1000 resultados para Constructive expression
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Cette thèse entend contribuer à la compréhension du processus de conception architecturale par le biais du concept de tectonique, notion dont l’historicité confirme une certaine diversité de significations, mais qui suscite une réflexion fondamentale sur le rapport entre l’esthétique architecturale et les moyens constructifs. La connaissance technique de la construction, constituée principalement au 18ème siècle, permettra une nouvelle réflexion sur le rapport entre l’esthétique architecturale et les moyens constructifs. Au 19ème siècle, moment de l’apparition du concept de « tectonique » dans le contexte du débat sur la notion de style, l’indéniable contribution de l’architecte et théoricien Gottfried Semper reconnaît la complexité matérielle de l’édifice. La reprise du terme au 20ème siècle par l’historien et théoricien Kenneth Frampton va quant à elle déplacer le sens de la tectonique vers l’idée d’un « potentiel d’expression constructive ». Ces deux auteurs représentent deux grandes approches tectoniques convergeant sur la nécessité, pour toute théorie de l’architecture, d’encourager une réflexion critique de la construction. Cette thèse se développe en deux parties, l’une retraçant l’histoire et les enjeux de la tectonique, l’autre, de nature plus concrète, cherchant à tester l’actualité du concept à travers une série d’analyses tectoniques de projets modernes et contemporains. À la croisée de deux contextes géographiques différents, le Canada et le Brésil, le corpus de projets de concours que nous avons constitué considère la tectonique comme un phénomène transculturel. Nous formulons l’hypothèse d’une « tectonique du projet », c’est-à-dire d’un espace théorique dans lequel les questions relatives au bâtiment s’élaborent dans des « tensions » dialectiques. L’actualité des catégories semperiennes, dans lesquelles les différents « éléments » du bâtiment représentent différentes techniques de construction, est revisitée à partir de l’étude des projets de Patkau Architects (1986) et de MMBB Arquitetos (1990). Une tension entre les expressions symbolique et formelle issues du matériau brut est plus explicite dans l’étude des projets de Ramoisy Tremblay architectes (2002) et de Brasil Arquitetura (2005). La théorie de la transformation de matériau (Stoffwechseltheorie) de Semper est réexaminée parallèlement dans les projets d’Arthur Erickson et Geoffrey Massey (1967) et de Paulo Mendes da Rocha (1969). Dans l’ensemble de tensions tectoniques présentes tout au long de la conception, nous avons retenu plus particulièrement : le contact avec le sol, la recherche d’une homogénéité constructive, ou son opposé, la recherche d’une variété matérielle et, finalement la tension entre la dimension représentationnelle et la dimension technique de l’architecture. La modélisation du concept de tectonique, par un ensemble de tensions auxquelles les concepteurs doivent s’adresser en phase de projet, confirme que des questions en apparence simplement « techniques » concernent en fait tout autant le génie de l’invention que la connaissance historique des idées architecturales.
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The general aim of this study can be summarized in contributin gempirical evidence on the existence, design, fabrication and functioning of the crossing trellis vaults asa constructive expression of the Spanish renaissance moved to the New Spain, today México, and their mutual relation.
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Para acercarnos al pensamiento creativo de Fernando Higueras como arquitecto, partimos del estudio de sus constantes creativas en evolución cronológica divididas en 9 direcciones de investigación. En ellas observamos la importancia de su obra NO CONSTRUIDA, como germen de las constantes creativas de su pensamiento y parte de ella la estudiamos, analizamos y reconstruimos gráficamente en 3D. Fernando Higueras aprendía de sus obras o propuestas arquitectónicas anteriores llegando a la madurez constructiva y formal colmada de Belleza a través de la composición y combinación de dichas constantes con pasmosa naturalidad. Además es importante añadir, para llegar a la comprensión de las constantes del pensamiento creativo del arquitecto, el componente de “intuición” de todo artista, de su modo de mirar y observar las cosas como fuente de inspiración. El “modo de mirar” del arquitecto nos habla de su sensibilidad al hábitat popular y vernáculo del hombre. Gracias a Antonio Miró en el período 1963-1970, Fernando Higueras pudo dar marco real a gran parte de sus ideas constructivas. El objeto de estudio del presente trabajo es llegar a las “invariantes” del arquitecto para comprender su pensamiento creativo. Los objetivos del presente estudio han sido conocer mejor su pensamiento, su obra desde un punto de vista cronológico-evolutivo para poder llegar a entender las relaciones y conexiones creativas entre unas y otras, observar y constatar la evolución de sus constantes creativas y compositivas, de analizar gráficamente parte de su obra no construida para llegar a la mejor comprensión de dichas constantes reconstruyéndolas con los medios gráficos digitales actuales. La reconstrucción en 3D de parte de su obra no construida constata la magnitud de su pensamiento creativo. La metodología empleada parte de la recopilación de toda la información necesaria, escritos, artículos en revistas o periódicos, críticas, observaciones, planos, proyectos, memorias, fotografías de la época, maquetas, opiniones de sus contemporáneos, familiares o amigos y visita de parte de su obra construida. A partir de ahí se fijan 9 direcciones de investigación para cada constante de su pensamiento creativo. En cada dirección se analiza desde dos puntos de vista diferentes. Un primer punto de vista teórico o cronológico-evolutivo a partir de la selección de algunas de sus obras construidas y no construidas. Y otro segundo punto de vista gráfico basándose en el estudio y reconstrucción de parte de su obra no construida. En resultado, se ha estudiado la evolución de su obra viendo las conexiones y relaciones entre unas y otras llegando a la madurez de sus constantes creativas en sus obras, algunas construidas y otras no construidas. Fernando Higueras se perfecciona así mismo, intentando hacer las cosas cada vez un poco mejor, llegando a dominar sus propias constantes en total madurez y expresión formal y constructiva. La elaboración de modelos tridimensionales en 13 proyectos de su obra no construida nos refresca la capacidad de su pensamiento creativo, además de analizar en parte de ellas los gérmenes constructivos y compositivos de muchas de sus ideas o constantes creativas. Finalmente, este trabajo ha contribuido a llegar a entender a Fernando Higueras en una dimensión más amplia, desde el frescor de su obra no construida hasta la capacidad de su pensamiento creativo, de la evolución de sus constantes, del estudio de sus últimos proyectos no construidos, de su sensibilidad a todas las artes y a todo lo que engloba Belleza. Las 360 láminas de dibujos que se aportan inician el estudio y análisis de su vasta obra no construida. ABSTRACT The analysis of Fernando Higueras's creative thought as an architect begins with a study of his main creative themes and their chronological evolution, divided into nine directions of research. Here we see the importance of his UNBUILT work as the germ of the creative themes of his thought, part of which we study, analyse and reconstruct graphically in 3-D. Fernando Higueras drew on his earlier architectural works and ideas and reached an ultimate constructive and formal maturity that was infused with beauty through composition and the amazingly natural combination of these keynote themes. In order to gain a greater understanding of the key themes of the architect's creative thought it is also worth noting the element of artists' intuition, their way of seeing and observing the world as a source of inspiration. The architect's "way of seeing" reveals his sensitivity to the popular and traditional human habitat. Thanks to Antonio Miró, in the period between 1963 and 1970 Fernando Higueras was able to provide a real framework for a large part of his constructive ideas. The object of study of the present work is to determine the architect's “invariables” as a means of understanding his creative thought. The aims of the present study are to explore his thoughts in greater depth, to examine his work from the chronological-evolutionary point of view for an insight into the relationships and the creative connections between them, to observe and apprehend the evolution of his main creative themes and compositional keynotes, to analyse graphically part of his unbuilt work in order to improve our understanding of these underlying themes through their reconstruction using the latest graphic digital resources. The 3-D reconstruction of part of his unbuilt work highlights the magnitude of his creative thought. The methodology used to collect all the necessary information includes an examination of his writings and articles in journals and newspapers, criticisms, observations, plans, projects, building specifications, period photographs, models, the opinions of his contemporaries, family and friends, and visits to some of his built work. Nine directions of research were then established for each main theme of his creative thought. Each direction includes an analysis from two different points of view: the first, theoretical or chronological-evolutionary aspect, based on a selection of some of his built and unbuilt works; and a second graphic aspect based on the study and reconstruction of part of his unbuilt work. The result is a survey of the evolution of his work with a view to establishing the connections and their interrelationships, through to the ultimate maturity of his creative themes in both his built and unbuilt work. Fernando Higueras is on a constant quest for excellence, a perpetual desire to do things a little better, until a point where he gains mastery over his own recurrent themes, in the fullness of maturity and of his formal and constructive expression. The creation of three-dimensional models in 13 projects of his unbuilt work offers a new look at the capacity of his creative thought, in addition to the analysis of the evidence in some of these projects of the constructive and compositional germs of many of his ideas and themes. Finally, this work has contributed to the understanding of Fernando Higueras in a broader dimension, from the freshness of his unbuilt work through to the capacity of his creative thought, the evolution of his main themes, the study of his final unbuilt works, his sensitivity to the arts as a whole and to everything beautiful. The 360 plates of illustrations provided form the basis of the study and analysis of his extensive unbuilt work.
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This paper addresses the theme of retrotif applied to buildings that belong to the modernist architectural production of historical interest located in the urban area of Natal . The overall objective is to identify and harmonize procedures for retrofit and architectural heritage preservation using elements of constructive analysis of expression and Benefit Cost Ratio ( BCR ) parameters established by the National Electric Energy Agency - ANEEL . The hypothesis put forward is that by stimulating the projetual year analysis , retrofit interventions , it is possible to obtain better results with projects RCB addressing the issues of preservation of architectural heritage . For both flow analysis of process solutions and proposals for action of elements and systems that seek to improve the energy performance of the building , restoring or preserving the architectural elements were developed . The proposed interventions undergo performance through computer simulations of systems such as DesignBuilder, Solar and Sun Tool. The energy results were converted to the analysis of RCB parameter and compared to the constructive expression of the project because the prenatal and intervention. From the results , a plot was constructed which results in a comparison between the RCB and the constructive expression of the simulated interventions
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Abstract Background Transcript enumeration methods such as SAGE, MPSS, and sequencing-by-synthesis EST "digital northern", are important high-throughput techniques for digital gene expression measurement. As other counting or voting processes, these measurements constitute compositional data exhibiting properties particular to the simplex space where the summation of the components is constrained. These properties are not present on regular Euclidean spaces, on which hybridization-based microarray data is often modeled. Therefore, pattern recognition methods commonly used for microarray data analysis may be non-informative for the data generated by transcript enumeration techniques since they ignore certain fundamental properties of this space. Results Here we present a software tool, Simcluster, designed to perform clustering analysis for data on the simplex space. We present Simcluster as a stand-alone command-line C package and as a user-friendly on-line tool. Both versions are available at: http://xerad.systemsbiology.net/simcluster. Conclusion Simcluster is designed in accordance with a well-established mathematical framework for compositional data analysis, which provides principled procedures for dealing with the simplex space, and is thus applicable in a number of contexts, including enumeration-based gene expression data.
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Characterized for the first time in erythrocytes, phosphatidylinositol phosphate kinases (PIP kinases) belong to a family of enzymes that generate various lipid messengers and participate in several cellular processes, including gene expression regulation. Recently, the PIPKIIα gene was found to be differentially expressed in reticulocytes from two siblings with hemoglobin H disease, suggesting a possible relationship between PIPKIIα and the production of globins. Here, we investigated PIPKIIα gene and protein expression and protein localization in hematopoietic-derived cells during their differentiation, and the effects of PIPKIIα silencing on K562 cells. PIPKIIα silencing resulted in an increase in α and γ globins and a decrease in the proliferation of K562 cells without affecting cell cycle progression and apoptosis. In conclusion, using a cell line model, we showed that PIPKIIα is widely expressed in hematopoietic-derived cells, is localized in their cytoplasm and nucleus, and is upregulated during erythroid differentiation. We also showed that PIPKIIα silencing can induce α and γ globin expression and decrease cell proliferation in K562 cells.
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Phospholipases A2 (PLA2) are key enzymes for production of lipid mediators. We previously demonstrated that a snake venom sPLA2 named MT-III leads to prostaglandin (PG)E2 biosynthesis in macrophages by inducing the expression of cyclooxygenase-2 (COX-2). Herein, we explored the molecular mechanisms and signaling pathways leading to these MT-III-induced effects. Results demonstrated that MT-III induced activation of the transcription factor NF-κB in isolated macrophages. By using NF-κB selective inhibitors, the involvement of this factor in MT-III-induced COX-2 expression and PGE2 production was demonstrated. Moreover, MT-III-induced COX-2 protein expression and PGE2 release were attenuated by pretreatment of macrophages with SB202190, and Ly294002, and H-7-dihydro compounds, indicating the involvement of p38MAPK, PI3K, and PKC pathways, respectively. Consistent with this, MT-III triggered early phosphorylation of p38MAPK, PI3K, and PKC. Furthermore, SB202190, H-7-dihydro, but not Ly294002 treatment, abrogated activation of NF-κB induced by MT-III. Altogether, these results show for the first time that the induction of COX-2 protein expression and PGE2 release, which occur via NF-κB activation induced by the sPLA2-MT-III in macrophages, are modulated by p38MAPK and PKC, but not by PI3K signaling proteins.
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Lutein (LT) is a carotenoid obtained by diet and despite its antioxidant activity had been biochemically reported, few studies are available concerning its influence on the expression of antioxidant genes. The expression of 84 genes implicated in antioxidant defense was quantified using quantitative reverse transcription polymerase chain reaction array. DNA damage was measured by comet assay and glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were quantified as biochemical parameters of oxidative stress in mouse kidney and liver. cDDP treatment reduced concentration of GSH and increased TBARS, parameters that were ameliorated in treatment associated with LT. cDDP altered the expression of 32 genes, increasing the expression of GPx2, APC, Nqo1 and CCs. LT changed the expression of 37 genes with an induction of 13 mainly oxygen transporters. In treatments associating cDDP and LT, 30 genes had their expression changed with a increase of the same genes of the cDDP treatment alone. These results suggest that LT might act scavenging reactive species and also inducing the expression of genes related to a better antioxidant response, highlighting the improvement of oxygen transport. This improved redox state of the cell through LT treatment could be related to the antigenotoxic and antioxidant effects observed.
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Differential gene expression analysis by suppression subtractive hybridization with correlation to the metabolic pathways involved in chronic myeloid leukemia (CML) may provide a new insight into the pathogenesis of CML. Among the overexpressed genes found in CML at diagnosis are SEPT5, RUNX1, MIER1, KPNA6 and FLT3, while PAN3, TOB1 and ITCH were decreased when compared to healthy volunteers. Some genes were identified and involved in CML for the first time, including TOB1, which showed a low expression in patients with CML during tyrosine kinase inhibitor treatment with no complete cytogenetic response. In agreement, reduced expression of TOB1 was also observed in resistant patients with CML compared to responsive patients. This might be related to the deregulation of apoptosis and the signaling pathway leading to resistance. Most of the identified genes were related to the regulation of nuclear factor κB (NF-κB), AKT, interferon and interleukin-4 (IL-4) in healthy cells. The results of this study combined with literature data show specific gene pathways that might be explored as markers to assess the evolution and prognosis of CML as well as identify new therapeutic targets.
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Bisphenol-A (BPA) is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β-cell function and gene expression in the major peripheral organs that control energy flux: white adipose tissue (WAT), the liver and skeletal muscle, in male offspring 17 and 28 weeks old. Pregnant mice were treated with a subcutaneous injection of 10 µg/kg/day of BPA or a vehicle from day 9 to 16 of pregnancy. One month old offspring were divided into four different groups: vehicle treated mice that ate a normal chow diet (Control group); BPA treated mice that also ate a normal chow diet (BPA); vehicle treated animals that had a high fat diet (HFD) and BPA treated animals that were fed HFD (HFD-BPA). The BPA group started to gain weight at 18 weeks old and caught up to the HFD group before week 28. The BPA group as well as the HFD and HFD-BPA ones presented fasting hyperglycemia, glucose intolerance and high levels of non-esterified fatty acids (NEFA) in plasma compared with the Control one. Glucose stimulated insulin release was disrupted, particularly in the HFD-BPA group. In WAT, the mRNA expression of the genes involved in fatty acid metabolism, Srebpc1, Pparα and Cpt1β was decreased by BPA to the same extent as with the HFD treatment. BPA treatment upregulated Pparγ and Prkaa1 genes in the liver; yet it diminished the expression of Cd36. Hepatic triglyceride levels were increased in all groups compared to control. In conclusion, male offspring from BPA-treated mothers presented symptoms of diabesity. This term refers to a form of diabetes which typically develops in later life and is associated with obesity.
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Congenital muscular dystrophy with laminin α2 chain deficiency (MDC1A) is one of the most severe forms of muscular disease and is characterized by severe muscle weakness and delayed motor milestones. The genetic basis of MDC1A is well known, yet the secondary mechanisms ultimately leading to muscle degeneration and subsequent connective tissue infiltration are not fully understood. In order to obtain new insights into the molecular mechanisms underlying MDC1A, we performed a comparative proteomic analysis of affected muscles (diaphragm and gastrocnemius) from laminin α2 chain-deficient dy(3K)/dy(3K) mice, using multidimensional protein identification technology combined with tandem mass tags. Out of the approximately 700 identified proteins, 113 and 101 proteins, respectively, were differentially expressed in the diseased gastrocnemius and diaphragm muscles compared with normal muscles. A large portion of these proteins are involved in different metabolic processes, bind calcium, or are expressed in the extracellular matrix. Our findings suggest that metabolic alterations and calcium dysregulation could be novel mechanisms that underlie MDC1A and might be targets that should be explored for therapy. Also, detailed knowledge of the composition of fibrotic tissue, rich in extracellular matrix proteins, in laminin α2 chain-deficient muscle might help in the design of future anti-fibrotic treatments. All MS data have been deposited in the ProteomeXchange with identifier PXD000978 (http://proteomecentral.proteomexchange.org/dataset/PXD000978).
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Nutrient restriction during the early stages of life usually leads to alterations in glucose homeostasis, mainly insulin secretion and sensitivity, increasing the risk of metabolic disorders in adulthood. Despite growing evidence regarding the importance of insulin clearance during glucose homeostasis in health and disease, no information exists about this process in malnourished animals. Thus, in the present study, we aimed to determine the effect of a nutrient-restricted diet on insulin clearance using a model in which 30-d-old C57BL/6 mice were exposed to a protein-restricted diet for 14 weeks. After this period, we evaluated many metabolic variables and extracted pancreatic islet, liver, gastrocnemius muscle (GCK) and white adipose tissue samples from the control (normal-protein diet) and restricted (low-protein diet, LP) mice. Insulin concentrations were determined using RIA and protein expression and phosphorylation by Western blot analysis. The LP mice exhibited lower body weight, glycaemia, and insulinaemia, increased glucose tolerance and altered insulin dynamics after the glucose challenge. The improved glucose tolerance could partially be explained by an increase in insulin sensitivity through the phosphorylation of the insulin receptor/protein kinase B and AMP-activated protein kinase/acetyl-CoA carboxylase in the liver, whereas the changes in insulin dynamics could be attributed to reduced insulin secretion coupled with reduced insulin clearance and lower insulin-degrading enzyme (IDE) expression in the liver and GCK. In summary, protein-restricted mice not only produce and secrete less insulin, but also remove and degrade less insulin. This phenomenon has the double benefit of sparing insulin while prolonging and potentiating its effects, probably due to the lower expression of IDE in the liver, possibly with long-term consequences.
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There is an increasing rate of papillary thyroid carcinomas that may never progress to cause symptoms or death. Predicting outcome and determining tumour aggressiveness could help diminish the number of patients submitted to aggressive treatments. We aimed to evaluate whether markers of the immune system response and of tumour-associated inflammation could predict outcome of differentiated thyroid cancer (DTC) patients. Retrospective cohort study. We studied 399 consecutive patients, including 325 papillary and 74 follicular thyroid carcinomas. Immune cell markers were evaluated using immunohistochemistry, including tumour-associated macrophages (CD68) and subsets of tumour-infiltrating lymphocytes (TIL), such as CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZYME B, CD69 and CD25. We also investigated the expression of cyclooxygenase 2 (COX2) in tumour cells and the presence of concurrent lymphocytic infiltration characterizing chronic thyroiditis. Concurrent lymphocytic infiltration characterizing chronic thyroiditis was observed in 29% of the cases. Among all the immunological parameters evaluated, only the enrichment of CD8+ lymphocytes (P = 0·001) and expression of COX2 (P =0·01) were associated with recurrence. A multivariate model analysis identified CD8+ TIL/COX2 as independent risk factor for recurrence. A multivariate analysis using Cox's proportional-hazards model adjusted for the presence of concurrent chronic thyroiditis demonstrated that the presence of concurrent chronic thyroiditis had no effect on prognostic prediction mediated by CD8+ TIL and COX2. In conclusion, we suggest the use of a relatively simple pathology tool to help select cases that may benefit of a more aggressive approach sparing the majority of patients from unnecessary procedures.
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Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7). P5'NI gene (NT5C3) gene sequencing revealed a further change in homozygosity at amino acid position 56 (p.R56G), located in a highly conserved region. Both patients developed gallstones; however the father, who had undergone surgery for the removal of stones, had extremely severe intrahepatic cholestasis and, liver biopsy revealed fibrosis and siderosis grade III, leading us to believe that the homozygosity of the UGT1A polymorphism was responsible for the more severe clinical features in the father. Moreover, our results show how the clinical expression of hemolytic anemia is influenced by epistatic factors and we describe a new mutation in the P5'N gene associated with enzyme deficiency, iron overload, and severe gallstone formation. To our knowledge, this is the first description of P5'N deficiency in South Americans.
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Squamous cell carcinoma is the most common neoplasm of the larynx and glottis, and its prognosis depends on the size of the lesion, level of local invasion, cervical lymphatic spread, and presence of distant metastases. Ki-67 (MKI67) is a protein present in the core, whose function is related to cell proliferation. To evaluate the expression of marker Ki-67 in squamous cell carcinoma of the larynx and glottis and its correlation to pathological findings. Experimental study with immunohistochemistry analysis of Ki-67, calculating the percentage of the cell proliferation index in glottic squamous cell carcinomas. Sixteen cases were analyzed, with six well-differentiated and 10 poorly/moderately differentiated tumors. There was a correlation between cell proliferation index and degree of cell differentiation, with higher proliferation in poorly/moderately differentiated tumors. The cell proliferation index, as measured by Ki-67, may be useful in the characterization of histological degree in glottic squamous cell tumors.