Universiẗat, Diss., 2002--Dortmund.

University, Diss., 2004--Bielefeld.

Proefschrift--Radboud Universiteit Nijmegen, 2007. / Description based on print version record. Includes bibliographical references (p. 211-216).

Resumo: Lesões na cartilagem articular representam um desafio para a Medicina Veterinária devido ao limitado potencial intrínseco de reparação. As células tronco mesenquimais (CTM) e o plasma rico em plaquetas (PRP) vêm sendo utilizados na reparação condral pela capacidade de imunomodulação, quimiotaxia, por diminuir a degradação da cartilagem articular e exercer efeito anti-inflamatório. Esse trabalho estudou a eficácia das CTM e do PRP no tratamento de lesões condrais articulares, experimentalmente induzidas em equinos, apresentando os benefícios e os principais obstáculos encontrados na aplicação clínica e cirúrgica de equinos. Para isso, foi induzida uma lesão condral, na tróclea medial femoral dos dois membros pélvicos de oito animais. Após 30 dias da indução dessa lesão os animais, divididos em quatro grupos, receberam os tratamentos propostos: com CTM (Grupo 1); PRP (Grupo 2); CTM e PRP (Grupo 3) e um controle sem tratamento (Grupo 4). As avaliações dos parâmetros clínico-laboratoriais foram realizadas antes da indução da lesão (T-0), quinzenalmente até 120 dias e aos 150 dias (T-150). Avaliações macroscópicas, histopatológicas e histoquímicas foram realizadas em T-0 e T- 150. Pôde-se observar discreta melhora clínico-laboratorial dos grupos tratados quando comparados ao grupo controle. Os exames macroscópicos, histopatológicos e histoquímicos revelaram um melhor tecido de reparação nos grupos tratados, principalmente nos grupos 2 e 3. Sendo assim, o implante autólogo de CTM e do PRP apresentou efeitos benéficos no tratamento de lesões condrais, experimentalmente induzidas em equinos / Abstract: Articular cartilage defects represent a challenge for Veterinary Medicine due to the limited intrinsic potential of repair. Mesenchymal Stem Cells (MSC) and Platelet-Rich Plasma (PRP) have been used in cartilage repair to promote immunomodulation, chemotaxis, to decrease the degradation of articular cartilage and to take antiinflammatory effect. This work aims to study the use of intralesional MSC and the PRP in the treatment of articular cartilage defects induced experimentally in horses, noting the benefits and challenges encountered in implementing clinical-surgical in horses. For this purpose, both patellofemoral joints of eight animals were approached by arthroscopic surgery to perform a cartilage defect, on the medial femoral trochlea. After 30 days of induction the animals, who were divided into four groups, received treatment with: MSC (Group 1), PRP (Group 2), MSC and PRP (Group 3) and a control without treatment (Group 4). The clinical and laboratory assessments were performed every 15 days in 120 days, with last analysis in day 150. The macroscopic and morphologic analyses were performed at 0 and 150 day. There were clinical and laboratory improvement in the treated groups compared with control group. The macroscopic and morphological analysis showed a better tissue repair in the treated groups, mainly in groups 2 and 3. Thus, the implantation of autologous MSC and PRP showed beneficial effects in the treatment of chondral lesions, experimentally induced in horses / Orientador: Ana Liz Garcia Alves / Coorientador: Marcos Jun Watanabe / Banca: Ligia Souza Lima Silveira da Mota / Banca: Raquel Yvone Arantes Baccarin / Mestre

Magister Chirurgiae Dentium (MChD) / Wound healing is a complex process characterised by the repair and reconstitution of lost or damaged tissue. By the mid 1990s, several methods were proposed to enhance wound healing of surgical sites by introducing high concentrations of human platelets to these areas. In the early 21st century, Choukroun et al (2006b) introduced a new type of platelet concentrate that was devoid of any additives, and required no specialised equipment for its production. This concentrate was termed Platelet-rich fibrin (PRF) and although various aspects of this biomaterial had been studied, very little is currently known about its storage properties. Aim: To determine whether storage time had a significant effect on the platelet concentration of Choukroun’s PRF Method: A total of 30 patients were enrolled into the study. Three blood samples of 10ml each were drawn from each patient. Two of the blood samples (Group A and Group B) were centrifuged to form PRF. The third sample was used to measure the baseline blood platelet concentration and was therefore not centrifuged. After PRF had formed in both test groups, it was removed from the test tubes at 2 different times i.e. immediately after centrifuge (Group A) or after 60 min of storage in the blood collecting tube (Group B). The remaining blood was then tested for platelet concentration and compared to each other and the baseline reading. Results: 14 males and 16 females participated in the study (average age 41.7 years). A mean blood platelet concentration of 282.8 ± 58.3 × 109/L was recorded for the baseline reading. Group A had a mean blood platelet concentration 7.9 ± 3.03 × 109/L. Group B had a mean blood platelet concentration of 4.0 ± 1.93 × 109/L. A statistically significant difference was seen between Groups A and B (p < 0.0001). Conclusions: Storage time has a significant effect of the platelet concentration of PRF. If stored over a period of 60 min, the platelet concentration of PRF increases. Further research is required to determine whether this finding is clinically significant.

The studies presented in this dissertation establish the dynamics of Eleven nineteen Lysine-rich leukemia (ELL) family of elongation factors during B cell differentiation and provide a description of ELL3 function in B cells. The transition from a mature naïve B cells into an activated B cell is dependent on a large increase in transcriptional output, which is followed by focused expression on secreted immunoglobulin upon terminal differentiation into plasma cell. While ELL family members have previously been implicated in alternative splicing at the immunoglobulin heavy chain locus in plasma cells, their presence and function prior to differentiation is currently not known. However, the use of elongation factors has been implied by the finding of mostly paused RNA polymerase II in the genome of naïve B cells. In the first study, the expression of transcriptional elongation factor ELL3 is shown to be restricted to activated B cells and B cell lymphomas. All three family members were characterized in B cell lymphoma cell lines, genome wide expression, microarray analysis and primary B cell stimulus. The expression of ELL3 was induced upon activation of B cells concurrently with family member ELL. In addition, the abundant expression of ELL3 was restricted to GC derived B cell lymphoma cell lines. While the expression of ELL is maintained, the expression of ELL3 is diminished and ELL2 is up-regulated in terminally differentiated plasma cells. The expression of master regulator of terminal plasma cell differentiation PRDM1 was inverse correlated with that of ELL3. To further establish PRDM1s role in regulating the ELL family member dynamics, global binding was assessed in plasma cell lines. Chromatin immunoprecipitation followed by quantitative PCR was utilized to identify direct association of PRDM1 at exclusively the ELL3 loci. Ectopic expression of PRDM1 in B cells down regulated the expression of ELL3. Furthermore, two consensus PRDM1 binding sites were defined at the ELL3 loci, which mediate significant repression of the promoter activity. Collectively, these experiments indicate that PRDM1 mediates the switch from ELL3 in B cells to ELL2 in plasma cells. The data presented in the final chapter aimed at defining a function for ELL3 in the cells that express it most abundantly, which are B cell lymphoma cell lines. Transient depletion of ELL3 in a Burkitt’s lymphoma cell line resulted in a diminished proliferation rate due to a severe disruption of DNA replication and its regulators minichromosome maintenance proteins. Additionally, compromised cell division and mitotic regulators were observed along with increased DNA damage and cell death. The data presented here demonstrate a key role for ELL3 in the proliferation and survival of B cell lymphomas and positions ELL3 as an attractive therapeutic target against B cell lymphoma’s with a germinal center origin.

Made available in DSpace on 2014-06-11T19:23:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-06-14Bitstream added on 2014-06-13T18:48:31Z : No. of bitstreams: 1 yamada_alm_me_botfmvz.pdf: 8714662 bytes, checksum: 3c5312366f54f7619e28b40986950ace (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Lesões na cartilagem articular representam um desafio para a Medicina Veterinária devido ao limitado potencial intrínseco de reparação. As células tronco mesenquimais (CTM) e o plasma rico em plaquetas (PRP) vêm sendo utilizados na reparação condral pela capacidade de imunomodulação, quimiotaxia, por diminuir a degradação da cartilagem articular e exercer efeito anti-inflamatório. Esse trabalho estudou a eficácia das CTM e do PRP no tratamento de lesões condrais articulares, experimentalmente induzidas em equinos, apresentando os benefícios e os principais obstáculos encontrados na aplicação clínica e cirúrgica de equinos. Para isso, foi induzida uma lesão condral, na tróclea medial femoral dos dois membros pélvicos de oito animais. Após 30 dias da indução dessa lesão os animais, divididos em quatro grupos, receberam os tratamentos propostos: com CTM (Grupo 1); PRP (Grupo 2); CTM e PRP (Grupo 3) e um controle sem tratamento (Grupo 4). As avaliações dos parâmetros clínico-laboratoriais foram realizadas antes da indução da lesão (T-0), quinzenalmente até 120 dias e aos 150 dias (T-150). Avaliações macroscópicas, histopatológicas e histoquímicas foram realizadas em T-0 e T- 150. Pôde-se observar discreta melhora clínico-laboratorial dos grupos tratados quando comparados ao grupo controle. Os exames macroscópicos, histopatológicos e histoquímicos revelaram um melhor tecido de reparação nos grupos tratados, principalmente nos grupos 2 e 3. Sendo assim, o implante autólogo de CTM e do PRP apresentou efeitos benéficos no tratamento de lesões condrais, experimentalmente induzidas em equinos / Articular cartilage defects represent a challenge for Veterinary Medicine due to the limited intrinsic potential of repair. Mesenchymal Stem Cells (MSC) and Platelet-Rich Plasma (PRP) have been used in cartilage repair to promote immunomodulation, chemotaxis, to decrease the degradation of articular cartilage and to take antiinflammatory effect. This work aims to study the use of intralesional MSC and the PRP in the treatment of articular cartilage defects induced experimentally in horses, noting the benefits and challenges encountered in implementing clinical-surgical in horses. For this purpose, both patellofemoral joints of eight animals were approached by arthroscopic surgery to perform a cartilage defect, on the medial femoral trochlea. After 30 days of induction the animals, who were divided into four groups, received treatment with: MSC (Group 1), PRP (Group 2), MSC and PRP (Group 3) and a control without treatment (Group 4). The clinical and laboratory assessments were performed every 15 days in 120 days, with last analysis in day 150. The macroscopic and morphologic analyses were performed at 0 and 150 day. There were clinical and laboratory improvement in the treated groups compared with control group. The macroscopic and morphological analysis showed a better tissue repair in the treated groups, mainly in groups 2 and 3. Thus, the implantation of autologous MSC and PRP showed beneficial effects in the treatment of chondral lesions, experimentally induced in horses

Real world systems like biological, social, technological, infrastructural and many others can be modeled as networks. The field of network science aims to study these complex networks and understand their structure and dynamics. A common feature of networks across domains is the distribution of the degree of the nodes according to a power-law (scale invariance). As a consequence of this skewness, the high degree nodes dominate the properties of these networks. The rich-club phenomenon is observed when the high degree or the rich nodes of the network prefer to connect amongst themselves. In the first part, the thesis investigates the rich-club phenomenon in higher order neighborhoods of the network by providing an elegant quantification using a geodesic distance based approach. This quantification helped in identifying networks where the trend and intensity of the rich-club phenomenon is significantly different in higher order neighborhoods compared to the immediate neighbors. The thesis also proposes a quantification of the importance of the non-rich nodes in the communication structure of the rich nodes, and broadly classify networks into core-periphery or cellular. Further a lack of universality is noticed in the structure of the networks belonging to a particular domain. It has been observed in the previous literature that the rich club connectivity dominates assortativity, a measure quantifying the mixing patterns in complex networks. Thus, assortativity is biased. To overcome such drawbacks, in the second part of the thesis proposes a novel measure called regularity. The analytical bounds on regularity and formulation of regularity for different network models are provided. Along with this a measure to quantify the mixing patterns of the neighborhood of a node called local regularity is also defined. The analysis on real-world network based on local regularity and degree distribution shows presence of both type of network, uniformly and non-uniformly mixed across different regions. Further normalized regularity is proposed to quantify the extent of preferential mixing in networks discounting the effect of degree distribution.

At the Castle Creek study area a remarkably well exposed section in the Isaac Formation, Windermere Supergroup, was measured to document potential lateral and vertical changes in facies. Here, a consistent lateral succession of facies was observed consisting of matrix-poor sandstone to clayey sandstone to bipartite bed to sandy claystone, collectively overlain by a thin-bedded turbidite and mudstone cap. These changes are interpreted to reflect particle settling in a negligibly-sheared sand-mud suspension following detachment from the margins of an avulsion jet. Vertically, similar facies stack to form packages 2-7 beds thick implying temporary stabilization of jet-margin dynamics. At a larger scale facies stack to form three stratal assemblages. SA-1: intercalated matrix-rich and matrix-poor strata and SA-2: matrix-rich strata stack vertically and laterally but then are sharply overlain everywhere by classical turbidites of SA-3, indicating a dramatic change from deposition immediately downflow of an avulsion node to conventional levee deposition.

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第14627号 / 工博第3095号 / 新制||工||1460(附属図書館) / 26979 / UT51-2009-D339 / 京都大学大学院工学研究科電子工学専攻 / (主査)教授 川上 養一, 教授 髙岡 義寛, 准教授 須田 淳 / 学位規則第4条第1項該当