The impact of aerobic exercise on brain's white matter integrity in the Alzheimer's disease and the aging population

The brain is the most complex organ in the body. Currently, its complicated functionality has not been fully understood. However, in the last decades an exponential growth on research publications emerged thanks to the use of in-vivo brain imaging techniques. One of these techniques pioneered for medical use in the early 1970s was known as nuclear magnetic resonance imaging based (now called magnetic resonance imaging [MRI]). Nowadays, the advances of MRI technology not only allowed us to characterize volumetric changes in specific brain structures but now we could identify different patterns of activation (e.g. functional MRI) or changes in structural brain connectivity (e.g. diffusion MRI). One of the benefits of using these techniques is that we could investigate changes that occur in disease-specific cohorts such as in the case of Alzheimer’s disease (AD), a neurodegenerative disease that affects mainly older populations. This disease has been known for over a century and even though great advances in technology and pharmacology have occurred, currently there is no cure for the disease. Hence, in this work I decided to investigate whether aerobic exercise, an emerging alternative method to pharmacological treatments, might provide neuroprotective effects to slow down the evident brain deterioration of AD using novel in-vivo diffusion imaging techniques. Previous reports in animal and human studies have supported these exercise-related neuro-protective mechanisms. Concurrently in AD participants, increased brain volumes have been positively associated with higher cardiorespiratory fitness levels, a direct marker of sustained physical activity and increased exercise. Thus, the goal of this work is to investigate further whether exercise influences the brain using structural connectivity analyses and novel diffusion imaging techniques that go beyond volumetric characterization. The approach I chose to present this work combined two important aspects of the investigation. First, I introduced important concepts based on the neuro-scientific work in relation to Alzheimer’s diseases, in-vivo imaging, and exercise physiology (Chapter 1). Secondly, I tried to describe in simple mathematics the physics of this novel diffusion imaging technique (Chapter 2) and supported a tract-specific diffusion imaging processing methodology (Chapter 3 and 4). Consequently, the later chapters combined both aspects of this investigation in a manuscript format (Chapter 5-8). Finally, I summarized my findings, include recommendations for similar studies, described future work, and stated a final conclusion of this work (Chapter 9)

Adequation of the TEKKEN test to evaluate the cracking in welds of API X-80 steel

Orientador: Roseana da Exaltação TrevisanDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia MecanicaResumo: No desenvolvimento deste trabalho utilizou-se o ensaio de auto-restrição TEKKEN com o propósito de adequar este teste para a avaliação do trincamento da junta soldada do aço API X80. Para a execução das soldas foi usado o processo de soldagem a arco com eletrodo tubular (FCAW), utilizando o aço API X80 e os eletrodos E71T-1 e E 71T8-K6. O desenvolvimento experimental realizou-se através do planejamento fatorial 23 (PF); as variáveis de influência estudadas foram: a temperatura de preaquecimento, o tipo de arame tubular e o tipo de chanfro do teste. Como variável de resposta foi avaliada a presença de trincas na junta soldada. Os resultados obtidos foram discutidos em função de duas energias de soldagem definidas em 2,0 kJ/mm e 1,0kJ/mm. A variação do insumo de calor teve como propósito aumentar a taxa de resfriamento e, consequentemente, aumentar a restrição do teste, induzindo ao trincamento a frio na junta soldada. Também foram avaliados o teor de hidrogênio residual, a microestrutura e a dureza resultantes. Neste trabalho concluiu-se que, apesar do alto teor de hidrogênio residual encontrado, da elevada taxa de resfriamento imposta durante o processo de soldagem e da presença de microestrutura suscetível, não foi observada a formação de trincas nos corpos de prova. Estes resultados foram atribuídos a inadequação do teste TEKKEN sobre o estudo da suscetibilidade ao trincamento do aço API X80.Abstract: In the development of this work was used the self-restraint TEKKEN test with the purpose to adequate this test for the evaluation of the cracking in the welded joint of API X80 steel. The Flux Cored Arc Welding (FCAW) process and the cored wires E71T-1 and E 71T8-K6 were used for the accomplishment in the welds of API X80 steel. The experimental were carried out with a factorial design 23 (PF); the input variables studied were: preheat temperature, the wire cored kind and the groove kind of the test. The output variable was always the presence of cracking in the weld joint. The results obtained were discussed in function of two heat input defined in: 2,0 kJ/mm and 1,0kJ/mm. The variation of the heat input was have the purpose of increase the cooling rate and, consequently increased the restraint of the test, to induced cold cracking in the weld joint. It was also evaluated the content of residual hydrogen, the microstructure and the hardness obtained. In this work can be concluded that, in the spite of, high content of residual hydrogen founded, and the high cooling rate, during the welding and the presence of susceptibility microstructure was not observed the formation of cracks in the test pieces. These results were attributed to the inadequate TEKKEN test over the susceptibility cracking API X80 steel studied.MestradoMateriais e Processos de FabricaçãoMestre em Engenharia Mecânic

Electro-mechanical characterization of piezo-metallic cellular solids for spine implants

Abstract Many different electrical stimulation methods are currently used to enhance bone growth in spine fusion. In this study, the feasibility of a novel electrical stimulation method using piezoelectric materials embedded into metallic cellular solid structures was presented. The aim of this study was to proof the feasibility to create a new generation of electrically stimulated implants that will mimic and enhance bone osteogenesis in the implanted area while preserving the mechanical characteristics of the environment where are implanted. Cellular composites with different geometric and dimensions were handcrafted and characterized mechanically and electrically. The following study was divided in two parts and was presented in two chapters with the mechanical and electro-mechanical characterization of the structures. First, structures with no piezoelectric plates were mechanically characterized. Non-linearity at small strain, negative compressive strain ratios (CSR), stress strain curves, modulus of elasticity and their relationship with relative densities were investigated. The feasibility of tailoring the mechanical parameters of the implants to mimic the characteristics of the replaced tissue by controlling its geometry, dimension and aspect ratio was investigated. Secondly, electromechanical structures (with embedded piezoelectric ceramics) were characterized when compressed axially. Electrical signals, force and displacements were recorded. Alternated electrical signals generated by the piezoelectric ceramics were electrically rectified and then compared to previous direct electrical current stimulators that have proven to enhance bone osteogenesis [1]. The feasibility to create implants that mimic the mechanical behavior of its environment and present embedded electrical stimulation was validated in this study. Additionally, finite element analysis (FEA) was used to validate the experimental results, design of optimal structures, and understanding in the influence on manufacturing parameters. Models with the same dimensions and geometries were created in FEA and compared to physically tested structures. After the experimental methods were finalized, the feasibility of this investigation and its potential use was discussed while conclusions were brought

Salivary immunity and lower respiratory tract infections in non-elite marathon runners

Peer ReviewedPostprint (published version

Por qué hace falta establecer límites a la globalización mediática: una mirada desde el psicoanálisis.

La globalización mediática ha transformado la forma en la que el individuo interacciona con los productos mediáticos y ha producido un cambio en la manera como los sujetos experimentan la realidad. Ante este hecho, es imperativo estudiar la necesidad de establecer límites a la globalización en esta esfera. El presente artículo tiene como objetivo abordar este fenómeno, en primera instancia analizando cómo el individuo tiene un libre acceso a los productos mediáticos como efecto de un proceso de desnacionalización y, posteriormente, revisar la interacción individuo-producto mediático, desde una perspectiva psicoanalítica. Como resultado surgen argumentos que a partir del psicoanálisis evidencian que la influencia de la globalización mediática marca una falta de pensamiento y crea una masificación de la mente de los individuos. Se concluye que es necesario trabajar desde diferentes estamentos de la sociedad para fomentar un pensamiento crítico frente a los contenidos mediáticos

Digital-Analog Quantum Simulations Using The Cross-Resonance Effect

Digital-analog quantum computation aims to reduce the currently infeasible resource requirements needed for near-term quantum information processing by replacing sequences of one- and two-qubit gates with a unitary transformation generated by the systems' underlying Hamiltonian. Inspired by this paradigm, we consider superconducting architectures and extend the cross-resonance effect, up to first order in perturbation theory, from a two-qubit interaction to an analog Hamiltonian acting on 1D chains and 2D square lattices which, in an appropriate reference frame, results in a purely two-local Hamiltonian. By augmenting the analog Hamiltonian dynamics with single-qubit gates we show how one may generate a larger variety of distinct analog Hamiltonians. We then synthesize unitary sequences, in which we toggle between the various analog Hamiltonians as needed, simulating the dynamics of Ising, $XY$, and Heisenberg spin models. Our dynamics simulations are Trotter error-free for the Ising and $XY$ models in 1D. We also show that the Trotter errors for 2D $XY$ and 1D Heisenberg chains are reduced, with respect to a digital decomposition, by a constant factor. In order to realize these important near-term speedups, we discuss the practical considerations needed to accurately characterize and calibrate our analog Hamiltonians for use in quantum simulations. We conclude with a discussion of how the Hamiltonian toggling techniques could be extended to derive new analog Hamiltonians which may be of use in more complex digital-analog quantum simulations for various models of interacting spins

Persistence and variation in microstructural design during the evolution of spider silk

The extraordinary mechanical performance of spider dragline silk is explained by its highly ordered microstructure and results from the sequences of its constituent proteins. This optimized microstructural organization simultaneously achieves high tensile strength and strain at breaking by taking advantage of weak molecular interactions. However, elucidating how the original design evolved over the 400 million year history of spider silk, and identifying the basic relationships between microstructural details and performance have proven difficult tasks. Here we show that the analysis of maximum supercontracted single spider silk fibers using X ray diffraction shows a complex picture of silk evolution where some key microstructural features are conserved phylogenetically while others show substantial variation even among closely related species. This new understanding helps elucidate which microstructural features need to be copied in order to produce the next generation of biomimetic silk fibers

Characterizing the role of brain derived neurotrophic factor genetic variation in Alzheimer’s Disease neurodegeneration

There is accumulating evidence that neurotrophins, like brain-derived neurotrophic factor (BDNF), may impact aging and Alzheimer's Disease. However, traditional genetic association studies have not found a clear relationship between BDNF and AD. Our goal was to test whether BDNF single nucleotide polymorphisms (SNPs) impact Alzheimer's Disease-related brain imaging and cognitive markers of disease. We completed an imaging genetics study on 645 Alzheimer's Disease Neuroimaging Initiative participants (ND=175, MCI=316, AD=154) who had cognitive, brain imaging, and genetics data at baseline and a subset of those with brain imaging data at two years. Samples were genotyped using the Illumina Human610-Quad BeadChip. 13 SNPs in BDNF were identified in the dataset following quality control measures (rs6265(Val66Met), rs12273363, rs11030094, rs925946, rs1050187, rs2203877, rs11030104, rs11030108, rs10835211, rs7934165, rs908867, rs1491850, rs1157459). We analyzed a subgroup of 8 SNPs that were in low linkage disequilibrium with each other. Automated brain morphometric measures were available through ADNI investigators, and we analyzed baseline cognitive scores, hippocampal and whole brain volumes, and rates of hippocampal and whole brain atrophy and rates of change in the ADAS-Cog over one and two years. Three out of eight BDNF SNPs analyzed were significantly associated with measures of cognitive decline (rs1157659, rs11030094, rs11030108). No SNPs were significantly associated with baseline brain volume measures, however six SNPs were significantly associated with hippocampal and/or whole brain atrophy over two years (rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850). We also found an interaction between the BDNF Val66Met SNP and age with whole brain volume. Our imaging-genetics analysis in a large dataset suggests that while BDNF genetic variation is not specifically associated with a diagnosis of AD, it appears to play a role in AD-related brain neurodegeneration

CIGB-300, a proapoptotic peptide, inhibits angiogenesis in vitro and in vivo

We have previously demonstrated that a proapoptotic cyclic peptide CIGB-300, formerly known as P15-Tat delivered into the cells by the cell-penetrating peptide Tat, was able to abrogate the CK2-mediated phosphorylation and induce tumor regression when injected directly into solid tumors in mice or by systemic administration. In this work, we studied the role of CIGB-300 on the main events that take place in angiogenesis. At non-cytotoxic doses, CIGB-300 was able to inhibit adhesion, migration, and tubular network formation induced by human umbilical vein endothelial cells (HUVEC) growing upon Matrigel in vitro. Likewise, we evaluated the cellular penetration and localization into the HUVEC cells of CIGB-300. Our results confirmed a quick cellular penetration and a cytoplasmic accumulation in the early minutes of incubation and a translocation into the nuclei beginning at 12h of treatment, with a strong presence in the perinuclear area. A microarray analysis was used to determine the genes affected by the treatment. We observed that CIGB-300 significantly decreased four genes strongly associated with tubulogenesis, growth, and differentiation of endothelial cells. The CIGB-300 was tested in vivo on chicken embryo chorioallantoic membranes (CAM), and a large number of newly formed blood vessels were significantly regressed. The results suggested that CIGB-300 has a potential as an antiangiogenic treatment. The mechanism of action may be associated with partial inhibition of VEGF and Notch pathways.Fil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Benavent Acero, Fernando Rodrigo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Perera, Yasser. Center for Genetic Engineering and Biotechnology; CubaFil: Rodríguez, Arielis. Center for Genetic Engineering and Biotechnology; CubaFil: Perea, Silvio E.. Center for Genetic Engineering and Biotechnology; CubaFil: Acevedo Castro, Boris. Center for Genetic Engineering and Biotechnology; CubaFil: Gomez, Roberto. No especifíca;Fil: Alonso, Daniel F.. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin