800 resultados para locality influences
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Climate variability and changes in the frequency of extremes events have a direct impact on crop damages and yield. In a former work of Capa et al. (2013) the crop yield variability has been studied using different reanalyses datasets with the aim of extending the time series of potential yield. The reliability of these time series have been checked using observational data. The influence of the sea surface temperature on the crop yield variability has been studied, finding a relation with El Niño phenomenon. The highest correlation between El Niño and yield was during 1960-1980. This study aims to analyse the dynamical mechanism of El Niño impacts on maize yield in Spain during 1960-1980 by comparison with atmospheric circulation patterns.
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La tesis afronta el análisis del itinerario vital de Fernando Távora, una vida entregada apasionadamente a una causa de refundación estética y conceptual de una arquitectura portuguesa condenada a la mediocridad y al ostracismo en el momento en que empieza a ejercer la profesión. La investigación se adentra en todos los aspectos que convergen en su dedicación al logro de aquella misión, pues la que él mismo probablemente llamaría orteguianamente su circunstancia, resulta inseparable de su pensamiento y de su obra. Se pretende establecer la riqueza y complejidad de la figura de Fernando Távora y su importancia como punto de inflexión en la evolución de la arquitectura portuguesa, que ha llegado a alcanzar el reconocimiento internacional en las últimas décadas, fundamentalmente a partir de la consagración de Álvaro Siza Vieira y la denominada Escuela de Oporto. Desde una posición de absoluta autonomía respecto de lo que acontece dentro y fuera de las fronteras portuguesas, su labor se distinguirá por su singularidad teórica y arquitectónica, no dejando por ello de influir decisivamente en su entorno cercano. Dos manifiestos escritos, el juvenil O problema da Casa Portuguesa y el posterior Da Organização do Espaço son elementos estructurantes de un pensamiento teórico que germina en una obra construida inseparable de aquel, de cuya coherencia dan testimonio los aquí considerados verdaderos manifiestos proyectuales del arquitecto. Efectivamente, se analizarán detalladamente como tales la Casa sobre o Mar –manifiesto inicial-, el Pabellón de Tenis –manifiesto de confirmación- y la Casa dos 24 -manifiesto final-, proyectos que vieron la luz en diferentes etapas de su trayectoria y constituyen la aplicación práctica de sus teorías en una sintaxis magistral. En estos tres proyectos es donde verdaderamente la tesis cobra cuerpo, pues suponen el reflejo de la verdadera aportación del arquitecto al pensamiento arquitectónico europeo, la foto fija de la proclamación de resultados de un proyecto arquitectónico integral en momentos muy significativos de su itinerario vital, cuya complejidad se entiende a través de las fases más descriptivas de este documento. Se mostrará cómo para acometer su proyecto integral de arquitectura, una causa de regeneración de la arquitectura portuguesa a partir de la síntesis entre modernidad y tradición, entre universalidad y localidad, tomaría de sus dos personajes más admirados, Le Corbusier y Pessoa, la fuerza moral y la energía que le permitieron acometer apasionadamente tamaña misión. En una infatigable búsqueda en lo global y lo local, Távora conseguirá prestar gran atención al contexto del lugar de intervención sin renunciar a sus convicciones modernas, introduciendo la historia y el dibujo como herramientas de conocimiento del mismo y posteriormente del proceso creativo. El método proyectivo resultante de este modelo, que transmitirá a través de su ejercicio docente a sucesivas generaciones de arquitectos, se convertirá en elemento estructurante de una tendencia surgida de las aulas portuenses, que la crítica internacional acabará denominando Escuela de Oporto en un sentido más amplio. Por su importancia dentro del itinerario profesional del[os] arquitecto[s] portuense[s], las fases más destacadas de su evolución a partir de los años 50 se analizarán en paralelo a una serie de obras representativas de diferentes momentos de la trayectoria de Fernando Távora. En este itinerario vital, a pesar de la originalidad de su pensamiento y su obra, se atisban ciertos paralelismos con grandes arquitectos del siglo XX, que esta tesis afronta. Se puede distinguir entre influencias pasajeras de algunos maestros modernos en los que Távora buscaba la confirmación a sus propias teorías, similitudes con arquitectos coetáneos cuya obra conoció y a los que se encontró cercano por la convergencia de algunos de sus criterios e incluso sorprendentes coincidencias con arquitectos desconocidos para él, entre las que cabe destacar la de los maestros de la Escuela de Madrid Alejandro de la Sota y Javier Sáenz de Oiza. Por último, en una alegoría con los heterónimos de Fernando Pessoa, se analiza desde una perspectiva personal fruto de la investigación y de las entrevistas mantenidas con todos ellos, la importante labor de Álvaro Siza Vieira, Alexandre Alves Costa y su hijo José Bernardo Távora como agentes coadyuvantes en la consecución del proyecto integral de arquitectura [y vida] de Fernando Távora. Sin lugar a dudas, Álvaro Siza constituye el personaje fundamental e imprescindible para que la arquitectura portuguesa alcanzase la privilegiada consideración que en la actualidad ostenta en la escena internacional. Un arquitecto consagrado que ocupa ya, y ocupará siempre, un lugar privilegiado en la breve lista de maestros míticos e irrepetibles de la arquitectura contemporánea. Con todo, cabe afirmar con la paráfrasis bíblica que da título a la tesis que ‘En el principio era Távora...’ ABSTRACT This thesis addresses the analysis of Fernando Távora’s life journey, a life that was passionately devoted to the cause of aesthetically and conceptually overhauling Portuguese architecture, which was doomed to mediocrity and ostracism at the time when he started practicing professionally. This research delves into all aspects converging in his dedication to achieving that mission, since what he himself would probably call his circumstance – in the manner of José Ortega y Gasset – is inseparable from his thinking and his work. This thesis seeks also to establish the richness and complexity of Fernando Távora’s figure and his importance as a turning point in the evolution of Portuguese architecture, which has gone on to achieve international recognition in recent decades, especially after the consecration of Álvaro Siza Vieira and the so-called School of Oporto. From an absolutely autonomous position with regard to what is happening within and outside Portuguese borders, his work will stand out due to its theoretical and architectural uniqueness – this not being a reason to prevent its decisive influence on his close surroundings. Two written manifestos, his early O problema da Casa Portuguesa and his subsequent Da Organização do Espaço, become structural elements of the theoretical thinking that develops into works which are built in parallel with the former. The coherence of this thinking is reflected on the hereby considered the architect’s true project manifestos. Indeed, we will analyse as such the Casa sobre o Mar (initial manifesto), the Tennis Pavilion (confirmation manifesto) and Casa dos 24 (final manifesto), projects which saw the light at different stages of his career and constitute the practical application of his theories in a masterful syntax. These are the three projects where the thesis takes shape, as they become the reflection of the architect’s true contribution to the European architectural school of thought; the still picture of the results proclamation of a whole architectural project at highly significant moments in his life journey, whose complexity can be understood through this document’s most descriptive phases. This study will show how, in order to carry out his architectural project – regenerate Portuguese architecture by synthesizing modernity and tradition, universality and locality –, Távora would take the moral strength and energy from his two most admired figures, Le Corbusier and Pessoa, allowing him to passionately undertake such a colossal mission. In a tireless search within the global and the local, Távora will manage to pay more attention to the context of the intervention place without compromising his modern convictions, by introducing history and drawing as knowledge tools of the place and eventually of the creative process. The resulting projective method of this model, which he will transmit to successive generations of architects through his teaching, will become a structural element of a trend emerged from the Oporto classrooms which international critique will end up denominating School of Porto in a broader sense. Due to its importance within Porto architect[s]’ professional career, the most prominent phases of its evolution as of the 50s will be analysed in parallel to a series of representative works from different moments in Fernando Távora’s career. Despite the originality of his thinking and his work, certain parallelisms with great architects from the 20th century can be found in Távora’s life journey, which this thesis will address. Amongst temporary influences of some modern masters in whom Távora sought confirmation of his own theories, similarities can be spotted with contemporary architects whose work he knew and to whom he felt close because of the convergence of some of his views. It is also possible to see surprising coincidences with architects he did not know, such as Alejandro de la Sota and Javier Sáenz de Oiza, masters from the School of Madrid. Finally, in an allegory with Fernando Pessoa’s heteronyms, this thesis studies – from a personal perspective based on research and the interviews held with all of them – the important work of Álvaro Siza Vieira, Alexandre Alves Costa and his son Jose Bernardo Távora as auxiliaries in the achievement of Fernando Távora’s complete architectural [and life] project. Without the slightest doubt, Álvaro Siza constitutes the essential figure thanks to whom Portuguese architecture would reach the advantaged position it holds nowadays in the international arena. An acclaimed architect, Siza already holds a privileged spot in the brief list of legendary and unrepeatable masters of contemporary architecture. Nevertheless, with the biblical paraphrase that entitles this thesis it can be claimed that ‘In the beginning was Távora…’
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Abf2p is a high mobility group (HMG) protein found in yeast mitochondria that is required for the maintenance of wild-type (ρ+) mtDNA in cells grown on fermentable carbon sources, and for efficient recombination of mtDNA markers in crosses. Here, we show by two-dimensional gel electrophoresis that Abf2p promotes or stabilizes Holliday recombination junction intermediates in ρ+ mtDNA in vivo but does not influence the high levels of recombination intermediates readily detected in the mtDNA of petite mutants (ρ−). mtDNA recombination junctions are not observed in ρ+ mtDNA of wild-type cells but are elevated to detectable levels in cells with a null allele of the MGT1 gene (Δmgt1), which codes for a mitochondrial cruciform-cutting endonuclease. The level of recombination intermediates in ρ+ mtDNA of Δmgt1 cells is decreased about 10-fold if those cells contain a null allele of the ABF2 gene. Overproduction of Abf2p by ≥ 10-fold in wild-type ρ+ cells, which leads to mtDNA instability, results in a dramatic increase in mtDNA recombination intermediates. Specific mutations in the two Abf2p HMG boxes required for DNA binding diminishes these responses. We conclude that Abf2p functions in the recombination of ρ+ mtDNA.
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Using the full-length and two engineered soluble forms (C1-C2 and Cla-C2) of type V adenylyl cyclase (ACV), we have investigated the role of an intramolecular interaction in ACV that modulates the ability of the α subunit of the stimulatory GTP-binding protein of AC (Gsα) to stimulate enzyme activity. Concentration–response curves with Gsα suggested the presence of high and low affinity sites on ACV, which interact with the G protein. Activation of enzyme by Gsα interaction at these two sites was most apparent in the C1a-C2 form of ACV, which lacks the C1b region (K572–F683). Yeast two-hybrid data demonstrated that the C1b region interacted with the C2 region and its 64-aa subdomain, C2I. Using peptides corresponding to the C2I region of ACV, we investigated the role of the C1b/C2I interaction on Gsα-mediated stimulation of C1-C2 and full-length ACV. Our data demonstrate that a 10-aa peptide corresponding to L1042–T1051 alters the profile of the activation curves of full-length and C1-C2 forms of ACV by different Gsα concentrations to mimic the activation profile observed with C1a-C2 ACV. The various peptides used in our studies did not alter forskolin-mediated stimulation of full-length and C1-C2 forms of ACV. We conclude that the C1b region of ACV interacts with the 10-aa region (L1042–T1051) in the C2 domain of the enzyme to modulate Gsα-elicited stimulation of activity.
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Improved strategies for synthesis make it possible to expand the range of glycopeptides available for detailed conformational studies. The glycopeptide 1 was synthesized using a new solid phase synthesis of carbohydrates and a convergent coupling to peptide followed by deprotection. Its conformational properties were subjected to NMR analysis and compared with a control peptide 2 prepared by conventional solid phase methods. Whereas peptide 2 fails to manifest any appreciable secondary structure, the glycopeptide 1 does show considerable conformational bias suggestive of an equilibrium between an ordered and a random state. The implications of this ordering effect for the larger issue of protein folding are considered.
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Under free running conditions, FREQUENCY (FRQ) protein, a central component of the Neurospora circadian clock, is progressively phosphorylated, becoming highly phosphorylated before its degradation late in the circadian day. To understand the biological function of FRQ phosphorylation, kinase inhibitors were used to block FRQ phosphorylation in vivo and the effects on FRQ and the clock observed. 6-dimethylaminopurine (a general kinase inhibitor) is able to block FRQ phosphorylation in vivo, reducing the rate of phosphorylation and the degradation of FRQ and lengthening the period of the clock in a dose-dependent manner. To confirm the role of FRQ phosphorylation in this clock effect, phosphorylation sites in FRQ were identified by systematic mutagenesis of the FRQ ORF. The mutation of one phosphorylation site at Ser-513 leads to a dramatic reduction of the rate of FRQ degradation and a very long period (>30 hr) of the clock. Taken together, these data strongly suggest that FRQ phosphorylation triggers its degradation, and the degradation rate of FRQ is a major determining factor for the period length of the Neurospora circadian clock.
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Phosphatidylcholine and phosphatidylethanolamine are the most abundant phospholipids in eukaryotic cells and thus have major roles in the formation and maintenance of vesicular membranes. In yeast, diacylglycerol accepts a phosphocholine moiety through a CPT1-derived cholinephosphotransferase activity to directly synthesize phosphatidylcholine. EPT1-derived activity can transfer either phosphocholine or phosphoethanolamine to diacylglcyerol in vitro, but is currently believed to primarily synthesize phosphatidylethanolamine in vivo. In this study we report that CPT1- and EPT1-derived cholinephosphotransferase activities can significantly overlap in vivo such that EPT1 can contribute to 60% of net phosphatidylcholine synthesis via the Kennedy pathway. Alterations in the level of diacylglycerol consumption through alterations in phosphatidylcholine synthesis directly correlated with the level of SEC14-dependent invertase secretion and affected cell viability. Administration of synthetic di8:0 diacylglycerol resulted in a partial rescue of cells from SEC14-mediated cell death. The addition of di8:0 diacylglycerol increased di8:0 diacylglycerol levels 20–40-fold over endogenous long-chain diacylglycerol levels. Di8:0 diacylglcyerol did not alter endogenous phospholipid metabolic pathways, nor was it converted to di8:0 phosphatidic acid.
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The spectrum of immunogenic epitopes presented by the H2-IAb MHC class II molecule to CD4+ T cells has been defined for two different (clade B and clade D) HIV envelope (gp140) glycoproteins. Hybridoma T cell lines were generated from mice immunized by a sequential prime and boost regime with DNA, recombinant vaccinia viruses, and protein. The epitopes recognized by reactive T cell hybridomas then were characterized with overlapping peptides synthesized to span the entire gp140 sequence. Evidence of clonality also was assessed with antibodies to T cell receptor Vα and Vβ chains. A total of 80 unique clonotypes were characterized from six individual mice. Immunogenic peptides were identified within only four regions of the HIV envelope. These epitope hotspots comprised relatively short sequences (≈20–80 aa in length) that were generally bordered by regions of heavy glycosylation. Analysis in the context of the gp120 crystal structure showed a pattern of uniform distribution to exposed, nonhelical strands of the protein. A likely explanation is that the physical location of the peptide within the native protein leads to differential antigen processing and consequent epitope selection.
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In laboratory rodents, caloric restriction (CR) retards several age-dependent physiological and biochemical changes in skeletal muscle, including increased steady-state levels of oxidative damage to lipids, DNA, and proteins. We have previously used high-density oligonucleotide arrays to show that CR can prevent or delay most of the major age-related transcriptional alterations in the gastrocnemius muscle of C57BL/6 mice. Here we report the effects of aging and adult-onset CR on the gene expression profile of 7,070 genes in the vastus lateralis muscle from rhesus monkeys. Gene expression analysis of aged rhesus monkeys (mean age of 26 years) was compared with that of young animals (mean age of 8 years). Aging resulted in a selective up-regulation of transcripts involved in inflammation and oxidative stress, and a down-regulation of genes involved in mitochondrial electron transport and oxidative phosphorylation. Middle-aged monkeys (mean age of 20 years) subjected to CR since early adulthood (mean age of 11 years) were studied to determine the gene expression profile induced by CR. CR resulted in an up-regulation of cytoskeletal protein-encoding genes, and also a decrease in the expression of genes involved in mitochondrial bioenergetics. Surprisingly, we did not observe any evidence for an inhibitory effect of adult-onset CR on age-related changes in gene expression. These results indicate that the induction of an oxidative stress-induced transcriptional response may be a common feature of aging in skeletal muscle of rodents and primates, but the extent to which CR modifies these responses may be species-specific.
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The hair follicle is a cyclic, self renewing epidermal structure which is thought to be controlled by signals from the dermal papilla, a specialized cluster of mesenchymal cells within the dermis. Topical treatments with 17-beta-estradiol to the clipped dorsal skin of mice arrested hair follicles in telogen and produced a profound and prolonged inhibition of hair growth while treatment with the biologically inactive stereoisomer, 17-alpha-estradiol, did not inhibit hair growth. Topical treatments with ICI 182,780, a pure estrogen receptor antagonist, caused the hair follicles to exit telogen and enter anagen, thereby initiating hair growth. Immunohistochemical staining for the estrogen receptor in skin revealed intense and specific staining of the nuclei of the cells of the dermal papilla. The expression of the estrogen receptor in the dermal papilla was hair cycle-dependent with the highest levels of expression associated with the telogen follicle. 17-beta-Estradiol-treated epidermis demonstrated a similar number of 5-bromo-2'-deoxyuridine (BrdUrd) S-phase cells as the control epidermis above telogen follicles; however, the number of BrdUrd S-phase basal cells in the control epidermis varied according to the phase of the cycle of the underlying hair follicles and ranged from 2.6% above telogen follicles to 7.0% above early anagen follicles. These findings indicate an estrogen receptor pathway within the dermal papilla regulates the telogen-anagen follicle transition and suggest that diffusible factors associated with the anagen follicle influence cell proliferation in the epidermis.
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Multimeric protein complexes in chloroplasts and mitochondria are generally composed of products of both nuclear and organelle genes of the cell. A central problem of eukaryotic cell biology is to identify and understand the molecular mechanisms for integrating the production and accumulation of the products of the two separate genomes. Ribulose bisphosphate carboxylase (Rubisco) is localized in the chloroplasts of photosynthetic eukaryotic cells and is composed of small subunits (SS) and large subunits (LS) coded for by nuclear rbcS and chloroplast rbcL genes, respectively. Transgenic tobacco plants containing antisense rbcS DNA have reduced levels of rbcS mRNA, normal levels of rbcL mRNA, and coordinately reduced LS and SS proteins. Our previous experiments indicated that the rate of translation of rbcL mRNA might be reduced in some antisense plants; direct evidence is presented here. After a short-term pulse there is less labeled LS protein in the transgenic plants than in wild-type plants, indicating that LS accumulation is controlled in the mutants at the translational and/or posttranslational levels. Consistent with a primary restriction at translation, fewer rbcL mRNAs are associated with polysomes of normal size and more are free or are associated with only a few ribosomes in the antisense plants. Effects of the rbcS antisense mutation on mRNA and protein accumulation, as well as on the distribution of mRNAs on polysomes, appear to be minimal for other chloroplast and nuclear photosynthetic genes. Our results suggest that SS protein abundance specifically contributes to the regulation of LS protein accumulation at the level of rbcL translation initiation.
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Previous studies have established that antigen presenting cells (APC) expressing major histocompatibility complex class II beta chains with truncated cytoplasmic domains are impaired in their capacity to activate T cells. While it had been widely accepted that this impairment is due to a defect in class II cytoplasmic domain-dependent signal transduction, we recently generated transgenic mice expressing only truncated class II beta chains, and functional analyses of APC from these mice revealed signaling-independent defects in antigen presentation. Here, we demonstrate that T cells primed on such transgenic APC respond better to stimulation by APC expressing truncated beta chains than by wild-type APC. This finding suggests that APC expressing truncated class II beta chains are not inherently defective in their antigen presenting capacity but, rather, may differ from wild-type APC in the peptide antigens that they present. Indeed, analysis of the peptides bound to class II molecules isolated from normal and transgenic spleen cells revealed clear differences. Most notably, the level of class II-associated invariant chain-derived peptides (CLIP) is significantly reduced in cells expressing only truncated beta chains. Prior studies have established that CLIP and antigenic peptides compete for binding to class II molecules. Thus, our results suggest that the cytoplasmic domain of the class II beta chain affects antigen presentation by influencing the level of CLIP/class II complexes.
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A method for simultaneous iontophoretic injections of the anterograde tracer Phaseolus vulgaris leukoagglutinin and the retrograde tracer fluorogold was used to characterize in the rat a hypothalamothalamocortical pathway ending in a region thought to regulate attentional mechanisms by way of eye and head movements. The relevant medial hypothalamic nuclei receive pheromonal information from the amygdala and project to specific parts of the thalamic nucleus reuniens and anteromedial nucleus, which then project to a specific lateral part of the retrosplenial area (or medial visual cortex). This cortical area receives a convergent input from the lateral posterior thalamic nucleus and projects to the superior colliculus. Bidirectional connections with the hippocampal formation suggest that activity in this circuit is modified by previous experience. Striking parallels with basal ganglia circuitry are noted.