Nuevo concepto de elementos estructurales horizontales de vidrio : placa autoportante y pretensada en forma de pi

En los últimos años, podemos darnos cuenta de la importancia que tienen las nuevas aplicaciones de vidrio especialmente en edificios turísticos donde el vértigo juega un papel importante en la visita. Sin embargo los sistemas constructivos no tienen un especial interés porque el vidrio laminado está siempre soportado por otro elemento de acero o incluso vidrio en forma de retícula. En la presente tesis voy a desarrollar una nueva solución de elemento autoportante de vidrio de gran tamaño haciendo seguro el uso del elemento para andar en el aire. El sueño de muchos arquitectos ha sido diseñar un edificio completamente transparente y a mí me gustaría contribuir a este sueño empezando a estudiar un forjado de vidrio como elemento estructural horizontal y para ello debemos cumplir requerimientos de seguridad. Uno de los objetivos es lograr un elemento lo más transparente y esbelto posible para el uso de pasarelas en vestíbulos de edificios. Las referencias construidas son bien conocidas, pero por otro lado Universidades europeas estudian continua estudiando el comportamiento del vidrio con diferentes láminas, adhesivos, apilados, insertos, sistemas de laminado, pretensado, pandeo lateral, seguridad post-rotura y muchos más aspectos necesarios. La metodología llevada a cabo en esta tesis ha sido primeramente diseñar un elemento industrial prefabricado horizontal de vidrio teniendo en cuenta todos los conceptos aprendidos en el estado del arte y la investigación para poder predimensionar el elemento. El siguiente paso será verificar el modelo por medio de cálculo analítico, simulación de elementos finitos y ensayos físicos. Para realizar los ensayos hay un paso intermedio teniendo que cambiar la hipótesis de carga uniforme a carga puntal para realizar el ensayo de flexión a 4 puntos normalizado y además cambiar a escala 1:2 para adaptarse al espacio de ensayo y ser viable económicamente. Finalmente compararé los resultados de tensión y deformación obtenidos por los tres métodos para extraer conclusiones. Sin embargo el problema de la seguridad no ha concluido, tendré que demostrar que el sistema es seguro después de que se produzca la rotura y para ello sólo dispongo de los ensayos como medio de demostración. El diseño es el resultado de la evolución de una viga tipo “I”; cuando es pretensada para obtener más resistencia, aparece el problema de pandeo lateral y éste es solucionado con una viga con sección en “T” cuya unión es resuelta con un cajeado longitudinal en la parte inferior del elemento horizontal. Las alas de éste crecen para recoger las cargas superficiales creando a su vez un punto débil en la unión que a su vez se soluciona duplicando la sección “TT” y haciendo trabajar dicho tablero de forma tan óptima como una viga continua. Dicha sección en vidrio como un único elemento pretensado es algo inédito. Además he diseñado unas escuadras metálicas en los extremos de los nervios como apoyo y placa de pretensión, así como una hendidura curva en el centro de los nervios para alojar los tirantes de acero de modo que al pretensar el tirante la placa corrija al menos la deformación por peso propio. Realizados los cambios geométricos de escala y las simplificaciones en el laminado y el adhesivo se programan la extracción de resultados desde 3 estadios diferentes: Sin pretensión y con pretensión de 750 Kg y de 1000Kg en cada nervio. Por cada estadio y por cada uno de los métodos, cálculo, simulación y ensayos, se extraen los datos de deformación y tensión en el punto medio de un nervio con el objetivo de hacer una comparación de resultados para obtener unas conclusiones, siempre en el campo de la elasticidad. Posteriormente incrementaré la carga hasta el momento de la rotura de la placa y después hasta el colapso teniendo en cuenta el tiempo y demostrando una rotura segura. El vidrio no tendrá un comportamiento plástico pero habrá sido controlado su comportamiento frágil manteniendo una carga y una deformación aceptable. ABSTRACT Over the past few years we have realized the importance of the new technologies regarding the application of glass in new buildings, especially those touristic places were the views and the heights are the reason of the visit. However, the construction systems of these glass platforms are not usually as interesting, because the laminated glass is always held by another steel substructure or even a grid-formed glass element. Throughout this thesis I am going to develop a new solution of a self-bearing element with big dimensions made out of glass, ensuring a safe solution to use as an element to walk on the air. The dream of many architects has been to create a building completely transparent, and I would like to contribute to this idea by making a glass slab as a horizontal structural element, for which we have to meet the security requirements. One of the goals is to achieve an element as transparent and slim as possible for the use in walkways of building lobbies. The glass buildings references are well known, but on the other hand the European Universities study the behaviour of the glass with different interlayers, adhesives, laminating systems, stacking, prestressed, buckling, safety, breakage and post-breakage capacity; and many other necessary aspects. The methodology followed in this thesis has been to first create a horizontal industrial prefabricated horizontal element of glass, taking into account all the concepts learned in the state of art and the investigation to be able to predimension this element. The next step will be to verify this model with an analytic calculus, a finite element modelling simulation and physical tests. To fulfil these tests there is an intermediate step, having to change the load hypothesis from a punctual one to make the test with a four points normalized deflexion, and also the scale of the sample was changed to 1:2 to adapt to the space of the test and make it economically possible. Finally, the results of tension and deformation obtained from the three methods have been compared to make the conclusions. However, the problem with safety has not concluded yet, for I will have to demonstrate that this system is safe even after its breakage, for which I can only use physical tests as a way of demonstration. The design is the result of the evolution of a typical “I” beam, which when it is prestressed to achieve more resistance, the effect of buckling overcomes, and this is solved with a “T” shaped beam, where the union is solved with a longitudinal groove on the inferior part of the horizontal element. The boards of this beam grow to cover the superficial loads, creating at the same time a weak point, which is solved by duplicating the section “TT” and therefore making this board work as optimal as a continuous beam. This glass section as a single prestressed element is unique. After the final design of the “π” glass plate was obtained and the composition of the laminated glass and interlayers has been predimensioned, the last connection elements must be contemplated. I have also designed a square steel shoe at the end of the beams, which will be the base and the prestressed board, as well as a curved slot in the centre of the nerves to accommodate the steel braces so that when this brace prestresses the board, at least the deformation due to its self-weight will be amended. Once I made the geometric changes of the scale and the simplifications on the laminating and the adhesive, the extraction on results overcomes from three different stages: without any pretension, with a pretension of 750 kg and with a pretension of 1000 kg on each rib. For each stage and for each one of the methods, calculus, simulation and tests, the deformation datum were extracted to obtain the conclusions, always in the field of the elasticity. Afterwards, I will increase the load until the moment of breakage of this board, and then until the collapse of the element, taking into account the time spent and demonstrating a safe breakage. The glass will not have a plastic behaviour, but its brittle behaviour has been controlled, keeping an acceptable load and deflection.

A Genetic Analysis of Interactions with Spc110p Reveals Distinct Functions of Spc97p and Spc98p, Components of the Yeast γ-Tubulin Complex

The spindle pole body (SPB) in Saccharomyces cerevisiae functions as the microtubule-organizing center. Spc110p is an essential structural component of the SPB and spans between the central and inner plaques of this multilamellar organelle. The amino terminus of Spc110p faces the inner plaque, the substructure from which spindle microtubules radiate. We have undertaken a synthetic lethal screen to identify mutations that enhance the phenotype of the temperature-sensitive spc110–221 allele, which encodes mutations in the amino terminus. The screen identified mutations in SPC97 and SPC98, two genes encoding components of the Tub4p complex in yeast. The spc98–63 allele is synthetic lethal only with spc110 alleles that encode mutations in the N terminus of Spc110p. In contrast, the spc97 alleles are synthetic lethal with spc110 alleles that encode mutations in either the N terminus or the C terminus. Using the two-hybrid assay, we show that the interactions of Spc110p with Spc97p and Spc98p are not equivalent. The N terminus of Spc110p displays a robust interaction with Spc98p in two different two-hybrid assays, while the interaction between Spc97p and Spc110p is not detectable in one strain and gives a weak signal in the other. Extra copies of SPC98 enhance the interaction between Spc97p and Spc110p, while extra copies of SPC97 interfere with the interaction between Spc98p and Spc110p. By testing the interactions between mutant proteins, we show that the lethal phenotype in spc98–63 spc110–221 cells is caused by the failure of Spc98–63p to interact with Spc110–221p. In contrast, the lethal phenotype in spc97–62 spc110–221 cells can be attributed to a decreased interaction between Spc97–62p and Spc98p. Together, these studies provide evidence that Spc110p directly links the Tub4p complex to the SPB. Moreover, an interaction between Spc98p and the amino-terminal region of Spc110p is a critical component of the linkage, whereas the interaction between Spc97p and Spc110p is dependent on Spc98p.

A functional genetic screen identifies regions at the C-terminal tail and death-domain of death-associated protein kinase that are critical for its proapoptotic activity

Death-associated protein kinase (DAP-kinase) is a Ca+2/calmodulin-regulated serine/threonine kinase with a multidomain structure that participates in apoptosis induced by a variety of signals. To identify regions in this protein that are critical for its proapoptotic activity, we performed a genetic screen on the basis of functional selection of short DAP-kinase-derived fragments that could protect cells from apoptosis by acting in a dominant-negative manner. We expressed a library of randomly fragmented DAP-kinase cDNA in HeLa cells and treated these cells with IFN-γ to induce apoptosis. Functional cDNA fragments were recovered from cells that survived the selection, and those in the sense orientation were examined further in a secondary screen for their ability to protect cells from DAP-kinase-dependent tumor necrosis factor-α-induced apoptosis. We isolated four biologically active peptides that mapped to the ankyrin repeats, the “linker” region, the death domain, and the C-terminal tail of DAP-kinase. Molecular modeling of the complete death domain provided a structural basis for the function of the death-domain-derived fragment by suggesting that the protective fragment constitutes a distinct substructure. The last fragment, spanning the C-terminal serine-rich tail, defined a new regulatory region. Ectopic expression of the tail peptide (17 amino acids) inhibited the function of DAP-kinase, whereas removal of this region from the complete protein caused enhancement of the killing activity, indicating that the C-terminal tail normally plays a negative regulatory role. Altogether, this unbiased screen highlighted functionally important regions in the protein and revealed an additional level of regulation of DAP-kinase apoptotic function that does not affect the catalytic activity.

Crystallographic comparison of the estrogen and progesterone receptor’s ligand binding domains

The 2.8-Å crystal structure of the complex formed by estradiol and the human estrogen receptor-α ligand binding domain (hERαLBD) is described and compared with the recently reported structure of the progesterone complex of the human progesterone receptor ligand binding domain, as well as with similar structures of steroid/nuclear receptor LBDs solved elsewhere. The hormone-bound hERαLBD forms a distinctly different and probably more physiologically important dimer interface than its progesterone counterpart. A comparison of the specificity determinants of hormone binding reveals a common structural theme of mutually supported van der Waals and hydrogen-bonded interactions involving highly conserved residues. The previously suggested mechanism by which the estrogen receptor distinguishes estradiol’s unique 3-hydroxy group from the 3-keto function of most other steroids is now described in atomic detail. Mapping of mutagenesis results points to a coactivator-binding surface that includes the region around the “signature sequence” as well as helix 12, where the ligand-dependent conformation of the activation function 2 core is similar in all previously solved steroid/nuclear receptor LBDs. A peculiar crystal packing event displaces helix 12 in the hERαLBD reported here, suggesting a higher degree of dynamic variability than expected for this critical substructure.

Molecular characterization and assembly of the needle complex of the Salmonella typhimurium type III protein secretion system

Many bacterial pathogens of plants and animals have evolved a specialized protein-secretion system termed type III to deliver bacterial proteins into host cells. These proteins stimulate or interfere with host cellular functions for the pathogen's benefit. The Salmonella typhimurium pathogenicity island 1 encodes one of these systems that mediates this bacterium's ability to enter nonphagocytic cells. Several components of this type III secretion system are organized in a supramolecular structure termed the needle complex. This structure is made of discrete substructures including a base that spans both membranes and a needle-like projection that extends outward from the bacterial surface. We demonstrate here that the type III secretion export apparatus is required for the assembly of the needle substructure but is dispensable for the assembly of the base. We show that the length of the needle segment is determined by the type III secretion associated protein InvJ. We report that InvG, PrgH, and PrgK constitute the base and that PrgI is the main component of the needle of the type III secretion complex. PrgI homologs are present in type III secretion systems from bacteria pathogenic for animals but are absent from bacteria pathogenic for plants. We hypothesize that the needle component may establish the specificity of type III secretion systems in delivering proteins into either plant or animal cells.

A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes.

The crystal structure of the xanthine oxidase-related molybdenum-iron protein aldehyde oxido-reductase from the sulfate reducing anaerobic Gram-negative bacterium Desulfovibrio gigas (Mop) was analyzed in its desulfo-, sulfo-, oxidized, reduced, and alcohol-bound forms at 1.8-A resolution. In the sulfo-form the molybdenum molybdopterin cytosine dinucleotide cofactor has a dithiolene-bound fac-[Mo, = O, = S, ---(OH2)] substructure. Bound inhibitory isopropanol in the inner compartment of the substrate binding tunnel is a model for the Michaelis complex of the reaction with aldehydes (H-C = O,-R). The reaction is proposed to proceed by transfer of the molybdenum-bound water molecule as OH- after proton transfer to Glu-869 to the carbonyl carbon of the substrate in concert with hydride transfer to the sulfido group to generate [MoIV, = O, -SH, ---(O-C = O, -R)). Dissociation of the carboxylic acid product may be facilitated by transient binding of Glu-869 to the molybdenum. The metal-bound water is replenished from a chain of internal water molecules. A second alcohol binding site in the spacious outer compartment may cause the strong substrate inhibition observed. This compartment is the putative binding site of large inhibitors of xanthine oxidase.

DANA elements: a family of composite, tRNA-derived short interspersed DNA elements associated with mutational activities in zebrafish (Danio rerio).

DNA is the first SINE isolated from zebrafish (Danio rerio) exhibiting all the hallmarks of these tRNA-derived elements. DANA is unique in its clearly defined substructure of distinct cassettes. In contrast to generic SINE elements, DANA appears to have been assembled by insertions of short sequences into a progenitor, tRNA-derived element. Once associated with each other, these subunits were amplified as a new transposable element with such a remarkable success that DANA-related sequences comprise approximately 10% of the modern zebrafish genome. At least some of the sequences comprised by the full-length element were capable of movement, forming a new group of mobile, composite transposons, one of which caused an insertional mutation in the zebrafish no tail gene. Being present only in the genus Danio, and estimated to be as old as the genus itself, DANA may have played a role in Danio speciation by massive amplification and genome-wide dispersion. There are extensive DNA polymorphisms between zebrafish populations and strains detected by PCR amplification using primers specific to DANA, suggesting that the DANA element will be useful as a molecular tool for genetic and phylogenetic analyses.

An extended Herschel drop-out source in the center of AS1063: a normal dusty galaxy at z=6.1 or SZ substructures?

In the course of our 870 μm APEX/LABOCA follow-up of the Herschel Lensing Survey we have detected a source in AS1063 (RXC J2248.7-4431) that has no counterparts in any of the Herschel PACS/SPIRE bands, it is a Herschel “drop-out” with S_870/S_500 ≥ 0.5. The 870 μm emission is extended and centered on the brightest cluster galaxy, suggesting either a multiply imaged background source or substructure in the Sunyaev-Zel’dovich increment due to inhomogeneities in the hot cluster gas of this merging cluster. We discuss both interpretations with emphasis on the putative lensed source. Based on the observed properties and on our lens model we find that this source may be the first submillimeter galaxy (SMG) with a moderate far-infrared (FIR) luminosity (L_FIR < 10^12 L_⊙) detected so far at z > 4. In deep HST observations we identified a multiply imaged z ~ 6 source and measured its spectroscopic redshift to be z = 6.107 with VLT/FORS. This source may be associated with the putative SMG, but it is most likely offset spatially by 10−30 kpc and they may be interacting galaxies. With a FIR luminosity in the range [5−15] × 10^11 L_⊙ corresponding to a star formation rate in the range [80−260] M_⊙ yr^-1, this SMG would be more representative of the z > 4 dusty galaxies than the extreme starbursts detected so far. With a total magnification of ~25 it would open a unique window to the normal dusty galaxies at the end of the epoch of reionization.

Europe's continental regionalism. CEPS Working Document No. 375, February 2013

This paper reviews the multiple forms of European continental regionalism, which takes the overall shape of a complex set of concentric circles, with a substructure of a core group within the EU based on the euro and Schengen areas, and several rings of neighbours outside, including the European Economic Area, the regions of the EU’s neighbourhood policy and finally some pan-European organisations. While all world regions have their own unique features, the European case offers some important lessons that should be of interest to other world regions. The first is what appears to be a relatively robust model for single market integration. The second consists of the lessons currently being learned on the hazards on monetary integration without adequate fiscal and political integration. The third lesson is another warning, over the difficulties of anticipating the political dynamics of integration processes once set in motion, often described in Europe as a ‘journey to an unknown destination’. The fourth consists of the EU’s current efforts to develop a comprehensive neighbourhood policy, which is encountering difficult issues of matching ambitious objectives with incentives of adequate weight. Nevertheless, the policy sees a landscape of positive and constructive relations between the EU and its neighbours, in marked contrast to some ugly conflictual or coercive features seen in the cases of other continental hegemons – the three BRIC states of China, India and Russia, but not the fourth one, Brazil.

Amino ozonides exhibit in vitro activity against Echinococcus multilocularis metacestodes.

Artemisinin is an antimalarial sesquiterpene lactone that contains a 1,2,4-trioxane heterocycle. Dihydroartemisinin and artesunate demonstrated activity against Echinococcus multilocularis metacestodes in vitro but were not effective in a mouse model. In this study, the in vitro effects of a small library of synthetic ozonides (1,2,4-trioxolanes) were investigated. Initial compound screening against E. multilocularis metacestodes was performed at 20μM, and selected ozonides were further assessed in dose-response studies in metacestode cultures and mammalian cells. Transmission electron microscopy (TEM) was employed to characterise compound-induced structural alterations. At 20μM, the most potent ozonides (OZ401, OZ455, OZ491 and OZ494) led to death of ca. 60-100% of the parasites. Subsequent dose-response experiments demonstrated that OZ401, OZ455 and OZ491, which contain an aminopropylether substructure, were the most potent, with 50% inhibitory concentrations ranging from 11μM to 14μM. Cytotoxicity for these three ozonides, assessed in human foreskin fibroblasts, rat hepatoma cells and green monkey epithelial kidney (Vero) cells, was evident only at high concentrations. TEM demonstrated that OZ401 and OZ491 treatment induced considerable metabolic impairment in metacestodes at 1 day post exposure. At Day 3 post exposure, the germinal layer was severely distorted, although some intact cells were still visible, demonstrating that not all cell types in the parasite tissue were equally affected. Complete destruction of the germinal layer was noted at 5 days post exposure. Synthetic ozonides could represent interesting leads that will be further investigated in a suitable in vivo model of E. multilocularis infection.

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.

The evolution of microRNA in primates

Thesis (Ph.D.)--University of Washington, 2016-06

Mode Localization in a Nearly Cyclic Symmetric System

Thesis (Ph.D.)--University of Washington, 2016-06

Modal characteristics of a flexible beam with multiple distributed actuators

A flexible structure with surface-bonded piezoceramic patches is modelled using Timoshenko beam theory. Exact mode shapes and natural frequencies associated with the flexural motion are computed for various piezoceramic distributed actuator arrangements. The effects of patch placement and of shear on the modal characteristics are demonstrated using a cantilevered beam as an example. Perfect bonding of the piezoceramic to the beam substructure is assumed, and for the purposes of this paper only passive piezoceramic properties are considered. The modelling technique and results obtained in a closed form are intended to assist investigations into the modelling and control of active structures with surface-bonded piezoceramic actuators. (C) 2003 Elsevier Science Ltd. All rights reserved.

Diffuse optical light in galaxy clusters. I. Abell 3888

We are undertaking a program to measure the characteristics of the intracluster light ( ICL; total flux, profile, color, and substructure) in a sample of 10 galaxy clusters with a range of cluster mass, morphology, and redshift. We present here the methods and results for the first cluster in that sample, A3888. We have identified an ICL component in A3888 in V and r that contains 13% +/- 5% of the total cluster light and extends to 700 h(70)(-1) kpc (similar to 0.3r(200)) from the center of the cluster. The ICL color in our smallest radial bin is V - r 0.3 +/- 0.1, similar to the central cluster elliptical galaxies. The ICL is redder than the galaxies at 400 h(70)(-1) kpc < r < 700 h(70)(-1) kpc, although the uncertainty in any one radial bin is high. Based on a comparison of V - r color with simple stellar models, the ICL contains a component that formed more than 7 Gyr ago ( at z less than 1) with a high-metallicity ( 1.0 Z(circle dot) < Z(ICL) less than or similar to 2.5 Z(circle dot)) and a more centralized component that contains stars formed within the past 5 Gyr ( at z similar to 1). The profile of the ICL can be roughly fitted by a shallow exponential in the outer regions and a steeper exponential in the central region. We also find a concentration of diffuse light around a small group of galaxies 1.4 h(70)(-1) Mpc from the center of the cluster. In addition, we find three low surface brightness features near the cluster center that are blue ( V - r 0.0) and contain a total flux of 0.1M*. Based on these observations and X-ray and galaxy morphology, we suggest that this cluster is entering a phase of significant merging of galaxy groups in the core, whereupon we expect the ICL fraction to grow significantly with the formation of a cD galaxy, as well as the infall of groups.