to perform the necessary checks, and certain parameters uncertainties. Also performed a complete process for SAR in the SETSI laboratory, located in El Casar, Guadalajara, where the necessary checks are made to carry out a serie of measures on mobile communications devices. These will be carried out first on a mobile phone at frequencies of GSM, UMTS and WiFi, in the configurations set by the standard, "touch" and "tilt 15 °" comparing the values obtained with the limits set by international standards. Finally, this section will perform certain actions with other configurations that are not included in the standard to try to get the maximum possible SAR values. Then a comparison is made between two devices, such as "tablet", this will make measurements in the band WIFI and discussed the results, related to the design of each. Subsequently, a budget of a SAR bench, detailing all components involved in SAR measures, but not included in it, maintenance costs or the costs associated with its use. Finally conclusions are explained detached from the realization of this project as well as the bibliography used on it.

Monitoring an earthfill dam using differential SAR interferometry: La Pedrera dam, Alicante, Spain

Surface displacement at the dykes of La Pedrera reservoir (SE Spain) has been measured by satellite differential Synthetic Aperture Radar (SAR) interferometry. At the main dyke, a displacement of about 13 cm along the satellite line of sight has been estimated between August 1995 and May 2010, from a dataset composed by ERS-1, ERS-2 and Envisat-ASAR images. Two independent short-term processing tasks were also carried out with ERS-2/Envisat-ASAR (from June 2008 to May 2010) and TerraSAR-X (from August 2008 to June 2010) images which have shown similar spatial and temporal displacement patterns. The joint analysis of historical instrument surveys and DInSAR-derived data has allowed the identification of a long-term deformation process which is reflected at the dam's surface and is also clearly recognizable in the inspection gallery. The plausible causes of the displacements measured by DInSAR are also discussed in the paper. Finally, DInSAR data have been used to compute the long-term settlement of La Pedrera dam, showing a good agreement with external studies. Consequently, this work demonstrates the integration of DInSAR with in-situ techniques which helps provide a complete spatial vision of the displacements in the dam thereby helping to differentiate the causal mechanisms.

Synthesis and cytotoxity of oxysterols:studies on the A,B ring polyoxygenated sterols

Oxysterols (OS), the polyoxygenated sterols, represent a class of potent regulatory molecules for important biological actions. Cytotoxicity of OS is one of the most important aspects in studies of OS bioactivities. However, studies, the structure-activity relationship (SAR) study in particular, have been hampered by the limited availability of structurally diverse OS in numbers and amounts. The aim of this project was to develop robust synthetic methods for the preparation of polyhydroxyl sterols, thereof, evaluate their cytotoxicity and establish structure-activity relationship. First, we found hydrophobicity of the side chain is essential for 7-HC's cytotoxicity, and a limited number of hydroxyl groups and a desired configuration on the A, B ring are required for a potent cytotoxicity of an OS, after syntheses and tests of a number of 7-HC's analogues against cancer cell lines. Then polyoxygenation of cholesterol A, B rings was explored. A preparative method for the synthesis of four diastereomerically pure cholest-4-en-3,6-diols was developed. Epoxidation on these cholest-4-en-3,6-diols showed that an allyl group exerts an auxiliary role in producing products with desired configuration in syntheses of the eight diastereomerically pure 45-epoxycholestane-3,6-diols. Reduction of the eight 45-epoxycholestane-3,6-diols produced all eight isomers of the cytotoxic 5α-acholestane 3β,5,6β-triol (CT) for the first time. Epoxide ring opening with protic or Lewis acids on the eight 45-epoxycholestane-3,6-diols are carefully studied. The results demonstrated a combination of an acid and a solvent affected the outcomes of a reaction dramatically. Acyl group participation and migration play an important role with numbers of substrates under certain conditions. All the eight 4,5-trans cholestane- 3,4,5,6-tetrols were synthesised through manipulation of acyl participation. Furthermore these reaction conditions were tested when a number of cholestane-3,4, 5,6,7-pentols and other C3-C7 oxygenated sterols were synthesised for the first time. Introduction of an oxygenated functional group through cholest-2-ene derivatives was studied. The elimination of 3-(4-toluenesulfonate) esters showed the interaction between the existing hydroxyls or acyls with the reaction centre often resulted in different products. The allyl oxidation, epoxidation and Epoxide ring opening reactions are investigated with these cholest-2-enes.

Design and implementation of a non-destructive defect detection technique based on UWB-SAR imaging

In the last twenty years aerospace and automotive industries started working widely with composite materials, which are not easy to test using classic Non-Destructive Inspection (NDI) techniques. Pairwise, the development of safety regulations sets higher and higher standards for the qualification and certification of those materials. In this thesis a new concept of a Non-Destructive defect detection technique is proposed, based on Ultrawide-Band (UWB) Synthetic Aperture Radar (SAR) imaging. Similar SAR methods are yet applied either in minefield [22] and head stroke [14] detection. Moreover feasibility studies have already demonstrated the validity of defect detection by means of UWB radars [12, 13]. The system was designed using a cheap commercial off-the-shelf radar device by Novelda and several tests of the developed system have been performed both on metallic specimen (aluminum plate) and on composite coupon (carbon fiber). The obtained results confirm the feasibility of the method and highlight the good performance of the developed system considered the radar resolution. In particular, the system is capable of discerning healthy coupons from damaged ones, and correctly reconstruct the reflectivity image of the tested defects, namely a 8 x 8 mm square bulge and a 5 mm drilled holes on metal specimen and a 5 mm drilled hole on composite coupon.

Experimental studies on comparison of microwave curing and thermal curing of epoxy resins used for alternative mould materials

In this present work attempts have been made to study the glass transition temperature of alternative mould materials by using both microwave heating and conventional oven heating. In this present work three epoxy resins, namely R2512, R2515 and R2516, which are commonly used for making injection moulds have been used in combination with two hardeners H2403 and H2409. The magnetron microwave generator used in this research is operating at a frequency of 2.45 GHz with a hollow rectangular waveguide. In order to distinguish the effects between the microwave and conventional heating, a number of experiments were performed to test their mechanical properties such as tensile and flexural strengths. Additionally, differential scanning calorimeter technique was implemented to measure the glass transition temperature on both microwave and conventional heating. This study provided necessary evidences to establish that microwave heated mould materials resulted with higher glass transition temperature than the conventional heating. Finally, attempts were also made to study the microstructure of microwave-cured materials by using a scanning electron microscope in order to analyze the morphology of cured specimens.