990 resultados para U-turn motif
Resumo:
Despite the extensive implementation of Superstreets on congested arterials, reliable methodologies for such designs remain unavailable. The purpose of this research is to fill the information gap by offering reliable tools to assist traffic professionals in the design of Superstreets with and without signal control. The entire tool developed in this thesis consists of three models. The first model is used to determine the minimum U-turn offset length for an Un-signalized Superstreet, given the arterial headway distribution of the traffic flows and the distribution of critical gaps among drivers. The second model is designed to estimate the queue size and its variation on each critical link in a signalized Superstreet, based on the given signal plan and the range of observed volumes. Recognizing that the operational performance of a Superstreet cannot be achieved without an effective signal plan, the third model is developed to produce a signal optimization method that can generate progression offsets for heavy arterial flows moving into and out of such an intersection design.
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Sm and Sm-like proteins are members of a family of small proteins that is widespread throughout eukaryotic kingdoms. These proteins form heteromers with one another and bind, as heteromeric complexes, to various RNAs, recognizing primarily short U-rich stretches. Interestingly, completion of several genome projects revealed that archaea also contain genes that may encode Sm-like proteins. Herein, we studied the properties of one Sm-like protein derived from the archaebacterium Archaeoglobus fulgidus and overexpressed in Escherichia coli. This single small protein closely reflects the properties of an Sm or Sm-like protein heteromer. It binds to RNA with a high specificity for oligo(U), and assembles onto the RNA to form a complex that exhibits, as judged by electron microscopy, a ring-like structure similar to the ones observed with the Sm core ribonucleoprotein and the like Sm (LSm) protein heteromer. Importantly, multivariate statistical analysis of negative-stain electron-microscopic images revealed a sevenfold symmetry for the observed ring structure, indicating that the proteins form a homoheptamer. These results support the structural model of the Sm proteins derived from crystallographic studies on Sm heterodimers and demonstrate that the Sm protein family evolved from a single ancestor that was present before the eukaryotic and archaeal kingdoms separated.
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Empire is central to U.S. history. When we see the U.S. projecting its influence on a global scale in today s world it is important to understand that U.S. empire has a long history. This dissertation offers a case study of colonialism and U.S. empire by discussing the social worlds, labor regimes, and culture of the U.S. Army during the conquest of southern Arizona and New Mexico (1866-1886). It highlights some of the defining principles, mentalities, and characteristics of U.S. imperialism and shows how U.S. forces have in years past constructed their power and represented themselves, their missions, and the places and peoples that faced U.S. imperialism/colonialism. Using insights from postcolonial studies and whiteness studies, this work balances its attention between discursive representations (army stories) and social experience (army actions), pays attention to silences in the process of historical production, and focuses on collective group mentalities and identities. In the end the army experience reveals an empire in denial constructed on the rule of difference and marked by frustration. White officers, their wives, and the white enlisted men not only wanted the monopoly of violence for the U.S. regime but also colonial (mental/cultural) authority and power, and constructed their identity, authority, and power in discourse and in the social contexts of the everyday through difference. Engaged in warfare against the Apaches, they did not recognize their actions as harmful or acknowledge the U.S. invasion as the bloody colonial conquest it was. White army personnel painted themselves and the army as liberators, represented colonial peoples as racial inferiors, approached colonial terrain in terms of struggle, and claimed that the region was a terrible periphery with little value before the arrival of white civilization. Officers and wives also wanted to place themselves at the top of colonial hierarchies as the refined and respectable class who led the regeneration of the colony by example: they tried to turn army villages into islands of civilization and made journeys, leisure, and domestic life to showcase their class sensibilities and level of sophistication. Often, however, their efforts failed, resulting in frustration and bitterness. Many blamed the colony and its peoples for their failures. The army itself was divided by race and class. All soldiers were treated as laborers unfit for self-government. White enlisted men, frustrated by their failures in colonial warfare and by constant manual labor, constructed worlds of resistance, whereas indigenous soldiers sought to negotiate the effects of colonialism by working in the army. As colonized labor their position was defined by tension between integration and exclusion and between freedom and colonial control.
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The peptide Boc-Gly-Dpg-Gly-Gly-Dpg-Gly-NHMe (1) has been synthesized to examine the conformational preferences of Dpg residues in the context of a poor helix promoting sequence. Single crystals of 1 were obtained in the space group P21/c with a = 13.716(2) Å, b = 12.960(2) Å, c = 22.266(4) Å, and β = 98.05(1)°; R = 6.3% for 3660 data with |Fo| > 4σ. The molecular conformation in crystals revealed that the Gly(1)-Dpg(2) segment adopts φ, ψ values distorted from those expected for an ideal type II‘ β-turn (φGly(1) = +72.0°, ψGly(1) = −166.0°; φDpg(2) = −54.0°, ψDpg(2) = −46.0°) with an inserted water molecule between Boc-CO and Gly(3)NH. The Gly(3)-Gly(4) segment adopts φ, ψ values which lie broadly in the right handed helical region (φGly(3) = −78.0°, ψGly(3) = −9.0°; φGly(4) = −80.0°, ψGly(4) = −18.0°). There is a chiral reversal at Dpg(5) which takes up φ, ψ values in the left handed helical region. The Dpg(5)-Gly(6) segment closely resembles an ideal type I‘ β-turn (φDpg(5) = +56.0°, ψDpg(5) = +32.0°; φGly(6) = +85.0°, ψGly(6) = −3.0°). Molecules of both chiral senses are found in the centrosymmetric crystal. The C-terminus forms a hydrated Schellman motif, with water insertion into the potential 6 → 1 hydrogen bond between Gly(1)CO and Gly(6)NH. NMR studies in CDCl3 suggest substantial retention of the multiple turn conformation observed in crystals. In solution the observed NOEs support local helical conformation at the two Dpg residues.
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Due to limited available therapeutic options, developing new lead compounds against hepatitis C virus is an urgent need. Human La protein stimulates hepatitis C virus translation through interaction with the hepatitis C viral RNA. A cyclic peptide mimicking the beta-turn of the human La protein that interacts with the viral RNA was synthesized. It inhibits hepatitis C viral RNA translation significantly better than the corresponding linear peptide at longer post-treatment times. The cyclic peptide also inhibited replication as measured by replicon RNA levels using real time RT-PCR. The cyclic peptide emerges as a promising lead compound against hepatitis C.
Resumo:
Human La protein is known to be an essential host factor for translation and replication of hepatitis C virus (HCV) RNA. Previously, we have demonstrated that residues responsible for interaction of human La protein with the HCV internal ribosomal entry site (IRES) around the initiator AUG within stem-loop IV form a beta-turn in the RNA recognition motif (RRM) structure. In this study, sequence alignment and mutagenesis suggest that the HCV RNA-interacting beta-turn is conserved only in humans and chimpanzees, the species primarily known to be infected by HCV. A 7-mer peptide corresponding to the HCV RNA-interacting region of human La inhibits HCV translation, whereas another peptide corresponding to the mouse La sequence was unable to do so. Furthermore, IRES-mediated translation was found to be significantly high in the presence of recombinant human La protein in vitro in rabbit reticulocyte lysate. We observed enhanced replication with HCV subgenomic and full-length replicons upon overexpression of either human La protein or a chimeric mouse La protein harboring a human La beta-turn sequence in mouse cells. Taken together, our results raise the possibility of creating an immunocompetent HCV mouse model using human-specific cell entry factors and a humanized form of La protein.
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Salt River Bay National Historical Park and Ecological Preserve (hereafter, SARI or the park) was created in 1992 to preserve, protect, and interpret nationally significant natural, historical, and cultural resources (United States Congress 1992). The diverse ecosystem within it includes a large mangrove forest, a submarine canyon, coral reefs, seagrass beds, coastal forests, and many other natural and developed landscape elements. These ecosystem components are, in turn, utilized by a great diversity of flora and fauna. A comprehensive spatial inventory of these ecosystems is required for successful management. To meet this need, the National Oceanic and Atmospheric Administration (NOAA) Biogeography Program, in consultation with the National Park Service (NPS) and the Government of the Virgin Islands Department of Planning and Natural Resources (VIDPNR), conducted an ecological characterization. The characterization consists of three complementary components: a text report, digital habitat maps, and a collection of historical aerial photographs. This ecological characterization provides managers with a suite of tools that, when coupled with the excellent pre-existing body of work on SARI resources, enables improved research and monitoring activities within the park (see Appendix F for a list of data products).
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The surface of the Earth is continuously undergoing changes as a result of weathering-erosion, plate tectonics and volcanic processes. Continental weathering-erosion with its complex rock-water interactions is the central process of global biochemical cycling of elements, and affects the long-term ocean atmosphere budget of carbon dioxide both through the consumption of carbonic acid during silicate weathering and through changes in the weathering and burial rates of organic carbon. Rates of the weathering-erosion depend on a variety of factors, in particular rock properties and chemical composition, climate (especially rainfall), structure, and elevation. They are quite variable on a regional scale. Thus, environmental changes in a region could be indicated by the history of weathering-erosion in the region. Recent attention has focused on increased silicate weathering of tectonically uplifted areas in the India-Asia collision zone as a possible cause for falling atmospheric CO_2 levels in the Cenozoic era. The wind blown dust deposits in the Loess Plateau is derived from the arid and semiarid regions in northwestern China, in turn, where the deposits have been derived from the Qinghai-Xizang Plateau and the high mountains around. Therefore, geochemistry of the wind blown loess-paleosol and red clay sequences may provide insight both to paleoenvironmental changes on the Loess Plateau, and to the uplift and weathering-erosion histories of the Qinghai-Xizang Plateau. In this paper, uranium-thorium series nuclides and cosmogenic ~(10)Be have been employed as tracers of weathering intensities and histories of the dust sediments in the Loess Plateau. Major elements, such as Na, Al, Fe etc., are also used to estimate degree of chemical alteration of the dust sediments and to rebuild the history of weathering on the Loess Plateau. First of all, using a low-level HPGe γ-ray detector, we measured U and Th series nuclides in 170 loess and paleosol samples from five sites in the Loess Plateau, going back 2.6 Ma. The results show that ~(238)U activities are disequilibrium with its daughter nuclide ~(230)Th in young loess-paleosol sequence, indicating that weathering was happened both in dust deposition site and in dust source regions. Using concentrations of ~(238)U and ~(232)Th in the samples, we estimated the amounts of ~(238)U leached out of from paleosols due to weathering. Further, based on analyses of ~(230)Th in paleosols deposited in the past ca. 140 ka, we determined when the paleosols weathered in the source regions. We conclude that most of the weathering in the dust-source regions may have occurred during the interglacials before dust deposition.
Resumo:
Celem artykułu jest zarys koncepcji paradygmatu nauki sprowadzonego do widowiska kulturowego. Zasadniczymi kontekstami dla naszych rozważań sa definicje paradygmatu podane przez T. S. Kuhna i Z. Kwiecińskiego. W nawiązaniu do nich zostanie wyłonionych siedem faz rozwoju/przekształceń paradygmatu, następnie sięgniemy do jego odniesień naukowych i mitycznych powiązanych z technologią, z różnymi formami i funkcjami rytuału oraz z procesem rytualizacji. W wyniku zebranych tutaj informacji dojdziemy do stanowiska, z którego może wynikać, że paradygmat nauki jest widowiskiem społeczno-kulturowym. Zestawione tutaj wnioski pozwolą nam przejść do przykładu związanego z wychowaniem, - z paradygmatem wychowania i wyjaśnić sobie, na czym polega – zgodnie z tytułem artykułu – różnica między uściskiem a uciskiem wychowania. Całość kończy podsumowanie, w którym omówimy związek technologii rytualizacji i polityczności z władzą oraz zestawię w punktach informacje na temat paradygmatu. (PS – w tytule u(ś)cisk można tłumaczyć: ucisk/uścisk)
Resumo:
The Na+/H+ exchanger regulatory factor (NHERF) binds to the tail of the beta2-adrenergic receptor and plays a role in adrenergic regulation of Na+/H+ exchange. NHERF contains two PDZ domains, the first of which is required for its interaction with the beta2 receptor. Mutagenesis studies of the beta2 receptor tail revealed that the optimal C-terminal motif for binding to the first PDZ domain of NHERF is D-S/T-x-L, a motif distinct from those recognized by other PDZ domains. The first PDZ domain of NHERF-2, a protein that is 52% identical to NHERF and also known as E3KARP, SIP-1, and TKA-1, exhibits binding preferences very similar to those of the first PDZ domain of NHERF. The delineation of the preferred binding motif for the first PDZ domain of the NHERF family of proteins allows for predictions for other proteins that may interact with NHERF or NHERF-2. For example, as would be predicted from the beta2 receptor tail mutagenesis studies, NHERF binds to the tail of the purinergic P2Y1 receptor, a seven-transmembrane receptor with an intracellular C-terminal tail ending in D-T-S-L. NHERF also binds to the tail of the cystic fibrosis transmembrane conductance regulator, which ends in D-T-R-L. Because the preferred binding motif of the first PDZ domain of the NHERF family of proteins is found at the C termini of a variety of intracellular proteins, NHERF and NHERF-2 may be multifunctional adaptor proteins involved in many previously unsuspected aspects of intracellular signaling.
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cERMIT is a computationally efficient motif discovery tool based on analyzing genome-wide quantitative regulatory evidence. Instead of pre-selecting promising candidate sequences, it utilizes information across all sequence regions to search for high-scoring motifs. We apply cERMIT on a range of direct binding and overexpression datasets; it substantially outperforms state-of-the-art approaches on curated ChIP-chip datasets, and easily scales to current mammalian ChIP-seq experiments with data on thousands of non-coding regions.
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Extensive drilling of the Great Barrier Reef (GBR) in the 70s and 80s illuminated the main factors controlling reef growth during the Holocene. However, questions remain about: (1) the precise nature and timing of reef "turnon" or initiation, (2) whether consistent spatio-temporal patterns occur in the bio-sedimentologic response of the reef to Holocene sea-level rise then stability, and (3) how these factors are expressed in the context of the different evolutionary states (juvenile-mature-senile reefs). Combining 21 new C14-AMS and 146 existing recalibrated radiocarbon and U/Th ages, we investigated the detailed spatial and temporal variations in sedimentary facies and coralgal assemblages in fifteen cores across four reefs (Wreck, Fairfax, One Tree and Fitzroy) from the Southern GBR. Our newly defined facies and assemblages record distinct chronostratigraphic patterns in the cores, displaying both lateral zonation across the different reefs and shallowing upwards sequences, characterised by a transition from deep (Porites/faviids) to shallow (Acropora/Isopora) coral types. The revised reef accretion curves show a significant lag period, ranging from 0.7-2 ka, between flooding of the antecedent Pleistocene substrate and Holocene reef turn-on. This lag period and dominance of more environmentally tolerant early colonizers (e.g., domal Porites and faviids), suggests initial conditions that were unfavourable for coral growth. We contend that higher input of fine siliciclastic material from regional terrigenous sources, exposure to hydrodynamic forces and colonisation in deeper waters are the main factors influencing initially reduced growth and development. All four reefs record a time lag and we argue that the size and shape of the antecedent platform is most important in determining the duration between flooding and recolonisation of the Holocene reef. Finally, our study of Capricorn Bunker Group Holocene reefs suggests that the size and shape of the antecedent substrate has a greater impact on reef evolution and final evolutionary state (mature vs. senile), than substrate depth alone.
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Ubiquitin ligases play a pivotal role in substrate recognition and ubiquitin transfer, yet little is known about the regulation of their catalytic activity. Nedd4 (neural-precursor-cell-expressed, developmentally down-regulated 4)-2 is an E3 ubiquitin ligase composed of a C2 domain, four WW domains (protein-protein interaction domains containing two conserved tryptophan residues) that bind PY motifs (L/PPXY) and a ubiquitin ligase HECT (homologous with E6-associated protein C-terminus) domain. In the present paper we show that the WW domains of Nedd4-2 bind (weakly) to a PY motif (LPXY) located within its own HECT domain and inhibit auto-ubiquitination. Pulse-chase experiments demonstrated that mutation of the HECT PY-motif decreases the stability of Nedd4-2, suggesting that it is involved in stabilization of this E3 ligase. Interestingly, the HECT PY-motif mutation does not affect ubiquitination or down-regulation of a known Nedd4-2 substrate, ENaC (epithelial sodium channel). ENaC ubiquitination, in turn, appears to promote Nedd4-2 self-ubiquitination. These results support a model in which the inter- or intra-molecular WW-domain-HECT PY-motif interaction stabilizes Nedd4-2 by preventing self-ubiquitination. Substrate binding disrupts this interaction, allowing self-ubiquitination of Nedd4-2 and subsequent degradation, resulting in down-regulation of Nedd4-2 once it has ubiquitinated its target. These findings also point to a novel mechanism employed by a ubiquitin ligase to regulate itself differentially compared with substrate ubiquitination and stability.
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La plupart des molécules d’ARN doivent se replier en structure tertiaire complexe afin d’accomplir leurs fonctions biologiques. Cependant, les déterminants d’une chaîne de polynucléotides qui sont nécessaires à son repliement et à ses interactions avec d’autres éléments sont essentiellement inconnus. L’établissement des relations structure-fonction dans les grandes molécules d’ARN passe inévitablement par l’analyse de chaque élément de leur structure de façon individuelle et en contexte avec d’autres éléments. À l’image d’une construction d’immeuble, une structure d’ARN est composée d’unités répétitives assemblées de façon spécifique. Les motifs récurrents d’ARN sont des arrangements de nucléotides retrouvés à différents endroits d’une structure tertiaire et possèdent des conformations identiques ou très similaires. Ainsi, une des étapes nécessaires à la compréhension de la structure et de la fonction des molécules d’ARN consiste à identifier de façon systématique les motifs récurrents et d’en effectuer une analyse comparative afin d’établir la séquence consensus. L’analyse de tous les cas d’empaquetage de doubles hélices dans la structure du ribosome a permis l’identification d’un nouvel arrangement nommé motif d’empaquetage le long du sillon (AGPM) (along-groove packing motif). Ce motif est retrouvé à 14 endroits dans la structure du ribosome de même qu’entre l’ARN ribosomique 23S et les molécules d’ARN de transfert liées aux sites ribosomaux P et E. Le motif se forme par l’empaquetage de deux doubles hélices via leur sillon mineur. Le squelette sucre-phosphate d’une hélice voyage le long du sillon mineur de l’autre hélice et vice versa. Dans chacune des hélices, la région de contact comprend quatre paires de bases. L’empaquetage le plus serré est retrouvé au centre de l’arrangement où l’on retrouve souvent une paire de bases GU dans une hélice interagissant avec une paire de bases Watson-Crick (WC) dans l’autre hélice. Même si la présence des paires de bases centrales GU versus WC au centre du motif augmente sa stabilité, d’autres alternatives existent pour différents représentants du motif. L’analyse comparative de trois librairies combinatoires de gènes d’AGPM, où les paires de bases centrales ont été variées de manière complètement aléatoire, a montré que le contexte structural influence l’étendue de la variabilité des séquences de nucléotides formant les paires de bases centrales. Le fait que l’identité des paires de bases centrales puisse varier suggérait la présence d’autres déterminants responsables au maintien de l’intégrité du motif. L’analyse de tous les contacts entre les hélices a révélé qu’en dehors du centre du motif, les interactions entre les squelettes sucre-phosphate s’effectuent via trois contacts ribose-ribose. Pour chacun de ces contacts, les riboses des nucléotides qui interagissent ensemble doivent adopter des positions particulières afin d’éviter qu’ils entrent en collision. Nous montrons que la position de ces riboses est modulée par des conformations spécifiques des paires de bases auxquelles ils appartiennent. Finalement, un autre motif récurrent identifié à l’intérieur même de la structure de trois cas d’AGPM a été nommé « adenosine-wedge ». Son analyse a révélé que ce dernier est lui-même composé d’un autre arrangement, nommé motif triangle-NAG (NAG-triangle). Nous montrons que le motif « adenosine-wedge » représente un arrangement complexe d’ARN composé de quatre éléments répétitifs, c’est-à-dire des motifs AGPM, « hook-turn », « A-minor » et triangle-NAG. Ceci illustre clairement l’arrangement hiérarchique des structures d’ARN qui peut aussi être observé pour d’autres motifs d’ARN. D’un point de vue plus global, mes résultats enrichissent notre compréhension générale du rôle des différents types d’interactions tertiaires dans la formation des molécules d’ARN complexes.
Resumo:
La excesiva proliferación de partidos políticos y listas a las corporaciones públicas, permitidas por la debilidad normativa de la Constitución de 1991 y la suspicacia de los políticos colombianos, hizo necesaria una reforma política en el año 2003. Esta reforma, manifestada en el Acto Legislativo 01 de 2003, modificó el sistema electoral colombiano; los cambios más visibles modificaron la forma de conversión de votos en escaños, la forma de candidatura y modalidad del voto, y la creación una barrera legal. Estas modificaciones llevaron a la reagrupación de los partidos políticos, pero no necesariamente a su fortalecimiento, ya que no establece las herramientas necesarias para la transparencia y la democratización interna de los partidos, que conllevarían a su real institucionalización. El Partido Social de Unidad Nacional , partido de La U-, es creado después de la implementación de la reforma y consigue la mayor votación nacional en sus primeras elecciones. Pero, ¿lo convierte ese resultado electoral en un partido fuerte?.