Validación de sistemas constructivos de los cerramientos de la edificación mediante la aplicación de los métodos de decisión multicriterio : aplicación al catálogo de elementos constructivos del Código Técnico de la Edificación

Como punto de partida para el desarrollo de la Tesis, se mantiene la hipótesis de que es posible establecer métodos de evaluación global sobre el grado de utilidad de los sistemas constructivos correspondientes a los cerramientos de la edificación. Tales métodos habrían de posibilitar, de entre una serie finita de sistemas alternativos, cuáles de ellos son los objetivamente más adecuados para su selección en un entorno de decisión concreto, y habrían de permitir fundamentar la justificación objetiva de tal decisión. Paralelamente a esta hipótesis de carácter general, se planteó desde el inicio la necesidad de comprobación de una hipótesis de partida particular según la cual los sistemas constructivos basados en la utilización de componentes prefabricados, o procesos de puesta en obra con un alto grado de industrialización arrojarían valores de utilidad mayores que los sistemas tradicionales basados en la albañilería. Para la verificación de estas dos hipótesis de partida se ha procedido inicialmente a la selección de un conjunto coherente de doce sistemas de cerramientos de la edificación que pudiese servir como testigo de su diversidad potencial, para proceder a su valoración comparativa. El método de valoración propuesto ha entrado a considerar una serie de factores de diversa índole que no son reducibles a un único parámetro o magnitud que permitiese una valoración de tipo lineal sobre su idoneidad relativa, ni que permitiese establecer un grado de prelación entre los distintos sistemas constructivos alternativos de manera absoluta. Para resolver este tour de force o desafío metodológico se ha acudido a la aplicación de metodologías de valoración que nos permitiesen establecer de forma racional dicha comparativa. Nos referimos a una serie de metodologías provenientes en primera instancia de las ciencias exactas, que reciben la denominación de métodos de ayuda a la decisión multicriterio, y en concreto el denominado método ELECTRE. Inicialmente, se ha planteado la aplicación del método de análisis sobre doce sistemas constructivos seleccionados de tal forma que representasen de forma adecuada las tres categorías establecidas para caracterizar la totalidad de sistemas constructivos posibles; por peso, grado de prefabricación y grado de ventilación. Si bien la combinación de las tres categorías básicas anteriormente señaladas produce un total de 18 subcategorías conceptuales, tomamos finalmente doce subcategorías dado que consideramos que es un número operativo suficiente por extenso para el análisis propuesto y elimina tipos no relevantes. Aplicado el método propuesto, a estos doce sistemas constructivos “testigo”, se constata el mayor grado de utilidad de los sistemas prefabricados, pesados y no ventilados. Al hilo del análisis realizado en la Parte II de la Tesis sobre los doce sistemas constructivos “testigo”, se ha realizado un volcado de los sistemas constructivos incluidos en el Catalogo de Elementos Constructivos del CTE (versión 2010) sobre las dieciocho subcategorías definidas en dicha Parte II para caracterizar los sistemas constructivos “testigo”. Posteriormente, se ha procedido a una parametrización de la totalidad de sistemas constructivos para cerramientos de fachadas incluidos en este Catálogo. La parametrización sistemática realizada ha permitido establecer, mediante el cálculo del valor medio que adoptan los parámetros de los sistemas pertenecientes a una misma familia de las establecidas por el Catálogo, una caracterización comparativa del grado de utilidad de dichas familias, tanto en lo relativo a cada uno de los parámetros como en una valoración global de sus valores, de carácter indicativo. Una vez realizada una parametrización completa de la totalidad de sistemas constructivos incluidos en el Catálogo, se ha realizado una simulación de aplicación de la metodología de validación desarrollada en la Parte II de la presente Tesis, con el objeto de comprobar su adecuación al caso. En conclusión, el desarrollo de una herramienta de apoyo a la decisión multicriterio aplicada al Catálogo de Elementos constructivos del CTE se ha demostrado técnicamente viable y arroja resultados significativos. Se han diseñado dos sistemas constructivos mediante la aplicación de la herramienta desarrollada, uno de fachada no ventilada y otro de fachada ventilada. Comparados estos dos sistemas constructivos mejorados con otros sistemas constructivos analizados Se comprueba el alto grado de utilidad objetiva de los dos sistemas diseñados en relación con el resto. La realización de este ejercicio de diseño de un sistema constructivo específico, que responde a los requerimientos de un decisor concreto viene a demostrar, así pues, la utilidad del algoritmo propuesto en su aplicación a los procesos de diseño de los sistemas constructivos. La tesis incorpora dos innovaciones metodológicas y tres innovaciones instrumentales. ABSTRACT The starting point for the thesis is the hypothesis that it is possible to devise suitability degree evaluation methods of building enclosure systems. Such methods should allow optimizing appraisal, given a specific domain of decision, among a finite number of alternative systems, and provide objective justification of such decision. Along with the above mentioned general assumption, a second hypothesis whereby constructive systems based on the use of prefabricated components, or high industrialization degree work processes, would throw efficiency values higher than traditional masonry systems needed to be tested. In order to validate these two hypothesis a coherent set of twelve enclosure systems that could serve as a reference sample of their potential diversity was selected and a comparative evaluation was carried out. The valuation method proposed has considered several different factors that are neither reducible to a single parameter or magnitude that would allow a linear evaluation of their relative suitability nor allow to establishing an absolute priority ranking between different alternative constructive systems. In order to resolve this tour de force or methodological challenge, valuation methodologies that enable use establishing rational assessments were used. We are referring to a number of methodologies taken from the exact sciences field, usually known as aid methods for multi-criteria decision, in particular the so-called ELECTRE method. Even though the combination of the mentioned three basic categories result in eighteen conceptual sub categories, we are finally considering just twelve since we deem it adequately extended for the our intended purpose and eliminates non relevant instances. The method of analysis was initially applied to the set of twelve selected constructive systems is a way that they could represent adequately the three previously established categories set out to characterize all possible enclosure systems, namely weight, prefabrication degree and ventilation degree. Once the proposed method is applied to the sample systems, the higher efficiency of the prefabricated, heavy and not ventilated systems was confirmed. In line with the analysis in Part II of the thesis on the twelve chosen enclosure systems, it has done an uploading data of construction systems listed in the Catalogue of constructive elements of the CTE (version 2010) according the eighteen subcategories used in this part II to characterize the construction systems taken as sample. Subsequently, a parameterization of all enclosure facade systems included in this catalog has been undertaken. The systematic parameterization has allowed to set, by means of calculating the average values of the parameters of the systems belonging to the same family of those established by the Catalog, a comparative characterization of the efficiency degree of these families, both in relation to each parameter as to an overall evaluation of its values, in a indicative way. After the parameterization of all enclosure systems included in the Catalog, a simulation of validation methodology application developed in Part II of this Thesis has been made, in order to assess its consistency to the referred case. In conclusion, the development of a multi-criteria decision aid tool, applied to the CTE Catalog of constructive elements, has proved to be technically feasible and yields significant results. Two building systems through the application of the developed tool, a non-ventilated façade and a ventilated façade have been designed. Comparing these two improved construction systems with other building systems analyzed, we were able to assess the high degree of objective efficiency of the two systems designed in relation to the rest. The exercise of designing a specific enclosure system that meets the requirements of a particular decision-maker hence shows the suitability of the proposed algorithm applied to the process of enclosure systems design. This Thesis includes two methodological innovations and three instrumental innovations.

DISLEXIA E ATENÇÃO

Dislexia é uma condição neurológica associada a deficiências na aquisição e processamento da linguagem. Variando em graus de gravidade, que se manifesta por dificuldades na linguagem receptiva e expressiva, incluindo processamento fonológico, na leitura, escrita, ortografia, caligrafia, e por vezes em aritmética. Dislexia é uma condição hereditária associada a diversas anormalidades neurológicas em áreas corticais visuais e auditivas. Uma das mais influentes teorias para explicar os sintomas disléxicos é a chamada hipótese magnocelular. Segundo esta hipótese, a dislexia resulta de processamento de informações visuais anormais, devido principalmente a disfunção no sistema magnocelular. Esta dissertação explora esta hipótese comparando quinze indivíduos com dislexia e quinze controles, com idades compreendidas entre os 18 e os 30 anos através de dois testes visuais de atenção. Ambos os experimentos avaliam tempo de reação a estímulos que apareciam em toda tela do computador, enquanto os indivíduos permaneciam instalados, com a cabeça apoiada por um chin rest e com os olhos fixos em um alvo central. O experimento I consistiu de estímulos (pequenos círculos) brancos apresentados em um fundo preto. No experimento II, a mesma metodologia foi utilizada, mas agora com os estímulos (pequenos círculos) verdes sobre um fundo vermelho. Os resultados foram analisados levando em consideração os quadrantes onde os estímulos foram apresentados. Pacientes e controles não diferiram em relação ao tempo de reação a estímulos apresentados no campo visual inferior, em comparação ao quadrante superior de um mesmo indivíduo. Considerando todos os quadrantes, disléxicos tiveram tempo de reação mais lento no experimento I, mas apresentaram tempos de reação semelhantes aos controles no experimento II. Estes resultados são compatíveis com anormalidades no sistema magnocelular. As implicações destes achados para a fisiopatologia da dislexia, bem como para o seu tratamento devem ser mais discutidos.(AU)

DISLEXIA E ATENÇÃO

Dislexia é uma condição neurológica associada a deficiências na aquisição e processamento da linguagem. Variando em graus de gravidade, que se manifesta por dificuldades na linguagem receptiva e expressiva, incluindo processamento fonológico, na leitura, escrita, ortografia, caligrafia, e por vezes em aritmética. Dislexia é uma condição hereditária associada a diversas anormalidades neurológicas em áreas corticais visuais e auditivas. Uma das mais influentes teorias para explicar os sintomas disléxicos é a chamada hipótese magnocelular. Segundo esta hipótese, a dislexia resulta de processamento de informações visuais anormais, devido principalmente a disfunção no sistema magnocelular. Esta dissertação explora esta hipótese comparando quinze indivíduos com dislexia e quinze controles, com idades compreendidas entre os 18 e os 30 anos através de dois testes visuais de atenção. Ambos os experimentos avaliam tempo de reação a estímulos que apareciam em toda tela do computador, enquanto os indivíduos permaneciam instalados, com a cabeça apoiada por um chin rest e com os olhos fixos em um alvo central. O experimento I consistiu de estímulos (pequenos círculos) brancos apresentados em um fundo preto. No experimento II, a mesma metodologia foi utilizada, mas agora com os estímulos (pequenos círculos) verdes sobre um fundo vermelho. Os resultados foram analisados levando em consideração os quadrantes onde os estímulos foram apresentados. Pacientes e controles não diferiram em relação ao tempo de reação a estímulos apresentados no campo visual inferior, em comparação ao quadrante superior de um mesmo indivíduo. Considerando todos os quadrantes, disléxicos tiveram tempo de reação mais lento no experimento I, mas apresentaram tempos de reação semelhantes aos controles no experimento II. Estes resultados são compatíveis com anormalidades no sistema magnocelular. As implicações destes achados para a fisiopatologia da dislexia, bem como para o seu tratamento devem ser mais discutidos.(AU)

Perceptual learning in motion discrimination that generalizes across motion directions

When human subjects discriminate motion directions of two visual stimuli, their discrimination improves with practice. This improved performance has been found to be specific to the practiced directions and does not transfer to new motion directions. Indeed, such stimulus-specific learning has become a trademark finding in almost all perceptual learning studies and has been used to infer the loci of learning in the brain. For example, learning in motion discrimination has been inferred to occur in the visual area MT (medial temporal cortex) of primates, where neurons are selectively tuned to motion directions. However, such motion discrimination task is extremely difficult, as is typical of most perceptual learning tasks. When the difficulty is moderately reduced, learning transfers to new motion directions. This result challenges the idea of using simple visual stimuli to infer the locus of learning in low-level visual processes and suggests that higher-level processing is essential even in “simple” perceptual learning tasks.

Altered phosphorylation and intracellular distribution of a (CUG)n triplet repeat RNA-binding protein in patients with myotonic dystrophy and in myotonin protein kinase knockout mice

Myotonic dystrophy (DM) is associated with expansion of CTG repeats in the 3′-untranslated region of the myotonin protein kinase (DMPK) gene. The molecular mechanism whereby expansion of the (CUG)n repeats in the 3′-untranslated region of DMPK gene induces DM is unknown. We previously isolated a protein with specific binding to CUG repeat sequences (CUG-BP/hNab50) that possibly plays a role in mRNA processing and/or transport. Here we present evidence that the phosphorylation status and intracellular distribution of the RNA CUG-binding protein, identical to hNab50 protein (CUG-BP/hNab50), are altered in homozygous DM patient and that CUG-BP/hNab50 is a substrate for DMPK both in vivo and in vitro. Data from two biological systems with reduced levels of DMPK, homozygous DM patient and DMPK knockout mice, show that DMPK regulates both phosphorylation and intracellular localization of the CUG-BP/hNab50 protein. Decreased levels of DMPK observed in DM patients and DMPK knockout mice led to the elevation of the hypophosphorylated form of CUG-BP/hNab50. Nuclear concentration of the hypophosphorylated CUG-BP/hNab50 isoform is increased in DMPK knockout mice and in homozygous DM patient. DMPK also interacts with and phosphorylates CUG-BP/hNab50 protein in vitro. DMPK-mediated phosphorylation of CUG-BP/hNab50 results in dramatic reduction of the CUG-BP2, hypophosphorylated isoform, accumulation of which was observed in the nuclei of DMPK knockout mice. These data suggest a feedback mechanism whereby decreased levels of DMPK could alter phosphorylation status of CUG-BP/hNab50, thus facilitating nuclear localization of CUG-BP/hNab50. Our results suggest that DM pathophysiology could be, in part, a result of sequestration of CUG-BP/hNab50 and, in part, of lowered DMPK levels, which, in turn, affect processing and transport of specific subclass of mRNAs.

WISP genes are members of the connective tissue growth factor family that are up-regulated in Wnt-1-transformed cells and aberrantly expressed in human colon tumors

Wnt family members are critical to many developmental processes, and components of the Wnt signaling pathway have been linked to tumorigenesis in familial and sporadic colon carcinomas. Here we report the identification of two genes, WISP-1 and WISP-2, that are up-regulated in the mouse mammary epithelial cell line C57MG transformed by Wnt-1, but not by Wnt-4. Together with a third related gene, WISP-3, these proteins define a subfamily of the connective tissue growth factor family. Two distinct systems demonstrated WISP induction to be associated with the expression of Wnt-1. These included (i) C57MG cells infected with a Wnt-1 retroviral vector or expressing Wnt-1 under the control of a tetracyline repressible promoter, and (ii) Wnt-1 transgenic mice. The WISP-1 gene was localized to human chromosome 8q24.1–8q24.3. WISP-1 genomic DNA was amplified in colon cancer cell lines and in human colon tumors and its RNA overexpressed (2- to >30-fold) in 84% of the tumors examined compared with patient-matched normal mucosa. WISP-3 mapped to chromosome 6q22–6q23 and also was overexpressed (4- to >40-fold) in 63% of the colon tumors analyzed. In contrast, WISP-2 mapped to human chromosome 20q12–20q13 and its DNA was amplified, but RNA expression was reduced (2- to >30-fold) in 79% of the tumors. These results suggest that the WISP genes may be downstream of Wnt-1 signaling and that aberrant levels of WISP expression in colon cancer may play a role in colon tumorigenesis.

Beryllofluoride mimics phosphorylation of NtrC and other bacterial response regulators

Two-component systems, sensor kinase-response regulator pairs, dominate bacterial signal transduction. Regulation is exerted by phosphorylation of an Asp in receiver domains of response regulators. Lability of the acyl phosphate linkage has limited structure determination for the active, phosphorylated forms of receiver domains. As assessed by both functional and structural criteria, beryllofluoride yields an excellent analogue of aspartyl phosphate in response regulator NtrC, a bacterial enhancer-binding protein. Beryllofluoride also appears to activate the chemotaxis, sporulation, osmosensing, and nitrate/nitrite response regulators CheY, Spo0F, OmpR, and NarL, respectively. NMR spectroscopic studies indicate that beryllofluoride will facilitate both biochemical and structural characterization of the active forms of receiver domains.

Effect of cellular filamentation on adventurous and social gliding motility of Myxococcus xanthus

Filamentous bacterial cells often provide biological information that is not readily evident in normal-size cells. In this study, the effect of cellular filamentation on gliding motility of Myxococcus xanthus, a Gram-negative social bacterium, was investigated. Elongation of the cell body had different effects on adventurous and social motility of M. xanthus. The rate of A-motility was insensitive to cell-body elongation whereas the rate of S-motility was reduced dramatically as the cell body got longer, indicating that these two motility systems work in different ways. The study also showed that filamentous wild-type cells glide smoothly with relatively straight, long cell bodies. However, filamentous cells of certain social motility mutants showed zigzag, tangled cell bodies on a solid surface, apparently a result of a lack of coordination between different fragments within the filaments. Further genetic and biochemical analyses indicated that the uncoordinated movements of these mutant filaments were correlated with the absence of cell surface fibril materials, indicating a possible new function for fibrils.

Cells that register logical relationships among proteins

Two-hybrid methods have augmented the classical genetic techniques biologists use to assign function to genes. Here, we describe construction of a two-bait interaction trap that uses yeast cells to register more complex protein relationships than those detected in existing two-hybrid systems. We show that such cells can identify bridge or connecting proteins and peptide aptamers that discriminate between closely related allelic variants. The protein relationships detected by these cells are analogous to classical genetic relationships, but lend themselves to systematic application to the products of entire genomes and combinatorial libraries. We show that, by performing logical operations on the phenotypic outputs of these complex cells and existing two-hybrid cells, we can make inferences about the topology and order of protein interactions. Finally, we show that cells that register such relationships can perform logical operations on protein inputs. Thus these cells will be useful for analysis of gene and allele function, and may also define a path for construction of biological computational devices.

Functional Domains of Rep2, a Transcriptional Activator Subunit for Res2–Cdc10, Controlling the Cell Cycle “Start”

In the fission yeast Schizosaccharomyces pombe, passage from G1 to S-phase requires the execution of the transcriptional factor complex that consists of the Cdc10 and Res1/2 molecules. This complex activates the MluI cell cycle box cis-element contained in genes essential for S-phase onset and progression. The rep2+ gene, isolated as a multicopy suppressor of a temperature-sensitive cdc10 mutant, has been postulated to encode a putative transcriptional activator subunit for the Res2–Cdc10 complex. To identify the rep2+ function and molecularly define its domain organization, we reconstituted the Res2–Cdc10 complex-dependent transcriptional activation in Saccharomyces cerevisiae. Reconstitution experiments, deletion analyses using one and two hybrid systems, and in vivo Res2 coimmunoprecipitation assays show that the Res2–Cdc10 complex itself can recognize but cannot activate MluI cell cycle box without Rep2, and that consistent with its postulated function, Rep2 contains 45-amino acid Res2 binding and 22-amino acid transcriptional activation domains in the middle and C terminus of the molecule, respectively. The functional essentiality of these domains is also demonstrated by their requirement for rescue of the cold-sensitive rep2 deletion mutant of fission yeast.

Spectral diffusion and the energy landscape of a protein

We present a novel type of spectral diffusion experiment in the millikelvin range to characterize the energy landscape of a protein as compared with that of a glass. We measure the time evolution of spectral holes for more than 300 hr after well-defined initial nonequilibrium conditions. We show that the model of noninteracting two-level systems can describe spectral diffusion in the glass, but fails for the protein. Our results further demonstrate that randomness in the energy landscape of a protein shows features of organization. There are “deep minimum” states separated by barriers, the heights of which we are able to estimate. The energy landscape of a glass is featureless by comparison.

Cadherin Sequences That Inhibit β-Catenin Signaling: A Study in Yeast and Mammalian Cells

Drosophila Armadillo and its mammalian homologue β-catenin are scaffolding proteins involved in the assembly of multiprotein complexes with diverse biological roles. They mediate adherens junction assembly, thus determining tissue architecture, and also transduce Wnt/Wingless intercellular signals, which regulate embryonic cell fates and, if inappropriately activated, contribute to tumorigenesis. To learn more about Armadillo/β-catenin's scaffolding function, we examined in detail its interaction with one of its protein targets, cadherin. We utilized two assay systems: the yeast two-hybrid system to study cadherin binding in the absence of Armadillo/β-catenin's other protein partners, and mammalian cells where interactions were assessed in their presence. We found that segments of the cadherin cytoplasmic tail as small as 23 amino acids bind Armadillo or β-catenin in yeast, whereas a slightly longer region is required for binding in mammalian cells. We used mutagenesis to identify critical amino acids required for cadherin interaction with Armadillo/β-catenin. Expression of such short cadherin sequences in mammalian cells did not affect adherens junctions but effectively inhibited β-catenin–mediated signaling. This suggests that the interaction between β-catenin and T cell factor family transcription factors is a sensitive target for disruption, making the use of analogues of these cadherin derivatives a potentially useful means to suppress tumor progression.

The yeast ZRT1 gene encodes the zinc transporter protein of a high-affinity uptake system induced by zinc limitation.

The yeast Saccharomyces cerevisiae has two separate systems for zinc uptake. One system has high affinity for substrate and is induced in zinc-deficient cells. The second system has lower affinity and is not highly regulated by zinc status. The ZRT1 gene encodes the transporter for the high-affinity system, called Zrt1p. The predicted amino acid sequence of Zrt1p is similar to that of Irt1p, a probable Fe(II) transporter from Arabidopsis thaliana. Like Irt1p, Zrt1p contains eight potential transmembrane domains and a possible metal-binding domain. Consistent with the proposed role of ZRT1 in zinc uptake, overexpressing this gene increased high-affinity uptake activity, whereas disrupting it eliminated that activity and resulted in poor growth of the mutant in zinc-limited media. Furthermore, ZRT1 mRNA levels and uptake activity were closely correlated, as was zinc-limited induction of a ZRT1-lacZ fusion. These results suggest that ZRT1 is regulated at the transcriptional level by the intracellular concentration of zinc. ZRT1 is an additional member of a growing family of metal transport proteins.

Phase separation in aqueous solutions of lens gamma-crystallins: special role of gamma s.

We have studied liquid-liquid phase separation in aqueous ternary solutions of calf lens gamma-crystallin proteins. Specifically, we have examined two ternary systems containing gamma s--namely, gamma IVa with gamma s in water and gamma II with gamma s in water. For each system, the phase-separation temperatures (Tph (phi)) alpha as a function of the overall protein volume fraction phi at various fixed compositions alpha (the "cloud-point curves") were measured. For the gamma IVa, gamma s, and water ternary solution, a binodal curve composed of pairs of coexisting points, (phi I, alpha 1) and (phi II, alpha II), at a fixed temperature (20 degrees C) was also determined. We observe that on the cloud-point curve the critical point is at a higher volume fraction than the maximum phase-separation temperature point. We also find that typically the difference in composition between the coexisting phases is at least as significant as the difference in volume fraction. We show that the asymmetric shape of the cloud-point curve is a consequence of this significant composition difference. Our observation that the phase-separation temperature of the mixtures in the high volume fraction region is strongly suppressed suggests that gamma s-crystallin may play an important role in maintaining the transparency of the lens.

Identification of a Drosophila G protein alpha subunit (dGq alpha-3) expressed in chemosensory cells and central neurons.

We have identified another Drosophila GTP-binding protein (G protein) alpha subunit, dGq alpha-3. Transcripts encoding dGq alpha-3 are derived from alternative splicing of the dGq alpha locus previously shown to encode two visual-system-specific transcripts [Lee, Y.-J., Dobbs, M.B., Verardi, M.L. & Hyde, D.R. (1990) Neuron 5, 889-898]. Immunolocalization studies using dGq alpha-3 isoform-specific antibodies and LacZ fusion genes show that dGq alpha-3 is expressed in chemosensory cells of the olfactory and taste structures, including a subset of olfactory and gustatory neurons, and in cells of the central nervous system, including neurons in the lamina ganglionaris. These data are consistent with a variety of roles for dGq alpha-3, including mediating a subset of olfactory and gustatory responses in Drosophila, and supports the idea that some chemosensory responses use G protein-coupled receptors and the second messenger inositol 1,4,5-trisphosphate.