T cells in chronic viral infections are featured by premature aging with accelerated telomere erosion, but the mechanisms underlying telomere attrition remain unclear. Here, we employed human CD4 T cells treated with KML001 (a telomere-targeting drug) as a model to investigate the role of telomere integrity in remodeling T cell senescence. We demonstrated that KML001 could inhibit cell proliferation, cytokine production, and promote apoptosis via disrupting telomere integrity and DNA repair machineries. Specifically, KML001-treated T cells increased dysfunctional telomere-induced foci (TIF), DNA damage marker γH2AX, and topoisomerase cleavage complex (TOPcc) accumulation, leading to telomere attrition. Mechanistically, KML001 compromised telomere integrity by inhibiting telomeric repeat binding factor 2 (TRF2), telomerase, topoisomerase I and II alpha (Top1/2a), and ataxia telangiectasia mutated (ATM) kinase activities. Importantly, these KML001-induced telomeric DNA damage and T cell senescent phenotype and machineries recapitulated our findings in patients with clinical HCV or HIV infection in that their T cells were also senescent with short telomeres and thus more vulnerable to KML001-induced apoptosis. These results shed new insights on the T cell aging network that is critical and essential in protecting chromosomal telomeres from unwanted DNA damage and securing T cell survival during cell crisis upon genomic insult.

Made available in DSpace on 2016-06-02T19:50:09Z (GMT). No. of bitstreams: 1 3422.pdf: 675720 bytes, checksum: f875737893548d0c2f3756cbcbe90359 (MD5) Previous issue date: 2010-10-25 / This study aimed to characterize the dynamics of technological innovation in Brazilian MIA segment. To achieve this objective this work realized a survey with IBGE information, the institution responsible for carrying out PINTECs occurred between 1998 and 2005, which allowed a quantitative analysis about technological innovations on MIA companies. In addition, a national scenario with a qualitative analysis was elaborated, based on surveys conducted by IBGE and on a field research in five MIA´s manufacturers companies of São Paulo state. Results indicate that technological changes have changed the way MIA companies treat the needs of their customers by improving the processes of development and manufacture of products. Moreover, it was found that the variables size and export orientation significantly influence the innovative activities. The influence of size company on innovative activity is justified by the fact that the larger companies find it easier to finance innovative projects and the returns of innovation are more expressive when the company has increased sales volume and the fixed costs are more easily absorbed. The export orientation also generates positive impacts on the ability to innovate, because the international competitiveness encourages investments in innovative activities. Exports, while facilitating the expansion of markets, contributing effectively to the reduction of fixed costs generated in the process of innovation. / Este trabalho teve o objetivo de caracterizar a dinâmica da inovação tecnológica do segmento de MIA no Brasil. Para isso foi realizado um levantamento de informações junto ao IBGE, instituição responsável pela realização das PINTECs ocorridas entre 1998 e 2005, que permitiram uma análise quantitativa acerca das inovações tecnológicas para empresas de MIA. Para complementar as informações quantitativas disponibilizadas pelo IBGE foi realizada uma pesquisa de campo em cinco empresas fabricantes de MIA localizadas no estado de São Paulo. Os resultados indicaram que as mudanças tecnológicas modificaram a forma como as empresas de MIA passaram a tratar as necessidades de seus clientes, melhorando os processos de desenvolvimento e fabricação de seus produtos. Além disso, verificou-se que as variáveis porte e orientação exportadora influenciam de forma significativa as atividades inovativas. A influência do porte da empresa sobre a atividade inovativa é justificada pelo fato que as firmas maiores têm mais facilidade para financiar projetos inovativos e os retornos das inovações são mais expressivos quando a empresa tem maior volume de vendas, uma vez que os custos fixos são mais facilmente absorvidos. A orientação exportadora também gera impactos positivos sobre a possibilidade de inovar, pois a competitividade internacional estimula os investimentos em atividades inovativas. As exportações, quando facilitam a ampliação dos mercados, contribuem efetivamente para a redução dos custos fixos gerados no processo de inovação.

This diploma thesis concerns issues of predictive and condition based maintenance system of machine tools with using a vibrodiagnostics. It studies and researches its impacts through the basic processes of the maintenance system and characterizes the vibration diagnosis as its tool and mean. There is also described a process of putting condition based maintenance into practice in the practical part of the thesis. The development is realized at Siemens Ltd. Brno with all its requirements and aspects such as a maintenance audit which means the decision on the suitability of condition based maintenance within the current maintenance system, technical analysis as a part of introduction of vibration diagnosis and the practical example of acquiring, recording and assessment of measured vibration. Prior to the end the economic evaluation of the planned predictive maintenance system and the design of the general model of development and implementation of the maintenance system into practice are included.

Final thesis deals with the structural and technological project of block of flats in Brno. Deal with division building construction and engineering structures, machineries, project schedule and financial plan. It is further focused on the rough construction of the main building structure, where processing technological study of the construction, project schedule, the project site equipment, budget and other documents that are necessary for the correct realization of construction.

Masters thesis is engaged of chosen parts of technological-buildig project of administrativ and housing complex of Sochorova in Brno, Žabovřesky. Contains technological-buildig study of first phase with brief description of advancement of construction with grafical scripts of particular steps, timetable and pecuniarytable of objects AB3, AB4, diagrams with various possibilities of using operatives. Thesis continous with calculation of entire first phase and item budged of object AB3(draft construction), statement of masurement, technical report of construction-technological AB3, plan of situaction of the building, technological manual of reiforced concrete ceiling of AB3 including plan of planking parts PERI, timetable, design of construction site equipment with technical report, proposal of machineries and crane, plane of inspections for chosen items, ecology and report about safety and health protecting on construction site.