Cette thèse traite de la conception de sondes fluorogènes incorporant des bras espaceurs auto-effondrables répondant à l’activité enzymatique.Ces travaux commencent par la synthèse d’une sonde modèle à trois composantes pour détecter l’activité de la Leucine AminoPeptidase (LAP). Le cœur de cette sonde est un espaceur cyclisant efficace (t1/2 cyclisation≈7sec) qui unit un substrat enzymatique à un fluorophore précipitant avec une stabilité exemplaire (pas de dégradation sur 15h d’incubation). Appliquée sur des cellules vivantes, cette sonde produit des précipités fluorescents qui marquent durablement les cellules. L’élaboration de sondes pour d’autres enzymes a cependant soulevé l’importance d’abaisser le seuil de solubilité du fluorophore.Cette thèse se penche également sur deux nouvelles conceptions de sondes à la spécificité améliorée. Alors que la première tente de réutiliser les efforts déployés pour obtenir des inhibiteurs hautement sélectifs, la seconde est basée sur deux transformations successives par deux enzymes indépendantes. Si la première solution a échoué jusqu’alors, la seconde nous a effectivement permis de différencier des populations cellulaires.Enfin, ce manuscrit détaille le développement d’une nouvelle génération d’espaceur permettant l’affinement de certaines propriétés des sondes. Focalisés sur l’amélioration de l’hydrosolubilité, les premiers exemples sont très prometteurs. Particulièrement, une sonde pour Péncilline G Amidase possède une hydrosolubilité 3500 fois supérieure à celle de son analogue commercial. Véritables multiprises chimiques, ces espaceurs devraient permettent de relever certains des grands défis de la chimie médicinale moderne. / This thesis concerns the design and evaluation of fluorogenic molecular probes that respond to enzyme activity via the help of self-immolative spacers.This work starts with the synthesis of a model three-component probe that detects the activity of Leucine AminoPeptidase (LAP). The heart of this probe is an efficient cyclizing spacer (t1/2 cyclization≈7sec) that links a specific enzyme substrate to a precipitating fluorophore with an exemplary stability (no false positive signal over 15h incubation). When incubated with live cells, this construct is processed by active LAP to yield fluorescent precipitates which lead to long-term cell-tagging. However, probes susceptible to other enzyme activity have indicated the interest in further reduction of the solubility threshold of ELF®97.This manuscript also describes two new strategies to improve the specificity of the probes. While the first tries to take advantage of the efforts made to develop highly selective inhibitors, the second is based on two consecutive transformations by two independent enzymes. The first strategy has not yet been successfully applied in our hands, but the second has led to a first prototype that allowed discriminating between different cell lines.Lastly, this thesis relates the design and synthesis of a new generation of cyclizing spacer which opens up a great number of possibilities to optimize probes’ properties. For example, a probe targeting Pencilline G Amidase and containing such a spacer possesses a hydrosolubility 3500 times higher than its commercial analogue. As true “molecular hubs”, these spacers may turn out to address the big challenges of modern imaging agent and prodrug development.

This thesis covers different topics in the field of synthetic organic chemistry combined with the field of surface science and glycobiology. First, the text presents a series of orthogonally protected oligosaccharides (tri-, penta-, and heptasaccharides) of varying length and structures, which are synthesized with the aim of developing novel heterobifunctional biocompatible cross-linkers. Successful conjugation with different chemical handles is also described and used to illustrate the potential implementation of defined carbohydrate based compounds have potential use in biosensing applications. The results of incubation experiments using living cells indicate that the linker is incorporated into cell surfaces and enriched in microdomains. Second, synthesis of various saccharide-terminated alkane thiols immobilized on gold surfaces is reported. The protein adsorption and antifouling characteristics of these surfaces were investigated using model proteins and the common fouling organisms, Ulva linza and Balanus amphitrite. Further, oligo(lactose)-based thiols (di-, tetra-, and hexasaccharides) were synthesized and immobilized on gold nanoparticles to investigate how well these rigid, rod-like oligosaccharides can stabilize such nanoparticles for future use in constructing hybrid nanoparticles. Finally, the thesis describes synthesis of a systematic series of oligo(ethylene) glycols possessing either hydrogen- or methyl-terminated groups. Investigation of the fundamental characteristics of self-assembled monolayers, will give important insights into the design of protein repellant surfaces.

O objetivo do trabalho foi avaliar o efeito do uso de espaçadores na adaptação marginal de copings confeccionados em ligas de Ni-Cr (Verabond II) (VB II) e Ni-Cr-Be (Verabond) (VB) e Titânio cp (Tritan) (Ti-cp) fundidos pela técnica de cera perdida. A partir de uma matriz metálica, foram obtidos 135 troquéis de gesso resinado tipo IV para confecção dos padrões de cera nas seguintes condições: sem a presença de espaçador (G0), com uma camada de espaçador (G1) e com duas camadas de espaçador (G2), com quinze repetições para cada grupo. Foi realizado o enceramento de cada troquel e os padrões de cera foram incluídos em revestimento adequado para cada material. Em cada anel de fundição foram incluídos 3 padrões de cera, sendo cada um correspondente a cada condição. Cada coping, adaptado à matriz metálica por meio de um dispositivo padronizador da pressão de assentamento, foi levado ao Microscópio Óptico para aferição das medidas da desadaptação marginal. Os dados obtidos (&micro;m) foram submetidos à análise estatística (ANOVA) e teste de Tukey (p<0.05). Para a condição material, a liga VB (118,73) não apresentou diferença estatisticamente significante em relação à liga VB II (93,40), sendo que estas apresentaram diferença estatisticamente significante em relação ao Ti-cp (168,35). Em relação ao fator espaçador, houve diferença estatisticamente significante entre as três condições (G0=177,31; G1=121,51 e G2=81,66). Com base nos dados obtidos pelo presente estudo, pode-se afirmar que a presença de duas camadas de espaçador propicia menor desadaptação marginal. / The purpose of the study was to evaluate the effect of using die spacers on the marginal fit of Ni Cr (Verabond II) (VB II) and Ni-Cr-Be (Verabond) (VB) alloys and commercially pure Titanium (Tritan) (Ti-cp) casting copings by the lost wax technique. Using a metal master die, 135 Resin Added Extra Hard Type IV Stone were obtained for the fabrication of wax patterns in the following conditions: without die spacer (G0), with one die spacer layer (G1); and with two die spacer layers (G2), with fifteen repetitions for each group. Each stone die was waxed and the wax patterns were invested as recommended by the manufacturer. Three wax patterns were embedded in each casting ring, each corresponding to a condition. Each coping, seated to the metal matrix by a Seating Pressure Standardizing Device (SPSD), was taken to the Optic Microscope for the measurement of marginal discrepancy. The obtained data (&micro;m) were submitted to statistical analysis (ANOVA) and Tukey test (p<0.05). There was not statistically significant difference among the materials VB II (93,40) and VB (118,73), and there was statistically significant different to Ti-cp (168,35) . In terms of the die spacer, there was a statistically significant difference among the three conditions (G0=177,31; G1=121,51 e G2=81,66). It was concluded that with two die spacer layers there is less marginal discrepancy.

O objetivo do trabalho foi avaliar o efeito do uso de espaçadores na adaptação marginal de copings confeccionados em ligas de Ni-Cr (Verabond II) (VB II) e Ni-Cr-Be (Verabond) (VB) e Titânio cp (Tritan) (Ti-cp) fundidos pela técnica de cera perdida. A partir de uma matriz metálica, foram obtidos 135 troquéis de gesso resinado tipo IV para confecção dos padrões de cera nas seguintes condições: sem a presença de espaçador (G0), com uma camada de espaçador (G1) e com duas camadas de espaçador (G2), com quinze repetições para cada grupo. Foi realizado o enceramento de cada troquel e os padrões de cera foram incluídos em revestimento adequado para cada material. Em cada anel de fundição foram incluídos 3 padrões de cera, sendo cada um correspondente a cada condição. Cada coping, adaptado à matriz metálica por meio de um dispositivo padronizador da pressão de assentamento, foi levado ao Microscópio Óptico para aferição das medidas da desadaptação marginal. Os dados obtidos (&micro;m) foram submetidos à análise estatística (ANOVA) e teste de Tukey (p<0.05). Para a condição material, a liga VB (118,73) não apresentou diferença estatisticamente significante em relação à liga VB II (93,40), sendo que estas apresentaram diferença estatisticamente significante em relação ao Ti-cp (168,35). Em relação ao fator espaçador, houve diferença estatisticamente significante entre as três condições (G0=177,31; G1=121,51 e G2=81,66). Com base nos dados obtidos pelo presente estudo, pode-se afirmar que a presença de duas camadas de espaçador propicia menor desadaptação marginal. / The purpose of the study was to evaluate the effect of using die spacers on the marginal fit of Ni Cr (Verabond II) (VB II) and Ni-Cr-Be (Verabond) (VB) alloys and commercially pure Titanium (Tritan) (Ti-cp) casting copings by the lost wax technique. Using a metal master die, 135 Resin Added Extra Hard Type IV Stone were obtained for the fabrication of wax patterns in the following conditions: without die spacer (G0), with one die spacer layer (G1); and with two die spacer layers (G2), with fifteen repetitions for each group. Each stone die was waxed and the wax patterns were invested as recommended by the manufacturer. Three wax patterns were embedded in each casting ring, each corresponding to a condition. Each coping, seated to the metal matrix by a Seating Pressure Standardizing Device (SPSD), was taken to the Optic Microscope for the measurement of marginal discrepancy. The obtained data (&micro;m) were submitted to statistical analysis (ANOVA) and Tukey test (p<0.05). There was not statistically significant difference among the materials VB II (93,40) and VB (118,73), and there was statistically significant different to Ti-cp (168,35) . In terms of the die spacer, there was a statistically significant difference among the three conditions (G0=177,31; G1=121,51 e G2=81,66). It was concluded that with two die spacer layers there is less marginal discrepancy.

Esta investigación se enmarca en tres dimensiones referidas al espacio escolar de los centros de Primaria en España: Histórica, legislativa y comparativa.En lo relativo a las dimensiones histórica y legislativa se ha pretendido hacer un seguimiento comentado de todas las disposiciones y normativas de cómo ha estado prescrito que debía ser el espacio escolar de los centros públicos primarios españoles desde 1857 (año de promulgación de la Ley Moyano) y 1985 (año de finalización del rastreo legislativo efectuado y de la lectura de la tesis).En cuanto a la dimensión comparativa, se ha procurado establecer por medio de cuadros una comparación entre las principales disposiciones legales en una serie de aspectos definitorios de tales normas legislativas acerca de cómo debían ser las escuelas de nuestro país: tipos de espacios, dimensiones, y utilización, principalmente.Es un trabajo inicial en este campo, poco investigado hasta el momento. / In this research is analysed the organization of spaces in Spanish primary schools from three complementary dimensions of analysis: history, legislation and comparison between regions.Relative to history and legislation, the research try to include a commented review of every With regard to historical and legislative dimensions have attempted to track all commented on how rules and regulations have been prescribed which should be the scholar of Spanish primary public schools since 1857 (the year of enactment of the called "Ley Moyano") and 1985 (year ending effected legislative tracking and reading of this work.)As to the comparative dimension, it has sought to establish using comparison tables the main laws in a number of defining aspects of such legislation should be about the schools in our country: types of spaces, dimensions, and use.It is an initial work in this field, little research so far.

No description available.

Experiments investigating complex flows in rod bundles with spacer grids that have mixing devices (such as flow mixing vanes) have mostly been performed using single-point measurements. Although these measurements allow local comparisons of experimental and numerical data they provide little insight because the discrepancies can be due to the integrated effects of many complex flow phenomena such as wake-wake, wake-vane, and vane-boundary layer interactions occurring simultaneously in a complex flow environment. In order to validate the simulations results, detailed comparison with experimental data must be done. This work describes an experimental database obtained using Time Resolved Particle Image Velocimetry (TR-PIV) measurements within a 5 x 5 rod bundle with spacer-grids. Measurements were performed using two different grid designs. One typical of Boiling Water Reactors (BWR) with swirl type mixing vanes and the other typical of Pressurized Water Reactors (PWR) with split type mixing vanes. High quality data was obtained in the vicinity of the grid using the multi-scale approach. One of the unique characteristic of this set-up is the use of the Matched Index of Refraction (MIR) technique employed in this investigation. This approach allows the use of high temporal and spatial non-intrusive dynamic measurement techniques to investigate the flow evolution below and immediately above the spacer. The experimental data presented includes explanation of the various cases tested such as test rig dimensions, measurement zones, the test equipment and the boundary conditions in order to provide appropriate data for comparison with Computational Fluid Dynamics (CFD) simulations. Turbulence parameters of the obtained data are analyzed in order to gain insight of the physical phenomena. The shape of the velocity profile at various distances from the spacer show important modifications passing the grid which delineates the significant effects of the presence of the grid spacer. Influence of the vanes wake in the global velocity was quantified to be up to a distance of 4 hydraulic diameters from the edge of the grid.Spatial and temporal correlations in the two measured dimensions were performed to quantify the time and length scales present in the flow in the vicinity of the grids and its influence in the flow modification induced by the vanes. Detection of vortex cores was performed using the vorticity, swirl strength and Galilean decomposition approach. The resulted cores were then tracked in time, in order to observe the evolution of the structures under the influence of the vanes for each grid. Vortex stretching was quantified in order to gain insight of the energy dissipation process normally associated with the phenomena. This work presents data in a single-phase flow situation and an analysis of these data for understanding complex flow structure. This data provide for the first time detailed temporal velocity full field which can be used to validate CFD codes.

This thesis is concerned with terahertz (THz) technology from both optical and electronic approaches. On the optical front, the investigation of optimised photoconductive switches included the characterisation, fabrication and testing of devices which can generate and detect THz radiation over the frequency range from DC to ~ 2.5 THz. These devices incorporated semiconductor photoconductors grown under low temperature (LT) Molecular Beam Epitaxy (MBE) conditions and using distributed Bragg reflectors (DBRs). The material properties were studied via numerous characterisation techniques which included Hall Effect and mid infrared reflections. Antenna structures were fabricated on the surface of the active layers and pulsed/continuous wave (CW) signal absorbed by these structures (under bias) generates photocurrent. With the help of the DBRs at certain wavelengths (800 nm and 1550 nm), the absorption coefficient at the corresponding illumination wavelength increased thus leading to significant increase of the THz output power while the materials kept the desirable photoconductive material properties such as high dark resistivity and high electron mobility. The inclusion of DBRs resulted in more than doubling of the THz peak signals across the entire operating frequency range and significant improvements in the relative THz power. For the THz electronic approach, a new type of InP-based Asymmetric Spacer Tunnel Diode (ASPAT), which can be used for high frequency detector, was studied. The asymmetric DC characteristics for this novel tunnel diode showed direct compatibility with high frequency zero-bias detector applications. The devices also showed an extreme thermal stability (less than 7.8% current change from 77 K to 400 K) as the main carrier transport mechanism of the ASPAT was tunnelling. Physical models for this ASPAT diode were developed for both DC (direct current) and AC (alternating current) simulations using the TCAD software tool SILVACO. The simulated DC results showed almost perfect matches with measurements across the entire temperature range from 77 K to 400 K. From RF (radio frequency) measurements, the intrinsic diode parameters were extracted and compared with measured data. The simulated zero biased detector circuits operating at 100 GHz and 240 GHz using the new InGaAs-AlAs ASPAT diode (4*4 micrometer square) showed comparable voltage sensitivities to state of the art Schottky barrier diodes (SBDs) detectors but with the added advantage of excellent thermal stability.

The diploma thesis deals with the design of a new technological process for the production of a spacer ring with a diameter of 212 mm in cooperation with the company Meopta – Optika, s.r.o. The production of this component according to the current process does not comply with the prescribed geometric tolerances of flatness of the face and radius runout with a tolerance field size of 0.005 mm. The work is a detailed analysis of the specified component and describes the current technological process, including the machines on which the spacer ring is manufactured. Based on the knowledge gained from the analysis of the current process, a new technological process was created. During the production according to this process, some geometric tolerances were also exceeded, but the values exceeding the prescribed tolerance field were significantly reduced. The department of production technology found the results to be sufficient and the spacer ring will be produced according to the new technological process. In the last part of the work are the costs of production of components according to both processes.

In this study we looked into an existing textile baby stroller seat and investigated whether there can be any advantage in changing the material to a spacer fabric from perspectives such as functionality, comfort, and sustainability. The subject of 3D knitting, and advanced knitting is being researched more and more because of its versatility in producing and changing parameters of knitted high quality products, but there is a lack of studies done on comfort for children when it comes to knitted spacer fabrics and not many studies have been done on spacer fabrics used for baby seats in strollers or other types of seats for children. A reason for further development and research in the area of 3D knitting is that it could be giving products a better appearance, functionality or potential for more sustainable pro-duction which could lead to better possibilities of producing more attractive advanced textile products. This could in turn make the producer more attractive among customers as well as stand out more amongst competitors on the market. Recently there has been attention on the use of warp knitted spacer fabrics in the application of cushioning to protect against impact. Thermoregulation, compression, air permeability and good energy absorption are some characteristics of spacer fabrics which are being further investigated in this study (Gokarneshan 2015). Another reason for further investigation of spacer fabrics, and their good cushioning properties, in child products is that it was shown in a previous study that children who are transported in carriers for bicycles are exposed to more vibration compared to children who are transported in automotive rides (Rothhamel 2023). A reason for examining the possibilities of replacing polyurethane foam with spacer fabric is that PU foams generally have lower air permeability in com-bination with higher heat resistance which can lead to problems regarding comfort. (Gokarneshan 2015). Testing of different spacer fabric samples was carried out based on air permeability, burst strength, and moisture management. These tests were then evaluated to determine the optimal parameters of a spacer fabric for increased comfort and functionality in an outdoor child product. Other tests that were carried out were specific tests for child products such bite test, finger probe test, and pulling test to examine the safety of each sample. We concluded that the optimal spacer fabric should be constructed of polyester rather than cotton to have as good wicking properties as possible. The fabric should have one side of the spacer fabric that does not consist of mesh so that the requirements from the finger probe test will be fulfilled. The other side of the spacer fabric should be constructed of a mesh structure to ensure good properties of air permeability. The holes should, however, not be too big since this might be less comfortable against the skin. The mesh structure recommended for this purpose is a hexagonal mesh which results in both good permeability of both water and air flow. The fabric should also be constructed with a multifilament for the spacer yarn for safety reasons.