How early inflammatory events affect bone nano properties at rheumatoid arthritis onset

Tese de doutoramento, Ciências Biomédicas (Ciências Biopatológicas), Universidade de Lisboa, Faculdade de Medicina, 2017Rheumatoid arthritis (RA) is a chronic, systemic and immune-mediated inflammatory disease that mainly affects the synovial membrane of multiple small joints. As a consequence, RA results in cartilage and bone damage, leading to functional impairment and an increase in morbidity and mortality. Early diagnosis and adequate treatment are critical to prevent RA progression, as joint destruction can occur immediately after its onset. The most characteristic feature of RA is synovial hyperplasia, which is mediated by several immune cells, such as T-cells, B-cells, neutrophils, macrophages and by a complex cytokine network, especially interleukin (IL)-1β, tumor necrosis factor (TNF) and IL-6. RA inflammatory environment induces osteoclastogenesis, promoting disturbances in skeletal bone remodeling, which ultimately leads to the development of secondary osteoporosis and consequent bone fragility. An opportunity for a more effective treatment intervention was identified in early RA, when permanent damage can be prevented and a higher number of patients can achieve remission. Early treatment intervention might also interfere systemically with bone biology preventing bone micro and nano architectural damage. The development of therapeutic strategies able to control both inflammation and bone degradation, with a high rate of disease remission, low incidence of side effects and low production costs is still an unmet medical need in RA. Our hypothesis is that the impact of inflammation on bone micro and nano properties (intrinsic bone tissue properties, independent of the overall bone architecture and directly dependent on the way bone cells, collagen and calcium crystals interact) occurs almost immediately, upon first symptoms, and that these effects can be prevented by early intervention with drugs able to control inflammation and capable of interfering also with bone metabolism. This thesis characterizes the early events of bone damage in RA and explores the effect of novel treatment interventions in this context. Accordingly, in the first part of this thesis, we used an adjuvant induced arthritis (AIA) rat model and observed a synovial sublining layer infiltration, increased lining layer cells, bone erosions and cartilage surface damage present since the early stages of arthritis, as well as increased levels of IL-6. This inflammatory environment promotes osteoclastogenesis, which is related to the observed local bone erosion and may interfere systemically with bone skeletal remodeling. Indeed, AIA animals showed an increased bone turnover, as depicted by increased CTX-I (Carboxy-terminal telopeptide of type I collagen) and P1NP (amino terminal propeptides of type I collagen) levels since the early stages of arthritis. Bone histology was consistent with this early onset spur of bone remodeling. Arthritic animals showed concentric lamellas in secondary osteons (SO), which are the consequence of intense bone remodeling. On the contrary, healthy animals presented more parallel-lamellae (PL) structures than SO structures and these PL structures are 10% harder than SO structures, representing the mature bone structure (normal bone remodeling). Thus, arthritic bone tissue was composed of a larger number of younger, less mineralized and less hard structures, explaining the reduced hardness that we have observed by nanoindentation. Moreover, an increased area occupied by osteocyte lacunae was detected early on in the arthritis process. This apparent change of osteocyte morphology might be related to bone necrosis, leading to mineral loss, decreased hardness and possibly mechanical weakness. In addition, we have also demonstrated that arthritis induces mineral and collagen loss in trabecular bone since the early phase of arthritis development. At a higher organizational level data, micro computed tomography (micro-CT) revealed in arthritic animals a lower fraction of cortical and trabecular bone volume with reduced trabecular thickness together with a higher trabecular separation, in comparison with controls. Results also demonstrated cortical differences in polar moment of inertia, suggesting mechanical weakness in arthritic groups since the early phase of arthritis. Furthermore, cortical and trabecular porosity were increased in the arthritic groups compared to healthy controls. We also confirmed these observations by classic histomorphometry, which demonstrated a decreased structural integrity in arthritic animals. Coherent with these structural defects, our results also showed that in very early arthritis bone has low mechanical competence. Altogether, these results revealed that inflammation promotes bone nano and micro structural disturbances, leading to bone fragility since the early stages of arthritis. In addition, we also provided the basis for using the AIA animal model of arthritis as an adequate model for studying the impact of inflammation on bone and for assessing candidate compounds for the control of arthritis and its associated bone damage. The quest for new RA treatments, more effective at inflammation and bone damage control, safer and less expensive is still a major need. Previously, we had demonstrated that celastrol, acts by downregulating IL1β and TNF production, was a promising RA therapeutic candidate. Herein we have demonstrated that celastrol was able to reduce the number of synovial B and T-cells as well as fibroblasts and CD68 macrophages. Accordingly, we showed that celastrol protects cartilage and bone from inflammation-induced focal damage. At a systemic level, we observed a reduction in bone turnover together with preservation of bone structural and mechanical properties. Moreover, celastrol therapy showed superior effects if administrated in an early phase of arthritis development, which highlights the importance of an early treatment to limit inflammation-induced bone damage. Tofacitinib was also tested in order to assess the effects on micro and nano structural and mechanical properties of bone in an AIA rat model of arthritis. Tofacitinib is a selective inhibitor of janus kinase 1 (JAK1) and janus kinase 3 (JAK 3). Results showed significant reduced arthritis manifestations, synovial tissue inflammation and bone erosions, accompanied by a reduced bone turnover rate and a predominance of parallel structures on bone tissue. At tissue level, measurements performed by nanoindentation showed that tofacitinib increased bone cortical and trabecular hardness. However, micro-CT and 3-point bending tests revealed that tofacitinib did not revert the effects of arthritis on cortical and trabecular bone structure and mechanical properties. This effect on bone might be related to the mechanism of action of tofacitinib which has complex and conflictual molecular interactions with bone. We suggest that these interactions have an overall negative effect not totally compensated by the benefits resulting from the control of inflammation. On the other hand, tofacitinib may require more exposure time to have an impact on bone quality. Overall, the results of the present thesis support the hypothesis that the impact of inflammation on bone micro and nano properties occurs almost immediately, upon the appearance of first symptoms. Moreover, these observed effects can be prevented by very early intervention with drugs able to control inflammation and capable of interfering with bone metabolism.Pfizer – ASPIRE 2013 Prize; ECTS/AMGEN Bone Biology 2014 Priz

Free dihedral actions on Abelian varieties

We give a simple construction for hyperelliptic varieties defined as the quotient of a complex torus by the action of a dihedral group that contains no translations and fixes no points. This generalizes a construction given by Catanese and Demleitner for $D_4$ in dimension three

La recherche pour l'utilisation durable des ressources minérales

L'utilisation éco-efficace des matières premières minérales non renouvelables est l'une des conditions du développement durable. Au moment de Rio+20, le défi reste considérable. La recherche est nécessaire au développement de l'économie circulaire et pour trouver des solutions afin de produire - avec moins d'eau, d'énergie et de déchet - les ressources primaires dont le monde aura besoin au cours des prochaines décennies. Cet article présente une introduction à la recherche française et européenne actuellement déployée dans le domaine des matières premières minérales

Um intelectual cosmopolita: trajetórias de Noah Sobe na (história da) educação

Full Professor of Cultural and Educational Policy Studies in the School of Education at Loyola University Chicago (USA), Noah W. Sobe specializes in the history of education, and in comparative and international education. His researches examine the global circulation of educational policies and practices with particular emphasis on the ways in which schools work as loci of resistance to the cultural impositions upon individuals, peoples, societies, and worlds. He is also interested in research methodologies in comparative education, investigating specifically how notions such as those of context, nation, transnational and global/globalization can be reconceptualized. Also, he dedicates himself to the history of affect and emotion in education, with focus on the history of boredom in school. His formation and access to the educational arena, as well as his theoretical and methodological choices are examined in this interview, which also discusses his academic connections to Brazilian researchers associated to Pontifical Catholic University of São Paulo (PUC-SP), to the School of Education and Institute of Brazilian Studies of the University of São Paulo, and explores his current attributions as Senior Project Officer in the United Nations Educational, Scientific and Cultural Organization (UNESCO) Education Research and Foresight program, part of the Futures of Education: Learning to Become initiative. The reflection also covers the effects of COVID-19 on the international educational scene. As a whole, this dialogue offers the readers a stimulating and contemporary arch of problematizations, among which the disturbing statement made by Noah Sobe that “future is a cultural fact”.Professor Titular de Estudos em Política Cultural e Educacional na Escola de Educação da Universidade Loyola em Chicago (EUA), Noah W. Sobe é especialista em história da educação, história comparada e educação internacional. Suas pesquisas examinam a circulação global de políticas e práticas educacionais com ênfase particular nas maneiras pelas quais as escolas funcionam como locais de resistência à imposição cultural a pessoas, povos, sociedades e mundos. Interessa-se também por metodologias de pesquisa em educação comparada, especificamente interrogando-se como as noções de contexto, nação, transnacional e globalização/global podem ser reconceitualizadas. Por fim, dedica-se ainda à história do afeto e da emoção na educação, com foco na história do tédio na escola. Sua formação e trânsito na arena educativa, bem como as escolhas teóricas e metodológicas são abordadas nesta entrevista, que se estende ainda sobre as relações tramadas com pesquisadores brasileiros associados à Pontifícia Universidade Católica de São Paulo (PUC-SP), à Faculdade de Educação e ao Instituto de Estudos Brasileiros da USP, e explora suas atuais atribuições como Oficial Sênior de Projeto no programa de Pesquisa e Prospecção em Educação da Organização das Nações Unidas para a Educação, a Ciência e a Cultura (UNESCO) junto à iniciativa Futures of Education: Learning to Become (“Futuros da Educação: Aprendendo a se Tornar”). A reflexão abrange também os efeitos da COVID-19 no cenário educativo internacional. Em seu conjunto, o diálogo entabulado oferece ao leitor um leque instigante e atual de problematizações, dentre as quais a inquietante afirmação feita por Noah Sobe de que o “futuro é um fato cultural”

Economia solidária como estratégia de distribuição de riqueza e desenvolvimento econômico e social no Brasil

TCC (graduação) - Universidade Federal de Santa Catarina. Centro Sócio-Econômico. Economia.Este trabalho apresentará as diferenças e similaridades entre a economia solidária e a economia colaborativa, e citará exemplos práticos de como elas são aplicadas nos dias atuais. A economia solidária surgiu como uma nova forma de organização do trabalho e como alternativa para geração de renda e inclusão social. As atividades classificadas como economia solidária se opõem à exploração dos recursos humanos e naturais, promovendo o desenvolvimento sustentável, ou seja, o crescimento econômico em harmonia com a proteção da natureza. O desenvolvimento das forças produtivas no sistema de capitalismo, através do aumento considerável da produtividade, conduz sintomaticamente para uma concentração cada vez maior da riqueza. Este aspecto do capitalismo faz com que os trabalhadores não consigam mais se identificar como seres autônomos, ao invés disso, se tornam dependentes do processo produtivo e vulneráveis às crises sistêmicas. Como resultado, iniciativas associativas espontâneas têm surgido no movimento social, o que se denomina Economia Solidária, que busca outras formas de garantir aos homens que tenham seu sustento, com base na solidariedade e na autogestão. Essas iniciativas, à medida que transitam da produção da riqueza ao controle consciente e planejado, como obra de homens associados, evidenciam um caráter de passagem para um outro modo de produção, como alternativa para a redução das desigualdades sociais no Brasil

Determinação de nitrato em vegetais (alface, espinafre), comercializados em mercados de João Pessoa

A busca cada vez maior por uma alimentação saudável, faz com que frutas e vegetais sejam consumidos em abundância, entretanto esses alimentos podem acumular substâncias como o nitrato, que quando ingerido é reduzido a nitrito, que tem efeito metahemoglobinizante e pode ser convertido em outros compostos n-nitrosos que apresentam efeitos cancerígenos, mutagênicos e teratogênicos. Esse trabalho teve como objetivo realizar a determinação de nitrato em vegetais (alface, espinafre) comercializados em mercados em João Pessoa a partir de metodologia espectrofotométrica proposta por CATALDO e colaboradores(1975), que se baseia na nitração do ácido salicílico sob condições altamente ácidas, o qual pode ser lido em espectrofotômetro a 410nm, em solução básica (pH>12), além de validar a metodologia. Foram analisadas 3 amostras de alface e de espinafre provenientes de 3 mercados diferentes. Os Resultados apresentados demonstram que a metodologia produz resultados satisfatórios, porém não foi possível validar a metodologia. Os teores de nitrato encontrados em alface foram mais altos que os encontrados em alguns estudos, porém ainda estão dentro do se encontra na literatura. Os alfaces apresentaram teores dentro dos limites e foram considerados seguros para o consumo. Duas das três amostras de espinafre apresentaram valores muito acima do permitido e são considerados impróprios para o consumo. Os resultados demonstram que os vegetais que são comercializados nos mercados de João Pessoa não passam por processos de fiscalização, o que deveria ser feito regularmente, pois substancias como o nitrato podem causar grandes danos à saúde humana.A busca cada vez maior por uma a limentação saudável, faz com que frutas e vegetais sejam consumidos em abundância, entretanto esses alimentos podem acumular substâncias como o nitrato, que quando ingerido é reduzido a nitrito, que tem efeito metahemoglobinizante e pode ser convertido em outros compostos n - nitrosos que apresentam efeitos cancerígenos, mutagênicos e teratogênicos . Esse trabalho teve como objetivo realizar a determinação de nitrato em vegetais (alface, espinafre) comercializados em mercados em João Pessoa a partir de metodol ogia espectrofotométrica proposta por CATALDO e colaboradores(1975) , que se baseia na nitração do ácido salicílico sob condições altamente ácidas, o qual pode ser lido em espectrofotômetro a 410nm, em solução básica (pH>12 ), além de validar a metodologia . Foram analisadas 3 amostras de alface e de espinafre provenientes de 3 mercados diferentes. Os Resultados apresentados demonstram que a metodologia produz resultados satisfatórios, porém não foi possível validar a metodologia. Os teores de nitrato encontra dos em alface foram mais altos que os encontrados em alguns estudos, porém ainda estão dentro do se encontra na literatura. Os alfaces apresentaram teores dentro dos limites e foram considerados seguros para o consumo. Duas das três amostras de espinafre a presentaram valores muito acima do permitido e são considerados impróprios para o consumo. Os resultados demonstram que os vegetais que são comercializados nos mercados de João Pessoa não passam por processos de fiscalização, o que deveria ser feito regul armente, pois substancias como o nitrato podem causar grandes danos à saúde humana

Biolistic transformation of grapevine using minimal gene cassette technology

The use of minimal gene cassettes (MCs), which are linear DNA fragments (promoter+open reading frame+terminator) lacking the vector backbone sequence, was compared to the traditional use of whole circular plasmids (CPs) for transformation of grapevine. Embryogenic cell suspensions of ‘Chardonnay' (Vitis vinifera L.) were transformed via particle co-bombardment using two nonlinked genes in either MCs or CPs. One construct contained the npt-II selectable marker and the second construct contained the MSI99 antimicrobial peptide gene. A total of five lines each from MC and CP treatments that showed positive signals by PCR for both the npt-II and MSI99 genes were selected. Southern blot analyses revealed up to five integration events in the DNA treatments. Transcription levels determined by semi-quantitative RT-PCR varied among transgenic lines. No significant differences were found in transgene transcription between lines from MC and CP transformation. The correlation between npt-II and MSI99 transcription levels was positive (P<0.05), however, no correlation between the transcription level and the number of integration events was observed. Transgenic lines presented a similar phenotype in leaf morphology and plant vigor compared to non-transgenic lines. Moreover, transgenic lines from both MC and CP DNA treatments produced fruit as did the non-transgenic lines in the third year of growth in the greenhouse. Our data confirm the effectiveness of the minimal cassette technology for genetic transformation of grapevine cultivar

Federação Portuguesa de Atletismo: breves notas sobre a comunicação estratégica no sector do atletismo em Portugal

Relatório de estágio apresentado à Escola Superior de Comunicação Social como parte dos requisitos para obtenção de grau de mestre em Gestão Estratégica das Relações Públicas.Apresenta-se neste relatório de estágio – condição para a obtenção do grau de mestre em Gestão estratégica das Relações Públicas – o que entendemos dever ser um plano estratégico de Comunicação para a Federação Portuguesa de Atletismo. O interesse deste trabalho centra-se essencialmente no aspecto inovador do papel das Relações Públicas no sector desportivo, questão ainda pouco trabalhada em Portugal. Este trabalho é o corolário de estágio desenvolvido entre 10 de Março e 15 de Junho de 2014 no gabinete de Eventos, Comunicação e Marketing da Federação Portuguesa de Atletismo.In this internship report – one of the conditions for obtaining the master degree in Strategic Public Relations Management – we discuss and present what we believe should be a strategic communication plan for the Portuguese Athletics Federation. The interest of this work focuses primarily on the innovative aspect of the role of Public Relations in the sports sector, issue still crafted in Portugal. This work is the corollary of an internship developed between 10 and June 15, 2014 at the events, Communications and Marketing of the Portuguese Athletics Federation

IN VITRO EVALUATION OF DENTINE ADHESIVE RESISTANCE AFTER APPLYING TWO IRRIGATION SEQUENCES

Objective: To evaluate the bond-strength (MPa) of an adhesive system to intracameral dentin after 2 different endodontic irrigation sequences.  Material and Methods: An in vitro double-blinded experimental cross-over study was conducted. 23 teeth were extracted, and sectioned, exposing the pulp chamber. Samples were separated into three groups: the first group (control) used a 0.9% saline solution; in the second group, the conventional sequence of irrigation of the University of Valparaíso was employed (5% NaOCl -18% EDTA-0.9% saline solution); and finally the third group, the experimental sequence was employed (5% NaOCl, 18% EDTA and 15% saline solution). The sealing technique was then conducted using universal 3M ESPE Single Bond adhesive and Filtek Z350 resin. Subsequently, the bond-strength test was performed in a microtensile, until fracture. Results: The control group had the highest values of frequency of adhesive and cohesive failure compared to the conventional and experimental group but presented a statistically non-significant association. As for the irrigation protocols, they did not show a major difference in their adhesive bond-strength when compared. Conclusion: The results of this study conclude that the adhesive resistance is not significantly modified by different irrigation protocols

Automatic classification of lithofacies using fast independent component analysis

The problem of automatic classification of facies was addressed using the Fast Independent Component Analysis (FastICA) of a data set of geophysical well logs of the Namorado Field, Campos Basin, Brazil, followed by a k-nearest neighbor (k-NN) classification. The goal of an automatic classification of facies is to produce spatial models of facies that assist the geological characterization of petroleum reservoirs. The FastICA technique provides a new data set that has the most stable and less Gaussian distribution possible. The k-NN classifies this new data set according to its characteristics. The previous application of FastICA improves the accuracy of the k-NN automatic classification and it also provides better results in comparison with the automatic classification by means of the Principal Component Analysis (PCA). © 2015 Sociedade Brasileira de Geofísica.The problem of automatic classification of facies was addressed using the Fast Independent Component Analysis (FastICA) of a data set of geophysical well logs of the Namorado Field, Campos Basin, Brazil, followed by a k-nearest neighbor (k-NN) classification. The goal of an automatic classification of facies is to produce spatial models of facies that assist the geological characterization of petroleum reservoirs. The FastICA technique provides a new data set that has the most stable and less Gaussian distribution possible. The k-NN classifies this new data set according to its characteristics. The previous application of FastICA improves the accuracy of the k-NN automatic classification and it also provides better results in comparison with the automatic classification by means of the Principal Component Analysis (PCA)331119126Barboza, E.G., (2005) Análise Estratigráfica Do Campo De Namorado Com Base Na interpretação Sísmica Tridimensional, 230p. , Doctorate Thesis – UFRGS, BrazilCardoso, J.F., Souloumiac, A., Blind beamforming for non Gaussian signals (1993) IEE Proceedings-F, 140 (6), pp. 362-370Casey, M.A., Method for extracting features from a mixture of signals (2001) Mitsubishi Electric Research Laboratories, , Inc., Cambridge, MA, U.S. Patent n. 6,321,200Comon, P., Independent Component Analysis: A new concept? (1994) Signal Processing, 36 (3), pp. 287-314Cover, T.M., Hart, P.E., Nearest neighbor pattern classification (1967) IEEE Transactions on Information Theory, 13 (1), pp. 21-27Dasarathy, B.V., (1991) Nearest Neighbor (NN) Norms: NN Pattern Classification Techniques, pp. 211-215. , IEEE Computer Society Press, Los Alamitos, Calif. WashingtonFlexa, R.T., Rade, A., Carrasquilla, A., Identificação de litotipos nos perfis de poço do Campo de Namorado (Bacia de Campos, Brasil) e do Lago Maracaibo (Venezuela) aplicando estatística multivariada (2004) Revista Brasileira De Geociências, 34 (4), pp. 571-578Françamm, Análise do uso da terra no município de Viçosa-MG mediado por classificações supervisionadas com Redes Neurais Artificiais e Maxver (2009) Revista Brasileira De Geografia Física, 2 (3), pp. 92-101Giannakopoulos, X., Karhunen, J., Oja, E., A Comparison of neural ICA algorithms using Real-world data (1999) International Joint Conference on Neural Networks, 2, pp. 888-893. , Washington, DCHyvärinen, A., Fast and Robust Fixed-Point Algorithms for IndependentComponentAnalysis (1999) IEEE Transactions on Neural Networks, 10 (3), pp. 626-634Hyvärinen, A., Oja, E., A Fast fixed-point algorithm for Independent Component Analysis (1997) Neural Computation, 9 (7), pp. 1483-1492Hyvärinen, A., Karhunen, J., Oja, E., (2001) Independent Component Analysis, 504p. , Wiley and Sons, New YorkKuhn, H.W., Tucker, A.W., Nonlinear programming (1951) Proceedings of Berkeleysymposium, 2, pp. 481-492. , Berkeley: University of California PressLeite, E.P., Souza Filho, C.R., TEXTNN – A MATLAB program for textural classification using neural networks (2009) Computers& Geosciences, 35 (10), pp. 2084-2094Macleod, A.J., A generalization of Newton-Raphson (1984) Int. J. Math. Educ. Sci. Technol., 15 (1), pp. 117-120Macqueen, J.B., Some Methods for classification and Analysis of Multivariate Observations (1967) Proceedings of Berkeley Symposium on Mathematical Statistics and Probability, 1, pp. 281-297. , 5., Berkeley, University of California PressMarchini, J.L., Heaton, C., Ripley, B.D., (2009) Fastica Algorithms to Perform ICA and Projection Pursuit, 1, pp. 1-11. , R package versionMurata, N., Ikeda, S., Ziehe, A., An approach to blind source separation based on temporal structure of speech signals (2001) Neurocomputing, 41, pp. 1-24Rosa, H., Suslick, S.B., Vidal, A.C., Sakai, G.K., Caracterização de eletrofácies por meio de ferramentas estatísticas multivariadas (2008) Rem: Rev. Esc. Minas, 61 (4), pp. 415-422Sancevero, S.S., Remacre, A.Z., Vidal, A.C., Portugal, R.S., Aplicação de técnicas de estatística multivariada na definição da litologia a partir de perfis geofísicos de poços (2008) Revista Brasileira De Geociências, 38 (1), pp. 61-74Toussaint, G.T., Geometric proximity graphs for improving nearest neighbor methods in instance-based learning and data mining (2005) International Journal of Computational Geometry and Applications, 15 (2), pp. 101-150Vidal, A.C., Sancevero, S.S., Remacre, A.Z., Costanzo, C.P., Modelagem Geoestatística 3D da Impedância Acústica para a Caracterização do Campo de Namorado (2007) Brazilian Journal of Geophysics, 25 (3), pp. 295-305Zhang, K., Chan, L., Dimension reduction as a deflation method in ICA (2006) Signal Processing Letters, IEEE, 13 (1), pp. 45-4