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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Vida nua: biopolítica na gestão da população de rua / Bare life: biopolitics in the management on homeless population

Barbosa, Aline Ramos [UNESP] 17 August 2017 (has links)
Submitted by ALINE RAMOS BARBOSA null (alinerbarbosa@gmail.com) on 2017-09-18T14:36:52Z No. of bitstreams: 1 Tese Aline R. Barbosa - arquivamento.pdf: 1801294 bytes, checksum: e24a246a4accfed6195d6eaf7cbff8af (MD5) / Approved for entry into archive by Monique Sasaki (sayumi_sasaki@hotmail.com) on 2017-09-19T19:50:21Z (GMT) No. of bitstreams: 1 barbosa_ar_dr_mar.pdf: 1801294 bytes, checksum: e24a246a4accfed6195d6eaf7cbff8af (MD5) / Made available in DSpace on 2017-09-19T19:50:21Z (GMT). No. of bitstreams: 1 barbosa_ar_dr_mar.pdf: 1801294 bytes, checksum: e24a246a4accfed6195d6eaf7cbff8af (MD5) Previous issue date: 2017-08-17 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Cette thèse analyse l’accueil intersectoriel (Santé et Assistance Sociale) destiné à la population sans domicile fixe (SDF) d’une commune moyenne de l’intérieur de l’État de São Paulo. Pour ce faire, on a réalisé une recherche sur le terrain dans l’équipement public nommé Casa Transitória « Adélia Portella Volpe » (Maison Transitoire « Adélia Portella Volpe ») et dans le réseau d’accueil intersectoriel de la population sans domicile fixe, dans la ville de Jaboticabal – SP. À partir des conceptions de biopolitique, de thanatopolitique et de vie nue, cette thèse analyse la gestion actuelle de cette population. Pour ce faire, on répertorie les données de la recherche sur le terrain, de l’analyse documentaire et du contexte de la guerre aux drogues, mis en évidence par le Programa Crack – é preciso vencer (Programme Crack – il faut vaincre), qui articule les domaines de la Santé, de l’Assistance Sociale et de la Sécurité Publique dans le plan national. Ainsi, l’argumentation de la thèse se structure selon deux perspectives d’analyse : a. une première plus « positive » des politiques publiques, qui les prend au sérieux et décrit leurs caractéristiques, leurs impasses et leurs limitations, c’est-à-dire, une analyse de ce que j’ai nommé « politiques de gouvernement » ; b. une seconde analyse, plus pessimiste, qui fait la critique des limites de l’État dans sa relation avec la population. Alors, on présente l’analyse du dispositif de gestion en marge de l’État et, ainsi, on travaille avec l’idée de « politiques d’État». Ces deux perspectives, quoique distinctes, font partie d’une même analyse. Et, dans n’importe laquelle de ces perspectives, les politiques publiques destinées à la population sans domicile fixe n’atteignent pas les buts qu’elles se proposent, à l’exception de celui du contrôle de cette population, ce qui renforce le dispositif et ne l’émancipe aucunement. / Esta tese analisa o acolhimento intersetorial (Saúde e Assistência Social) para a população em situação de rua de um município de médio porte do interior paulista. Para tal intento, foi realizada uma pesquisa de campo no equipamento público denominado Casa Transitória “Adélia Portella Volpe” e na rede de acolhimento intersetorial da população em situação de rua, em Jaboticabal-SP. A partir das concepções de biopolítica, tanatopolítica e vida nua, esta tese analisa a gestão atual da população de rua. Para isso, são elencados os dados da pesquisa de campo, a análise documental e o contexto de guerra às drogas, evidenciado pelo Programa Crack – é preciso vencer, que articula Saúde, Assistência Social e Segurança Pública no plano nacional. Desta forma, a argumentação da tese se estrutura em duas perspectivas de análise: a. uma primeira mais “positiva” das políticas públicas, que as leva a sério e descreve suas características, impasses e limitações. Ou seja, uma análise do que denominei “políticas de governo”; b. uma segunda análise, mais pessimista, que faz a crítica do próprio limite do Estado em sua relação com a população. Então, apresenta a análise do dispositivo de gestão nas margens do Estado. E, desta forma, trabalha com a ideia de “políticas de Estado”. Ambas perspectivas, embora distintas, fazem parte de uma mesma análise. E, em qualquer uma das duas perspectivas, as políticas públicas destinadas para população em situação de rua não dão conta do que se propõem. A não ser o controle desta população, que reforça o dispositivo e em nada emancipa. / This thesis analyses the intersectorial host institution (health and social assistance) for homeless population in a small town located near São Paulo. For this purpose, a field research was carried out on the public equipment called Casa Transitória (Halfway House) “AdéliaPortela Volpe” and on the intersectorial network of homeless people, in Jaboticabal-SP. From the conceptions of biopolitics, thanatopolitics and bare life, this thesis analyses the current management about homeless population. In this regard, it listed the field research data, documentary analysis and the war on drugs context, indicated by the Programa Crack – é preciso vencer (Crack Program – It needs overcome), that articulates Health, Social Assistance and Public Security at national level. Thus, the argument of the thesis has two perspectives: a. the first one is more “positive” about public policy, which understand seriously and describe its characteristics, problems and restrictions. In other words, an analysis I named “government policies”; b. the second, a more pessimist analysis, criticizes the limits of State in its relationship with the population. So, it presents an analysis of management device in the margins of the State. Both perspectives, although different, are part of the same investigation. And, both perspectives the public polices intended to homeless population does not get effective results. Except for the control of this population, which reinforce the device and does not emancipate anybody.
42

Applications of nonlinear stochastic discount factors in performance analysis and tail risk

Ardison, Kym Marcel Martins 12 April 2018 (has links)
Submitted by Kym Marcel Martins Ardison (kymmarcel@gmail.com) on 2018-09-16T17:36:08Z No. of bitstreams: 1 TESE.pdf: 3325190 bytes, checksum: e1bbe47dabd1e2befe53e9ace94ab46b (MD5) / Approved for entry into archive by GILSON ROCHA MIRANDA (gilson.miranda@fgv.br) on 2018-10-25T19:43:48Z (GMT) No. of bitstreams: 1 TESE.pdf: 3325190 bytes, checksum: e1bbe47dabd1e2befe53e9ace94ab46b (MD5) / Made available in DSpace on 2018-10-29T20:07:02Z (GMT). No. of bitstreams: 1 TESE.pdf: 3325190 bytes, checksum: e1bbe47dabd1e2befe53e9ace94ab46b (MD5) Previous issue date: 2018-04-12 / We propose a new class of performance measures for Hedge Fund (HF) returns based on a family of empirically identi able stochastic discount factors (SDFs). These SDF-based measures incorporate no-arbitrage pricing restrictions and naturally embed information about higher-order mixed moments between HF and benchmark factors returns. We provide full asymptotic theory for our SDF estimators that allows us to test for the statistical signi cance of each fund's performance and for the relevance of individual benchmark factors in identifying each proposed measure. Empirically, we apply our methodology to a large panel of individual hedge fund returns, revealing sizable di erences across performance measures implied by di erent exposures to higher-order mixed moments. Moreover, when we compare SDF-based measures to the traditional linear regression approach (Jensen's alpha), our measures identify a signi cantly smaller fraction of funds in the cross-section of HFs with statistically signi cant performances
43

Evaluating the Scalability of SDF Single-chip Multiprocessor Architecture Using Automatically Parallelizing Code

Zhang, Yuhua 12 1900 (has links)
Advances in integrated circuit technology continue to provide more and more transistors on a chip. Computer architects are faced with the challenge of finding the best way to translate these resources into high performance. The challenge in the design of next generation CPU (central processing unit) lies not on trying to use up the silicon area, but on finding smart ways to make use of the wealth of transistors now available. In addition, the next generation architecture should offer high throughout performance, scalability, modularity, and low energy consumption, instead of an architecture that is suitable for only one class of applications or users, or only emphasize faster clock rate. A program exhibits different types of parallelism: instruction level parallelism (ILP), thread level parallelism (TLP), or data level parallelism (DLP). Likewise, architectures can be designed to exploit one or more of these types of parallelism. It is generally not possible to design architectures that can take advantage of all three types of parallelism without using very complex hardware structures and complex compiler optimizations. We present the state-of-art architecture SDF (scheduled data flowed) which explores the TLP parallelism as much as that is supplied by that application. We implement a SDF single-chip multiprocessor constructed from simpler processors and execute the automatically parallelizing application on the single-chip multiprocessor. SDF has many desirable features such as high throughput, scalability, and low power consumption, which meet the requirements of the next generation of CPU design. Compared with superscalar, VLIW (very long instruction word), and SMT (simultaneous multithreading), the experiment results show that for application with very little parallelism SDF is comparable to other architectures, for applications with large amounts of parallelism SDF outperforms other architectures.
44

Fusing Stereo Measurements into a Global 3D Representation

Blåwiik, Per January 2021 (has links)
The report describes the thesis project with the aim of fusing an arbitrary sequence of stereo measurements into a global 3D representation in real-time. The proposed method involves an octree-based signed distance function for representing the 3D environment, where the geomtric data is fused together using a cumulative weighted update function, and finally rendered by incremental mesh extraction using the marching cubes algorithm. The result of the project was a prototype system, integrated into a real-time stereo reconstruction system, which was evaluated by benchmark tests as well as qualitative comparisons with an older method of overlapping meshes. / <p>Examensarbetet är utfört vid Institutionen för teknik och naturvetenskap (ITN) vid Tekniska fakulteten, Linköpings universitet</p>
45

Hardware Synthesis of Synchronous Data Flow Models

Koecher, Matthew R. 06 April 2004 (has links) (PDF)
Synchronous Dataflow (SDF) graphs are a convenient way to represent many signal processing and dataflow operations. Nodes within SDF graphs represent computation while arcs represent dependencies between nodes. Using a graph representation, SDF graphs formally specify a dataflow algorithm without any assumptions on the final implementation. This allows an SDF model to be synthesized into a variety of implementation techniques including both software and hardware. This thesis presents a technique for generating an abstract hardware representation from SDF models. The techniques presented here operate on SDF models defined structurally within the Ptolemy modeling environment. The behavior of the nodes within Ptolemy SDF models is specified in software and can be simple, such as a single arithmetic operation, or arbitrarily complex. This thesis presents a technique for extracting the behavior of a limited class of SDF nodes defined in software and generating a structural description of the SDF model based on primitive arithmetic and logical operations. This synthesized graph can be used for subsequent hardware synthesis transformations.
46

A Study of Breast Cancer Cell Adhesion to Endothelium in Response to Cytokine Stimulus

Henson, Karissa A. 26 July 2010 (has links)
No description available.
47

Design Space Decomposition for Cognitive and Software Defined Radios

Fayez, Almohanad Samir 07 June 2013 (has links)
Software Defined Radios (SDRs) lend themselves to flexibility and extensibility because they<br />depend on software to implement radio functionality. Cognitive Engines (CEs) introduce<br />intelligence to radio by monitoring radio performance through a set of meters and configuring<br />the underlying radio design by modifying its knobs. In Cognitive Radio (CR) applications,<br />CEs intelligently monitor radio performance and reconfigure them to meet it application<br />and RF channel needs. While the issue of introducing computational knobs and meters<br />is mentioned in literature, there has been little work on the practical issues involved in<br />introducing such computational radio controls.<br /><br />This dissertation decomposes the radio definition to reactive models for the CE domain<br />and real-time, or dataflow models, for the SDR domain. By allowing such design space<br />decomposition, CEs are able to define implementation independent radio graphs and rely on<br />a model transformation layer to transform reactive radio models to real-time radio models<br />for implementation. The definition of knobs and meters in the CE domain is based on<br />properties of the dataflow models used in implementing SDRs. A framework for developing<br />this work is presented, and proof of concept radio applications are discussed to demonstrate<br />how CEs can gain insight into computational aspects of their radio implementation during<br />their reconfiguration decision process.<br /> / Ph. D.
48

Associação entre o consumo de oxigênio e as alterações na microcirculação de pacientes pediátricos com choque séptico / Association between oxygen consumption and microcirculatory alterations in pediatric patients with septic shock

Daniella Mancino da Luz Caixeta 20 June 2015 (has links)
Choque séptico é caracterizado por desequilíbrio entre o transporte e o consumo de oxigênio, podendo acarretar hipóxia tecidual. A disfunção microcirculatória, característica cardinal da fisiopatologia do choque séptico, causa má distribuição de fluxo sanguíneo microvascular e, consequentemente, shunt de oxigênio, disóxia tissular e, teoricamente, diminuição no consumo de oxigênio (VO2) pela célula. No presente estudo, foi investigada a associação entre alterações microcirculatórias causadas pela sepse e o consumo de oxigênio em pacientes pediátricos. Dezessete crianças com choque séptico ressuscitadas foram estudadas em quatro momentos durante a internação na unidade de terapia intensiva (dentro de 24, 48 e 72 horas após a admissão ou diagnóstico de choque e após a resolução deste, antes da extubação traqueal). A microcirculação sublingual foi avaliada utilizando o método de imagem Sidestream dark field (SDF) e o VO2 foi calculado através da calorimetria indireta. Outras variáveis hemodinâmicas, como transporte de oxigênio, índice cardíaco, pressão arterial invasiva, lactato arterial e saturação venosa central, foram coletadas. Embora as variáveis hemodinâmicas tenham se mantido em níveis satisfatórios, graves alterações na microcirculação foram visualizadas, especialmente na densidade de vasos pequenos perfundidos (DVPP), na proporção de vasos pequenos perfundidos (PVPP) e no índice de fluxo microvascular (MFI). Foram encontradas assosciações significativas entre o VO2 e os parâmetros da microcirculação: dVO2 e dDVPP (&#946; coefficient= 6,875; p<0,001), dVO2 e dPVPP (&#946; coefficient=92,246; p<0,001) e dVO2 e dMFI (&#946; coefficient=21,213; p<0,001). Não foram encontradas correlações entre as alterações microcirculatórias e as outras variáveis. Em conclusão, este estudo mostrou que pacientes pediátricos com choque séptico apresentaram grave disfunção microvascular e que o fluxo microcirculatório alterado estava associado ao VO2, podendo estar implicado na fisiopatologia da disóxia tecidual da sepse. / Septic shock is characterized by the imbalance between oxygen delivery and consumption leading to tissue hypoxia. Microcirculatory dysfunction, a key element of septic shock pathogenesis, elicits maldistribution of microvascular blood flow and consenquently oxygen shunt, tissue oxygenation debt and, theoretically, impaired oxygen consumption (VO2). In this study, it was investigated if there is an association between microcirculatory changes and VO2 in pediatric patients with septic shock. Seventeen resuscitated patients with septic shock were studied in four moments (within 24hr, 48hr and 72hr of the admission or diagnosis of shock and after its resolution, prior to extubation). Sublingual microcirculation was evaluated using Sidestream dark field (SDF) imaging and VO2 was measured directly by indirect calorimetry. Other hemodynamic variables, like cardiac index, oxygen delivery, invasive arterial pressure, arterial lactate and central venous oxygen saturation were also recorded. Although global hemodynamic variables were within satisfactory ranges, microvascular variables were markedly altered, especially microvascular flow index (MFI), proportion of perfused small vessels (PPV) and perfused small vessel density (PVD). Significant associations between oxygen consumption and microcirculatory parameters were found: dVO2 and dPVD (&#946; coefficient= 6.875; p<0.001), dVO2 and dPPV (&#946; coefficient=92.246; p<0.001) and dVO2 and dMFI (&#946; coefficient=21.213; p<0.001). There was no correlation between microcirculatory alterations and other variables in this study. In conclusion, this study showed that pediatric patients with septic shock presented severe microcirculatory dysfunction and abnormal microvascular blood flow could be associated to oxygen consumption.
49

Mecanismos moleculares da ação dos glicocorticóides endógenos e da anexina-A1 sobre o tráfego de neutrófilos: caracterização da ação sobre os  eixos SDF-1&#945;/CXCR4 e IL-17/IL-23/G-CSF / Molecular mechanisms of endogenous glucocorticoid and annexin-a1 actions on neutrophil traffic: characterization of this action on the SDF-1&#945;/CXCR4 e IL-17/IL23/G-CSF axis

Machado, Isabel Daufenback 17 December 2013 (has links)
O tráfego de leucócitos é um processo complexo, dependente da ação de inúmeras substâncias químicas, além da perfeita interação celular. Desta forma, este estudo teve como objetivo avaliar a ação dos GCe e da ANXA1 sobre o eixo SDF-1&#945;/CXCR4 e IL-17/IL-23/G-CSF e sobre a expressão de moléculas de adesão CD18, CD49d e CD62L. Foram utilizados camundongos machos Balb/C selvagens (WT) ou ANXA1-/-. As avaliações foram realizadas em condições basais, na presença de altas concentrações de GCe e na vigência de processo inflamatório, induzidos pela administração de ACTH (5 &#181;g/animal, i.p.) ou pela injeção de LPS (100 &#181;g/kg, i.p.), respectivamente, ou na ausência da ação dos GCe, pela ação do RU 38486 (RU, 10 mg/kg, i.p.). A participação da ANXA1 e do receptor FPR2 foi avaliada pelo pré-tratamento com Ac2-26 (1 mg/Kg, i.p.) ou com BOC2 (10 &#181;g/animal, i.p.) durante 4 dias, 1 vez ao dia. A quantificação total e diferencial das células foi realizada em câmara de Neubauer e em esfregaços corados por May-Grunwald ou citometria de fluxo. As quantificações de CXCR2, CXCR4, FPR2, CD18, CD49d, CD62L e maturação granulocítica (CD11b/Ly6G) em células da medula e da circulação foram realizadas por citometria de fluxo. A expressão de ANXA1 nos tecidos do estomago e do baço foi realizada por western blotting e nas células da medula óssea e sangue circulante foi realizada por imunofluorescência. As quantificações de IL-17, IL-23, G-CSF, SDF-1&#945; e corticosterona foram realizadas por ELISA. A quimiotaxia de neutrófilos da medula óssea e sangue periférico foi ensaiada na placa de quimiotaxia com filtro de poro de 8 &#181;m. A fagocitose de neutrófilos apoptóticos por macrófagos da medula óssea foi avaliada por ensaio in vitro. Para verificar os efeitos do ACTH na migração de neutrófilos no processo inflamatório, foi empregado o modelo de bolsa de ar (100 &#181;g/mL; LPS); e o comportamento dos leucócitos circulantes de animais tratados com ACTH foi avaliado pela técnica de microscopia intravital. Os resultados obtidos, que estão apresentados em quatro temáticas, mostraram que: 1) neutrófilos da medula óssea e sangue periférico expressam ANXA1 no citoplasma e membrana, bem como o receptor FPR2, constitutivamente, e a expressão de ambos é regulada pelos GCe. A ANXA1, via receptor FPR2 expresso em células da medula óssea, controlam a maturação neutrofílica e o tráfego destas células da medula óssea para o sangue. A ANXA1, via interação ao FPR2, controla o clearance de neutrófilos do sangue para a medula óssea, modulando o eixo SDF-1&#945;/CXCR4; 2) A administração do ACTH causa neutrofilia e os neutrófilos circulantes são ANXA1+, CD18+, CD49d+, CD62L+, mostrando que injeção do ACTH in vivo altera o fenótipo destas células na circulação. Estas modificações alteram o comportamento dos neutrófilos na circulação, bem como a migração para a bolsa de ar na vigência de inflamação e para os tecidos de clearance. Estes efeitos podem ser dependentes, pelo menos em parte, da inibição de migração orientada, já que quimiotaxia frente ao fMLP ou ao SDF-1&#945; estavam reduzidas. Ainda, o clearance de neutrófilos é reduzido em animais tratados com o ACTH pela menor atividade fagocítica e secretora dos macrófagos medulares; 3) Animais tratados com RU 38486 e ANXA1-/- mobilizam granulócitos da medula óssea para o sangue circulante e, deste compartimento para o foco de inflamação com maior intensidade que o observado em animais controles. O eixo IL-17/IL-23/G-CSF parece estar envolvido na granulopoiese e na mobilização de neutrófilos para o sangue durante a inflamação, mas não é alvo de ação da ANXA1 e o GCe nesta etapa do processo inflamatório. Adicionalmente, foi observado que na vigência de peritonite, as moléculas de adesão, CD49d e CD62L estão envolvidas no processo de migração de neutrófilos da medula óssea para o sangue. Os resultados aqui obtidos permitem concluir que os GCe e a ANXA1 são relevantes para granulopoiese e tráfego dos neutrófilos da medula óssea em condições fisiológicas e na vigência de processo inflamatório. Ainda, em conjunto com os dados da literatura, os nossos resultados podem sugerir a participação da ANXA1 dos GCe na plasticidade fenotípica dos neutrófilos de acordo com os estímulos a que são submetidos, e podem auxiliar na compreensão dos novos conceitos sobre a produção, tempo de vida, localização e funções de neutrófilos. / The traffic leukocytes is a complex process dependent on the action of severals chemical mediators, in addition to perfect cell interaction. Therefore, this study aimed to evaluate the effect of GCe and ANXA1 on SDF-1&#945;/CXCR4 and IL-17/IL-23/G-CSF and on the expression of adhesion molecules CD18, CD49d and CD62L. Balb/C wild type and ANXA1-/- male mice were employed. The analysis were performed at physiological conditions, in the presence of high concentrations of GCe and during of inflammatory process induced by ACTH administration (5 &#181;g/animal, i.p.) or LPS injection (100 &#181;g/kg, i.p.), respectively or in the absence of GCe action, by the action of RU 38486 (RU, 10 mg/kg , i.p.). The involvement of the receptor FPR2 and ANXA1 was assessed by pre-treatment with Ac2-26 (1 mg/kg, i.p.) or BOC2 (10 &#181;g/animal, i.p.) for 4 days, once a day. The quantification of total and differential cell was performed in a Neubauer chamber and stained smears by May-Grunwald and flow cytometry. Quantification of expression of CXCR2, CXCR4, FPR2, CD18, CD49d, CD62L and granulocytic maturation (CD11b/Ly6G) in the bone marrow and circulation were performed by flow cytometry. The expression of ANXA1 on tissues was performed by western blotting and on cells from bone marrow and blood by immunocytochemistry. Quantification of IL-17, IL-23, G-CSF, SDF-1&#945; and corticosterone were performed by ELISA. The chemotaxis of neutrophils from the bone marrow and blood was tested in the chemotaxis chamber with filter pore of 8 microns. The phagocytosis of apoptotic neutrophils by bone marrow macrophages was assessed by in vitro assay. To investigate the effects of ACTH in the migration of neutrophils in the inflammatory process, the model employed was air pouch (100 &#181;g/ ml, LPS), and the behavior of circulating leukocytes from animals treated with ACTH were evaluated by intravital microscopy. The results obtained, which are presented in three sections, showed that: 1) neutrophils from the bone marrow and blood expressed ANXA1 in the cytoplasm and membrane, as well as FPR2, constitutively and the expression of both is regulated by GCe. The ANXA1 via FPR2 receptor expressed in bone marrow cells, controls the neutrophilic maturation and traffic of these cells from the bone marrow into the blood. The ANXA1 via interaction to FPR2 controls the clearance of neutrophils from the blood to the bone marrow by modulating the SDF-1&#945;/CXCR4 axis; 2) the administration of ACTH induces neutrophilia and the circulating neutrophils are ANXA1+, CD18+, CD49d+ and CD62L+, showing that the injection of ACTH in vivo alters the phenotype of these cells in the blood. These modifications alter the behavior of neutrophils in the blood, as well as the migration to the air pouch in the presence of inflammation and to the tissue clearance, and these effects may be dependent, at least in part, on inhibition of migration oriented events, as chemotaxis in response to fMLP or SDF-1&#945; were reduced. Further, the clearance of neutrophils is reduced in animals treated with ACTH due to the lower phagocytic and secretory activity of medullary macrophages; 3) Animals treated with RU 38486 and ANXA1-/- mobilize granulocytes from bone marrow into the blood, and from this compartment to the focus of inflammation with higher intensity than that observed in the control group. The axis IL-17/IL-23/G-CSF seems to be involved in granulopoiesis and mobilization of neutrophils into the blood during inflammation, but it is not the target of action of ANXA1 and GCe at this step of inflammatory process. Additionally, it was observed that in the presence of peritonitis, the adhesion molecules, CD49d and CD62L are involved in the migration of neutrophils from the bone marrow into the blood. The results obtained allow concluding that the GCe and ANXA1 are relevant to the granulopoiesis and the traffic of neutrophils from bone marrow under physiological conditions and in the presence of inflammation. Furthermore, together with literature data, the data presented here may suggest the involvement of ANXA1 the GCe in phenotypic plasticity of neutrophils according to the stimuli that are submitted, and may support to understand the new concepts of production, half-life, location and function of neutrophils.
50

Characterization of stromal cell-derived factor-1 (SDF-1) and glycoprotein nmb (GPNMB) in cardiac pathophysiology

Mühlstedt, Silke 08 February 2013 (has links)
Ischämische Herzerkrankungen stellen die weltweit häufigste Todesursache dar. Das Chemokin SDF-1 zählt zu den vielversprechendsten neuen Therapietargets. Allerdings werden die dem SDF-1 Effekt zugrunde liegenden Mechanismen kontrovers diskutiert. Um den Einfluss von SDF-1 auf die Herzregeneration aufzuklären, wurden transgene Ratten generiert, welche SDF-1 in Kardiomyozyten überexprimieren. Die basale Herzfunktion war in diesen Ratten nicht verändert, jedoch zeigte sich nach Herzinfarkt eine Verschlechterung der kardialen Funktion. Des Weiteren ließen sich eine verstärkte Fibrosebildung, ein Anstieg neutrophiler Granulozyten im Blut sowie eine erhöhte Einwanderung von Makrophagen in die Herzen transgener Ratten feststellen. Dagegen waren die Anlockung von Stammzellen und die Blutgefäßneubildung nicht verändert. Diese Daten bestätigen, dass kardiales SDF-1 eine nachteilige Wirkung ausüben kann, indem es entzündliche Prozesse im geschädigten Gewebe beeinflusst. Ferner wurde ein Microarray-basiertes Screening in kardialem Gewebe nach Herzinfarkt durchgeführt. Ziel der Studie war die Identifizierung neuer Moleküle, deren Rolle bei Herzerkrankungen bislang unbekannt ist. Das Screening brachte das Glykoprotein GPNMB hervor, welches an fibrotischen Prozessen nach Gewebeschädigung beteiligt ist. Wir untersuchten das Protein mit Hilfe des DBA/2J Mausstammes, in dem kein funktionelles GPNMB vorhanden ist. Die Untersuchung dieser Mäuse ergab keine Veränderungen der basalen Herzfunktion, nach Herzinfarkt zeigte sich jedoch eine verbesserte kardiale Funktion sowie erhöhte Hämoglobinkonzentrationen im Blut. Außerdem war die Funktion von Makrophagen verändert. Darüber hinaus fanden wir erhöhte Konzentrationen von GPNMB in Plasmaproben von Patienten nach akutem Herzinfarkt. Zusammenfassend weisen die Ergebnisse darauf hin, dass GPNMB nicht nur ein vielversprechendes Therapietarget, sondern auch einen potenziellen Biomarker für ischämische Herzerkrankungen darstellt. / Ischemic heart diseases are a major cause of death worldwide due to the postmitotic state of the heart. The chemokine SDF-1 is one of the most promising novel therapeutic targets due to its ability to attract leukocytes and stem cells. However, the role of different cardiac cell types in this process remains elusive and underlying mechanisms have been controversially discussed. To clarify the role of SDF-1 and its receptor CXCR4 in myocardial regeneration, we generated transgenic rats overexpressing SDF-1 in cardiomyocytes. The function of the heart at baseline was not altered in these rats, whereas the induction of myocardial infarction resulted in impaired cardiac function and remodeling. This finding was accompanied by increased fibrosis, neutrophil blood counts and macrophage infiltration into the heart. On the other hand, stem cell recruitment and neovascularization were not altered in SDF-1 transgenic rats. In conclusion, our findings confirm that the SDF-1/CXCR4 axis can have adverse effects by affecting the inflammatory state of the healing heart. In addition, a microarray-based screening was conducted in rat hearts after myocardial infarction with the aim to discover yet unknown molecules involved in cardiac repair. This screening yielded GPNMB, a glycoprotein known to be involved in inflammatory and fibrotic processes after tissue injury. We studied the protein further using DBA/2J mice that lack functional levels of GPNMB. While the cardiac function was normal in these mice at baseline, induction of myocardial infarction revealed a preservation of cardiac function, less dilatation as well as higher red blood cell and hemoglobin levels. Moreover, the absence of GPNMB resulted in an altered activity and distribution of macrophages. We also found increased levels of GPNMB in plasma of patients after myocardial infarction. In conclusion, our findings suggest that GPNMB might constitute a novel therapeutic target and biomarker of acute ischemic heart diseases.

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