L'accroissement des connaissances, structurales et fonctionnelles, des protéines nous donne désormais une vision plus précise des phénomènes d'interaction. L'utilisation de ces informations pour le développement de ligands permettrait d'obtenir de nouveaux composés, capables d'interagir avec diverses cibles d'intérêt, et d'améliorer notre compréhension de ces interactions. Ce travail présente le développement d'une nouvelle méthode de conception de ligands protéiques, laquelle repose sur le transfert d'un groupe de résidus, appartenant à un ligand connu et contribuant de façon importante à la liaison avec une cible d'intérêt, sur une protéine hôte, de moins de 100 résidus (mini-protéines). L'identification de protéines hôtes, aptes à reproduire l'interaction après transfert du motif, est réalisée de manière systématique à partir des structures présentes dans la PDB. L'approche a été appliquée pour le développement de ligands du canal Kv1.2, à partir de connaissances structurales et fonctionnelles de l'interaction de ce même canal avec la toxine BgK. Trois ligands, possédant des constantes d'inhibition micro molaires, ont été ainsi conçus. Ces résultats démontrent la possibilité de mettre en application une méthode de conception de ligands, basée sur le transfert de motifs de « hotspots », sur une plateforme structurale de nature protéique, dont les aspects stérique et électrostatique sont compatibles avec une interaction donnée.

The use of geophysical techniques to image the interiors of active volcanoes can provide a better understanding of their structure and plumbing. The need for such information is especially critical for undersea volcanoes, whose environment makes them difficult to investigate. Because undersea volcanoes are made up of highly magnetic basaltic rock, it is possible to use variations in the magnetic field to explore the internal structure of such edifices. This study combines magnetic survey data from 12 research cruises to make a magnetic anomaly map of volcanically active Loihi, located in the Hawaiian Island chain. NRM intensities and susceptibility measurements were measured from recovered rock samples and suggest that magnetic properties of Loihi are widely varied (NRM intensities range from 1-157 A/m and susceptibilities from 1.26 x 10-3 to 3.62 x 10-2 S.I.). The average NRM intensity is 26 A/m. The size and strength of magnetic source bodies were determined by using various modeling techniques. A strongly magnetized shield can explain most of the anomaly with a large nonmagnetic zone inside, beneath the summit. Prominent magnetic highs are located along Loihi's north and south rift zone dikes and modeling solutions suggest strongly magnetized source bodies in these areas as well as a thin, magnetic layer atop the nonmagnetic zone. The strong magnetic anomalies found along the volcano's rift zones cannot be readily attributed to recent lava flows at the surface. Instead, the source bodies must continue several kilometers in depth to give reasonable magnetization values and are interpreted as dike intrusions. Nonmagnetic anomalies at the summit and south of the summit suggest the presence of a magma system. The model solution suggests Loihi is an inhomogeneously magnetized seamount with highly magnetic dike intrusions along the rift zones with a nonmagnetic body at its center overlain with a magnetic layer.

<p><p>One of the most significant discoveries from mutational analysis of protein interfaces is that often a large percentage of interface residues negligibly perturb the binding energy upon mutation, while residues in a few critical "hotspots" drastically reduce affinity when mutated. The organization of protein interfaces into hotspots has a number of important implications. For example, small interfaces can have high affinity, and when multiple binding partners are generated to the same protein, they are predisposed to binding the same regions and often have the same hotspots. Even small molecules that bind to interfaces and disrupt protein-protein interactions (PPIs) tend to bind at hotspots. This suggests that some hotspot-forming sites on protein surfaces are <italic>intrinsically</italic> more apt to form protein interfaces. These observations paint a hotspot-centric picture of PPI energetics, and present a question of fundamental importance which remains largely unanswered: <italic>why are hotspots hot?</italic></p></p><p><p>In order to gain insight into the nature of hotspots I experimentally examined the small, but high-affinity interface between the synthetically evolved ankyrin repeat protein Off7 with E. coli maltose binding protein by characterization of mutant variants and redesigned interfaces. In order to characterize many mutants, I developed two high-throughput assays to measure protein-protein binding that integrate with existing technology for the high-throughput fabrication of genes. The first is an ELISA-based method using in vitro expressed protein for semi-quantitative analysis of affinity. Starting from DNA encoding protein partners, binding data is obtained in just a few hours; no exogenous purification is required. For the second assay, I develop data fitting methods and thermodynamic framework for determination of binding free energies from binding-induced shifts in protein thermal stability monitored with Sypro Orange.</p></p><p><p>Analysis of Off7/MBP variants using these methods reveals that conservative mutagenesis or local computational repacking is tolerated for many residues in the interface without drastic loss of affinity, except for a single essential hotspot. This hotspot contains a Tyr-His-Asp hydrogen bonding network reminiscent of a common catalytic motif. Substitution of the tyrosine with phenylalanine shows that a single hydrogen bond across the interface is critical for binding. Analysis of the protein database by structural bioinformatics shows that, although rare, this motif is present in other naturally evolved interfaces. Such a triad was found in the homodimeric interface of PH0642 from Pyrococcus horikoshii, and is conserved between many homologues in the nitrilase superfamily, meeting one of the key criteria by which potential hotspots can be identified. This analysis supports a number of analogies between hotspot residues and catalytic residues in enzyme active sites, and raises the intriguing possibility that hotspots may be associated with other structural motifs that could be used for identification or design of PPIs.</p></p> / Dissertation

The use of geophysical techniques to image the interiors of active volcanoes can provide a better understanding of their structure and plumbing. The need for such information is especially critical for undersea volcanoes, whose environment makes them difficult to investigate. Because undersea volcanoes are made up of highly magnetic basaltic rock, it is possible to use variations in the magnetic field to explore the internal structure of such edifices. This study combines magnetic survey data from 12 research cruises to make a magnetic anomaly map of volcanically active Loihi, located in the Hawaiian Island chain. NRM intensities and susceptibility measurements were measured from recovered rock samples and suggest that magnetic properties of Loihi are widely varied (NRM intensities range from 1-157 A/m and susceptibilities from 1.26 x 10-3 to 3.62 x 10-2 S.I.). The average NRM intensity is 26 A/m. The size and strength of magnetic source bodies were determined by using various modeling techniques. A strongly magnetized shield can explain most of the anomaly with a large nonmagnetic zone inside, beneath the summit. Prominent magnetic highs are located along Loihi's north and south rift zone dikes and modeling solutions suggest strongly magnetized source bodies in these areas as well as a thin, magnetic layer atop the nonmagnetic zone. The strong magnetic anomalies found along the volcano's rift zones cannot be readily attributed to recent lava flows at the surface. Instead, the source bodies must continue several kilometers in depth to give reasonable magnetization values and are interpreted as dike intrusions. Nonmagnetic anomalies at the summit and south of the summit suggest the presence of a magma system. The model solution suggests Loihi is an inhomogeneously magnetized seamount with highly magnetic dike intrusions along the rift zones with a nonmagnetic body at its center overlain with a magnetic layer.

Oceanic lithosphere constitutes the upper boundary layer of the Earth’s convecting mantle. Its structure and evolution provide a vital window on the dynamics of the mantle and important clues to how the motions of Earth’s surface plates are coupled to convection in the mantle below. The three-dimensional shear-velocity structure of the upper mantle beneath the Atlantic Ocean is investigated to gain insight into processes that drive formation of oceanic lithosphere. Travel times are measured for approximately 10,000 fundamental-mode Rayleigh waves, in the period range 30-130 seconds, traversing the Atlantic basin. Paths with >30% of their length through continental upper mantle are excluded to maximize sensitivity to the oceanic upper mantle. The lateral distribution of Rayleigh wave phase velocity in the Atlantic upper mantle is explored with two approaches. One, phase velocity is allowed to vary only as a function of seafloor age. Two, a general two-dimensional parameterization is utilized in order to capture perturbations to age-dependent structure. Phase velocity shows a strong dependence on seafloor age, and removing age-dependent velocity from the 2-D maps highlights areas of anomalously low velocity, almost all of which are proximal to locations of hotspot volcanism. Depth-dependent variations in vertically-polarized shear velocity (Vsv) are determined with two sets of 3-D models: a layered model that requires constant VSV in each depth layer, and a splined model that allows VSV to vary continuously with depth. At shallow depths (~75 km) the seismic structure shows the expected dependence on seafloor age. At greater depths (~200 km) high-velocity lithosphere is found only beneath the oldest seafloor; velocity variations beneath younger seafloor may result from temperature or compositional variations within the asthenosphere. The age-dependent phase velocities are used to constrain temperature in the mantle and show that, in contrast to previous results for the Pacific, phase velocities for the Atlantic are not consistent with a half-space cooling model but are best explained by a plate-cooling model with thickness of 75 km and mantle temperature of 1400oC. Comparison with data such as basalt chemistry and seafloor elevation helps to separate thermal and compositional effects on shear velocity.

xv, 151 p. : ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / To explain the origin of several distinct aspects of the Galápagos volcanic hotspot, such as the broad geographical extent of recent volcanism and the unusual pattern of geochemical anomalies, we conducted seismic tomography studies of the upper mantle and crust beneath the Galápagos Archipelago. The studies combine measurements of group and phase velocities of surface waves and delay times of body waves. We find that upper mantle seismic velocities are lower than those beneath other regions of comparable age in the Pacific and consistent with an excess temperature of 30 to 150°C and ∼0.5% melt. We attribute the excess temperature and presence of melt to an upwelling thermal mantle plume. Crustal seismic velocity is up to 25% lower than that of very young crust at the East Pacific Rise (EPR) and is comparable to that of Hawaii, which we attribute to heating by increased intrusive activity above the Galápagos plume and the construction of a highly porous volcanic platform. In addition, we find that the Galápagos hotspot is underlain by a high-velocity region whose thickness varies from 40 to 100 km. The tomographic images reveal that the upwelling mantle plume tilts northward (towards the nearby Galápagos Spreading Center) as it rises and then spreads laterally when it reaches the bottom the lid. The lid, which we attribute to residuum from melting, is thickest where it is farthest from the spreading center, suggesting that ridge processes may affect the generation and amount of thinning of the residuum layer. In addition, the thickness of the lid correlates well with the geographical pattern of geochemical anomalies of erupted lavas, suggesting that the lid may control the final depth of decompression melting. We conclude that many of the distinct characteristics of the Galápagos can be attributed to the interaction of the upwelling plume with the lid and the nearby ridge. We further suggest that the ridge affects the geometry of plume upwelling in the upper mantle and also the pattern of lateral spreading of the plume due to its effect on the thickness of the residuum layer. This dissertation includes previously published co-authored material. / Committee in charge: Dr. Douglas R. Toomey, Chairperson; Dr. Eugene Humphreys, Member; Dr. Emilie Hooft Toomey, Member; Dr. Paul Wallace, Member; Dr. John Conery, Outside Member

Submitted by Mario BC (mario@bc.ufrpe.br) on 2016-05-20T16:02:58Z No. of bitstreams: 1 Diego Vicente de Souza Ferreira.pdf: 4348458 bytes, checksum: d170ec08e8b19561b0eff75d6b69c040 (MD5) / Made available in DSpace on 2016-05-20T16:02:58Z (GMT). No. of bitstreams: 1 Diego Vicente de Souza Ferreira.pdf: 4348458 bytes, checksum: d170ec08e8b19561b0eff75d6b69c040 (MD5) Previous issue date: 2016-02-18 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / In this work we analyze the complexity of stream flow in the São Francisco River and hot-pixels detected in Amazonia, in order to evaluate the effects of human activity. Permutation entropy is employed which takes into account temporal causality by comparing consecutive values within the series. We also use this entropy method to analyze rainfall regime in Pernambuco, Brazil. For the São Francisco River, we analyze the influence of the Sobradinho dam construction on the hydrological regime. The results show that entropy of stream flow increases after the dam’s construction in 1979, which indicates more disordered and less predictable dynamics. For hot-pixels detected in Amazonia, the increase in entropy is related to severe droughts in 2005, 2007, and 2010. For temporal series of precipitation in Pernambuco, entropy values decrease with distance from the coast, indicating more predictability of monthly rainfall in the zona de mata and agreste regions, and less predictable rainfall dynamics in the sertão and vale do São Francisco regions. / Neste trabalho foi analisada a complexidade das séries temporais de vazão do rio São Francisco e de queimadas na Amazônia, para avaliar as alterações causadas pela atividade humana. Utilizou-se o método entropia de permutação (Permutation entropy) que incorpora a relação temporal entre os valores da série analisada, utilizando uma representação simbólica baseada na comparação dos valores consecutivos da série. Este método também foi usado para analisar regime de chuva de Pernambuco. Para a vazão do rio São Francisco avaliou se a influência da construção da barragem Sobradinho no regime hidrológico. Os resultados das análises da série temporal de vazão para o período 1929-2009 mostraram que a entropia aumentou depois da construção da barragem Sobradinho indicando uma dinâmica de vazão mais desordenada e menos previsível neste período. Os resultados obtidos para série temporal diária de queimadas detectadas na Amazônia durante o período 1999-2012, mostraram um aumento da entropia relacionado com secas que ocorreram em 2005, 2007 e 2010. Em relação aos dados de precipitação de Pernambuco, os valores da entropia de permutação diminuem com o aumento da distância das estações do litoral, indicando maior variabilidade e menor previsibilidade das chuvas mensais nas regiões próximas a zona da mata e agreste, e menor variabilidade e maior previsibilidade nas regiões próximas ao sertão e vale do São Francisco.

Detta examensarbete är gjort på uppdrag av Fiber Optik Valley. Huvuduppdraget i projektet var att skapa ett fungerande betalningssystem för en hotspot och att utveckla företagets webbsida. Hotspotsystemet som baserades på en gratistjänst från Public IP, är tänkt att kunna fungera delvis autonomt utan ägarens ingripande. Företagets webbsida skapades i en Flex2-utvecklingsmiljö och produkten blev en Adobe Flash-applikation. För att få ett dynamiskt och konfigurerbart system skapades även en kontrollpanel till webbsidan åt företagets webbadministratörer, så att innehållet på sidan ska kunna förändras utan att behöva kompilera om koden. Kontrollpanelen säkrades också med en inloggningsprocess. Som underliggande motor och som ersättning för brister i Flash-funktionaliteten, användes Simple PHP-tjänster mellan Flash-applikationen och PHP-skripten på servern. Betalningssystemet utvecklades med hjälp av PHP, MySQL och JavaScript. I systemet ingår PayPal’s IPN-tjänster för penningtransaktioner och validering av transaktioner. En självständig AMP-server, Apache2, MySQL och PHP5.0, lades till hotspotsystemet för att minska behovet av att ha en webbsida på ett externt webbhotell. / This graduation work was done as a assignment from Fiber Optic City company based in Hudiksvall Sweden. The base assignment was to create an automated payment system for a Hotspot network and a company web page. The hotspot system should work as a standalone service. The company has already a working free-of-charge service that is offered to its customers and is based on Public IP system. The company webpage was done with the help of a development suite called Flex2 and the result was an Adobe Flash application. To increase webpage dynamics a second page was developed for the company to have the ability to change and configure the main company webpage. An authentication service was deployed to configuration page to increase its security. As an engine and a substitute for lack of functionality and security in Adobe Flash simplePHP web service was used to connect Flash with a PHP script on its server. The payment system was developed with the help of PHP, MySQL and JavaScript. The system uses Paypal IPN service for money transaction and transaction validation A standalone web server with Apache2, PHP 5.0 and MySQL was deployed to the hotspot system to reduce the need of having an authentication system on a commercial Internet based web hotel.

Master’s thesis deals with the design and realization of a hotspot system for more Operators, it solves problems of QoS, billing of transferred data and distribution of services via a common wireless interface. The theoretic part is oriented to the selection of a suitable technology and explanation of a legislation, which relates to an activity of the hotspot‘s network. The practical part solves the choice of hardware, design and realization of the experimental network. In conclusion are tested transit parameters of the network and its functionality.

The 7.7 Ma Kimberly Member of the Cassia Formation is part of a succession of A-type rhyolites associated with the Yellowstone hotspot track. It was sampled by the Kimberly core that was drilled on the Snake River Plain as part of Project HOTSPOT (Shervais, et al., 2013). The Kimberly Member is a 170 m thick high-silica rhyolite lava flow containing quartz, plagioclase, anorthoclase, sanidine, augite, pigeonite, magnetite, ilmenite, zircon, and apatite. δ 18O of zircon ranges from 0 to 4.9‰ (Colón et al., 2018), typical low values for the Snake River Plain. Quartz is intensely embayed. Exsolved and resorbed pigeonite cores are mantled by augite. REE-poor apatite cores are resorbed and oscillatory zones truncated by rims with SiO2 as high as 12.8 wt% and LREEtot up to 4.7%. There are three chemically distinct feldspars. Rounded and pitted anorthoclase (Or21 Ab64 An15) mantles plagioclase (An20 to An40) cores. Sanidine (Or47 Ab48 An05) forms thin, subhedral drapes on the outer edges of anorthoclase. Sanidine also fills some of the sieved holes in plagioclase and anorthoclase. There are two chemically distinct glasses, a light glass (~95%) and a dark glass (~5%). Relative to the light glass, the dark is enriched in Al2O3 , CaO, and Na2O and depleted in Fe2O3 and K2O. The dark glass is depleted in Rb and enriched in Sr and Ba, but they have similar concentrations of the high field strength elements (Y, Zr, Nb, Hf, and Ta). LREE are slightly more enriched in the dark glass than in the light glass. Temperatures of 926°C (magnetite-ilmenite thermometry with QUILF), 894°C (pigeonite-augite pairs with QUILF), and 889°C (zircon-saturation) are calculated for the magma. Although Fe-Ti oxides appear to have equilibrated with melt before eruption, most of the other phases preserve strong evidence of disequilibrium. These complex mineral textures also indicate assimilation and mixing processes. We propose a pigeonite-bearing, dry, metasomatized, A-type granite was fragmented and assimilated by the Kimberly member, mantling exsolved pigeonite with augite. Also incorporated into the Kimberly member were volcanic xenocrysts indicative of rhyolite assimilation or magma mixing. These components are embayed volcanic quartz, and composite plagioclase-anorthoclase grains (mantled by sanidine upon assimilation). Complex zircon grains could be sourced from metasomatized rhyolite or intrusion, and complex apatite grains could be due to mixing or assimilation. We propose the distinct glass types are caused by mingling of the Kimberly magma with the melted metasomatized assimilant. This scenario demonstrates the complexity of open system processes involved in some Snake River Plain magmas.