895 resultados para Democratic consensus


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El presente trabajo aborda el análisis de la idea de monumentalidad, así como el diseño y la construcción de monumentos concretos, a la finalización de la Segunda Guerra Mundial, prestando especial atención al intento del Movimiento Moderno de introducirse en un campo que hasta entonces le había sido ajeno. Entendiendo que el monumento es ante todo un artefacto para la memoria, y analizando las teorías de sociólogos como Émile Durkheim, Maurice Halbwachs, Jan Assmann o Iwona Irwin-Zarecka, la tesis se propone explicar el papel que juegan los monumentos en la creación de una memoria colectiva que, a diferencia de la historia, es una recopilación selectiva de acontecimientos del pasado cuyo fin es procurar y celebrar la permanencia del grupo social. También se propone analizar el papel del monumento como elemento de estabilidad en el paisaje urbano que genera de forma natural el apego de los ciudadanos, puesto que forma parte destacada del marco espacial en el que se han desarrollado sus vidas. Desde estas dos facetas se pretende justificar la necesidad de monumentos que experimenta cualquier grupo social, y por qué las guerras, que ponen en peligro la estructura, e incluso la propia vida del grupo, son acontecimientos que generan una tendencia especial a la construcción de monumentos que conjuren el peligro al que éste se ha visto sometido. Se explicarán las razones por las que la conmemoración de la Segunda Guerra Mundial se volvió especialmente problemática. Entre las principales, la desaparición de fronteras entre frente y retaguardia, entre objetivos militares y civiles; por otra parte la despersonalización de la acción bélica como consecuencia de la aplicación de la tecnología; en tercer lugar el papel de los medios de comunicación de masas, que por primera vez en la historia irrumpieron de forma masiva en una guerra, y ofrecían imágenes instantáneas, más impactantes y con un aura de realidad con la que el monumento convencional no era capaz de competir; en cuarto lugar el inicio de la era atómica, que enfrentaba por primera vez a la humanidad a la posibilidad de su destrucción total; y finalmente la experiencia del Holocausto, en cuanto que aniquilación carente de objetivo e ideología, que se servía del progreso de la ciencia para ganar en eficiencia, y que puso de manifiesto la manipulabilidad de la tecnología al servicio de unos intereses particulares. Como respuesta a esta dificultad para la conmemoración, se popularizaron dos fórmulas hasta entonces marginales que podemos considerar características del momento: una de ellas es el living memorial, que trataba de ofrecer una lectura constructiva de la guerra poniendo de relieve determinadas funciones prácticas de carácter democrático, cultural, deportivo, etc. que se presentaban como los frutos por los que se había combatido en la guerra. En esta fórmula es donde el Movimiento Moderno encontró la posibilidad de abordar nuevos proyectos, en los que la función estaba presente pero no era el ingrediente determinante, lo que obligaría a un enriquecimiento del lenguaje con el que responder a la dimensión emotiva del monumento. Y si bien hay en esta época edificios modernos que podemos calificar justamente de monumentos, el desplazamiento del centro del debate teórico hacia cuestiones estilísticas y expresivas limitó considerablemente la claridad de los enunciados anteriores y la posibilidad de consenso. Dentro de los living memorials, las sedes de la Organización de Naciones Unidas y sus correspondientes agencias representaron la mayor esperanza del Movimiento Moderno por construir un auténtico monumento. Sin embargo, el sistema de trabajo en grupo, con su correspondiente conflicto de personalidades, la ausencia de proyección de los edificios sobre el espacio urbano anexo, y sobre todo el propio descrédito que comenzaron a sufrir las instituciones con el comienzo de la Guerra Fría, frustraron esta posibilidad. La segunda fórmula conmemorativa sería el monumento de advertencia o mahnmal, que renuncia a cualquier rasgo de heroísmo o romanticismo, y se concentra simplemente en advertir de los riesgos que implica la guerra. Dicha fórmula se aplicó fundamentalmente en los países vencidos, y generalmente no por iniciativa propia, sino como imposición de los vencedores, que de alguna forma aprovechaban la ocasión para hacer examen de conciencia lejos de la opinión pública de sus respectivos países. ABSTRACT This paper explores the idea of monumentality through the analysis of the design and construction of several monuments at the end ofWorldWar II. It pays particular attention to the attempt of the Modern Movement to enter a field that had been ignored until this moment. With the assumption that a monument is primarily a mnemonic device, this thesis focuses on the thinking of sociologists like Émile Durkheim, Maurice Halbwachs, Jan Assmann or Iwona Irwin-Zarecka, with the aim of explaining the role of monuments in the creation of a collective memory which, unlike history, consists of past events selected in order to secure and celebrate the permanence of a social group. It also considers the role of monuments as elements of stability in the urban landscape that naturally get assimilated by society, since they are prominent elements in the shared spaces of daily life. These two features explain the need felt by any society for monuments, and how wars, events that endanger the structure and even the existence of that same society, generate a special tendency to build monuments to conjure that inherent danger. The reasons why the memorializing of World War II became especially problematic will be explained. Primary among them is the blurring of boundaries between the front line and the domestic front, between military and civilian targets; moreover, the depersonalization of warfare as a result of advances in technology; thirdly, the role of mass media, which for the first time in history extensively covered a war, instantly broadcasting images of such power and with such an aura of reality that conventional monuments became obsolete; fourthly, the beginning of the atomic age, which meant that mankind faced the possibility of complete destruction; and finally the Holocaust, a racial annihilation devoid of purpose and ideology, which took advantage of scientific progress to gain efficiency, manipulating technology to serve particular interests. In response to this difficulty in commemorating wars, two formulas hitherto marginal gained such popularity as to become prototypes: one was the living memorial, offering a constructive reading of the war by hosting certain practical functions of democratic, cultural or sporting nature. Living memorials presented themselves as the image of the outcome for which the war had been fought. The Modern Movement found in this formula the opportunity for tackling new projects, in which function was present but not as the determining ingredient; in turn, they would require an enhancement of language in order to account for the emotional dimension of the monument. And while there are modern buildings at this time that we can justly describe as monuments, the displacement of the focus of the theoretical debate to stylistic and expressive issues considerably limited the clarity of previous statements and the possibility of consensus. Among all living memorials, the headquarters of the United Nations Organization and its satellite agencies represented the ultimate hope of the Modern Movement to build an authentic monument. However, the group-based design process, the fight of egos it caused, the lack of presence of these buildings over the adjacent urban space, and especially the very discredit that these institutions began to suffer with the onset of the Cold War, all thwarted this expectation. The second commemorative formula was the warning monument or Mahnmal, which rejects any trace of heroism or romanticism, and simply focuses on warning about the risks of war. This formula was mainly used in defeated countries, and generally not on their own initiative, but as an imposition of the victors, which seized the opportunity to do some soul-searching far away from the public opinion of their respective countries.

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Autonomously replicating sequence (ARS) elements, which function as the cis-acting chromosomal replicators in the yeast Saccharomyces cerevisiae, depend upon an essential copy of the 11-bp ARS consensus sequence (ACS) for activity. Analysis of the chromosome III replicator ARS309 unexpectedly revealed that its essential ACS differs from the canonical ACS at two positions. One of the changes observed in ARS309 inactivates other ARS elements. This atypical ACS binds the origin recognition complex efficiently and is required for chromosomal replication origin activity. Comparison of the essential ACS of ARS309 with the essential regions of other ARS elements revealed an expanded 17-bp conserved sequence that efficiently predicts the essential core of ARS elements.

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p53 tumor suppressor protein negatively regulates cell growth, mainly through the transactivation of its downstream target genes. As a sequence-specific DNA binding transcription factor, p53 specifically binds to a 20-bp consensus motif 5′-PuPuPuC(A/T) (T/A)GPyPyPyPuPuPuC(A/T)(T/A)GPyPyPy-3′. We have now identified, partially purified, and characterized an additional ≈40-kDa nuclear protein, p53CP (p53 competing protein), that specifically binds to the consensus p53 binding sites found in several p53 downstream target genes, including Waf-1, Gadd45, Mdm2, Bax, and RGC. The minimal sequence requirement for binding is a 14-bp motif, 5′-CTTGCTTGAACAGG-3′ [5′-C(A/T)(T/A)GPyPyPyPuPuPuC(A/T)(T/A)G-3′], which includes the central nucleotides of the typical p53 binding site with one mismatch. p53CP and p53 (complexed with antibody) showed a similar binding specificity to Waf-1 site but differences in Gadd45 and T3SF binding. Like p53, p53CP also binds both double- and single-stranded DNA oligonucleotides. Important to note, cell cycle blockers and DNA damaging reagents, which induce p53 binding activity, were found to inhibit p53CP binding in p53-positive, but not in p53-negative, cells. This finding suggested a p53-dependent coordinate regulation of p53 and p53CP in response to external stimuli. p53CP therefore could be a third member of the p53 family, in addition to p53 and p73, a newly identified p53 homolog. p53CP, if sequestering p53 from its DNA binding sites through competitive binding, may provide a novel mechanism of p53 inactivation. Alternatively, p53CP may have p53-like functions by binding and transactivating p53 downstream target genes. Cloning of the p53CP gene ultimately will resolve this issue.

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IFNγ, once called the macrophage-activating factor, stimulates many genes in macrophages, ultimately leading to the elicitation of innate immunity. IFNγ's functions depend on the activation of STAT1, which stimulates transcription of IFNγ-inducible genes through the GAS element. The IFN consensus sequence binding protein (icsbγ or IFN regulatory factor 8), encoding a transcription factor of the IFN regulatory factor family, is one of such IFNγ-inducible genes in macrophages. We found that macrophages from ICSBP−/− mice were defective in inducing some IFNγ-responsive genes, even though they were capable of activating STAT1 in response to IFNγ. Accordingly, IFNγ activation of luciferase reporters fused to the GAS element was severely impaired in ICSBP−/− macrophages, but transfection of ICSBP resulted in marked stimulation of these reporters. Consistent with its role in activating IFNγ-responsive promoters, ICSBP stimulated reporter activity in a GAS-specific manner, even in the absence of IFNγ treatment, and in STAT1 negative cells. Indicative of a mechanism for this stimulation, DNA affinity binding assays revealed that endogenous ICSBP was recruited to a multiprotein complex that bound to GAS. These results suggest that ICSBP, when induced by IFNγ through STAT1, in turn generates a second wave of transcription from GAS-containing promoters, thereby contributing to the elicitation of IFNγ's unique activities in immune cells.

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STACK is a tool for detection and visualisation of expressed transcript variation in the context of developmental and pathological states. The datasystem organises and reconstructs human transcripts from available public data in the context of expression state. The expression state of a transcript can include developmental state, pathological association, site of expression and isoform of expressed transcript. STACK consensus transcripts are reconstructed from clusters that capture and reflect the growing evidence of transcript diversity. The comprehensive capture of transcript variants is achieved by the use of a novel clustering approach that is tolerant of sub-sequence diversity and does not rely on pairwise alignment. This is in contrast with other gene indexing projects. STACK is generated at least four times a year and represents the exhaustive processing of all publicly available human EST data extracted from GenBank. This processed information can be explored through 15 tissue-specific categories, a disease-related category and a whole-body index and is accessible via WWW at http://www.sanbi.ac.za/Dbases.html. STACK represents a broadly applicable resource, as it is the only reconstructed transcript database for which the tools for its generation are also broadly available (http://www.sanbi.ac.za/CODES).

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X-linked hypohidrotic ectodermal dysplasia (XLHED) is a heritable disorder of the ED-1 gene disrupting the morphogenesis of ectodermal structures. The ED-1 gene product, ectodysplasin-A (EDA), is a tumor necrosis factor (TNF) family member and is synthesized as a membrane-anchored precursor protein with the TNF core motif located in the C-terminal domain. The stalk region of EDA contains the sequence -Arg-Val-Arg-Arg156-Asn-Lys-Arg159-, representing overlapping consensus cleavage sites (Arg-X-Lys/Arg-Arg↓) for the proprotein convertase furin. Missense mutations in four of the five basic residues within this sequence account for ≈20% of all known XLHED cases, with mutations occurring most frequently at Arg156, which is shared by the two consensus furin sites. These analyses suggest that cleavage at the furin site(s) in the stalk region is required for the EDA-mediated cell-to-cell signaling that regulates the morphogenesis of ectodermal appendages. Here we show that the 50-kDa EDA parent molecule is cleaved at -Arg156Asn-Lys-Arg159↓- to release the soluble C-terminal fragment containing the TNF core domain. This cleavage appears to be catalyzed by furin, as release of the TNF domain was blocked either by expression of the furin inhibitor α1-PDX or by expression of EDA in furin-deficient LoVo cells. These results demonstrate that mutation of a functional furin cleavage site in a developmental signaling molecule is a basis for human disease (XLHED) and raise the possibility that furin cleavage may regulate the ability of EDA to act as a juxtacrine or paracrine factor.

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Tissue and cell-type specific expression of the rat osteocalcin (rOC) gene involves the interplay of multiple transcriptional regulatory factors. In this report we demonstrate that AML-1 (acute myeloid leukemia-1), a DNA-binding protein whose genes are disrupted by chromosomal translocations in several human leukemias, interacts with a sequence essential for enhancing tissue-restricted expression of the rOC gene. Deletion analysis of rOC promoter-chloramphenicol acetyltransferase constructs demonstrates that an AML-1-binding sequence within the proximal promoter (-138 to -130 nt) contributes to 75% of the level of osteocalcin gene expression. The activation potential of the AML-1-binding sequence has been established by overexpressing AML-1 in osteoblastic as well as in nonosseous cell lines. Overexpression not only enhances rOC promoter activity in osteoblasts but also mediates OC promoter activity in a nonosseous human fibroblastic cell line. A probe containing this site forms a sequence specific protein-DNA complex with nuclear extracts from osteoblastic cells but not from nonosseous cells. Antisera supershift experiments indicate the presence of AML-1 and its partner protein core-binding factor beta in this osteoblast-restricted complex. Mutations of the critical AML-1-binding nucleotides abrogate formation of the complex and strongly diminish promoter activity. These results indicate that an AML-1 related protein is functional in cells of the osteoblastic lineage and that the AML-1-binding site is a regulatory element important for osteoblast-specific transcriptional activation of the rOC gene.

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A key event in Ras-mediated signal transduction and transformation involves Ras interaction with its downstream effector targets. Although substantial evidence has established that the Raf-1 serine/threonine kinase is a critical effector of Ras function, there is increasing evidence that Ras function is mediated through interaction with multiple effectors to trigger Raf-independent signaling pathways. In addition to the two Ras GTPase activating proteins (GAPs; p120- and NF1-GAP), other candidate effectors include activators of the Ras-related Ral proteins (RalGDS and RGL) and phosphatidylinositol 3-kinase. Interaction between Ras and its effectors requires an intact Ras effector domain and involves preferential recognition of active Ras-GTP. Surprisingly, these functionally diverse effectors lack significant sequence homology and no consensus Ras binding sequence has been described. We have now identified a consensus Ras binding sequence shared among a subset of Ras effectors. We have also shown that peptides containing this sequence from Raf-1 (RKTFLKLA) and NF1-GAP (RRFFLDIA) block NF1-GAP stimulation of Ras GTPase activity and Ras-mediated activation of mitogen-activated protein kinases. In summary, the identification of a consensus Ras-GTP binding sequence establishes a structural basis for the ability of diverse effector proteins to interact with Ras-GTP. Furthermore, our demonstration that peptides that contain Ras-GTP binding sequences can block Ras function provides a step toward the development of anti-Ras agents.

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Alu repeats are interspersed repetitive DNA elements specific to primates that are present in 500,000 to 1 million copies. We show here that an Alu sequence encodes functional binding sites for retinoic acid receptors, which are members of the nuclear receptor family of transcription factors. The consensus sequences for the evolutionarily recent Alu subclasses contain three hexamer half sites, related to the consensus AGGTCA, arranged as direct repeats with a spacing of 2 bp, which is consistent with the binding specificities of retinoic acid receptors. An analysis was made of the DNA binding and transactivation potential of these sites from an Alu sequence that has been previously implicated in the regulation of the keratin K18 gene. These Alu double half sites are shown to bind bacterially synthesized retinoic acid receptors as assayed by electrophoretic mobility shift assays. These sites are further shown to function as a retinoic acid response element in transiently transfected CV-1 cells, increasing transcription of a reporter gene by a factor of approximately 35-fold. This transactivation requires cotransfection with vectors expressing retinoic acid receptors, as well as the presence of all-trans-retinoic acid, which is consistent with the known function of retinoic acid receptors as ligand-inducible transcription factors. The random insertion of potentially thousands of Alu repeats containing retinoic acid response elements throughout the primate genome is likely to have altered the expression of numerous genes, thereby contributing to evolutionary potential.

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The WW domain has previously been described as a motif of 38 semiconserved residues found in seemingly unrelated proteins, such as dystrophin, Yes-associated protein (YAP), and two transcriptional regulators, Rsp-5 and FE65. The molecular function of the WW domain has been unknown until this time. Using a functional screen of a cDNA expression library, we have identified two putative ligands of the WW domain of YAP, which we named WBP-1 and WBP-2. Peptide sequence comparison between the two partial clones revealed a homologous region consisting of a proline-rich domain followed by a tyrosine residue (with the shared sequence PPPPY), which we shall call the PY motif. Binding assays and site-specific mutagenesis have shown that the PY motif binds with relatively high affinity and specificity to the WW domain of YAP, with the preliminary consensus XPPXY being critical for binding. Herein, we have implicated the WW domain with a role in mediating protein-protein interactions, as a variant of the paradigm set by Src homology 3 domains and their proline-rich ligands.

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Members of the IRF family mediate transcriptional responses to interferons (IFNs) and to virus infection. So far, proteins of this family have been studied only among mammalian species. Here we report the isolation of cDNA clones encoding two members of this family from chicken, interferon consensus sequence-binding protein (ICSBP) and IRF-1. The predicted chicken ICSBP and IRF-1 proteins show high levels of sequence similarity to their corresponding human and mouse counterparts. Sequence identities in the putative DNA-binding domains of chicken and human ICSBP and IRF-1 were 97% and 89%, respectively, whereas the C-terminal regions showed identities of 64% and 51%; sequence relationships with mouse ICSBP and IRF-1 are very similar. Chicken ICSBP was found to be expressed in several embryonic tissues, and both chicken IRF-1 and ICSBP were strongly induced in chicken fibroblasts by IFN treatment, supporting the involvement of these factors in IFN-regulated gene expression. The presence of proteins homologous to mammalian IRF family members, together with earlier observations on the occurrence of functionally homologous IFN-responsive elements in chicken and mammalian genes, highlights the conservation of transcriptional mechanisms in the IFN system, a finding that contrasts with the extensive sequence and functional divergence of the IFNs.

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The audiovisual as a tool for social change among youth in social exclusion situations in Guatemala (2004-2014)” is the title of this research paper which aims to study the organizations and projects that have worked with video tools and participatory methodology with young people in marginalized social sectors in order to improve their opportunities and social inclusion. The purpose of this study also includes the analysis of the finish video products as well as the impact of the projects on the youth participants. Guatemala is a country with deep rooted and historical social inequality. This situation is currently reflected by the high violence rates, the extreme poverty and the exclusion of populations, including youth. As social participants, young people have much to say about the construction of a future plan for the country, but they are not heard. That’s why it is so important to facilitate a youth voice and research the tools that can help reach that goal. The participatory methodologies are based on the popular education theories developed by the Latinamerican School with authors such as Paulo Freire, Juan Díaz Bordenave, Jesús Martín Barbero and Mario Kaplún, among others. These methodologies have proved to be a lateral way to face the educational process by promoting dialogue, analysis, consensus search and consciousness-raising. In addition, these methodologies provide a more democratic way to format educational processes that provide students tools to promote an active attitude towards social questions. They can develop their own role of responsibility in the improvement of their own lives and contribute to the progress of their community. This research is based on observation, an extensive bibliographical review, analysis protocols for the study of video materials and projects and closed structured interviews with facilitators and project coordinators. It includes open qualitative interviews with some selected participants and with other specialists in order to complete the necessary information to structure the historical, social and political context of Guatemala...

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Since 2008, international speculation about the viability of Kim Jong-Il's leadership in North Korea has been at the forefront of diplomatic discussions. North Korea is known to be a secretive state where human rights violations abound. This paper discusses the history of leadership and government in North Korea since World War II, the current human rights situation in the country, the role of China, and potential successors to Kim Jong-Il. The ramifications of impending regime change are discussed in terms of North Korea's human rights issues and economic problems. While current efforts at diplomacy have proved ineffective, the need for concerned nations, intergovernmental organizations, and non-governmental organizations to be prepared to engage North Korea after Kim Jong-Il is imperative.