Microstructural design of a new zirconia based material for dental implants

Un dels materials més rellevants en les últimes dècades és la zircònia (ZrO2) degut a les seves excel·lents propietats mecàniques. Degut a les seves propietats, aquest material s’ha utilitzat àmpliament en aplicacions dentals i ortopèdiques. Avui en dia continua sent un material àmpliament estudiat, ja que es volen trobar noves maneres per millora l’osteointegració i prevenir els problemes relacionats amb la degradació hidrotèrmica. En aquest projecte final de grau (TFG), l’objectiu principal és aconseguir conformar un implant dental. S’ha intentat conformar amb tres materials base zircònia; 3Y-ZrO2, 12Ce-ZrO2 i un composite de 3Y/12Ce-ZrO2. Per tal d’aconseguir aquest objectiu s’han utilitzat dues tècniques, la impressió 3D, mitjançant la tècnica del Robocasting també coneguda com Direct Ink Writing (DIW), i el fresat. En el transcurs del TFG, s’ha hagut de caracteritzar la pols de partida, en termes de mida de gra i cristal·linitat, així com les propietats tant microestructurals com mecàniques mitjançant tècniques avançades de caracterització (com per exemple microscòpia electrònica de rastreig, difracció de rajos X, entre altres) dels diferents materials tant processats mitjançant tècniques de processat tradicional, Cold Isostatic Pressing (CIP) com mitjançant impressió 3D. Finalment, s’han investigat les propietats tant microestructurals com mecàniques en condicions de servei, per això les mostres han estat degradades hidrotèrmicament. La caracterització de la pols així com la seva cristal·linitat ha permès observar que els diferents materials d’estudi en aquest TFG poden ser impresos en 3D, i que les seves propietats mecàniques resultants no es veuen molt afectades en comparació amb les propietats obtingudes quan els materials han estat conformats mitjançant tècniques tradicionals. A més s’ha pogut comprovar com el material composite 85/15-ZrO2 no ha patit degradació hidrotèrmica en concordança amb el que hi ha reportat a la literatura. Pel que fa a la impressió d’implants,s’ha aconseguit imprimir l’implant amb diferents longituds, 24, 17 i 12 mm el qual implica un 600%, 400 % y 200% superior a l’original, respectivament; fet que posa de manifest que la tècnica emprada d’impressió 3D es una tècnica viable per a realitzar aquest tipus de geometria i, amb un control més precís de la pols de partida així com dels paràmetres d’impressió, es pot arribar a imprimir amb les mesures reals. Per contra, les tècniques de mecanitzat tradicionals no han donat els resultats esperats, ja que les eines usades s’han vist superades per l’alta duresa dels materials estudiats en aquest TFG.Uno de los materiales más relevantes en las últimas décadas es la circonia (ZrO2) debido a sus excelentes propiedades mecánicas. Debido a sus propiedades, este material se ha utilizado ampliamente en aplicaciones dentales y ortopédicas. Hoy en día continúa siendo un material ampliamente estudiado, puesto que se quiere encontrar nuevas maneras para mejorar la osteointegración y prevenir problemas relacionados con la degradación hidrotérmica. En este proyecto final de grado (TFG), el objetivo principal es conseguir conformar un implante dental. Se ha intentado conformar con tres materiales base circonia; 3Y-ZrO2, 12Ce-ZrO2 y un composite 3Y/12Ce-ZrO2. Para conseguir este objetivo se han utilizado dos técnicas, la impresión 3D, mediante la técnica del Robocasting también conocida como Direct Ink Writing (DIW), y el fresado. En el transcurso del TFG, se ha tenido que caracterizar el polvo de partida, en términos de tamaño de grano y cristalinidad, así como las propiedades tanto microestructurales como mecánicas mediante técnicas avanzadas de caracterización (como por ejemplo microscopia electrónica de barrido, difracción de rayos X, entre otros) de los diferentes materiales tanto procesados mediante técnicas de procesado tradicional, Cold Isostatic Pressing (CIP) como mediante impresión 3D. Finalmente, se han investigado las propiedades tanto microestructurales como mecánicas en condiciones de servicio, por eso las muestras han sido degradadas hidrotermalmente. La caracterización del polvo así como su cristalinidad ha permitido observar que los diferentes materiales estudiados en este TFG pueden ser imprimidos en 3D, y que sus propiedades mecánicas resultantes no se ven muy afectadas en comparación con las propiedades obtenidas cuando los materiales han sido conformados mediante técnicas tradicionales. Además, se ha podido comprobar como el material composite 85/15-ZrO2 no ha sufrido degradación hidrotérmica en concordancia con lo que hay reportado en la literatura. En cuanto a la impresión de implantes, se ha conseguido imprimir el implante con diferentes longitudes, 24, 17 y 12 mm lo cual implica un 600%, 400% y 200% de escalado respecto al tamaño original, respectivamente; hecho que pone de manifiesto que la técnica empleada de impresión 3D es una técnica viable para realizar este tipo de geometría y, con un control más preciso del polvo de partida así como de los parámetros de impresión, se puede llegar a imprimir con las medidas reales. Por el contrario, las técnicas de mecanizado tradicionales no han dado los resultados esperados, puesto que las herramientas usadas se han visto superadas por la alta dureza de los materiales estudiados en este TFG.One of the most important materials in the last decades is the zirconia (ZrO2) due to its excellent mechanical properties. Due to its properties, this material has been widely used in dental and orthopaedic applications. Nowadays it remains under investigation, as new ways are to be found to improve the osseointegration and prevent the issues related to the hydrothermal degradation. In this Bachelor’s degree project, the main objective is to achieve the shaping of a dental implant. Three zirconia-based materials have been used; 3Y-ZrO2, 12Ce-ZrO2 and a composite of 3Y/12Ce-ZrO2. To achieve this objective, two techniques have been used, 3D printing, using the Robocasting technique also known as Direct Ink Writing (DIW), and milling. In the course of this Bachelor’s degree project, it has been necessary to characterise the starting powders, in terms of grain size and crystallinity, as well as the microstructural and mechanical properties by means of advanced characterization techniques (such as scanning electron microscopy, X-Ray Diffraction, among others) of the different materials both processed by traditional processing techniques, Cold Isostatic Pressing (CIP) and 3D printing. Finally, both microstructural and mechanical properties have been investigated under service conditions, so the samples have been hydrothermally degraded. The characterization of the powder as well as its crystallinity has allowed to observe that the different materials studied in this Bachelor’s degree project can be 3D printed, and that their resulting mechanical properties are not much affected in comparison with the properties obtained when the materials have been made by traditional techniques. Furthermore, it has been verified that the 85/15- ZrO2 composite materials has not suffered hydrothermal degradation as accordance in the literature. As for the 3D printing of implants, it has been possible to print the implant with different lengths, 24, 17 and 12 mm, which implies 600%, 400% and 200% more than the original, respectively; this fact shows that the 3D printing technique used is a viable technique for this type of geometry and, with more precise control of the starting powder as well as the 3D printing parameters, it is possible to print with the real measurements. On the other hand, traditional machining techniques have not given the expected results, since the tools used have been overcome by the high hardness of the materials studied in this bachelor’s degree project

Synthesis of Combretastatin A-4 and 3 0 -Aminocombretastatin A-4 derivatives with Aminoacid Containing Pendants and Study of their Interaction with Tubulin and as Downregulators of the VEGF, hTERT and c-Myc Gene Expression

Natural product combretastatin A-4 (CA-4) and its nitrogenated analogue 3 0 -aminocombretastatin A-4 (AmCA-4) have shown promising antitumor activities. In this study, a range of CA-4 and AmCA-4 derivatives containing amino acid pendants have been synthesized in order to compare their biological actions with those of their parent compounds. Thus, inhibition of cell proliferation on tumor cell lines HT-29, MCF-7 and A-549, as well as on the nontumor cell line HEK-273; in vitro tubulin polymerization; mitotic cell arrest; action on the microtubule cell network and inhibition of VEGF, hTERT, and c-Myc genes have been evaluated. Some AmCA-4 derivatives bearing L-amino acids exhibited inhibition of cell proliferation at low nanomolar levels exceeding the values shown by AmCA-4. Furthermore, while CA-4 and AmCA-4 derivatives do not show significant effects on the in vitro tubulin polymerization and cell cycle arrest, some selected CA-4 and AmCA-4 derivatives are able to cause total depolymerization of the microtubule network on A-549 cells. The best results were obtained in the inhibition of gene expression, particularly on the VEGF gene, in which some AmCA-4 derivatives greatly exceeded the inhibition values achieved by the parent compound

Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids

The synthesis and biological activities (cytotoxicity, leishmanicidal, and trypanocidal) of 11 triclosan–hydrazone hybrids are described herein. The structure of the products was elucidated by spectral data (NMR, IR) and mass spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leishmania species in Colombia, and against Trypanosoma cruzi, which is the major pathogenic species to Chagas disease in humans. In addition, the cytotoxic activity of the synthesized compounds was evaluated against human U-937 macrophages. Hydrazone hybrids were obtained as E-synperiplanar and E-antiperiplanar conformers. Nine of them were active against L. (V) panamensis (5a–5d, 5f–5j) and eight of them against T. cruzi (5a, 5c, 5d, 5f–5j), with EC50 values lower than 40 µM. The compounds 5c, 5e, and 5h exhibit the best selectivity index against both L. (V) panamensis and T. cruzi, with values ranging from 5.90 to 16.55, thus showing potential as starting compounds for the eventual development of drugs against these parasites. The presence of hydroxy or methoxy groups in positions 2 and 4 of the aromatic ring of the benzylidene moiety increases both activity and cytotoxicity. There is no clear relationship between the antiprotozoal activity and the methylation pattern of the hydroxy groups, since in some cases methylation decreases the activity (5d vs. 5g) while in other cases the activity is increased (5c vs. 5f and 5i vs. 5j

Semi-automatic GUI platform to characterize brain development in preterm children using ultrasound images

The third trimester of pregnancy is the most critical period for human brain development, during which significant changes occur in the morphology of the brain. The development of sulci and gyri allows for a considerable increase in the brain surface. In preterm newborns, these changes occur in an extrauterine environment that may cause a disruption of the normal brain maturation process. We hypothesize that a normalized atlas of brain maturation with cerebral ultrasound images from birth to term equivalent age will help clinicians assess these changes. This work proposes a semi-automatic Graphical User Interface (GUI) platform for segmenting the main cerebral sulci in the clinical setting from ultrasound images. This platform has been obtained from images of a cerebral ultrasound neonatal database images provided by two clinical researchers from the Hospital Sant Joan de Déu in Barcelona, Spain. The primary objective is to provide a user-friendly design platform for clinicians for running and visualizing an atlas of images validated by medical experts. This GUI offers different segmentation approaches and pre-processing tools and is user-friendly and designed for running, visualizing images, and segmenting the principal sulci. The presented results are discussed in detail in this paper, providing an exhaustive analysis of the proposed approach’s effectiveness.Peer ReviewedPostprint (published version

Aryl urea based scaffolds for multitarget drug discovery in anticancer immunotherapies

Twenty-one styryl and phenethyl aryl ureas have been synthetized and biologically evaluated as multitarget inhibitors of Vascular endothelial growth factor receptor-2 VEGFR-2 and programmed death-ligand-1 (PD-L1) proteins in order to overcome resistance phenomena offered by cancer. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, MCF-7, HeLa and A549), on the endothelial cell line human microvascular endothelial cells (HMEC)-1 and on the non-tumor cell line human embryonic kidney cells (HEK)-293 has been determined. Some derivatives were evaluated for their antiangiogenic properties such as their ability to inhibit microvessel formation using HMEC-1 or their effect on VEGFR-2 in both cancer and endothelial cell lines. In addition, the immunomodulator action of a number of selected compounds was also studied on PD-L1 and c-Myc proteins. Compounds 16 and 23 (Z) and (E)-styryl p-bromophenyl urea, respectively, showed better results than sorafenib in down-regulation of VEGFR-2 and also improved the effect of the anti-PD-L1 compound BMS-8 on both targets, PD-L1 and c-Myc proteins

Resolución geométrica de la cinemática inversa de un robot sin muñeca esférica

Una de las aplicaciones más conocidas del álgebra geométrica en la ingenierìa consiste en proporcionar una formulación compacta de la cinemática de los robots manipuladores serie. Sin embargo, el uso de álgebra geométrica en el campo de la robótica está aún en sus inicios, y todavía hay varios problemas abiertos que pueden ser tratados con esta elegante y compacta formulación. En esta línea, el presente artículo introduce una estrategia basada en el álgebra geométrica conforme para resolver el problema de la cinemática inversa para un robot manipulador de 6 grados de libertad (GdL) sin muñeca esférica, para el cual es conocido que el problema de la cinemática inversa no tiene, en general, solución analítica. Para ello, la estrategia propuesta en este artículo se basará en la explotación de las propiedades algebraicas y geométricas del álgebra geométrica conforme como, por ejemplo, que toda isometría se puede representar de manera compacta como un rotor, y que los objetos geométricos no son más que multivectores.Peer ReviewedPostprint (author's final draft

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

The synthesis, cytotoxicity, anti-leishmanial and anti-trypanosomal activities of twelve triclosan-caffeic acid hybrids are described herein. The structure of the synthesized products was elucidated by a com- bination of spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis , which is the most prevalent Leishmania species in Colombia, and against Trypanosoma cruzi, which is the pathogenic species to humans. Cytotoxicity was evaluated against hu- man U-937 macrophages. Eight compounds were active against L. (V) panamensis ( 18 e 23, 26 and 30 ) and eight of them against T. cruzi ( 19 e 22 , 24 and 28 e 30 ) with EC 50 values lower than 40 m M. Compounds 19 e 22 , 24 and 28 e 30 showed higher activities than benznidazole (BNZ). Esters 19 and 21 were the most active compounds for both L. (V) panamensis and T. cruzi with 3.82 and 11.65 m M and 8.25 and 8.69 m M, respectively. Compounds 19 e 22 , 24 and 28 e 30 showed higher activities than benznidazole (BNZ). Most of the compounds showed antiprotozoal activity and with exception of 18 , 26 and 28 , the remaining compounds were toxic for mammalian cells, yet they have potential to be considered as candidates for anti-trypanosomal and anti-leishmanial drug development. The activity is dependent on the length of the alkyl linker with compound 19 , bearing a four-carbon alkyl chain, the most performing hybrid. In general, hydroxyl groups increase both activity and cytotoxicity and the presence of the double bond in the side chain is not decisive for cytotoxicity and anti-protozoal activity

Synthesis, leishmanicidal, trypanocidal and cytotoxic activities of quinoline-chalcone and quinoline-chromone hybrids

We report herein the synthesis and biological activities (cytotoxicity, leishmanicidal and trypanocidal) of six quinoline-chalcone and five quinoline-chromone hybrids. The synthesized compounds were evaluated against amastigotes forms of Leishmania (V) panamensis, which is the most prevalent Leishmania species in Colombia and Trypanosoma cruzi, which is the major pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Compounds 8–12, 20, 23 and 24 showed activity against Leishmania (V) panamensis, while compounds 9, 10, 12, 20 and 23 had activity against Trypanosoma cruzi with EC50 values lower than 18 mg mL−1. 20 was the most active compound for both Leishmania (V) panamensis and Trypanosoma cruzi with EC50 of 6.11 ± 0.26 μg mL−1 (16.91 μM) and 4.09 ± 0.24 (11.32 μM), respectively. All hybrids compounds showed better activity than the anti-leishmanial drug meglumine antimoniate. Compounds 20 and 23 showed higher activity than benznidazole, the current anti-trypanosomal drug. Although these compounds showed toxicity for mammalian U-937 cells,they still have the potential to be considered as candidates to antileishmanial or trypanocydal drug development

Synthesis and Antiproliferative Activity of 3 and 7-Styrylcoumarins

A series of styrylcoumarins were obtained via Mizoroki-Heck reactions between 3-bromo-4-methyl7-(octyloxy)-2H-chromen-2-one or 2-oxo-2H-chromen-7-yl trifluoromethanesulfonate and functionalized styrenes. The structures of the products were elucidated by spectroscopic analysis. All compounds were evaluated against SW480 and CHO-K1 cell lines. A number of hybrids showed good antiproliferative activity. Among the tested compounds, hybrids 6e, 10c and 10d, exhibited the highest activity (IC50- SW480/48h = 6,92; 1,01 and 5,33 µM, respectively) and selectivity (IS48h = >400; 67,8 and 7,2, respectively). In addition, these compounds were able to preserve their activities over time. The results achieved by these hybrids were even better than the lead compounds (coumarin and resveratrol) and the standard drug (5-FU). As regards structure-activity relationship it seems that the location of the styryl group on the coumarin structure and the presence of the hydroxyl group on the phenyl ring were determinant for the activity

Las nuevas condiciones del trabajo en el contexto de la globalización económica : ¿Hacia un nuevo derecho del trabajo?

Esta obra es resultado de la investigación que se llevó a cabo a lo largo de tres años (2012-2015), la cual se enriqueció mediante reuniones de análisis y discusión en torno a temas como la globalización, la innovación tecnológica, la flexibilización y precarización del mercado de trabajo, el cambio institucional, las condiciones salariales, el papel de los sindicatos, la tendencia de la educación en la preparación de mano de obra, la migración, los derechos humanos y la equidad de género en la relación laboral. Se complementó el trabajo de los especialistas con un seminario internacional en el que se discutieron los resultados de las investigaciones realizadas para el proyecto