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Targeting Holliday JunctionsHamilton, Christopher 12 August 2014 (has links)
Holliday junctions are formed as an intermediate during DNA recombination as the two strands come together. Recombination occurs during meiosis, and also during DNA double strand repair. Trapping this branched intermediate could prevent DNA repair from occurring in cells which would prove beneficial during cancer treatment. There are many enzymes that cleave Holliday junctions. One such enzyme, T7 Endonuclease I, was specifically chosen to detect ligand binding at the core of the junction since its binding and cleavage of cruciforms is well documented. Specialized bifunctional ligands were studied in this project that were designed to bind DNA structures that are held in close proximity to one another. These compounds have two identical binding modules that are connected by a linker of various length and rigidity, with each module binding very weakly; however, when both modules bind the binding affinity is greatly enhanced. The interactions of these compounds with cruciforms are currently being studied.
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Identification of forming limits of sheet metals with an in-plane biaxial tensile test / Identification des limites de formage des tôles minces à partir d'un essai de traction biaxialeSong, Xiao 27 March 2018 (has links)
Les procédés de mise en forme des tôles minces sont largement utilisés dans l'industrie. L’utilisation optimale des alliages légers ou des aciers à haute résistance, propices à des économies d’énergie dans le domaine des transports, nécessite une connaissance approfondie de leurs limites de formabilité. Classiquement, la formabilité d’une tôle est caractérisée par l’apparition d’une striction localisée. Cependant, pour des chargements spécifiques (chemins de déformation complexes ...), la rupture caractérise la formabilité du matériau, la courbe limite de formage à rupture (CLFR) plutôt que celle à striction (CLFS) doit alors être considérée. Pour identifier la CLFS et la CLFR pour des chemins de déformation linéaires et non-linéaires, les méthodes conventionnelles requièrent différents dispositifs expérimentaux et différentes formes d'éprouvette pour atteindre une large gamme de chemins de déformation. L'essai de traction biaxiale, associé à une éprouvette cruciforme, est possible pour la réaliser. De plus, le changement de chemin est activé au cours de l’essai, sans déchargement. Le premier objectif de cette étude est de montrer que l'essai de traction biaxiale, associé à une forme unique d'éprouvette cruciforme, permet de tracer la CLFS et la CLFR pour plusieurs chemins de déformation, qu’ils soient linéaires ou non-linéaires. En premier lieu, des essais ont été réalisés sur des tôles d’alliage d’aluminium 5086 (épaisseur initiale de 4 mm) à partir d’une forme d’éprouvette déjà proposée au laboratoire. Une nouvelle forme d'éprouvette cruciforme a été proposée pour des tôles moins épaisses (2 mm), plus répandues. Cet éprouvette a été validée pour étudier la formabilité d’un acier dual phase DP600 pour plusieurs chemins de déformation. Le deuxième objectif est de discuter la validité de critères classiques de rupture ductile. Pour les deux matériaux, un critère a finalement été identifié pour prédire assez précisément les résultats expérimentaux. / Sheet metal forming is very common in industry for producing various components. The optimal use of light alloys or high strength steels in transportation for energy economy, requires in-depth analysis of their formability. Usually, the formability of sheet metal is controlled by the onset of localized necking. However, under specific loadings (complex strain paths...), fracture characterizes the formability and the forming limit curve at fracture (FLCF) instead of the forming limit curve at necking (FLCN) should be considered. For identifying FLCN and FLCF under linear and non-linear strain paths, conventional methods require different experimental devices and geometrical specifications of specimen to cover a wide range of strain paths. However, using the in-plane biaxial tensile test with just one shape of cruciform is sufficient for that, even changes of strain path without unloading can be made during the test. The first objective of this study is to show that the in-plane biaxial tensile test with a single type of cruciform specimen permits to investigate the FLCN and FLCF of sheet metals under different linear and non-linear strain paths. Firstly, the forming limit strains at fracture of AA5086 sheet (t=4 mm) under linear and non-linear strain paths have been characterized, by testing an existed dedicated cruciform specimen. Thinner sheet metals are often used in industry, so a new shape of cruciform specimen with an original thickness of 2 mm was proposed. This specimen is successfully used to investigate the formability of DP600 sheet under linear and two types of non-linear strain paths. The second objective is to discuss the validity of commonly used ductile fracture criteria to predict the onset of fracture. Some ductile fracture criteria were used to produce numerical FLCFs for AA5086 and DP600 sheet. Finally, for the two tested materials, it is possible to find a criterion to predict the experimental FLCFs for either linear or non-linear strain paths.
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Take up the cross (Mark 8:34 and par.) : the history and function of the cross saying in earliest ChristianityRumple, John Glenn January 2008 (has links)
The principal contention of this thesis is that the earliest Christians viewed the crucifixion of Jesus as paradigmatic for discipleship, confirmation of which can be found in the history and function of a particular saying ascribed to Jesus, namely the ‘cross saying’ (Mk 8:34 and par.). To verify this claim, I explore both the literary tradition and material culture of early Christianity as they relate to the cross saying, explicating the various ways that “taking up the cross” functioned to ensure unwavering loyalty to Jesus. Taking a traditional exegetical approach, I also engage recent work on sapiential literature (mainly Q) and Historical Jesus studies, observing the diverse ways in which the first several generations of Jesus’ followers adapted this saying—both as an aphorism for inclusion in gospels, and in the development of cognate versions useful in more theological settings (e.g., Gal 2:20). Proceeding diachronically via a textual analysis of the cross saying in Q, the Synoptics, and then the Gospel of Thomas, I trace the ways in which the composers of these texts addressed the different social situations of their audiences in an effort to secure commitment to Jesus (or, in the case of Gos. Thom., conformity to his enlightened teachings). Then, turning from the literature to the social and political environment of the New Testament, I note the radical reversal, occurring early in Christian thought, which transformed the crucifixion of Jesus from a shameful social experience into one of honour, and worthy of emulation. Even more significant in terms of current research, I break from the opinions of several New Testament scholars in finding little evidence that the cross saying (presuming it was dominical) functioned as a call to political insurrection. Rather, as evidenced in Christian material culture from the second and third centuries (symbols, the orant prayer posture, making the ‘sign of the cross,’ and so on), the association of crucifixion with discipleship was understood primarily in terms of religious devotion to Jesus.
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Composite RCS frame systems: construction and peformanceSteele, John Phillip 30 September 2004 (has links)
The objective of this research program is to further evaluate the performance and constructability of reinforced concrete (RC) column-steel beam-slab systems (RCS) for use in low- to mid-rise space frame buildings located in regions of high wind loads and/or moderate seismicity. To better understand these systems, two full scale RCS cruciform specimens were tested under bidirectional quasi-static reversed cyclic loading. The experimental portion of this research program included the construction and testing of two full-scale cruciform specimens with identical overall dimensions but with different joint detailing. The two joint details evaluated were joint cover plates and face bearing plates with localized transverse ties. The construction process was recorded in detail and related to actual field construction practices. The specimens were tested experimentally in quasi-static reversed cyclic loading in both orthogonal loading directions while a constant axial force was applied to the column, to simulate the wind loads in a subassembly of a prototype building. To compliment the experimental work, nonlinear analyses were performed to evaluate the specimen strength and hysteretic degradation parameters for RCS systems. In addition, current recommendations in the literature on the design of RCS joints were used to estimate specimen joint strength and were compared with the experimental findings.
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Two-photon absorption in cruciform and dipolar chromophores: excitonic interactions and response to metal ionsSiegel, Nisan Naftali 04 June 2010 (has links)
Structure-property relationships for two-photon absorption (2PA) in branched organic chromophores is a topic of current interest, as is the design of chromophores with advantageous properties for two-photon laser scanning microscopy (2PLSM). The main goals of this dissertation were to study and explain the one-photon absorption (1PA) and 2PA properties of cruciform chromophores based on 1,4-distyryl-2,5-bis(phenylethynyl)benzene with varying electron donor (D) and acceptor (A) groups, and to characterize the 2PLSM-relevant response of some of these chromophores and a set of dipolar chromophores to binding with zinc ions. The compounds were studied by 1PA, fluorescence and 2PA spectroscopy. A ππ* exciton model was developed to explain the spectral properties of the 1,4-distyryl-2,5-bis(phenylethynyl)benzene cruciform with no D or A groups or with four identical D groups at the termini of the linear arms of the chromophore. This model indicated that there is some coupling and mixing of the lowest excited states e of the linear arms, leading to splitting of the 1PA spectrum of the cruciform. There was little coupling or mixing of the higher excited states e′ accessed in 2PA, leading to a two-band 2PA spectrum for the chromophore, in contrast to cruciform compounds in the literature with identical conjugated arms, which have one visible 2PA band. For cruciforms with D groups on the styryl arm and A character on the terminal phenyls of the phenylethynyl arms (D/A cruciforms), the ππ* exciton model was complemented with a charge-transfer (CT) exciton model describing interactions of charge-transfer pathways between the D and A groups. This model explained the broadness of the 1PA band of D/A cruciforms as well as the two 2PA bands observed for these chromophores.
The fluorescence and 2PA spectral responses to binding of Zn²⁺ ions to the D or A groups of some cruciform compounds were also assessed, to provide insight into the design of new analyte-sensing cruciforms for 2PLSM that take advantage of enhancement or reduction of D/A character upon analyte binding. It was found that canceling charge donation from the D groups in differing D/A cruciforms resulted in fluorescence and 2PA spectra nearly indistinguishable from each other, suggesting that turn-off of D groups is not an optimal modality of 2PLSM analyte sensing in cruciforms. Binding Zn²⁺ to A groups was shown to result in an increase in the D/A character of the cruciform, with fluorescence peak energies that changed depending on the location of the A group. It is suggested that the use of non-binding donors and analyte-binding A groups in differing patterns on the arms could be a valuable design motif to achieve 2PLSM sensor compounds based on this cruciform structure.
The 2PA spectra of a set of dipolar Zn²⁺ sensing dyes designed for ratiometric imaging in 2PLSM were also studied. These dyes had moderate 2PA strength, with redshifts of fluorescence 2PA spectra on Zn²⁺ binding. The isosbestic point of 2PA of most chromophores was within the range of 2PLSM excitation sources commonly used, rendering these dyes good candidates for use in ratiometric sensing in 2PLSM.
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Composite RCS frame systems: construction and peformanceSteele, John Phillip 30 September 2004 (has links)
The objective of this research program is to further evaluate the performance and constructability of reinforced concrete (RC) column-steel beam-slab systems (RCS) for use in low- to mid-rise space frame buildings located in regions of high wind loads and/or moderate seismicity. To better understand these systems, two full scale RCS cruciform specimens were tested under bidirectional quasi-static reversed cyclic loading. The experimental portion of this research program included the construction and testing of two full-scale cruciform specimens with identical overall dimensions but with different joint detailing. The two joint details evaluated were joint cover plates and face bearing plates with localized transverse ties. The construction process was recorded in detail and related to actual field construction practices. The specimens were tested experimentally in quasi-static reversed cyclic loading in both orthogonal loading directions while a constant axial force was applied to the column, to simulate the wind loads in a subassembly of a prototype building. To compliment the experimental work, nonlinear analyses were performed to evaluate the specimen strength and hysteretic degradation parameters for RCS systems. In addition, current recommendations in the literature on the design of RCS joints were used to estimate specimen joint strength and were compared with the experimental findings.
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Analýza lokalizace inverzních repetic v bakteriálních genomech / Analyses of inverted repeats localization in bacterial genomesŠedý, Michal January 2021 (has links)
Inverted repeats (IR) are common part of DNA of all living prokaryotic and eukaryotic organisms. Inverted repeats plays an important role in the regulation of basics cells processes. They are responsible for formation of cruciform structures. Inverted repeats also cause genomic instability and can be a source of numerous mutations. Cruciform structures can be recognized by DNA-binding proteins and can also act as a transcriptional regulators. Using the Palindrome Analyser tool, the frequency of IR and localization of inverted repeats in bacterial genomes was analyzed. The frequency of IR across the bacterial genome is variable. The frequency of short inverted repeats shows an approximately quadratic dependence on the %GC content in the genome with a minimum of about 50% of GC content. The localization of inverted repeats with respect to “annotated features” show a non-random distribution. The frequency of IR for most features is higher “outside” than “inside”.
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Analýza lokálních struktur v molekulách DNA / Analysis of local structures in DNA moleculesNyczová, Adéla January 2021 (has links)
Local DNA structures are alternative DNA conformations which can be formed aside from typical B-DNA conformation. These structures often play pivotal roles in regulation of basic biological processes, such as DNA replication, transcription or binding of specific ligands. This biological significance makes alternative DNA secondary structures a potential drug target. In this diploma thesis, local structures in genomes of viruses from Flaviviridae and Retroviridae families are analysed using bioinformatics tools. Furthermore, these structures are visualised using atomic force microscopy.
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Poverty, Disease, and Port Cities: Global Exchanges in Hospital Architecture during the Age of ExplorationAbdon Guimaraes, Danielle January 2020 (has links)
This dissertation examines the cross-cultural circulation of the cruciform design for hospitals as the early modern architectural response to charitable and urban crises, considering the emergence of the plan in Italy and its rapid dissemination during the Age of Exploration (1400-1700). Despite recent media attention on makeshift hospitals, refugee camps, and reconstruction efforts worldwide following natural disasters, wars, and pandemics, the urgency of devising architectural and urban responses to human crises associated with poverty, disease, and migration is not a new phenomenon. While today these issues are often addressed in isolation, during the early modern period, they factored into a broader, ‘ecological’ understanding of health that drove the construction of hospitals and shelters for the sick poor, enmeshing these institutions into larger social, public health, and environmental strategies.</DISS_para> <DISS_para>Using the cruciform design as a connecting thread, I investigate links among port cities in Italy, Iberia, and the New World as they struggled with unprecedented challenges in sanitation, poverty, and medical assistance. As a result of intensified contact and circulation, ports are ideal sites for a study of architectural and urban innovations targeting urban crises. My project employs sociologist Immanuel Wallerstein’s model of ‘world cities’ to construe early modern ports as globally-networked cities that actively imported the latest advancements to achieve cultural and political centrality. Moving away from a formalist analysis, I integrate the building fabric with the contexts that inflected its adaptations, considering the role of the cruciform design in hospitals whose architecture and infrastructure promoted medical and sanitary innovations in the building itself and surrounding urban area, including developments to facilitate the disposal of human waste and the removal of dead bodies. My study combines archival evidence, archaeological data, and architectural and urban plans with contemporary knowledge of public and environmental health. This interdisciplinary approach highlights why political authorities sought and re-interpreted the cruciform design, isolating the innovative aspects responsible for the fast spread of this typology across Europe and Latin America. </DISS_para> <DISS_para>My Introduction (Chapter 1) examines the development of the cruciform typology as a result of charitable reforms occurring in northern Italy in the mid-fifteenth century. Building on early modern medical knowledge, I introduce the innovations associated with the design and consider the role of Filarete’s Treatise on Architecture (ca. 1460-64) in the circulation of architectural concepts during the period. Chapter 2 addresses the Ospedale di Messer Gesù Cristo (1474) in Venice in a longer history of Venetian reform. More specifically, I investigate the change in the mission of the Ospedale, as well as its architecture, from the perspective of military and urban crises faced by the Republic in the late fifteenth century. My discussion expands to Iberia in Chapter 3, with a study of the Hospital Real de Todos-os-Santos (1492) in Lisbon, an institution commissioned by the Portuguese monarchy to solve Lisbon’s crises of social welfare and public health. In particular, this chapter analyzes the Portuguese adoption of foreign and local strategies in charitable reform and the architecture of the hospital in view of larger public health strategies. Chapter 4 centers on the Hospital de las Cinco Llagas (1503) in Seville, especially considering the upsurge of at-risk women in Seville due to Spain’s male-driven colonization endeavors in the New World. Investigating the move and expansion of the hospital in 1549, I demonstrate how the architecture of the institution balanced innovations with the necessity to guarantee the invisibility and isolation of the institution’s female patients. Finally, Chapter 5, which also serves as a conclusion, addresses the translation of the cruciform typology to the New World. I compare the adoption of the plan in the Hospital San Nicolás de Bari (1503), located in the Spanish colony of Santo Domingo, with the different strategies of the Portuguese monarchy in colonial Salvador as evidenced by the Hospital da Cidade (1549).</DISS_para> <DISS_para>This dissertation contributes to the field in three ways. First, I demonstrate the actual reasons for the cruciform plan’s success rather than assuming the ‘natural’ replication of an Italian design as has been traditional in scholarship centered on this topic. Second, my case studies show the mobility and circulation of scientific and technological knowledge across southern Europe and between the Old and New Worlds, innovatively recognizing the impact of this flux on the built and urban fabrics of early modern cities. Finally, by shifting the scholarly discourse from Italy to the agency of Iberian and New World patrons, my dissertation opens the field for contributions from the so-called historical periphery, promoting a global understanding of early modern architecture and urbanism. / Art History
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ex-centricityHuffman, Frank 11 February 2004 (has links)
Out of a dialog of order and building, the cruciform finds presence in the plan and section of a temporally significant house. This is a study of the dialectic between the ideal and the empirical in architecture. / Master of Architecture
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