Aerodynamic Optimization of High-Speed Trains Nose using a Genetic Algorithm and Artificial Neural Network

An aerodynamic optimization of the train aerodynamic characteristics in term of front wind action sensitivity is carried out in this paper. In particular, a genetic algorithm (GA) is used to perform a shape optimization study of a high-speed train nose. The nose is parametrically defined via Bézier Curves, including a wider range of geometries in the design space as possible optimal solutions. Using a GA, the main disadvantage to deal with is the large number of evaluations need before finding such optimal. Here it is proposed the use of metamodels to replace Navier-Stokes solver. Among all the posibilities, Rsponse Surface Models and Artificial Neural Networks (ANN) are considered. Best results of prediction and generalization are obtained with ANN and those are applied in GA code. The paper shows the feasibility of using GA in combination with ANN for this problem, and solutions achieved are included.

La barrera del análisis estructural y la representación gráfica en el desarrollo de los proyectos arquitectónicos: el caso de la Ópera de Sidney

En numerosas ocasiones a lo largo de la historia la imaginación de los creadores ha ido por delante de las posibilidades técnicas de cada momento. Así, muchas de estas nuevas ideas han requerido largos periodos de tiempo para materializarse como realidad construida, hasta que el desarrollo tecnológico e industrial hubo alcanzado un grado de madurez suficiente. En el campo de la arquitectura, estas limitaciones técnicas se han ido acotando paulatinamente hasta desembocar en la situación actual en la que cualquier planteamiento formal puede ser representado gráficamente y analizado desde un punto de vista estructural, superádose de este modo la barrera existente históricamente en el tratamiento de las formas. A lo largo del presente tesis doctoral se analiza cómo la formulación del Método de los Elementos Finitos en la década de los cincuenta y las curvas de Bézier en la década de los sesenta del siglo pasado y la posterior generalización de los ordenadores personales y de los programas informáticos asociados (C.A.D. y F.E.M. principalmente) en los estudios de arquitectura e ingeniería a partir de la década de los noventa, posibilitó el desarrollo de cualquier propuesta arquitectónica, por compleja que ésta fuese, provocando una verdadera revolución a nivel formal en el mundo de la arquitectura, especialmente en el campo de la edificación singular o icónica. Se estudia este proceso a través de ocho edificios; cuatro anteriores y otros tantos posteriores a la desaparición de la barrera anteriormente referida, establecida de forma simbólica en la década de los años ochenta del siglo XX: Frontón de Recoletos en Madrid, Edificio Seagram en Nueva York, Habitat ’67 en Montreal, Ópera de Sídney, museo Guggenheim de Bilbao, ampliación del Victoria & Albert Museum en Londres, tanatorio “Meiso no Mori” en Gifu y nueva sede de la CCTV en Pekín. De entre ellos, la Ópera de Sídney, obra del arquitecto danés Jørn Utzon, condensa gran parte de los aspectos relevantes investigados en relación a la influencia que los métodos de representación y análisis estructural ejercen en la concepción y construcción de las obras de arquitectura. Por este motivo y por considerarse un hito de la arquitectura a nivel global se toma como caso de estudio. La idea general del edificio, que data de 1956, se enmarca en una época inmediatamente anterior a la del desarrollo científico y tecnológico anteriormente referido. Esta ausencia de herramientas de diseño disponibles acordes a la complejidad formal de la propuesta planteada condicionó enormente la marcha del proyecto, dilatándose dramáticamente en el tiempo y disparándose su coste hasta el punto de que el propio arquitecto danés fue separado de las obras antes de su conclusión. Además, la solución estructural finalmente construida de las cubiertas dista mucho de la prevista por Utzon inicialmente. Donde él había imaginado unas finas láminas de hormigón flotando sobre el paisaje se materializó una estructura más pesada, formada por costillas pretensadas de hormigón con unas secciones notablemente mayores. La forma también debió ser modificada de modo ostensible respecto a la propuesta inicial. Si este edificio se pretendiese construir en la actualidad, con toda seguridad el curso de los acontecimientos se desarrollaría por senderos muy diferentes. Ante este supuesto, se plantean las siguientes cuestiones: ¿sería posible realizar un análisis estructural de la cubierta laminar planteada por Utzon inicialmente en el concurso con las herramientas disponibles en la actualidad?; ¿sería dicha propuesta viable estructuralmente?. A lo largo de las siguientes páginas se pretende dar respuesta a estas cuestiones, poniendo de relieve el impacto que los ordenadores personales y los programas informáticos asociados han tenido en la manera de concebir y construir edificios. También se han analizado variantes a la solución laminar planteada en la fase de concurso, a través de las cuales, tratando en la medida de lo posible de ajustarse a las sugerencias que Ove Arup y su equipo realizaron a Jørn Utzon a lo largo del dilatado proceso de proyecto, mejorar el comportamiento general de la estructura del edificio. Por último, se ha pretendido partir de cero y plantear, desde una perspectiva contemporánea, posibles enfoques metodológicos aplicables a la búsqueda de soluciones estructurales compatibles con la forma propuesta originalmente por Utzon para las cubiertas de la Ópera de Sídney y que nunca llegó a ser construida (ni analizada), considerando para ello los medios tecnológicos, científicos e industriales disponibles en la actualidad. Abstract On numerous occasions throughout history the imagination of creators has gone well beyond of the technical possibilities of their time. Many new ideas have required a long period to materialize, until the technological and industrial development had time to catch up. In the architecture field, these technical limitations have gradually tightened leading to the current situation in which any formal approach can be represented and analyzed from a structural point of view, thus concluding that the structural analysis and the graphical representation’s barrier in the development of architectural projects has dissappeared. Throughout the following pages it is examined how the development of the Finite Element Method in the fifties and the Bezier curves in the sixties of the last century and the subsequent spread of personal computers and specialized software in the architectural and engineering offices from the nineties, enabled the development of any architectural proposal independently of its complexity. This has caused a revolution at a formal level in architecture, especially in the field of iconic building. This process is analyzed through eight buildings, four of them before and another four after the disappearance of the above mentioned barrier, roughly established in the eighties of the last century: Fronton Recoletos in Madrid, Seagram Building in New York Habitat '67 in Montreal, Sydney Opera House, Guggenheim Museum Bilbao, Victoria & Albert Museum extension in London, Crematorium “Meiso no Mori” in Gifu and the new CCTV headquarters in Beijing. Among them, the Sydney Opera House, designed by Danish architect Jørn Utzon, condenses many of the main aspects previously investigated regarding the impact of representation methods and structural analysis on the design and construction of architectural projects. For this reason and also because it is considered a global architecture milestone, it is selected as a case study. The building’s general idea, which dates from 1956, is framed at a time immediately preceding the above mentioned scientific and technological development. This lack of available design tools in accordance with the proposal’s formal complexity conditioned enormously the project’s progress, leading to a dramatic delay and multiplying the final budget disproportionately to the point that the Danish architect himself was separated from the works before completion. Furthermore, the built structure differs dramatically from the architect’s initial vision. Where Utzon saw a thin concrete shell floating over the landscape a heavier structure was built, consisting of prestressed concrete ribs with a significantly greater size. The geometry also had to be modified. If this building were to built today, the course of events surely would walk very different paths. Given this assumption, a number of questions could then be formulated: Would it be possible to perform a structural analysis of Utzon’s initially proposed competition-free-ways roof’s geometry with the tools available nowadays?; Would this proposal be structurally feasable?. Throughout the following pages it is intended to clarify this issues, highlighting personal computers and associated software’s impact in building design and construction procedures, especially in the field of iconic building. Variants have also been analyzed for the laminar solution proposed in the competition phase, through which, trying as far as possible to comply with the suggestions that Ove Arup and his team did to Jørn Utzon along the lengthy process project, improving the overall performance of the building structure. Finally, we have started from scratch and analyzed, from a contemporary perspective, possible structural solutions compatible with Utzon’s Opera House’s original geometry and vision –proposal that was never built (nor even analyzed)-, taking into consideration the technological, scientific and industrial means currently available.

Modelos sin malla en simulación numérica de estructuras aeroespaciales

La presente Tesis Doctoral aborda la introducción de la Partición de Unidad de Bernstein en la forma débil de Galerkin para la resolución de problemas de condiciones de contorno en el ámbito del análisis estructural. La familia de funciones base de Bernstein conforma un sistema generador del espacio de funciones polinómicas que permite construir aproximaciones numéricas para las que no se requiere la existencia de malla: las funciones de forma, de soporte global, dependen únicamente del orden de aproximación elegido y de la parametrización o mapping del dominio, estando las posiciones nodales implícitamente definidas. El desarrollo de la formulación está precedido por una revisión bibliográfica que, con su punto de partida en el Método de Elementos Finitos, recorre las principales técnicas de resolución sin malla de Ecuaciones Diferenciales en Derivadas Parciales, incluyendo los conocidos como Métodos Meshless y los métodos espectrales. En este contexto, en la Tesis se somete la aproximación Bernstein-Galerkin a validación en tests uni y bidimensionales clásicos de la Mecánica Estructural. Se estudian aspectos de la implementación tales como la consistencia, la capacidad de reproducción, la naturaleza no interpolante en la frontera, el planteamiento con refinamiento h-p o el acoplamiento con otras aproximaciones numéricas. Un bloque importante de la investigación se dedica al análisis de estrategias de optimización computacional, especialmente en lo referente a la reducción del tiempo de máquina asociado a la generación y operación con matrices llenas. Finalmente, se realiza aplicación a dos casos de referencia de estructuras aeronáuticas, el análisis de esfuerzos en un angular de material anisotrópico y la evaluación de factores de intensidad de esfuerzos de la Mecánica de Fractura mediante un modelo con Partición de Unidad de Bernstein acoplada a una malla de elementos finitos. ABSTRACT This Doctoral Thesis deals with the introduction of Bernstein Partition of Unity into Galerkin weak form to solve boundary value problems in the field of structural analysis. The family of Bernstein basis functions constitutes a spanning set of the space of polynomial functions that allows the construction of numerical approximations that do not require the presence of a mesh: the shape functions, which are globally-supported, are determined only by the selected approximation order and the parametrization or mapping of the domain, being the nodal positions implicitly defined. The exposition of the formulation is preceded by a revision of bibliography which begins with the review of the Finite Element Method and covers the main techniques to solve Partial Differential Equations without the use of mesh, including the so-called Meshless Methods and the spectral methods. In this context, in the Thesis the Bernstein-Galerkin approximation is subjected to validation in one- and two-dimensional classic benchmarks of Structural Mechanics. Implementation aspects such as consistency, reproduction capability, non-interpolating nature at boundaries, h-p refinement strategy or coupling with other numerical approximations are studied. An important part of the investigation focuses on the analysis and optimization of computational efficiency, mainly regarding the reduction of the CPU cost associated with the generation and handling of full matrices. Finally, application to two reference cases of aeronautic structures is performed: the stress analysis in an anisotropic angle part and the evaluation of stress intensity factors of Fracture Mechanics by means of a coupled Bernstein Partition of Unity - finite element mesh model.

Inhibition of granulocytic differentiation by mNotch1

Effective hematopoiesis requires the commitment of pluripotent and multipotent stem cells to distinct differentiation pathways, proliferation and maturation of cells in the various lineages, and preservation of pluripotent progenitors to provide continuous renewal of mature blood cells. While the importance of positive and negative cytokines in regulating proliferation and maturation of hematopoietic cells has been well documented, the factors and molecular processes involved in lineage commitment and self-renewal of multipotent progenitors have not yet been defined. In other developmental systems, cellular interactions mediated by members of the Notch gene family have been shown to influence cell fate determination by multipotent progenitors. We previously described the expression of the human Notch1 homolog, TAN-1, in immature hematopoietic precursors. We now demonstrate that constitutive expression of the activated intracellular domain of mouse Notch1 in 32D myeloid progenitors inhibits granulocytic differentiation and permits expansion of undifferentiated cells, findings consistent with the known function of Notch in other systems.

Oncogenic mutation in the Kit receptor tyrosine kinase alters substrate specificity and induces degradation of the protein tyrosine phosphatase SHP-1

Activating mutations in the Kit receptor tyrosine kinase have been identified in both rodent and human mast cell leukemia. One activating Kit mutation substitutes a valine for aspartic acid at codon 816 (D816V) and is frequently observed in human mastocytosis. Mutation at the equivalent position in the murine c-kit gene, involving a substitution of tyrosine for aspartic acid (D814Y), has been described in the mouse mastocytoma cell line P815. We have investigated the mechanism of oncogenic activation by this mutation. Expression of this mutant Kit receptor tyrosine kinase in a mast cell line led to the selective tyrosine phosphorylation of a 130-kDa protein and the degradation, through the ubiquitin-dependent proteolytic pathway, of a 65-kDa phosphoprotein. The 65-kDa protein was identified as the src homology domain 2 (SH2)-containing protein tyrosine phosphatase SHP-1, a negative regulator of signaling by Kit and other hematopoietic receptors, and the protein product of the murine motheaten locus. This mutation also altered the sites of receptor autophosphorylation and peptide substrate selectivity. Thus, this mutation activates the oncogenic potential of Kit by a novel mechanism involving an alteration in Kit substrate recognition and the degradation of SHP-1, an attenuator of the Kit signaling pathway.

The targeting pathway of Escherichia coli presecretory and integral membrane proteins is specified by the hydrophobicity of the targeting signal

Previous studies have demonstrated that presecretory proteins such as maltose binding protein (MBP) and outer membrane protein A (OmpA) are targeted to the Escherichia coli inner membrane by the molecular chaperone SecB, but that integral membrane proteins are targeted by the signal recognition particle (SRP). In vitro studies have suggested that trigger factor binds to a sequence near the N terminus of the mature region of OmpA and shunts the protein into the SecB pathway by blocking an interaction between SRP and the signal peptide. By contrast, we have found that the targeting pathway of a protein under physiological conditions is dictated by the composition of its targeting signal. Replacement of the MBP or OmpA signal peptide with the first transmembrane segment of AcrB abolished the dependence on SecB for transport and rerouted both proteins into the SRP targeting pathway. More modest alterations of the MBP signal peptide that simply increase its hydrophobicity also promoted SRP binding. Furthermore, we obtained evidence that SRP has a low affinity for typical signal peptides in vivo. These results imply that different classes of E. coli proteins are targeted by distinct pathways because bacterial SRP binds to a more restricted range of targeting signals than its eukaryotic counterpart.

Structural aspects of activation pathways of aspartic protease zymogens and viral 3C protease precursors

The three-dimensional structures of the inactive protein precursors (zymogens) of the serine, cysteine, aspartic, and metalloprotease classes of proteolytic enzymes are known. Comparisons of these structures with those of the mature, active proteases reveal that, in general, the preformed, active conformations of the residues involved in catalysis are rendered sterically inaccessible to substrates by the residues of the zymogens’ N-terminal extensions or prosegments. The prosegments interact in nonsubstrate-like fashions with the residues of the active sites in most of the cases. The gastric aspartic proteases have a well-characterized zymogen conversion pathway. Structures of human progastricsin, the inactive intermediate 2, and active human pepsin are known and have been used to define the conversion pathway. The structure of the zymogen precursor of plasmepsin II, the malarial aspartic protease, shows a new twist on the mode of inactivation used by the gastric zymogens. The prosegment of proplasmepsin disrupts the active conformation of the two catalytic aspartic acid residues by inducing a major reorientation of the two domains of the mature protease. The picornaviral 2A and 3C proteases have a chymotrypsin-like tertiary structure but with a cysteine nucleophile. These enzymes cleave themselves from the viral polyprotein in cis (intramolecular cleavage) and carry out trans cleavages of other scissile peptides important for the virus life cycle. Although the structure of the precursor viral polyprotein is unknown, it probably resembles the organization of the proenzymes of the bacterial serine proteases, subtilisin, and α-lytic protease. Cleavage of the prosegment is known to occur in cis for these precursor molecules.

cAMP-response element modulator tau is a positive regulator of testis angiotensin converting enzyme transcription.

Testis angiotensin-converting enzyme (ACE) is a unique form of ACE, only produced by male germ cells, and results from a testis-specific promoter found within the ACE gene. We have investigated the role of cAMP-response element modulator (CREM)tau in testis ACE transcription. In gel shift experiments, testes nuclear proteins retard an oligonucleotide containing the cAMP-response element (CRE) found at position -55 in the testis ACE promoter. Anti-CREM antibody supershifts this complex. Competitive gel shift shows that recombinant CREM tau protein and testis nuclear proteins have a similar specificity of binding to the tests ACE CRE. Functional analysis using in vitro transcription and transfection studies also demonstrate that CREM tau protein is a transcriptional activator of the testis ACE promoter. Western blot analysis identifies CREM tau protein in the protein-DNA complex formed between nuclear proteins and the testis ACE CRE motif. This analysis also identified other CREM isoforms in the gel-shifted complex, which are thought to be CREM tau 1/2, CREM alpha/beta, and S-CREM. These data indicate that CREM tau isoforms play an important role as a positive regulator in the tissue-specific expression of testis ACE.