861 resultados para Beatrice
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En un mundo cada vez más poblado y complejo, el flujo de datos se incrementa a pasos gigantescos y la tecnología avanza en la profundización de temas cada día más concretos y específicos. A la vez, se ha entrado de lleno en la era digital, proporcionando infinitud de posibilidades de conectar campos de la ciencia, de la comunicación y del arte, que antes eran disciplinas independientes. Añadir la capa sonora en el ámbito arquitectónico intenta darle un significado más amplio al hecho de proyectar espacios. El sonido provee conjuntos de información cognitiva, tanto relacionados con los procesos mentales del conocimiento, la percepción, el razonamiento, la memoria, la opinión, como con los sentimientos y emociones. Al percibir el espacio, no somos conscientes del complejo proceso en el que se implican diversos sentidos, siendo el sentido de la audición un importante protagonista. El sonido, aun siendo parte del entorno en el que está inmerso, también afecta a este contexto y forma parte de los datos que adquirimos al leer entornos espaciales. Esta tesis investiga las relaciones en el marco de digitalización actual e implica la introducción de parámetros y datos vivos. Al mismo tiempo, y desde un punto de vista perceptivo, pone énfasis en la manera que el sonido puede ser un factor esencial como generador y conformador de espacios y analiza las distintas acciones sonoras que inciden en el cuerpo humano. El interés de ‘Espacios Sónicos’ se centra en que puede significar un aporte a los conocimientos arquitectónicos formulados hasta ahora únicamente desde fundamentos espaciales estáticos. Si entendemos la materia no sólo como un sólido, sino, como un compuesto de partículas en vibración constante; la arquitectura, que es el arte de componer la materia que nos rodea, también debería ser entendida como la composición de cuerpos vibrantes o cuerpos pulsantes. ABSTRACT In a more populated and complex world, data flow increases by leaps and bounds, and technological progress extends every day into more concrete and specific topics. Today's world is dramatically changing our soundscape. People live in new sound environments, very differently from the ones they used to. From a biological point of view, our ever-changing society is suffering neural mutations due to the irreversible inclusion of the technological layer in our lives. We have fully entered the digital age, providing infinitude of possibilities for connecting fields of science, arts and communication, previously being independent disciplines. Adding the sound layer to the architectural field attempts to give further real meaning to the act of designing spaces. Sound provides arrays of cognitive information: Whether related to mental processes of knowledge, reasoning, memory, opinion, perception, or to affects and emotions. When perceiving space, we’re not aware of the complex process through which we read it involving various senses, being the sense of hearing one important protagonist. Sound, being itself part of the surroundings in which it is immersed, also affects such context, being part of the data we acquire when reading spatial environments. This research investigates the relationship involving the inclusion of real-time data and specific parameters into an experimental sound-scan frame. It also emphasizes how sound can be essential as generator and activator of spaces and analyzes sound actions affecting the body. 'Sonic spaces' focuses in what it means to contribute to architectural knowledge, which is so far formulated only from static space fundamentals. If the matter must be understood not only as solid, but also as a compound of particles in constant vibration, architecture - which is the art of composing the matter that surrounds us - should also be understood as the composition of vibrating and pulsating bodies.
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Our mission consists in 4 key objectives: Quantify the number of sunspots during the solar maximum, and also characterize their activity and magnetism. Demonstrate the reliability of a mission in LEO orbit, for an effective solar observation. Technology demonstrator: we will take on board an experiment: the PTF (Polymer Filter test in flight ), associated with visible cameras. Investigation of the potential for exploitation of ground space market through the sale of images taken in flight.
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Considering the well established role of nonclassical HLA-G class I molecules in inhibiting natural killer (NK) cell function, the consequence of abnormal HLA-G expression in malignant cells should be the escape of tumors from immunosurveillance. To examine this hypothesis, we analyzed HLA-G expression and NK sensitivity in human malignant melanoma cells. Our analysis of three melanoma cell lines and ex vivo biopsy demonstrated that (i) IGR and M74 human melanoma cell lines exhibit a high level of HLA-G transcription with differential HLA-G isoform transcription and protein expression patterns, (ii) a higher level of HLA-G transcription ex vivo is detected in a skin melanoma metastasis biopsy compared with a healthy skin fragment from the same individual, and (iii) HLA-G protein isoforms other than membrane-bound HLA-G1 protect IGR from NK lysis. It thus appears of critical importance to consider the specific role of HLA-G expression in tumors in the design of future cancer immunotherapies.
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Iron is an essential nutrient for the survival of most organisms and has played a central role in the virulence of many infectious disease pathogens. Mycobacterial IdeR is an iron-dependent repressor that shows 80% identity in the functional domains with its corynebacterial homologue, DtxR (diphtheria toxin repressor). We have transformed Mycobacterium tuberculosis with a vector expressing an iron-independent, positive dominant, corynebacterial dtxR hyperrepressor, DtxR(E175K). Western blots of whole-cell lysates of M. tuberculosis expressing the dtxR(E175K) gene revealed the stable expression of the mutant protein in mycobacteria. BALB/c mice were infected by tail vein injection with 2 × 105 organisms of wild type or M. tuberculosis transformed with the dtxR mutant. At 16 weeks, there was a 1.2 log reduction in bacterial survivors in both spleen (P = 0.0002) and lungs (P = 0.006) with M. tuberculosis DtxR(E175K). A phenotypic difference in colonial morphology between the two strains also was noted. A computerized search of the M. tuberculosis genome for the palindromic consensus sequence to which DtxR and IdeR bind revealed six putative “iron boxes” within 200 bp of an ORF. Using a gel-shift assay we showed that purified DtxR binds to the operator region of five of these boxes. Attenuation of M. tuberculosis can be achieved by the insertion of a plasmid containing a constitutively active, iron-insensitive repressor, DtxR(E175K), which is a homologue of IdeR. Our results strongly suggest that IdeR controls genes essential for virulence in M. tuberculosis.
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Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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This paper forms part of Lukasz Mikolajczyk's PhD dissertation, which is supervised by Karen Milek
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The expression of cell-specialization genes is likely to be changing in tumor cells as their differentiation declines. Functional changes in these genes might yield unusual peptide epitopes with anti-tumor potential and could occur without modification in the DNA sequence of the gene. Melanomas undergo a characteristic decline in melanization that may reflect altered contributions of key melanocytic genes such as tyrosinase. Quantitative reverse transcriptase–PCR of the wild-type (C) tyrosinase gene in transgenic (C57BL/6 strain) mouse melanomas has revealed a shift toward alternative splicing of the pre-mRNA that generated increased levels of the Δ1b and Δ1d mRNA splice variants. The spontaneous c2j albino mutation of tyrosinase (in the C57BL/6 strain) changes the pre-mRNA splicing pattern. In c2j/c2j melanomas, alternative splicing was again increased. However, while some mRNAs (notably Δ1b) present in C/C were obligatorily absent, others (Δ3 and Δ1d) were elevated. In c2j/c2j melanomas, the percentage of total tyrosinase transcripts attributable to Δ3 reached approximately 2-fold the incidence in c2j/c2j or C/C skin melanocytes. The percentage attributable to Δ1d rose to approximately 2-fold the incidence in c2j/c2j skin, and to 10-fold that in C/C skin. These differences provide a basis for unique mouse models in which the melanoma arises in skin grafted from a C/C or c2j/c2j transgenic donor to a transgenic host of the same or opposite tyrosinase genotype. Immunotherapy designs then could be based on augmenting those antigenic peptides that are novel or overrepresented in a tumor relative to the syngeneic host.
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Melanomas tend to become less pigmented in the course of malignant progression. Thus, as proliferation increases, the tumors are decreasingly characterized by the tissue-specific phenotype of normally differentiated melanocytes. To learn whether the decline in melanization is associated with a shift from constitutive to alternative splicing of some pigment gene pre-mRNAs, melanomas were collected from Tyr-SV40E transgenic mice of the standard C57BL/6 strain. The mRNAs of the tyrosinase gene, which has a key role in melanogenesis, were analyzed by quantitative reverse transcriptase–PCR in 34 samples from 16 cutaneous tumors and 9 metastases. The cutaneous tumors included some cases with distinct melanotic and amelanotic zones, which were separately analyzed. All tyrosinase transcripts found in the melanomas were also found in normal skin melanocytes. However, the Δ1b and Δ1d alternatively spliced transcripts, due to deletions within the first exon, were specifically augmented in most of the tumors over their very low levels in skin; the exceptions were some all-amelanotic tumors in which no tyrosinase transcripts were detected. The level of Δ1b rose as high as 11.3% of total tyrosinase mRNAs as compared with 0.6% in skin; Δ1d reached 4.0% as compared with 0.8% in skin. Expression of these splice variants was highest in the melanotic components of zonal primary tumors, relatively lower in their amelanotic components, and still lower in all-amelanotic primary tumors and amelanotic metastases. The increase in Δ1b and Δ1d transcripts may be predicted to increase the levels of unusual peptides, which could have antigenic potential in the tumors, especially in the relatively early phases of malignancy. Analyses of the alternative transcripts of other pigment genes may identify additional candidate antigens, ultimately enabling melanoma cells in all phases of the disease to be represented as a basis for immune intervention.
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We have obtained an experimental estimate of the free energy change associated with variations at the interface between protein subunits, a subject that has raised considerable interest since the concept of accessible surface area was introduced by Lee and Richards [Lee, B. & Richards, F. M. (1971) J. Mol. Biol. 55, 379–400]. We determined by analytical ultracentrifugation the dimer–tetramer equilibrium constant of five single and three double mutants of human Hb. One mutation is at the stationary α1β1 interface, and all of the others are at the sliding α1β2 interface where cleavage of the tetramer into dimers and ligand-linked allosteric changes are known to occur. A surprisingly good linear correlation between the change in the free energy of association of the mutants and the change in buried hydrophobic surface area was obtained, after corrections for the energetic cost of losing steric complementarity at the αβ dimer interface. The slope yields an interface stabilization free energy of −15 ± 1.2 cal/mol upon burial of 1 Å2 of hydrophobic surface, in very good agreement with the theoretical estimate given by Eisenberg and McLachlan [Eisenberg, D. & McLachlan, A. D. (1986) Nature (London) 319, 199–203].
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The membrane proteins of peripheral light-harvesting complexes (LHCs) bind chlorophylls and carotenoids and transfer energy to the reaction centers for photosynthesis. LHCs of chlorophytes, chromophytes, dinophytes, and rhodophytes are similar in that they have three transmembrane regions and several highly conserved Chl-binding residues. All LHCs bind Chl a, but in specific taxa certain characteristic pigments accompany Chl a: Chl b and lutein in chlorophytes, Chl c and fucoxanthin in chromophytes, Chl c and peridinin in dinophytes, and zeaxanthin in rhodophytes. The specificity of pigment binding was examined by in vitro reconstitution of various pigments with a simple light-harvesting protein (LHCaR1), from a red alga (Porphyridium cruentum), that normally has eight Chl a and four zeaxanthin molecules. The pigments typical of a chlorophyte (Spinacea oleracea), a chromophyte (Thallasiosira fluviatilis), and a dinophyte (Prorocentrum micans) were found to functionally bind to this protein as evidenced by their participation in energy transfer to Chl a, the terminal pigment. This is a demonstration of a functional relatedness of rhodophyte and higher plant LHCs. The results suggest that eight Chl-binding sites per polypeptide are an ancestral trait, and that the flexibility to bind various Chl and carotenoid pigments may have been retained throughout the evolution of LHCs.