A distribuição angular de fótons espalhados (perfil de espalhamento) pode fornecer informações sobre as estruturas que compõe um tecido biológico, permitindo, a partir da análise desta, identificar a presença de anormalidades no tecido. A proposta deste trabalho foi desenvolver um procedimento experimental de medidas do perfil de espalhamento de tecidos mamários normais e alterados e, posteriormente, correlacionar as informações contidas neste com informações histopatológicas do tecido. Os perfis de espalhamento foram medidos no intervalo de momento transferido entre 0,2<= ? <=6,2 nm-1, utilizando um difractômetro Siemens D-5005, com ânodo de cobre e operando no modo reflexão. As amostras de tecidos mamários, foram previamente classificadas como tecidos normais, fibroadenomas e carcinomas. As intensidades medidas foram corrigidas por atenuação, efeitos geométricos e pela variação angular do feixe incidente. A eficácia do procedimento experimental foi validada através do uso de dados de referência para amostras de água. Os resultados mostraram que o perfil de espalhamento é uma característica única de cada tipo de tecido, sendo sua forma relacionada à morfologia microscópica do tecido. Na região em que x<=0,35 nm-1, verificou-se estatisticamente que as informações contidas nos perfis de espalhamento permitem a diferenciação entre tecidos normais e alterados. / Angular distribution of photons scattered by tissues (scattering profile) gives detailed information of structures within them and provides an alternative mean of distinguishing pathologies. The proposal of this work was to develop an experimental procedure to determine scattering profiles from breast tissues (normal and neoplastic) and to correlate the information contained in these profiles with histopathological information. The scattering profiles were measured in the interval of momentum transfer 0,2 ? ? ? 6,2 nm-1, using a powder diffractomer apparatus (Siemens D-5005), with copper anode and operation in reflection mode. The breast samples were previously histopathologically classified as normal tissues, fibroadenomes and carcinomas. The measured angular distribution was corrected by attenuation, geometric effect and the angular variation of the incident beam. The effectiveness of the experimental procedure was validated through the use of water reference data. The results shown that, scattering profile is unique impression of each type of tissue, being correlated with the microscopic morphological features. In the region where ? ? 0,35 nm-1, were statistically verified that the information contained in the scattering profiles allow the differentiation between normal and neoplastic breast tissues.

As propriedades de espalhamento de raios X e atenuação de tecidos mamários normais (adiposo e fibroglandular), neoplásicos (benigno e maligno) e vários materiais tecido-equivalente (nylon, poliacetato, polimetilmetacrilato (PMMA), água, músculo-equivalente, osso-equivalente e adiposo-equivalente) foram determinados usando um sistema de raios X dispersivo em energia (SRXDE). O SRXDE consistiu de um tubo de raios X com anodo de tungstênio operando a 60kVp, um goniômetro e dois detectores: um detector de telureto de cádmio (CdTe), posicionado a 7 graus com relação ao feixe incidente usado para detectar a distribuição em energia dos fótons espalhados (numa faixa de momento transferido de 0,5nm-1 - 3,5nm-1) e um detector de silício (Silicon Drift Detector, SDD), posicionado a zero graus e usado para detectar a distribuição em energia do feixe transmitido (com amostra) ou do feixe incidente (sem amostra). A distribuição espectral foi processada para se obter o perfil de espalhamento e o coeficiente de atenuação linear de 100 amostras de tecidos mamários (59 normal, 30 maligno e 11 benigno). Este sistema foi, também, aplicado ao estudo de regiões de transição entre tecidos com diferentes composições. Os resultados encontrados neste trabalho mostram que os tecidos mamários podem ser caracterizados através de suas propriedades de atenuação e espalhamento. Perfis de espalhamento neoplásico apresentam formato do pico principal significativamente diferente na faixa de momento transferido de 0,8nm-1 - 2,0nm-1, aos tecidos normais. Especificamente, o tecido adiposo apresentou um perfil de espalhamento muito diferente (pico principal em 1,12nm-1 e LMA de 0,33nm-1) quando comparado com tecidos neoplásico maligno e benigno e normal fibroglandular (pico principal em torno de 1,54nm-1 e LMA em torno de 0,73nm-1). O coeficiente de atenuação linear observado para os tecidos maligno, benigno e fibroglandular são muito similares e mostraram diferenças menores que 8% para energias entre 10 e 35keV. Entretanto, o tecido adiposo apresentou diferenças significativas com relação aos outros tecidos em toda faixa de energia (diferenças de até 40% foram observadas). Os resultados obtidos da varredura espacial das amostras heterogêneas mostram que o sistema desenvolvido permite o estudo de regiões de transição entre tecidos com diferentes composições. Finalmente, nossos resultados foram comparados com dados experimentais previamente publicados na literatura, mostrando boa concordância dentro das incertezas estatísticas. / The X-ray scattering and attenuation properties for normal (adipose and glandular) and neoplastic (benign and malignant) breast tissues and several tissue-equivalent materials (nylon, polyacetate, polymethylmethacrylate (PMMA), water, muscle-equivalent, bone-equivalent and adipose-equivalent) were determined using an energy dispersive X-ray system (EDXS). The EDXS consisted of a tungsten anode X-ray tube operating at 60kVp, a goniometer, and two detectors: a Cadmium Telluride (CdTe) detector, positioned at 7 degrees with relation to the incident beam used for detecting the energy distribution of scattered photons (over the momentum transfer range of 0,5nm-1- 3,5nm-1) and a Silicon Drift Detector (SSD), positioned at zero degree used for detecting the energy distribution of the transmitted beam (with the sample) or the incident beam (without the sample). The spectra distributions were processed to obtaine the scattering profile and the linear attenuation coefficient of 100 samples of breast tissues (59 normal, 30 malignant and 11 benign). This system was also applied to the study of the transition regions between tissues with different composition. The results found in this work show that breast tissues may be characterized through their attenuation and scattering properties. Neoplastic scattering profiles presented format and the main peak position significantly different in the range of momentum transfer from 0,8nm-1- 2,0nm-1, to normal tissues. Specifically, adipose tissue presented a very different scattering profile (main peak at 1,12nm-1and FWHM of 0,33nm-1) when compared with malignant, benign and also normal glandular tissues (main peak around 1,54nm-1and FWHM about of 0,73nm-1). The linear attenuation coefficient observed for malignant, benign and normal glandular tissues were quite similar and showed differences smaller than 8% for energies between 10 and 35keV. However, adipose tissue presented significant differences from the others tissues type in all energy range (differences up to 40% were observed). The results of the spatial scan of heterogeneous samples show that the developed system allows the study of transition regions between tissues with different composition. Finally, our results were compared with previous experimental data showing a good agreement within the experimental uncertainties

New and more efficient magnetic materials for energy applications are a big necessity for sustainable future. Whether the application is energy conversion or refrigeration, materials based on sustainable elements should be used, which discards all rare earth elements. For energy conversion, permanent magnets with high magnetisation and working temperature are needed whereas for refrigeration, the entropy difference between the non-magnetised and magnetised states should be large. For this reason, magnetic materials have been synthesised with high temperature methods and structurally and magnetically characterised with the aim of making a material with potential for large scale applications. To really determine the cause of the physical properties the connections between structure (crystalline and magnetic) and, mainly, the magnetic properties have been studied thoroughly. The materials that have been studied have all been iron based and exhibit properties with potential for the applications in mind. The first system, for permanent magnet applications, was Fe5SiB2. It was found to be unsuitable for a permanent magnet, however, an interesting magnetic behaviour was studied at low temperatures. The magnetic behaviour arose from a change in the magnetic structure which was solved by using neutron diffraction. Substitutions with phosphorus (Fe5Si1-xPxB2) and cobalt (Fe1-xCox)5PB2 were then performed to improve the permanent magnet potential. While the permanent magnetic potential was not improved with cobalt substitutions the magnetic transition temperature could be greatly controlled, a real benefit for magnetic refrigeration. For this purpose AlFe2B2 was also studied, and there it was found, conclusively, that the material undergoes a second order transition, making it unsuitable for magnetic cooling. However, the magnetic structure was solved with two different methods and was found to be ferromagnetic with all magnetic moments aligned along the crystallographic a-direction. Lastly, the origin of magnetic cooling was studied in Fe2P, and can be linked to the interactions between the magnetic and atomic vibrations.

Real-time coherent Grazing-Incidence Small-Angle X-ray Scattering was used to investigate the average kinetics and the fluctuation dynamics during self-organized ion beam nano-patterning of two semiconductor surfaces: silicon at room temperature and germanium heated above its recrystallation temperature. For silicon nano-patterning, initially flat samples at room temperature were bombarded by a broad collimated beam of 1keV Ar+ and Kr+ ions at 65° polar angle, leading to the amorphization of the ion-irradiated surfaces and the spontaneous formation of nanoscale ripples. The temporal evolution of the average X-ray scattering intensity shows the evolution of average kinetics, while the fluctuation dynamics can be investigated by correlation of X-ray speckles. The surface behavior at early times can be explained within a linear theory framework. The transition away from the linear theory behavior is observed in the dynamics since the intensity correlation function quickly evolves into a compressed exponential decay on length scales corresponding to the peak wavelength and a stretched exponential decay on shorter length scales. The correlation times for silicon nano-patterning are maximum at the ripple wavelengths while they are smaller at other wavelengths. This has notable similarities and differences with the phenomenon of de Gennes narrowing. Overall, this dynamics behavior is found to be consistent with the simulations of a nonlinear growth model by Harrison et al. Following the formation of self-organized nano-ripples, they move across the surface. Homodyne X-ray alone cannot detect the motion, but because of the gradient of ion flux across the sample, we were able to measure in-situ the corresponding ripple velocity gradient by cross-correlating speckles and tracking their movements. For germanium nano-patterning at an elevated temperature, flat germanium samples kept at 300°C were bombarded by 1keV Ar+ ions at normal incidence. Unlike the case when surfaces are amorphizated during room temperature bombardment, the crystalline nano-pattern formation occurs mainly due to a surface instability caused by the Ehrlich-Schwoebel barrier. By using a linear theory analysis on the X-ray scattering intensities in the early times, we measured the contribution of the Ehrlich-Schwoebel barrier to the crystalline nano-patterning kinetics.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第22240号 / 理博第4554号 / 新制||理||1654(附属図書館) / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査)准教授 松田 和博, 教授 田中 耕一郎, 教授 佐々 真一 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM

The objective of this work is the synthesis of highly functionalized hybrid organic/inorganic materials by the polycondensation of bis[3-(trimethoxysilyl) propyl]amine in the presence of surfactants. High contents of amine groups were achieved by carrying out the syntheses without an inorganic cross-linker. The silsesquioxanes obtained had a mesoporous structure. The stability of their porous system in the absence of an inorganic cross-linker was enhanced by the precursor's bridged structure. The material structures were studied by FT-IR spectroscopy, Porosimetry, X-Ray Diffraction and Small Angle X-Ray Scattering methods. A material prepared in the presence of dodecylamine as a template had a higher surface area and narrower pore size distribution while the use of sodium dodecyl sulfate resulted in the formation of mesopores with a wide size distribution. Surface amine groups in silsesquioxanes were accessible for adsorption of small molecules of acidic nature.

The phosphatidylinositol-3-kinase α (PI3Kα) is a heterodimeric enzyme that is composed of a p85α regulatory subunit and a p110α catalytic subunit. PI3Kα plays a critical role in cell survival, growth and differentiation, and is the most frequently mutated pathway in human cancers. The PI3Kα pathway is also targeted by many viruses, such as the human immunodeficiency virus (HIV-1), the herpes simplex virus 1 (HSV-1) or the influenza A virus, to create favourable conditions for viral replication. The regulatory p85α stabilizes the catalytic p110α, but keeps it in an inhibited state. Various ligands can bind to p85α and allosterically activate p110α, but the mechanisms are still ill-defined. Intriguingly, p85α also binds to, and activates, the PTEN phosphatase, which is the antagonist of p110α. Previous studies indicated that only p85α monomers bind to the catalytic p110α subunit, whereas only p85α dimers bind to PTEN. These findings suggest that the balance of p85α monomers and dimers regulates the PI3Kα pathway, and that interrupting this equilibrium could lead to disease development. However, the molecular mechanism for p85α dimerization is controversial, and it is unknown why PTEN only binds to p85α dimers, whereas p110α only binds to p85α monomers. Here we set out to elucidate these questions, and to gain further understanding of how p85α ligands influence p85α dimerization and promote activation of p110α. We first established a comprehensive library of p85α fragments and protocols for their production and purification. By combining biophysical and structural methods such as small angle X-ray scattering, X-ray crystallography, nuclear magnetic resonance, microscale thermophoresis, and chemical crosslinking, we investigated the contributions of all p85α domains to dimerization and ligand binding. Contrarily to the prevailing thought in the field, we find that p85α dimerization and ligand recognition involves multiple domains, including those that directly bind to and inhibit p110α. This finding allows us to suggest a molecular mechanism that links p85α dimerization and allosteric p110α activation through ligands.

京都大学 / 新制・課程博士 / 博士(農学) / 甲第23520号 / 農博第2467号 / 新制||農||1086(附属図書館) / 学位論文||R3||N5351(農学部図書室) / 京都大学大学院農学研究科食品生物科学専攻 / (主査)教授 谷 史人, 教授 保川 清, 准教授 中川 究也 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

No description available.

Iron (Fe) oxy-hydroxides such as ferrihydrite (Fh) are ubiquitous in surface environments. Because of their high surface area and high reactive surface, they can immobilize environmental contaminants and nutrients (e.g., oxyanions) through adsorption. Ferrihydrite is metastable and eventually transforms to hematite (Hm), goethite (Gt), and lepidocrocite (Lp). Although the Fh formation and transformation and oxyanion adsorption on its surface have been separately studied, the coupled interaction of these processes is only partly understood. The impact of oxyanion surface complexes on the rate and pathway of Fh transformation was studied. Results show that AsO43- and SO42- inner-sphere complexes decrease the rate of Fh transformation and induce the formation of Hm. In contrast, NO3- outer-sphere complexes promote the formation of Gt. We then investigated the impact of oxyanion (AsO43- and PO43-) surface loading on the rate and pathway of Fh transformation. The results show that the rate of Fh transformation decreases, and more Hm forms with increasing the oxyanion surface loading. Cryogenic transmission electron microscopy (Cryo-TEM) was also used to study the effect of oxyanion surface complexes (NO3- and PO43-) on the nucleation and growth of Gt and Hm during Fh transformation. Our results show that Gt first was formed from Fh dissolution and then grew by oriented attachment. In contrast, Hm formed after the aggregation of Fh particles. We propose that NO3- outer-sphere complexes hydrate the surface and promote the Gt formation through a dissolution/crystallization pathway, while PO43- inner-sphere complexes dehydrate the surface and induce more Hm through an aggregation pathway. In the final project, we investigated the formation of Fh from Fe oxy-hydroxide clusters. The results showed that increasing pH increased the size and structural order of particles that resemble 2-line Fh. Also, the particle size of aged samples at pHs 1.5 and 2.5 increased with time, and they transformed to Gt and Lp. In this work, we develop new ways to study the formation and transformation of Fh. These methods and information can be used to develop further studies towards a comprehensive understanding of Fh formation and transformation in other environmental conditions, such as redox systems. / Doctor of Philosophy / Iron (Fe) oxy-hydroxides nanoparticles are composed of Fe, oxygen (O), and water (H2O). One of the most famous Fe nanoparticles is ferrihydrite (Fh), which is commonly found in soils, sediments, and water. Ferrihydrite surface is positively charged and adsorbs negatively charged ions such as oxyanions, which are important contaminants (e.g., arsenate; AsO43- and sulfate; SO42) and nutrients (e.g., phosphate; PO43- and nitrate; NO3-) in drinking water in the US and around the world. The structure of Fh is not stable, and it transforms to other Fe oxy-hydroxides such as goethite (Gt), hematite (Hm), and lepidocrocite (Lp). Pre-adsorbed oxyanions may release during Fh transformation and impact water and soil quality. Additionally, oxyanion adsorption may affect the formation and transformation of Fh, which is not fully understood. In this work, we investigate how oxyanions change the rate and pathway of Fh transformation. The results show that the strong binding of AsO43- and SO42- slows down the rate of Fh transformation and favors the formation of Hm as opposed to Gt. While weak adsorption of NO3- promotes the formation of more Gt. We also study the transformation of Fh in the presence of different oxyanions (AsO43- and PO43-) concentrations. The results show that the rate at which Fh transforms to Gt and Hm decreases, and more Hm forms with increasing the concentration of oxyanions on the Fh surface. Interestingly, results also show that weekly bounded NO3- and SO42- could be released to the solution phase, while strongly adsorbed AsO43- and PO43- could remain on the surface during the ferrihydrite transformation. We also used an imaging technique (Cryogenic transmission electron microscopy; Cryo-TEM) to study the effect of oxyanion surface complexes (NO3- and PO43-) on the formation and growth of Gt and Hm during the Fh transformation. The results show that Gt first was formed from Fh and then grew to larger particles. In contrast, for the formation of Hm, Fh particles first aggregate, form larger particles, and then transform to Hm. In the final project, we investigate the formation of Fh from Fe oxy-hydroxide cluster precursors. Results show that Fe oxy-hydroxide clusters can be the potential precursors for forming Fh during the rapid hydrolysis of Fe(III) solutions. However, when these precursors are aged, they do not form Fh and transform to Gt and Lp, which have stable structures. In this work, we develop new ways to study the formation and transformation of Fh, which will have implications for understanding how and when contaminant remobilization will occur during Fh formation and transformation.