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The cellular origin of synovial osteoclasts in inflammatory arthritisAzadi, Kian Armand McCollum 09 June 2020 (has links)
Inflammatory arthritis (IA) is a debilitating disease that is characterized by joint destruction. This destruction is caused by osteoclasts (OCLs) degrading bone within the synovium, however the exact cellular origins of these synovial OCLs is not well understood. We hypothesize that the synovial OCLs seen in IA are independently derived from two contributing cell lineages: the canonical source of OCL which are Hematopoietic Stem Cell (HSC) derived monocytes and the newly described Erythro-Myeloid Progenitor (EMP). To explore the contribution of these two lineages to synovial OCL, we used Cx3cr1CreERT2;Rosa26LSL-tdTomato mice to label EMP-derived cells, and Flt3Cre;Rosa26LSL-YFP to label HSC-derived cells. Using immunofluorescent histology, we found that synovial OCLs formed under arthritic conditions derive from both HSC and EMP-progenitors, suggesting the possibility that regulatory mechanisms unique to each developmental lineage promote OCL differentiation in arthritic joints. In support of these observations, in IA we detected two populations of mononuclear cells, as possible osteoclast precursors, that express both the OCL marker TRAP and the monocytic/macrophage marker CD68. These mononuclear TRAP+ CD68+ cell populations are found within the inflamed synovium and in bone periosteal surfaces of arthritic joints, and are mostly EMP derived, however, the HSC lineage significantly contributes to osteoclast formation, as suggested by our lineage-tracing strategy. We are currently investigating the dynamics of these cell populations during the early, peak, and resolution stages in an acute murine model of IA. To better understand regulatory differences between OCL derived from each of these lineages, we plan to isolate EMP- and HSC-derived OCLs directly from joints to study their precise phenotype, cytokine differentiation requirements, resorptive capacity and transcriptional activity, by flow cytometry, in vitro cell cultures and single cell RNA sequencing, respectively.
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Effects of a Multinutrient Supplement on Anxiety, Aggression, and Impulsivity in a Normal Rat PopulationDymond, Sarah Roxanne January 2011 (has links)
Using natural supplementation as a treatment tool for mental health problems is becoming increasingly popular. Several studies using a multinutrient supplement called EMPowerplus (EMP+) have been conducted in humans with disorders such as Attention-Deficit/Hyperactivity Disorder (ADHD), but no studies have been conducted in animals or humans without disorders. Therefore, to address the gaps in the literature, the aim of this study was to assess the effects of EMP+ in a rat population on anxiety, aggression, and impulsivity which may be present in people who do not have a disorder. To investigate this, 40 male and 40 female rats were fed a diet consisting of 0%, 1.25%, 2.5% or 5% EMP+. They were tested during adolescence (PND 52-53) and again during mid-adulthood (PND 116-117) for anxiety and aggression, and during early adulthood (PND 92-96) and again during late adulthood (PND 127-130) for impulsivity. Due to the impact of the September 4th 2010 7.1 magnitude earthquake, data for some rats had to be excluded from anxiety and aggression analyses, leaving a sample size of 29 males and 34 females. Although there were no treatment main effects for any of the three behaviours, there were significant interaction effects between treatment and sex for measures of anxiety and aggression, showing that each sex reacted differently to the supplement. Male rats became less anxious, while female rats became more anxious. Of the five aggressive behaviours observed, significant interactions were found between treatment and sex for rough paw and allogrooming frequency. There were no significant effects involving treatment for impulsivity, but male rats were more impulsive when they were older (PND 127-130). Overall, the effects of EMP+ on the rats’ anxious, aggressive, and impulsive behaviours were mixed, and it is likely that the 7.1 magnitude earthquake and its subsequent aftershocks played a role in these results.
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Genetic studies of phenotypic variants in the woodland strawberry, (Fragaria vesca)Holt, Sarah Hudson 24 October 2011 (has links)
The diploid woodland strawberry (Fragaria vesca) is a rapidly developing translational model for members of the family Rosaceae and other plants. This thesis represents some of the first forward genetics studies evaluating putative T-DNA insertional mutants in F. vesca. The observed phenotypes include alterations to floral development, anthocyanin pigmentation and leaf structure.
The floral development mutant named green petal (gp) was not associated with the T-DNA insertions present. Based on similar phenotypes induced by mutation of transcription factors involved in floral development of Arabidopsis thaliana, we used a BLAST search of the F. vesca genome hybrid gene models to identify 30 candidate genes that may have caused the gp phenotype. Expression analysis of these genes revealed that it was due to a 37 bp deletion in a SEPALLATA3-like E-Class MADS box transcription factor. This mutation altered organ structure in the three inner whorls of the flower, affecting fertility and fruit development. The deletion was demonstrated to segregate with the mutant phenotype in a segregating population of 92 individuals, 22 of which had green petals.
The anthocyanin biosynthesis mutant named white runner (wr) lacked red pigmentation in the stems and runners. The T-DNA insertion in this line was located in a highly repetitive LTR retrotransposon region, which complicated analysis. Segregation analysis of the wr lines revealed that the phenotype was unassociated with the T-DNA insertion as well. We used a targeted expression analysis of three critical structural genes in the flavonoid biosynthesis pathway that revealed a 20 bp deletion in the gene encoding flavanone 3-hydroxylase, an enzyme necessary for the production of flavonols, anthocyanins and proanthocyanidins. In an F2 segregating population, this deletion co-segregated with the phenotype.
The third mutant line presented here displayed a curly leaf (cl) phenotype and was found to harbor a T-DNA insertion in a gene encoding a putative erythroblast macrophage attacher protein (EMP). Sequence and protein domain analysis indicated that FvEMP was related to the mammalian EMP protein that functions in cytoskeletal dynamics and red blood cell enucleation. Complementation analysis confirmed that introduction of the wild type FvEMP gene into the cl mutant plants restored wild type leaf phenotype. Further morphological analysis revealed additional pleiotropic effects of the mutation, including abnormalities in seed set and germination, pollen tube growth, adhesion of the abaxial epidermal layer to the mesophyll layer and reduced petiolule length. These phenotypes are consistent with actin binding and microtubule associated protein mutants in other plant species.
Insertional mutagenesis is a critical molecular tool for model crop development. These studies highlight the precautions that must be taken when evaluating insertional mutants. These mutants are excellent tools for studying their respective disrupted gene function. The in depth molecular analysis of the mutants presented in this work was only possible because of the availability of the Fragaria vesca genome which was used extensively to identify T-DNA insertion sites and recover candidate gene sequences for expression analysis. / Ph. D.
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Neradiační účinky nukleárních útoků / No-radiation effects of nuclear attacksŠIROKÝ, Miroslav January 2007 (has links)
No-radiation effects of nuclear attacks create a big group of possible impacts on society. The first task of diploma thesis is to compile basic complex of known principles, features and descriptions of behaviour of electro technical materials, mainly in the sphere of electromagnetic fields and their interaction with surroundings on various (attack induced) outer conditions. These features are verified and demonstrated through laboratory measurements taken on basic components of the latest ICT devices. The second task is to compile the whole complex of findings and observations about SW models creations on interpersonal parallel communication. Acquired results are verified on the small group of 27 people.
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Functional heterogeneity and characterization of synovial macrophages in inflammatory arthritisNelson, Hannah K. H. 24 November 2021 (has links)
Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that targets joints, resulting in in permanent disability. Synovial macrophages have been implicated in the pathogenesis of RA; however, their exact origins and functions remains unclear. In this study, we show evidence that synovial macrophages are mostly derived from embryonic origin during normal development. Macrophages are derived from either hematopoietic stem cells (HSC) or erythro-myeloid progenitors (EMP), and it is postulated that different subpopulations of synovial macrophages may have distinct functions contributing to either homeostasis or inflammation. To investigate the phenotypes of synovial macrophage populations and characterize their lineage-specific functions in arthritic joints, we utilized both cell lineage-tracing and K/BxN serum-transfer arthritis mouse models. Utilizing Flt3Cre;Rosa26LSL-YFP mice to label HSC-derived cells, we demonstrated that there is minimal HSC contribution to synovial macrophage populations during homeostasis. Use of RankCre;Rosa26LSL-YFP and Cx3cr1CreERT2;Rosa26LSL-tdTomato mice to label EMP-derived cells corroborated the finding that the EMP compartment maintains the largest contribution to synovial macrophage populations during normal development. Analysis of macrophages in Csf1rMericreMer;Rosa26-LSLtdTomato mice provided definitive prove that synovial macrophages derived from yolk-sac EMP precursors in adult mice. Use of serum transfer arthritis (STA) mice demonstrated that while most macrophages in the inflamed synovium were EMP-derived, there was a marked increase in HSC-derived cells compared to those present in homeostasis. Although this study has contributed to eluding that the heterogeneity of synovial macrophages in both homeostasis and inflammatory arthritis (IA) is complex and lineage-specific, further studies are needed to clearly define lineage-specific functions of macrophages in synovial tissues and in IA.
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Modelovací nástroj pro grafický návrh komponentových systémů / A Tool for Modelling of Component-Based SystemsZemko, Zoltán January 2013 (has links)
Component-based Software Engineering describes a complex information system as a set of components. The thesis seeks to highlight the benefits of this approach. Also defines terms such as standard software, component software, and others. It provides an introduction to the modeling techniques of component-based systems in UML. The second half of the document describes the structure of the Eclipse Modeling Project. The reader by these lines should obtain a theoretical overview of the development of modeling tools under Eclipse. The document includes design and implementation process description of the tool for modeling component-based systems which has been developed using the Eclipse Modeling Framework and Graphical Modeling Framework.
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A MASTER THESIS ON PORTING THE ENTERPRISE ARCHITECTURE ANALYSIS TOOL TO ECLIPSE MODELING PROJECTIvanov, Stanislav January 2011 (has links)
This master thesis is a part of the ongoing research on EAT development project. Its main goal is to research whether Eclipse Modeling Project can be used as an alternative platform to using NetBeans in implementing EAT tool. In order to fulfill this goal, it contains analysis of the current EAT tool version and design research of a new version using EMP. The design addresses most of the issues related to building a new version and eventually recommends porting EAT to EMP.
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High-intensity Ultra-fast Laser Interaction TechnologiesBernath, Robert Thomas 01 January 2007 (has links)
To our knowledge this is the first comprehensive study of laser-induced effects generated at intermediate distances using self-channeled femtosecond laser pulses. Studies performed were made both experimentally and theoretically with the use of novel modeling techniques. Peak laser pulse powers above 3 GW allow beam propagation without divergence for up to several kilometers. In this regime, experiments were performed at 30 meters from the laser system in a custom propagation and target range, utilizing the Laser Plasma Laboratory's Terawatt laser system. Experiments included investigations of laser ablation; electromagnetic pulsed (EMP) radiation generation over the 1-18 GHz region; shockwave formation in air and solid media; optical coupling of channeled pulses into transparent media; and, conservation of energy in these interactions. The use of bursts of femtosecond pulses was found to increase the ablation rate significantly over single-pulse ablation in both air and vacuum. EMP generation from near-field focused and distance-propagated pulses was investigated. Field strengths upwards of 400 V/m/[Lambda] for vacuum focusing and 25 V/m/[Lambda] for self-channeled pulses were observed. The total field strengths over 1-18 GHz measured at distance surpassed 12 kV/m. Shockwaves generated in transparent media at 30 meters were observed as a function of time. It was found that the interaction conditions control the formation and propagation of the shock fronts into the medium. Due to the processes involved in self-channeling, significant fractions of the laser pulse were coupled into the target materials, resulting in internal optical and exit-surface damage. Basic estimations on the conservation of energy in the interaction are presented. The results of the experiments are supported by hydrodynamic plasma physics code and acoustic modeling.
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EFL learning/writing development in the Internet environment: A case study from pre-medical students' perspectivesMuangsamai, Pornsiri 07 November 2003 (has links)
No description available.
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Limites e possibilidades do Ensino Médio Politécnico : um estudo em escolas de Porto Alegre - RSReis, Jonas Tarcísio 20 March 2018 (has links)
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Previous issue date: 2018-03-20 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O compromisso dessa tese é com o avanço no campo da análise da implementação de políticas educacionais, de desvelar os meandros dos processos de correlação de forças inerentes à dinâmica de confrontação entre ideias arraigadas na escola e ideias trazidas por novas políticas. O objetivo geral foi analisar a implementação do Ensino Médio Politécnico (EMP), buscando compreender os seus limites e possibilidades e as posições ideológicas presentes na defesa ou na recusa a esta reforma curricular implementada pela Secretaria de Estado da Educação do Rio Grande do Sul (SEDUC-RS) no quadriênio 2011-2014. A base teórico-metodológica da investigação constituiu-se no materialismo histórico dialético. O banco de dados esteve composto por documentos publicados pela mantenedora para a implementação do EMP, a legislação educacional vigente, entrevistas semiestruturadas realizadas com sujeitos formuladores e implementadores da política, na mantenedora e em quatro escolas do município de Porto Alegre. Para a interpretação e tratamento dos dados utilizamos princípios da Análise Documental. A tese está dividida em nove capítulos incluindo as considerações finais. Os resultados apontaram que: a origem dessa política está em fundamentos socialistas e da Educação Popular (EP); a pesquisa no Seminário Integrado (SI) e a Avaliação Emancipatória (AE) assumiram espaço central. Muitos trabalhos realizados pelos alunos tiveram orientação aproximada ao conceito de Trabalho Socialmente Necessário, cunhado nos primeiros anos da educação soviética, ajudando a formar sujeitos capazes de produzir uma consciência de que são capazes de fazer aquilo que se propõem enquanto seres humanos. A AE também gerou muita polêmica e embates ideológicos; as escolas que já tinham conhecimento e/ou experiências com os conceitos inerentes ao EMP obtiveram melhores resultados na implementação; a ideologia da meritocracia materializada nas práticas escolares, como na avaliação seletiva e classificatória e no conteudismo constituiu uma forte resistência a implementação. Entretanto, com o EMP, o Estado tentou mobilizar-se para formar sujeitos emancipados capazes de transformarem a sociedade, mas não conseguiu conquistar política e ideologicamente a necessária influência para consensuar com o todo da sociedade acerca da sua positividade, por não ter o sindicato como aliado ao, principalmente, não ter pagado o Piso Salarial Nacional no básico da carreira, também por ter encontrado um quadro de baixos incentivos à inovação pedagógica na rede, com um modelo de ensino calcado no currículo fragmentado, numa pedagogia bancária e numa avaliação seletiva e classificatória. Igualmente por barreiras na formação docente, aliada a uma histórica falta de investimentos na infraestrutura escolar. Outro motivo foi, por fim, a gestão da SEDUC-RS ter implementado a proposta sem um tempo maior para debates com as comunidades escolares; houve uma desacomodação e um processo de correlação de forças entre o novo e o velho dentro das escolas, sendo travado de certa forma um enfrentamento aos processos de exclusão escolar. Essa pesquisa ajuda a identificar os meandros dos limites e das possibilidades de uma política de reestruturação curricular que objetivou promover a emancipação humana no Ensino Médio, contra um secular modelo escolar meritocrático, objetivando em último grau a conformação da igualdade substantiva e da justiça social real. / The commitment of this thesis is with the advancement in the field of analysis of the implementation of educational policies, to unveil the meanderings of the processes of forces correlation inherent to the dynamics of confrontation between ideas rooted in the school and ideas brought about by new policies. The general objective was to analyze the implementation of the Polytechnic High School (EMP), seeking to understand its limits and possibilities and the ideological positions present in the defense or refusal of this curricular reform implemented by the State Secretariat of Education of Rio Grande do Sul (SEDUC –RS/ BRAZIL) in the quadrennium 2011-2014. The theoretical-methodological basis of the investigation was constituted in dialectical historical materialism. The database consisted of documents published by SEDUC-RS for the implementation of the EMP, current educational legislation, semi-structured interviews with policy creators and implementers, at SEDUC-RS and at four schools in the city of Porto Alegre. For the interpretation and treatment of the data we use principles of Documentary Analysis. The thesis is divided into nine chapters including the final considerations. The results showed that: the origin of this policy lies in socialist and Popular Education (EP) fundamentals; the research in the Integrated Seminar (SI) and the Emancipatory Assessment (EA) took center stage. Many of the works carried out by the students have had approximate orientation to the concept of Socially Necessary Work created in the early years of Soviet education, helping to form subjects capable of producing an awareness that they are capable of doing what they propose as human beings. The AE also generated much controversy and ideological clashes; the schools that already had knowledge and / or experiences with the concepts inherent to the EMP obtained better results in the implementation; the ideology of meritocracy embodied in school practices, as in selective and classificatory evaluation and in content, constituted a strong resistance to implementation. However, with the EMP, the State attempted to mobilize to form emancipated subjects capable of transforming society, but failed to conquer politically and ideologically the necessary influence to reach agreement with the whole of society about its positivity, for not having the Syndicate as an ally, mainly, not having paid the National Salary Floor in the basic of the teaching career, also for having found a scenario of low incentives for pedagogical innovation in schools, with a teaching model based on the fragmented curriculum, in a banking pedagogy and a selective and classificatory evaluation. Also by barriers in teacher training, coupled with a historic lack of investments in school infrastructure. Another reason was that SEDUC-RS management had implemented the proposal without a longer time for discussions with school communities; there was a dismantling and a process of forces correlation between the new and old within the schools, being, in a certain way, a confrontation with the processes of school exclusion. This research helps to identify the intricacies of the limits and possibilities of a curricular restructuring policy aimed at promoting human emancipation in high school, against a secular meritocratic school model, aiming ultimately at the conformation of substantive equality and real social justice.
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