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1
Lundin, Marika. "Verifiering av adsorption och elueringsmetod för identifiering av RhG-antikroppar." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-96825.
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Syftet med examensarbetet var att verifiera adsorptions- och elueringsmetod för detektion av G-antikroppar. Detta för att transfusionsmedicin i Karlskrona själva ska kunna genomföra utredning av G-antikroppar. En RhD-negativ gravid kvinna som bär på ett RhD-positivt barn är i behov av RhD-profylax. Har kvinnan redan bildat antikroppar mot RhD finns inte behovet av RhD-profylax. En RhD-negativ gravid kvinna som inte får RhD-profylax kan bilda antikroppar mot fostrets RhD-positiva erytrocyter vilket kan få allvarliga konsekvenser så som hemolytisk sjukdom hos foster och nyfödda. Då RhD-profylax är en dyr bristvara tas blodprover på mamman för att kontrollera fostrets RhD och kontrollera eventuellt behov av RhD-profylax. Det kontrolleras även om kvinnan har bildat några D-antikroppar. Problem som kan uppstå är att G-antikroppar serologisk liknar D och C-antikroppar, skulle då inte Gantikropparna upptäckas utan det anses vara D-antikroppar kommer den gravida kvinnan att gå miste om RhD-profylax hon är i behov av. Att urskilja D och Cantikroppar från att vara G-antikroppar genomförs med adsorption och eluering. I dagens läge genomför inte transfusionsmedicin i Karlskrona detta själva utan skickar proverna till Lund som genomför utredningen av G-antikroppar. Verifieringen genomfördes med hjälp av Lunds metodbeskrivningar för adsorption och eluering. Till verifieringen användes 7 patientprover som alla innehöll D och C-antikroppar, varav 5 kom från gravida kvinnor. Färska erytrocyter (< 72 h) användes för adsorption och eluering av antikropparna. Resultaten visade på att ett av proverna innehöll Gantikroppar i kombination med C-antikroppar och resterande sex prover innehöll D- och C-antikroppar. Resultaten blev som förväntat och metoden kunde godkännas för användning på transfusionsmedicin i Karlskrona.
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Kuniechick, Natasha. "Produção do fator estimulador de colônias de granulócitos humano recombinante (rhG-CSF) em biorreator." Pontifícia Universidade Católica do Rio Grande do Sul, 2013. http://hdl.handle.net/10923/5520.
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Previous issue date: 2013The granulocyte colony-stimulating factor (G-CSF) is a major hematopoietic cytokine involved in the immune defense against infectious agents, stimulating and regulating the proliferation, survival and differentiation of neutrophils precursor cells in the bone marrow. The G-CSF molecule has a 174 amino acids sequence, with a molecular weight of approximately 18. 8 kDa. As a strategy for neutropenia prevention, G-CSF (or filgrastim) has been successfully used in cancer patients whose treatment requires high doses of chemotherapy, in both adults and children. Moreover, this biopharmaceutical may be used to strengthen the immune system in patients with HIV, pneumonia, infections resulting from diabetes, leukemia and febrile neutropenia. Currently, filgrastim is not produced in Brazil, which obligates the government to import this medicine. Due to its wide clinical application, the large scale production of G-CSF is required to supply the demand of national market. In this work, a protocol to obtain this protein was developed using overexpression and cultivation in a bioreactor, solubilization and purification of recombinant G-CSF. The protein was expressed in Escherichia coli host cells C41(DE3) cultures grown in bioreactor using a fed-batch strategy. The expression of the recombinant protein was induced by IPTG. A linear ascending feeding strategy permitted high plasmid stability, low accumulation of acetate in the culture medium, a biomass of approximately 31 g/ L and high expression levels of the protein in the form of inclusion bodies which were solubilized using 2 M urea and alkaline pH. The recombinant protein was purified and yielded approximately 1. 22 mg of homogeneous recombinant protein per gram of wet cells, corresponding to a volumetric yield of 151. 5 mg of rhG-CSF per liter of culture medium. A mass spectrometry analysis was performed, confirming the identity of the recombinant protein. Our work shows a simple and effective strategy to obtain recombinant hG-CSF, stimulating and encouraging a future production of a national biosimilar.
O fator estimulador de colônias de granulócitos (G-CSF) é uma das principais citocinas hematopoiéticas envolvidas na defesa do sistema imune contra agentes infecciosos, estimulando e regulando a proliferação, sobrevivência e diferenciação das células precursoras de neutrófilos na medula óssea. É uma molécula que possui uma sequência de 174 aminoácidos, com peso molecular de aproximadamente 18,8 kDa. Como estratégia de prevenção da neutropenia, o G-CSF (ou filgrastima) é utilizado clinicamente com sucesso em pacientes com câncer, cujo tratamento requer altas doses de quimioterapia, tanto em adultos como em crianças. Além disso, o G-CSF pode ser utilizado para reforçar o sistema imunológico em pacientes com HIV, pneumonia, infecções decorrentes da diabetes, leucemia e neutropenia febril. Atualmente, a filgrastima não é produzida no Brasil, consequentemente, todo medicamento adquirido pelo governo é importado. Tendo em vista sua ampla aplicação clínica, a produção em larga escala do G-CSF se faz necessária para suprir a demanda do mercado nacional e diminuir os custos com importação desse biofármaco. Neste trabalho um protocolo para a produção desta proteína foi desenvolvido, utilizando técnicas de DNA recombinante por meio de experimentos de superexpressão e cultivo em biorreator, solubilização e purificação da G-CSF recombinante. A proteína foi expressa em células Escherichia coli C41(DE3) em cultivos de batelada alimentada em biorreactor, utilizando indução com IPTG e uma estratégia de alimentação linear ascendente, que nos permitiu obter um alto percentual de estabilidade plasmidial, baixo acúmulo de acetato no meio de cultivo, uma biomassa de aproximadamente 31 g/ L e elevados níveis de expressão da proteína em forma de corpos de inclusão, que foram solubilizados utilizando ureia 2 M e pH alcalino. A proteína recombinante foi purificada obtendo-se aproximadamente 1,22 mg de proteína recombinante homogênea por grama de células úmida, correspondendo a um rendimento volumétrico de 151,5 mg de rhG-CSF por litro de meio de cultura. Uma análise por espectrometria de massa também foi realizada, confirmando a identidade da proteína recombinante. Nosso trabalho mostra uma estratégia simples e eficaz para obter hG-CSF recombinante, contribuindo e estimulando a futura produção de um biossimilar nacional.
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Gomes, Fernanda Resende. "Expressão do fator estimulador de colônia de granulócito humano recombinante (rhG-CSF) em Escherichia coli." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-13082010-163827/.
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O Fator estimulador de colônias de granulócitos humano recombinante (rhG-CSF) produzido em Escherichia coli é uma proteína não glicosilada com 175 aminoácidos, de grande importância clínica para o tratamento de neutropenias. O presente trabalho propõe a construção de dois sistemas de expressão em E. coli, um sistema para obtenção do rhG-CSF no citoplasma e outro para secreção da proteína recombinante no meio de cultura utilizando a sequência sinal da L-asparaginase II. Os dois sistemas de expressão foram testados e comparados. A partir desses dados, passou-se para as etapas de obtenção do rhG-CSF com o sistema de expressão sem a sequência sinal. As etapas de renaturação e purificação foram eficientes obtendo-se uma proteína com adequado grau de pureza, integridade estrutural e atividade biológica. Essa proteína também foi utilizada com sucesso para a produção de anticorpos policlonais em camundongos. Com os resultados obtidos, a proteína rhG-CSF mostrou-se viável para estudos posteriores em bioreatores e produção em escala-piloto.The recombinant human granulocyte colony stimulating factor (rhG-CSF) is a non-glycosylated protein with 175 amino acids. This factor plays an important role in hematopoietic cell proliferation and has been widely used for treating neutropenia. The purpose of this work is to construct two expression systems in E. coli; a system for obtaining rhG-CSF in the cytoplasm and the other for secretion of recombinant protein in the culture medium using the signal sequence of L-asparaginase II. The two expression systems were tested and compared. From these data, the next steps for obtaining the rhG-CSF were done with the expression system without the signal sequence. The refolding and purification steps were efficient, resulting in a protein with adequate purity, structural integrity and biological activity. This protein has also been successfully used for the production of polyclonal antibodies in mice. With these results, the protein rhG-CSF was feasible for further studies in bioreactors and pilot scale production.
4
Carmo, Fillipe Luiz Rosa do. "Clonagem, expressão e caracterização do fator estimulador de colônia de granulócito humano recombinante (rhG-CSF) em Escherichia coli." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-17042015-112052/.
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O sistema de expressão em Escherichia coli foi o primeiro a ser utilizado para produzir produtos farmacêuticos recombinantes e tem muitas vantagens quando comparado com sistemas eucarióticos, como o fácil cultivo, baixo custo e alto potencial de produção. O fator estimulador de colônias de granulócito (G-CSF) atua principalmente promovendo a maturação dos neutrófilos e estimulando sua atividade fagocítica e quimiotática, além de estar envolvido com o processo de segmentação nuclear dessas células. O fator estimulador de colônias de granulócitos humano recombinante (rhG-CSF) tem sido produzido por engenharia genética em Escherichia coli, e é usado no tratamento de diversas patologias, sobretudo em neutropenias provocadas pela quimioterapia usada no tratamento de tumores, pela radioterapia e pelo uso de drogas que suprimem a produção de células mieloides. Desse modo, o presente estudo teve como objetivo a expressão da proteína rhGCSF em bactérias Escherichia coli. A clonagem do gene rhG-CSF no vetor de expressão pET-28a(+) foi realizada nos sítios de restrição das enzimas EcoRI e XhoI, e a expressão da proteína recombinante em cepas de bactéria Escherichia coli BL21DE3 foi obtida com sucesso. A proteína rhG-CSF, fundida à cauda de seis histidinas, foi purificada com êxito e identificada pelas técnicas de Western Blotting e por espectrometria de massas. São necessários estudos para avaliar a integridade estrutural e atividade biológica da proteína produzida, que se confirmada, possibilita que esta seja produzida em escala piloto.The expression system in Escherichia coli was the first to be used to produce recombinant pharmaceuticals and has many advantages compared to eukaryotic systems, such as easy cultivation and high production potential at low costs. The granulocyte colony (G-CSF) stimulating factor acts primarily by promoting the maturation of neutrophils and stimulating their phagocytic and chemotactic activity. G-CSF is also involved with the process of neutrophils nuclear segmentation. The recombinant human granulocyte colonies stimulating factor (rhG-CSF) has been produced by genetic engineering in Escherichia coli, and it is used to treat of several conditions, especially neutropenia caused by chemotherapy used in the treatment of tumors, by radiotherapy and by the use of drugs that suppress the production of myeloid cells. The present study aimed the expression of rhG-CSF protein in Escherichia coli bacteria. The cloning of rhG-CSF gene in the expression vector pET- 28a (+) was carried out on the restriction sites of the EcoRI and XhoI enzymes. Expression of the recombinant protein in Escherichia coli BL21DE3 was successfully achieved. The rhG-CSF protein, fused with a six histidine tag, was obtained and successfully purified and identified by the Western Blotting and by mass spectrometry techniques. Studies are needed to assess the structural integrity and biological activity of the protein produced, which, if confirmed, enables the production on a pilot scale.
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Kuniechick, Natasha. "Produ??o do fator estimulador de col?nias de granul?citos humano recombinante (rhG-CSF) em biorreator." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2013. http://tede2.pucrs.br/tede2/handle/tede/5478.
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Previous issue date: 2013-03-27The granulocyte colony-stimulating factor (G-CSF) is a major hematopoietic cytokine involved in the immune defense against infectious agents, stimulating and regulating the proliferation, survival and differentiation of neutrophils precursor cells in the bone marrow. The G-CSF molecule has a 174 amino acids sequence, with a molecular weight of approximately 18.8 kDa. As a strategy for neutropenia prevention, G-CSF (or filgrastim) has been successfully used in cancer patients whose treatment requires high doses of chemotherapy, in both adults and children. Moreover, this biopharmaceutical may be used to strengthen the immune system in patients with HIV, pneumonia, infections resulting from diabetes, leukemia and febrile neutropenia. Currently, filgrastim is not produced in Brazil, which obligates the government to import this medicine. Due to its wide clinical application, the large scale production of G-CSF is required to supply the demand of national market. In this work, a protocol to obtain this protein was developed using overexpression and cultivation in a bioreactor, solubilization and purification of recombinant G-CSF. The protein was expressed in Escherichia coli host cells C41(DE3) cultures grown in bioreactor using a fed-batch strategy. The expression of the recombinant protein was induced by IPTG. A linear ascending feeding strategy permitted high plasmid stability, low accumulation of acetate in the culture medium, a biomass of approximately 31 g/ L and high expression levels of the protein in the form of inclusion bodies which were solubilized using 2 M urea and alkaline pH. The recombinant protein was purified and yielded approximately 1.22 mg of homogeneous recombinant protein per gram of wet cells, corresponding to a volumetric yield of 151.5 mg of rhG-CSF per liter of culture medium. A mass spectrometry analysis was performed, confirming the identity of the recombinant protein. Our work shows a simple and effective strategy to obtain recombinant hG-CSF, stimulating and encouraging a future production of a national biosimilar.
O fator estimulador de col?nias de granul?citos (G-CSF) ? uma das principais citocinas hematopoi?ticas envolvidas na defesa do sistema imune contra agentes infecciosos, estimulando e regulando a prolifera??o, sobreviv?ncia e diferencia??o das c?lulas precursoras de neutr?filos na medula ?ssea. ? uma mol?cula que possui uma sequ?ncia de 174 amino?cidos, com peso molecular de aproximadamente 18,8 kDa. Como estrat?gia de preven??o da neutropenia, o G-CSF (ou filgrastima) ? utilizado clinicamente com sucesso em pacientes com c?ncer, cujo tratamento requer altas doses de quimioterapia, tanto em adultos como em crian?as. Al?m disso, o G-CSF pode ser utilizado para refor?ar o sistema imunol?gico em pacientes com HIV, pneumonia, infec??es decorrentes da diabetes, leucemia e neutropenia febril. Atualmente, a filgrastima n?o ? produzida no Brasil, consequentemente, todo medicamento adquirido pelo governo ? importado. Tendo em vista sua ampla aplica??o cl?nica, a produ??o em larga escala do G-CSF se faz necess?ria para suprir a demanda do mercado nacional e diminuir os custos com importa??o desse biof?rmaco. Neste trabalho um protocolo para a produ??o desta prote?na foi desenvolvido, utilizando t?cnicas de DNA recombinante por meio de experimentos de superexpress?o e cultivo em biorreator, solubiliza??o e purifica??o da G-CSF recombinante. A prote?na foi expressa em c?lulas Escherichia coli C41(DE3) em cultivos de batelada alimentada em biorreactor, utilizando indu??o com IPTG e uma estrat?gia de alimenta??o linear ascendente, que nos permitiu obter um alto percentual de estabilidade plasmidial, baixo ac?mulo de acetato no meio de cultivo, uma biomassa de aproximadamente 31 g/ L e elevados n?veis de express?o da prote?na em forma de corpos de inclus?o, que foram solubilizados utilizando ureia 2 M e pH alcalino. A prote?na recombinante foi purificada obtendo-se aproximadamente 1,22 mg de prote?na recombinante homog?nea por grama de c?lulas ?mida, correspondendo a um rendimento volum?trico de 151,5 mg de rhG-CSF por litro de meio de cultura. Uma an?lise por espectrometria de massa tamb?m foi realizada, confirmando a identidade da prote?na recombinante. Nosso trabalho mostra uma estrat?gia simples e eficaz para obter hG-CSF recombinante, contribuindo e estimulando a futura produ??o de um biossimilar nacional.
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Wiik, H. (Heikki). "Inflammatory response following abdominal surgery and its modulation by recombinant human granulocyte colony-stimulating factor (rhG-CSF, filgrastim)." Doctoral thesis, University of Oulu, 2002. http://urn.fi/urn:isbn:9514268474.
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Abstract
The effects of perioperative filgrastim (rhG-CSF) and surgery per se on the postoperative acute phase reaction were studied by assessing leukocyte functions, cytokine levels and tenascin-C (Tn-C) and procollagen propeptide (PINP, PIIINP) concentrations in different body fluid compartments in patients undergoing gastrointestinal surgery.
Thirty consecutive patients were randomized to receive either filgrastim or placebo for five days, starting 12 hours before colorectal surgery. Filgrastim treatment led to marked neutrophilia with decreased neutrophil migration in peripheral blood but not in peritoneal fluid 48 hours postoperatively. Neutrophil phagocytosis and bacterial killing did not differ between the groups. Filgrastim caused increased postoperative expression of neutrophil CD11b/CD18 in blood but not in peritoneal fluid or wound fluid. CD11b/CD18 expression was higher in both wound fluid and peritoneal fluid than in blood in the placebo group. The expression of neutrophil CD62L was higher in blood than in peritoneal fluid or wound fluid in both groups. The serum concentration of interleukin (IL)-8 was lower in the filgrastim group 5 hours postoperatively. The concentrations of IL-1β, IL-6, transforming growth factor (TGF)-β and IL-10 did not differ between the groups. The cytokine levels were markedly higher locally in the wound and in the peritoneal cavity compared to circulating blood. No adverse events attributable to filgrastim were seen.
Leukocyte counts, neutrophil and monocyte functions and the levels of IL-6, IL-8 and granulocyte colony-stimulating factor (G-CSF) were measured from 18 patients before and after colorectal surgery. Surgery caused an increase in neutrophil and monocyte counts along with lymphocytopenia. Neutrophil phagocytosis was decreased 4 and 24 hours postoperatively, but normalized after that. A distinct systemic cytokine response was seen postoperatively.
In a study with 24 patients, Tn-C concentration increased in wound fluid during the first postoperative week after abdominal surgery. The Tn-C level was markedly higher in wound fluid than in serum.
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Granström, Pontus, Lisa Larsson, and Oscar Lönnerheden. "”Handboll är ju en så jävla komplex sport” : Kompetenskrav i elithandboll, en jämförelse mellan elitlagstränare och RHG-instruktörer." Thesis, Linnéuniversitetet, Institutionen för idrottsvetenskap (ID), 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-45551.
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I Sverige ger Riksidrottsgymnasier (RIG) elever chansen att kombinera sina studier med idrott. Målen med RIG innefattar att eleverna som examineras ska ges goda förutsättningar att lyckas nå internationell elitnivå som senior. Statistik över hur RIG-studenter uppfyller dessa mål saknas dock. Syftet med uppsatsen är att analysera vad som ligger i kompetensbegreppet elithandbollspelare ur en elitlagstränares synvinkel samt att jämföra detta med hur instruktörerna vid Rikshandbollsgymnasiet (RHG) uppfattar samma begrepp. Det är också vår ambition att redogöra för elithandbollstränares uppfattning om skillnader mellan examinerade elever från RIG-handboll och spelare som gått Nationell idrottsutbildning (NIU) eller gymnasium utan handbollsinriktning. Genom en kvalitativ studie har vi med semistrukturerade intervjuer och en fokusgrupp samlat in empiri från ett målinriktat urval. I analysen ställs empirin mot tidigare forskning och de teorier vi redogör för. Studiens resultat visar att synen på kompetens som krävs för en elithandbollspelare till stor del är likvärdig mellan elitlagstränare och instruktörer vid RHG. Generellt har elitlagstränare inom den svenska handbollen bättre kunskap om NIU och är osäkra om skillnaden mellan NIU och RIG. Även kunskapen om spelare som går eller har gått RHG är låg hos elittränarna. Den största skillnad som elittränarna ser mellan RHG-studenter och andra spelare är att RHG spelare upplevs som proffsigare och mer teoretiskt kunniga.
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Azevedo, Wellington Morais de. "Transplante alogenico de celulas-tronco perifericas mobilizadas por rhG-CSF, não manipuladas in vitro, para tratamento de neoplasias hematologicas." [s.n.], 1995. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308632.
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Orientador: Carmino Antonio de SouzaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Transplantes autoplásticos de células-tronco periféricas (CTP) já vêm sendo realizados há algum tempo, tendo mostrado algumas vantagens em relação aos transplantes do mesmo tipo que utilizam medula óssea. Dentre estas vantagens, destaca-se a capacidade das CTP de produzir uma "pega" mais rápida do enxerto, encurtando o período de aplasia de medula óssea que se segue ao condicionamento do paciente. A coleta de CTP por aférese oferece maior conforto ao doador, que não precisa ser submetido à anestesia geral e às numerosas punções da crista ilíaca necessárias à obtenção do número de células suficientes para o transplante. Apesar das evidentes vantagens observadas no cenário autoplástico, a aplicação da mesma técnica aos transplantes alogênicos só se iniciou no começo dos anos 90. Este retardo se deveu ao temor de que os enxertos de CTP alogênicas, mais ricos em células T imunocompetentes, pudessem acarretar aumentos na incidência e gravidade da doença do enxerto-contra-o-hospedeiro (DECH). Outro empecilho à realização desses transplantes é a ecessidade de mobilização das CTP para a circulação sangüínea, que se fez possível nos transplantes autoplásticos, inicialmente, pelo uso de quimioterápicos citotóxicos; tal prática seria eticamente condenável em doadores sadios e, só mais recentemente, os fatores de crescimento hematopoiético humanos, obtidos por tecnologia de recombinação gênica (rhGCSF), ofereceram uma alternativa mais segura para conseguir essa mobilização. Neste estudo, não controlado analisamos os resultados de dezessete transplantes alogênios de CTP, comparando-os com aqueles obtidos em um grupo-controle que recebeu, contemporaneamente, transplantes alogênicos convencionais de medula óssea. O objetivo foi o de se estudar, comparativamente, o perfil de "pega" dos enxertos de CTP, assim como a morbidade associada ao procedimento. Para tanto, foram comparados vários parâmetros entre os dois grupos, que incluíram: tempo de "pega" do enxerto, tempo de permanência no hospital após o transplante, necessidade de transfusões, número de dias em uso de antimicrobianos ou nutrição parenteral, níveis séricos máximos de creatinina e bilirrubina, incidência e gravidade de DECH aguda, entre outros. Procuramos avaliar ainda os eventuais efeitos colaterais a curto prazo do rhG-CSF nos doadores. Os resultados mostraram que a incidência e gravidade da DECH aguda foram comparáveis entre os dois grupos, assim como a morbidade geral relacionada ao transplante. De fato, os transplantes com CTP apresentaram "pega" mais rápida e permitiram alta hospitalar mais precoce. A mobilização de CTP pelo uso de rhG-CSF e sua obtenção por sessões únicas de aférese mostraram-se, no período estudado, livres de efeitos colaterais ou complicações clínicas sérias para os doadores. O número de células foi suficiente para garantir a "pega" e estabilidade do enxerto em todos os pacientes, não se observando rejeições ou "falhas de pega". Aparentemente, as vantagens oferecidas pelas CTP em transplantes autoplástiéos também se aplicam aos transplantes alogênicos. Os resultados sugerem ser a técnica viável, porém devem ser interpretados com cautela devido às limitações metodológicas do estudo, que incluem o curto tempo de seguimento dos pacientes e a realização de análise de dados de grupos de pacientes distribuídos sem "randomização"
Abstract: Autologous blood stem celI (BSC) transplantation is already a welI established medical procedure, which has shown some advantages over the use of bone marrow for the same purpose. A faster engraftment rate is observed in these transplants, consequently shortening the period of marrow aplasia that folIows the conditioning phase. Besides, BSC colIection by apheresis offers more cornfort to the donors, avoiding the need for general anesthesia and marrow aspiration in order to obtain sufficient numbers of stem celIs for engraftment. Despite alI these advantages, the use of allogeneic BSC for transplantation did not start until the beginning of the Nineties. The application of the technique had always been hampered by the fear. that BSC grafts, which contain a larger amount of immunocompetent T -celIs, could result in intolerable increases of graft-versus-host disease (GVHD) incidence and severity. ColIection ofBSC by apheresis requires that these celIs first be mobilized to the circulation, a task acomplished initially by the use of antinoeplastic cytotoxic drugs. The administration of such agents to healthy donors would be a clearly unnacceptable practice, and, only Tecently, recombinant human hematopoietic growth factors (rhG-CSF) have offered a reasonable alternative for this purpose. In thi~ study, we retrospectively analyze the results of seventeen allogeneic BSC transplants, comparing them to those obtained in a control group of patients who received conventional allogeneic marrow transplants contemporarily fashion. The objective was to study the engraftment profile of the BSC grafts, as welI as the general transplant-associated morbidity. For this purpose, several parameters were assessed and compared between the two groups, including: time to engraftment, transfusion needs, number of days under antimicrobial treatment and parenteral nutrition, maximal serum levels of creatinine and bilirubin, incidence and severity of acute GVHD, among others. We also analyzed the eventual short-term deleterious effects of rhG-CSF upon donors. The results have pointed to a comparable incidence and severity of acute GVHD in the two populations, as well as similar transplant-associated morbidity profiles. Indeed, BSC grafts produced significantly faster engraftment and shorter hospital stays. Donor stem cell mobilization by rhG-CSF and their collection by single apheresis sessions have been devoid of significant side-effects or clinical complications in the study period. The numbers of cells collected have always proven sufficient to promote good engraftment, with no documentated of rejection or any other kind of graft failure. It seems apparent that the advantages offered by autologous BSC transplants can be shared by their allogeneic counterparts. The results suggest that allogeneic BSC transplantation is a feasible procedure, but one must not forget that this was not a randomized, prospective study, and that our follow-up time was not long enough to permit safe conclusions about the issue. More studies are necessary until we can replace alogeneic BSC transplantation for conventional bone marrow transplants
Doutorado
Clinica Medica
Doutor em Clínica Médica
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RONZINO, ANDREA. "Unpacking Robin Hood gardens: the troubled history of a British public housing project (1952) 1963/1972 (2018)." Doctoral thesis, Politecnico di Torino, 2021. http://hdl.handle.net/11583/2914548.
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Kazi, Samreen H. "Minimum tile-derived microsatellite markers improve the physical map of the soybean genome and the Flyer and Hartwig genetic map at Rhg, Rfs and yield loci /." Available to subscribers only, 2005. http://proquest.umi.com/pqdweb?did=1075682461&sid=1&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Thesis (M.S.)--Southern Illinois University Carbondale, 2005."Department of Molecular Biology, Microbiology and Biochemisty." Includes bibliographical references (leaves 154-176). Also available online.
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Wiese, Kai Boris. "Therapie der Pseudomonas aeruginosa-Sepsis mit rhG-CSF (Filgrastim) unter besonderer Berücksichtigung der hämodynamischen Veränderungen und des klinischen Verlaufes eine experimentelle Studie am nicht anästhesierten, invasiv instrumentierten Schwein /." [S.l.] : [s.n.], 1998. http://www.diss.fu-berlin.de/1998/100/index.html.
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Miura, Ernani. "Uso do fator estimulador de colônias de granulócitos humanos rhG-CSF no tratamento da sepse neonatal precoce em recém-nascidos prematuros : um estudo duplo-cego, randomizado e controlado por placebo." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 1998. http://hdl.handle.net/10183/164514.
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Objetivos: Avaliar a eficácia do uso do rhG-CSF no tratamento da sepse neonatal precoce em recém-nascidos prematuros bem como a resposta das citocinas hematopoéticas e do sistema hematológico. Material e Métodos: Foi realizado um estudo randomizado duplo-cego. Foram incluídos recém-nascidos prematuros com menos de 5 dias de vida com diagnóstico de sepse clínica. O grupo tratamento (GT) recebeu 10 J.tg/kg/d de rhG-CSF, por via intravenosa, uma vez ao dia, por 3 dias consecutivos, e o grupo placebo (GB) recebeu o mesmo volume de placebo, também por via intravenosa, por 3 dias consecutivos. Todos os recém-nascidos foram acompanhados até o óbito ou alta hospitalar. TNF-a, IL-6, GM-CSF, G-CSF, contagem de leucócitos (CL), contagem absoluta de neutrófilos (ANC), relação neutrófilos imaturos/neutrófilos totais (I/T), contagem de plaquetas (CP) e concentração de hemoglobina (Hb) foram estudadas inicialmente antes da administração da primeira dose, 24 horas, 72 horas e 1 O dias após a primeira dose do tratamento e do placebo. Foi feita aspiração da medula óssea 7 dias após a primeira dose. A relação NSP /NPP (NSP = estoque de reserva medular de neutrófilos; NPP = estoque proliferativo medular de neutrófilos) e NSP foram avaliados. O estudo foi aprovado pelo comitê de ética do Hospital de Clínicas de Porto Alegre e foi obtido consentimento escrito dos pais dos pacientes. Resultados: Quarenta e quatro recém-nascidos prematuros foram incluídos no estudo, 22 em cada grupo. Não houve diferenças entre ambos os grupos em relação a: idade gestacional média (GT: 29,4 ± 3, 1; GP: 30,7 ± 2,9 semanas); média do peso ao nascer (GT: 1376 ± 491 ; GP: 1404 ± 508 g); mediana do escore de Apgar no quinto minuto de vida; mediana do escore SNAP (escore fisiológico agudo neonatal) nas primeiras 24 horas de vida (GT: 8, variação: 3 - 28; GP: 9,5, variação: O - 23); média do tempo de hospitalização (GT: 40; GP: 35 dias); mediana dos níveis de TNF-u, IL-6, GM-CSF, IIT, CP e Hb em todos os momentos estudados. Apesar da taxa de mortalidade nos primeiros 7 dias de vida ter sido 13,6% menor no GT (mortalidade nos primeiros 7 dias de vida= GT: O; GP: 3) (mortalidade dos 8 aos 28 dias de vida GT: 5; GP: 3 ), não houve diferenças estatisticamente significativa. A incidência de infecção hospitalar durante todo o tempo de internação foi significativamente menor no GT do que no GP (GT: 2; GP: 9; p < 0,03). As medianas dos níveis de G-CSF, CL e ANC foram significativamente maiores no GT do que no GP com 24 horas (GCS = GT: 2568 pg/ml; GP: 56 pg/ml, p < 0,0001; CL = GT: 15200 mm3 ; GP: 8100 mm3 p < 0,005; ANC = GT: 9522 mm3 ; GP: 4526 mm3 p < 0,005) e 72 horas após o início do tratamento (G-CSF = GT: 129 pg/ml; GP: 37,5 pg/ml p < 0,007; CL = GT: 23100 mm3 ; GP: 9250 mm3 p < 0,00002; ANC = GT: 16843 mm3 ; GP: 4703 mm3 p < 0,00002). A média NSP e a relação NSP/NPP foi significativamente maior no GT do que no GP (NSP = GT: 58,4 ± 8%; GP: 47,8 ± 11,2% p < 0,003; NSPINPP = GT: 4,2 ± 2,5; GP: 2,6 ± 1,2 p < 0,05). Conclusões: A administração de rhG-CSF no tratamento da sepse neonatal precoce em recém-nascidos prematuros pode reduzir a mortalidade nos primeiros 7 dias de vida e principalmente, a incidência de infecção hospitalar. Provoca ainda um aumento na contagem de leucócitos e na contagem absoluta de neutrófilos 24 e 72 horas após o início do tratamento, e um aumento na NSP e na relação NSPINPP 7 dias após o início do tratamento.Objectives: To evaluate the efficacy o f the use of rhG-CSF in the treatment of early neonatal sepsis in premature infants and to asses cytokine and hematologic values in septic premature newborn infants after treatment with rhG-CSF Methods: A double blind randomized study was performed. Premature newborn infants were included in the study if they had a clinicai diagnosis of sepsis in the first 5 days of life. Treatment group (TG) received 10 j..tg/kg/day ofthe rhG-CSF IV once a day for 3 consecutive days, and the placebo group (PG) received the same volume of placebo IV as the TG for 3 consecutive days. Ali the included newboms were followed up to death or hospital discharge. TNF-a, IL-6, GM-CSF, G-CSF, leucocyte count (LC), absolute neutrophil count (ANC), immature/total neutrophil ratio (I/T), platelet count (PC), and hemoglobin concentration (Hb) were studied just before administration o f the first dose, 24 hours, 72 hours and 1 O days after the first dose o f treatment. Bone marrow aspiration was performed 7 days after the first dose oftreatment. NSP (neutrophil storage pool) and NSPINPP (neutrophil proliferative pool) ratio were evaluated. The study was approved by the ethics committee of the Hospital de Clínicas de Porto Alegre and informed consent o f the parents were obatined. Results: Forty-four premature newborn infants were included in the study, twenty two in each group. Mean gestational ages (TG: 29.4 ± 3.1; PG: 30.7 ± 2.9 weeks), mean birth weights (TG: 1376 ± 491; PG: 1404 ± 508 grams), median Apgar scores in the fifth minutes of life, median SNAP (score for neonatal acute physiology) scores in the first 24 hours oflife (TG: 8, range: 3-28; PG: 9.5, range: O- 23), and mean lenght of hospital stay (TG: 40; PG: 35) were similar in both groups. Median TNF-u, IL-6, GM-CSF, I!f ratio, PC and Hb in all studied moments were similar in both groups. Although the survival rate in the first 7 days o f li f e was 13.6% higher in the TG than in the PG, there was no significant statistical difference (mortality in the first 7 days oflife TG =O; PG: 3), (mortality from 8 to 28 days oflife TG: 5; PG: 3 ). The occurrence o f nosocomial infection during the whole hospital stay was significant lower in the TGthan in the PG (TG: 2; PG: 9, p < 0.03). Median G-CSF leveis, LC, and ANC were significantly higher in the TG than in PG at 24 hours (G-CSF = TG: 2568 pg/ml; PG: 56 pg/ml, p < 0.00001; LC = TG: 15200 mm3 ; PG:8100 mm3 , p < 0.005; ANC = TG: 9522; PG: 4526, p < O. 005) and 72 hours after onset o f treatment (G-CSF = TG: 129 pg/ml; PG: 37.5, p < 0.007; LC = TG: 23100 mm3 ; PG: 9250 mm3 , p < 0.00002; ANC = TG: 16843 mm3 ; PG: 4703 mm3 , p < 0.00002). Mean NSP and NSP/NPP ratio were significantly higher in TG than in PG (NSP = TG: 58.4% ± 8%; PG: 47.8 ± 11.2%, p < 0.003; NSP/NPP ratio = TG: 4.2 ± 2.5; PG: 2.6 ± 1.2, p < 0.05). Condusions: Administration of rhG-CSF to a septic premature newborn infants may decrease the mortality in the first 7 days of life, and mainly the incidence of nosocomial infection. Also rhG-CSF administration causes an increase o f LC and ANC 24 and 72 hours after onset o f treatment, and an increase in NSP and NSP /NPP ratio 7 days after treatment.
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Godoy, Aline Vieira [UNESP]. "Avaliação leucométrica e citofluorométrica do sangue periférico de cães com linfoma, após uso de rhG-CSF, submetidos à alta dose de ciclofosfamida seguida ou não de transplante autólogo de medula óssea." Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/101127.
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O presente estudo teve como objetivos avaliar seqüencial e temporalmente o quadro leucocitário de dez cães portadores de linfoma em remissão, submetidos à alta dose de ciclofosfamida, durante o uso do estimulador de colônia de granulócitos (GCSF, filgrastine) seguido ou não do transplante autólogo de medula óssea (TMO), bem como quantificar células CD34+ no sangue periférico dos referidos cães. Para tal avaliação foram utilizados três grupos experimentais, sendo o grupo 1 (G1) formado por cinco animais em remissão de linfoma que passaram por alta dose de ciclofosfamida e TMO seguido do uso de G-CSF; o grupo 2 (G2) formado por cinco animais em remissão de linfoma que sofreram alta dose de ciclofosfamida seguida do uso de G-CSF e o grupo 3 (G3) formado por dez animais saudáveis que receberam apenas o G-CSF. O transplante consistiu na colheita de medula óssea, preparo e congelamento da bolsa que continha células medulares em suspensão, condicionamento do paciente com 500mg/m2 de ciclofosfamida, infusão das células hematopoéticas e aplicação do G-CSF. Para avaliar a recuperação hematopoética pós-transplante foi realizado leucograma e análise citométrica do sangue nos dias 7, 8, 9, 10 e 11 após condicionamento. O nadir médio dos neutrófilos segmentados (NS) no grupo com transplante de medula óssea (G1) foi 425 NS/mL, e no grupo sem TMO (G2) foi 637,4 NS/μL e ocorreu sete dias após alta-dose de quimioterápico em ambos os grupos. A duração média da neutropenia foi de três dias. Nenhum animal apresentou febre ou sepse após a alta dose de ciclofosfamida. A dose de 5μg/kg/dia durante quatro dias de filgrastine foi insuficiente na mobilização adequada de células CD34+ nos três grupos estudados, sendo necessários novos estudos para este propósito. Desta maneira, pode-se comprovar o fato de que o uso do G-CSF leva a reduções significativas na incidência...
The aims of this research were to provide an analysis of several counts of leucocytes values in dogs with lymphoma in remission phase, undergone to high-dose chemotherapy with cyclophosphamide, during treatment with granulocyte colonystimulating factor (G-CSF, filgrastine), followed or not by autologous bone marrow transplantation (BMT), as well to quantify CD34+ cells of peripheral blood from that dogs. For this purpose, three experimental groups were considered. Five dogs in clinical remission undergone to high-dose chemotherapy with cyclophosphamide and BMT, followed by G-CSF use were included in group 1 (G1), while group 2 (G2) was consisted by five dogs undergone to high-dose chemotherapy with cyclophosphamide, followed by G-CSF. Group 3 (G3) was composed of ten healthy dogs undergone to GCSF only. Transplantation consisted of bone marrow harvest, managing and freezing bags containing lifted marrow cells, cyclophosphamide conditioning (500mg/m2), hematopoietic cells infusion and treatment with G-CSF. After transplantation, hematopoietic recovery was evaluated by means of leukograms and flow cytofluorimetrical analysis on days 7, 8, 9, 10 and 11 after conditioning. Mean nadir neutrophil (NS) counts in group undergone transplantation (G1) was 425 NS/mL versus 637,4 NS/μL in group without BMT (G2). Nadir was observed on the seventh day after high-dose chemotherapy in both groups and neutropenia mean time was three days. Fever or sepsis was not observed in any dog after high-dose cyclophosphamide. Four days of filgrastine treatment in dose of 5μg/Kg, daily, was not enough to mobilize CD34+ cells appropriately in three groups analyzed, requiring new studies for this purpose. Considering these results, it is possible to conclude that G-CSF significantly reduces the incidence, severity and duration of neutropenia
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Godoy, Aline Vieira. "Avaliação leucométrica e citofluorométrica do sangue periférico de cães com linfoma, após uso de rhG-CSF, submetidos à alta dose de ciclofosfamida seguida ou não de transplante autólogo de medula óssea /." Jaboticabal : [s.n.], 2010. http://hdl.handle.net/11449/101127.
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Orientador: Aureo Evangelista SantanaBanca: Andrigo Barboza de Nardi
Banca: Ana Paula Massae Nakage Canesin
Banca: Paola Castro Moraes
Banca: Rosemeri de Oliveira Vasconcelos
Resumo: O presente estudo teve como objetivos avaliar seqüencial e temporalmente o quadro leucocitário de dez cães portadores de linfoma em remissão, submetidos à alta dose de ciclofosfamida, durante o uso do estimulador de colônia de granulócitos (GCSF, filgrastine) seguido ou não do transplante autólogo de medula óssea (TMO), bem como quantificar células CD34+ no sangue periférico dos referidos cães. Para tal avaliação foram utilizados três grupos experimentais, sendo o grupo 1 (G1) formado por cinco animais em remissão de linfoma que passaram por alta dose de ciclofosfamida e TMO seguido do uso de G-CSF; o grupo 2 (G2) formado por cinco animais em remissão de linfoma que sofreram alta dose de ciclofosfamida seguida do uso de G-CSF e o grupo 3 (G3) formado por dez animais saudáveis que receberam apenas o G-CSF. O transplante consistiu na colheita de medula óssea, preparo e congelamento da bolsa que continha células medulares em suspensão, condicionamento do paciente com 500mg/m2 de ciclofosfamida, infusão das células hematopoéticas e aplicação do G-CSF. Para avaliar a recuperação hematopoética pós-transplante foi realizado leucograma e análise citométrica do sangue nos dias 7, 8, 9, 10 e 11 após condicionamento. O nadir médio dos neutrófilos segmentados (NS) no grupo com transplante de medula óssea (G1) foi 425 NS/mL, e no grupo sem TMO (G2) foi 637,4 NS/μL e ocorreu sete dias após alta-dose de quimioterápico em ambos os grupos. A duração média da neutropenia foi de três dias. Nenhum animal apresentou febre ou sepse após a alta dose de ciclofosfamida. A dose de 5μg/kg/dia durante quatro dias de filgrastine foi insuficiente na mobilização adequada de células CD34+ nos três grupos estudados, sendo necessários novos estudos para este propósito. Desta maneira, pode-se comprovar o fato de que o uso do G-CSF leva a reduções significativas na incidência... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The aims of this research were to provide an analysis of several counts of leucocytes values in dogs with lymphoma in remission phase, undergone to high-dose chemotherapy with cyclophosphamide, during treatment with granulocyte colonystimulating factor (G-CSF, filgrastine), followed or not by autologous bone marrow transplantation (BMT), as well to quantify CD34+ cells of peripheral blood from that dogs. For this purpose, three experimental groups were considered. Five dogs in clinical remission undergone to high-dose chemotherapy with cyclophosphamide and BMT, followed by G-CSF use were included in group 1 (G1), while group 2 (G2) was consisted by five dogs undergone to high-dose chemotherapy with cyclophosphamide, followed by G-CSF. Group 3 (G3) was composed of ten healthy dogs undergone to GCSF only. Transplantation consisted of bone marrow harvest, managing and freezing bags containing lifted marrow cells, cyclophosphamide conditioning (500mg/m2), hematopoietic cells infusion and treatment with G-CSF. After transplantation, hematopoietic recovery was evaluated by means of leukograms and flow cytofluorimetrical analysis on days 7, 8, 9, 10 and 11 after conditioning. Mean nadir neutrophil (NS) counts in group undergone transplantation (G1) was 425 NS/mL versus 637,4 NS/μL in group without BMT (G2). Nadir was observed on the seventh day after high-dose chemotherapy in both groups and neutropenia mean time was three days. Fever or sepsis was not observed in any dog after high-dose cyclophosphamide. Four days of filgrastine treatment in dose of 5μg/Kg, daily, was not enough to mobilize CD34+ cells appropriately in three groups analyzed, requiring new studies for this purpose. Considering these results, it is possible to conclude that G-CSF significantly reduces the incidence, severity and duration of neutropenia
Doutor
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Scarcia, Margherita. "Rho GTPases required for angiogenesis : role and regulation of RhoG." Thesis, University of Leeds, 2013. http://etheses.whiterose.ac.uk/5417/.
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Angiogenesis is the formation of new blood vessels from pre-existing ones and it is necessary for physiological processes such as normal development, and pathological conditions like cancer growth and metastatic cell dissemination. In order to form new blood vessels, endothelial cells, the cells that line the blood vessels, must go through a number of distinct cellular processes. In order to sprout, cells have to initially detach from the vessel wall, migrate and divide. Endothelial cells must then establish new cell junctions and form functional lumens. During these processes the endothelial cell actin cytoskeleton and cell morphology change dramatically. The Rho family of small GTPases are key regulators of such morphological changes. Whilst the prototypical family members Rho, Rac and Cdc42 have been implicated in different aspects of endothelial cell behavior such as migration and cell assembly, other Rho GTPase family members are less characterized. The aim of this study has been to understand the role of the Rho GTPase RhoG in vessel formation and to identify its regulators and downstream effectors. For this purpose organotypic co-culture system was employed of endothelial cells and fibroblasts that gives rise to three-dimensional capillary-like tubes as an in vitro tool to model vessel development. Using RNAi-mediated knockdown in the endothelial cells in the in vitro coculture system, the role of putative regulators (guanine nucleotide exchange factors) and downstream effectors in angiogenesis was analysed and players that control lateral filopdia formation were identified. Pulldown assays that determine the activation status of Rho GTPases and gene overexpression and protein co-immunoprecipitation assays were then used to confirm phenotypic results seen in the co-culture assay. Using this system, a novel non-canonical SGEF-RhoG-DOCK4-Rac1-DOCK9-Cdc42 signaling module was identified that controls filopodia formation during endothelial cell assembly and sprouting. Knockdown of components of this signaling module block lateral filopodia formation, while tip filopodia persist suggesting that that different sub-populations of endothelial cell filopodia exist that are regulated independently during tubule morphogenesis. Mechanistic studies carried out in the course of this study showed that DOCK4 and DOCK9 interact with each other and with the RhoG effector ELMO. Complex formation of DOCK9 with ELMO is through DOCK4 whereas DOCK4 interacts directly with DOCK9. Domain deletion studies showed that DOCK4 interacts with DOCK9 via its SH3 domain. In summary, this work has identified a new signaling cascade that drives vessel formation via lateral filopodia formation and sprouting and demonstrated for the first time an interaction between a Rac1 exchange factor (DOCK4) and a Cdc42 exchange factor (DOCK9). In addition to providing new information about the process of angiogenic sprouting and functional interaction between different GEFs, the signaling components identified in this study may constitute useful therapeutic targets in pathological angiogenesis in cancer and other diseases.
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Silva, Ana Lívia Motta [UNESP]. "Efeito do fator estimulante de colônia de granulócitos recombinante humano (rhG-CSF) sobre o número de leucócitos, plaquetas e sobre a mobilização de células-tronco hematopoéticas CD34+ para o sangue periférico de cães sadios." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/89182.
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O rhG-CSF é uma citocina que eleva o número de neutrófilos e também mobiliza células-tronco hematopoéticas (CTH) para o sangue periférico, porém sua aplicação pode ocasionar a queda de plaquetas. O objetivo do presente trabalho foi estabelecer entre três diferentes doses (5, 10 e 20μg/Kg/dia) do rhG-CSF qual proporcione mobilização de pelo menos 10 CTH CD34+/μL ao sangue periférico, elevação do número de neutrófilos, além de avaliar seu efeito sobre o número de plaquetas em cães sadios. O rhG-CSF (filgrastine) foi aplicado em cães sadios durante quatro dias e a contagem no número de CTH CD34+/μL, neutrófilos e plaquetas foi obtida durante a aplicação da citocina e sete dias após o término da aplicação. A leucocitose ocorreu devido à elevação dose-dependente de neutrófilos segmentados que ocorreu 24 horas após a primeira aplicação do medicamento com diferença estatística. Entretanto, 48 horas após a última dose, os valores retornaram aos níveis basais nos três grupos. O número de plaquetas reduziu após a primeira dose e não recuperou até o último momento de avaliação. Em relação às CTH CD34+, para os grupos que receberam 10 e 20μg/Kg/dia ocorreu elevação dose–dependente 24h após primeira aplicação com diferença estatística; no grupo que recebeu 5μg/Kg/dia os valores não elevaram. A dose de 5μg/Kg/dia foi suficiente para elevar os valores de neutrófilos, porém não acarretou na mobilização de CTH CD34+. As três doses administradas aos animais levou a queda nos valores de plaquetas, sendo necessária precaução ao administrar em cães trombocitopenicos
The rhG-CSF is a cytokine that increase the number of neutrophils and also mobilizes hematopoietic stem cell (HSC) to peripheral blood, but their application can cause a drop in platelets. The aim this work was to establish between three different doses (5, 10 e 20 μg/kg/day) of rhG-CSF which provides mobilization at least 10 HSC CD34+/μL to peripheral blood, increased number of neutrophils and to evaluate its effect on the number platelets in normal dogs. The rhG-CSF (Filgrastine®) was applied from healthy dogs for four days and couting the number of HSC CD34+, neutrophils and platelets was obtained during the application of cytokine and seven days after the application. The leukocytosis occurred due to increase dose relation of segmented neutrophils that occurred 24 hours after the first application of the drug with a statistical difference. However, 48 hours after the last dose, the values returned to baseline levels in the three groups. The number of platelets reduced after the first dose and not returns to the last time point. Regarding the number HSC CD34+, for the groups receiving 10 and 20 μg/kg/day occurred increase dose relation 24 hours after the first application with a statistical difference; in the group that received 5 μg/kg/day, values did not improve. The dose of 5 μg/kg/day was enough to raise the values of neutrophils, but did not result in the mobilization of HSC CD34+. All three doses administered to animals led to a drop in platelets, necessitating caution when administering in thrombocytopenic dogs
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Silva, Ana Lívia Motta. "Efeito do fator estimulante de colônia de granulócitos recombinante humano (rhG-CSF) sobre o número de leucócitos, plaquetas e sobre a mobilização de células-tronco hematopoéticas CD34+ para o sangue periférico de cães sadios /." Jaboticabal, 2012. http://hdl.handle.net/11449/89182.
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Orientador: Aureo Evangelista SantanaCoorientador: Ana Paula Massae Nakage Canesin
Banca: Sabryna Gouveia Calazans
Banca: Daniel Paulino Junior
Resumo: O rhG-CSF é uma citocina que eleva o número de neutrófilos e também mobiliza células-tronco hematopoéticas (CTH) para o sangue periférico, porém sua aplicação pode ocasionar a queda de plaquetas. O objetivo do presente trabalho foi estabelecer entre três diferentes doses (5, 10 e 20μg/Kg/dia) do rhG-CSF qual proporcione mobilização de pelo menos 10 CTH CD34+/μL ao sangue periférico, elevação do número de neutrófilos, além de avaliar seu efeito sobre o número de plaquetas em cães sadios. O rhG-CSF (filgrastine) foi aplicado em cães sadios durante quatro dias e a contagem no número de CTH CD34+/μL, neutrófilos e plaquetas foi obtida durante a aplicação da citocina e sete dias após o término da aplicação. A leucocitose ocorreu devido à elevação dose-dependente de neutrófilos segmentados que ocorreu 24 horas após a primeira aplicação do medicamento com diferença estatística. Entretanto, 48 horas após a última dose, os valores retornaram aos níveis basais nos três grupos. O número de plaquetas reduziu após a primeira dose e não recuperou até o último momento de avaliação. Em relação às CTH CD34+, para os grupos que receberam 10 e 20μg/Kg/dia ocorreu elevação dose-dependente 24h após primeira aplicação com diferença estatística; no grupo que recebeu 5μg/Kg/dia os valores não elevaram. A dose de 5μg/Kg/dia foi suficiente para elevar os valores de neutrófilos, porém não acarretou na mobilização de CTH CD34+. As três doses administradas aos animais levou a queda nos valores de plaquetas, sendo necessária precaução ao administrar em cães trombocitopenicos
Abstract: The rhG-CSF is a cytokine that increase the number of neutrophils and also mobilizes hematopoietic stem cell (HSC) to peripheral blood, but their application can cause a drop in platelets. The aim this work was to establish between three different doses (5, 10 e 20 μg/kg/day) of rhG-CSF which provides mobilization at least 10 HSC CD34+/μL to peripheral blood, increased number of neutrophils and to evaluate its effect on the number platelets in normal dogs. The rhG-CSF (Filgrastine®) was applied from healthy dogs for four days and couting the number of HSC CD34+, neutrophils and platelets was obtained during the application of cytokine and seven days after the application. The leukocytosis occurred due to increase dose relation of segmented neutrophils that occurred 24 hours after the first application of the drug with a statistical difference. However, 48 hours after the last dose, the values returned to baseline levels in the three groups. The number of platelets reduced after the first dose and not returns to the last time point. Regarding the number HSC CD34+, for the groups receiving 10 and 20 μg/kg/day occurred increase dose relation 24 hours after the first application with a statistical difference; in the group that received 5 μg/kg/day, values did not improve. The dose of 5 μg/kg/day was enough to raise the values of neutrophils, but did not result in the mobilization of HSC CD34+. All three doses administered to animals led to a drop in platelets, necessitating caution when administering in thrombocytopenic dogs
Mestre
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Benjelloun, Fatine. "Etude fonctionnelle De Glycoprotéines RhAG et RhCG : implication Dans le Transport de l'Ammonium." Paris 6, 2004. http://www.theses.fr/2004PA066371.
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Zidi-Yahiaoui, Nedjma. "Propriétés structurales et fonctionnelles des protéines RhBG et RhCG, transporteur d'ammonium chez les mammifères." Paris 7, 2008. http://www.theses.fr/2008PA077133.
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Les protéines Rhésus des mammifères appartiennent à la superfamille Amt/Mep/Rh des transporteurs d'ammonium identifiés chez les bactéries, les levures, les plantes et les animaux. Alors que RhCE, RhD et RhAG sont spécifiquement érythroïdes, les protéines RhBG et RhCG sont exprimées dans divers organes impliqués dans le métabolisme et le transport de l'ammonium. Nous avons étudié les propriétés fonctionnelles des transporteurs RhBG et RhCG humains exprimés dans les cellules HEK293 et MDCK. La fonction de transport d'ammonium dans les cellules transfectées et sauvages a été analysée par le suivi des variations du pH intracellulaire en présence d'un gradient d'ammonium. Cette étude a été réalisée par spectrofluorimétrie en flux interrompu en utilisant une sonde fluorescente sensible au pH. Nous avons observé une alcalinisation très rapide et une énergie d'activation plus faible des cellules transfectées comparées aux cellules sauvages. Nos résultats montrent que les protéines RhBG et RhCG facilitent les mouvements de NH₃ à travers la membrane plasmique des cellules et apparaissent ainsi comme des canaux à NH₃. Sur la base de la structure 3D des canaux à NH3 bactériens, l'AmtB d'Escherichia coli et la Rh50 de Nitrosomonas europaea, et d'une modélisation par homologie des protéines Rh humaines selon la méthode HCA, nous avons identifié les différents acides aminés critiques pour la fonction du canal RhCG et comparé les mécanismes de transport d'ammonium des canaux Rh et de l'EcAmtB. Cette étude a permis de mettre en évidence des similitudes et des différences dans le mécanisme de transport d'ammonium via les transporteurs de la famille Amt et les protéines RhThe mammalian Rh (Rhesus) proteins (RhCE, RhD, RhAG, RhBG and RhCG) belong to the Amt/Mep/Rh superfamily of ammonium transportera identified in bacteria, yeasts, plants and animals. Whereas RhCE, RhD and RhAG are erythroid specific, RhBG and RhCG are expressed in key organs associated with ammonium transport and metabolism particularly in kidney and liver. We have investigated the ammonium transport function of human RhBG and RhCG by comparing intracellular pH variation in wild type and transfected MDCK and HEK293 cells in the presence of an ammonium (NH₄⁺/NH₃) gradient. Stopped-flow spectrofluorimetry analysis, using a pH-sensitive probe, revealed, as compared with wild type cells, a low temperature-dependence of ammonium transport and a faster alkalinisation phase in RhBG and RhCG-transfected cells. Our results show that NH₃ movement across the plasma membrane is facilitated by RhBG and RhCG indicating that these proteins behave as NH₃ channels. Homology models based on crystallographic structures o the bacterial NH₃ channels Escherichia coli AmtB (EcAmtB) and Nitrosomonas europaea Rh5( (A/eRh50) confirms a channel structure for human Rh glycoproteins. Based on the 3D structure, we have highlighted critical residues involved in Rh channel activity and specific mechanistics of NH transport as compared to EcAmtB. This study reveals similarities and differences in ammonia transport mechanism through EcAmtB and human Rh proteins. These functional specificities might be related to the different physiological nitrogen roles in bacteria and mammals
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SECOUE, MARINETTE. "Epitaxie "par jets moleculaires sur gaas des composes du rhodium rh2 : :(a)s et rhga"." Rennes 1, 1987. http://www.theses.fr/1987REN10068.
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Deposition dans un bati d'epitaxie par jet moleculaire de rh::(2) as sur ga as. Rh::(2) as peut etre obtenu en couche mince, mais l'epitaxie n'est pas realisee selon les directions souhaitees et le compose n'est pas thermiquement stable jusqu'a 600c. Etude du diagramme ternaire rh-ga-asd afin de trouver un compose thermiquement stable. Le compose rh ga apparait stable jusqu'a 600c, il a donc ete depose sur ga as. L'accord de maille n'est cependant pas suffisamment bon pour permettre d'envisager une reepitaxie de bonne qualite du gaas sur rhga
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Biver, Sophie. "Invalidation des gènes codant pour les facteurs Rhésus Rhcg et Rhbg: analyse du phénotype des souris invalidées." Doctoral thesis, Universite Libre de Bruxelles, 2007. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210734.
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Les reins jouent un rôle majeur dans la régulation de l'homéostasie acide-base. La production et l'excrétion rénale d'ammonium assurent environ deux tiers de l'excrétion nette d'acides dans les conditions normales et jusqu'à 90% en situation d'acidose métabolique. Bien que l'excrétion d'ammonium soit un processus finement régulé et capital au maintien de l'équilibre acido-basique, à ce jour aucun transporteur spécifique d'ammonium n'a été décrit chez les mammifères. Les protéines Rhésus Rhcg et Rhbg, membres distants de la famille des transporteurs d'ammonium Mep/Amt, semblaient de bons candidats à cette fonction. L'invalidation du gène Rhcg puis celle de Rhbg ont donc été entreprises chez la souris afin d'estimer leur rôle potentiel dans le transport de l'ammonium.Doctorat en sciences, Spécialisation biologie moléculaire
info:eu-repo/semantics/nonPublished
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Vignal, Emmanuel. "Polymérisation de l'actine GTPases de la famille Rho : caractérisation et étude d'un effecteur de la Petite GTPase RhoG." Montpellier 2, 2001. http://www.theses.fr/2001MON20042.
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Gonçalves, Ana Rosária Oliveira. "Procedimentos de licenciamento de utilizações de água nas regiões hidrográficas do Sado e Mira (RH6) e do Guadiana (RH7)." Master's thesis, Universidade de Évora, 2012. http://hdl.handle.net/10174/18244.
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Actualmente a água é um valor patrimonial ecológico e social que satisfaz funções em detrimento do seu uso. Face a este modelo, é necessário efetuar uma gestão integrada de recursos naturais, onde a água desempenha um papel decisivo. O presente quadro legal e institucional português, assente na Directiva Quadro da Água, aponta claramente para uma visão de protecção e utilização sustentável das massas de águas subterrâneas e de superfície, quer sejam interiores, estuarinas ou costeiras. Nesta perspectiva, visando a melhoria contínua dos serviços prestados, apostando na modernização e simplificação administrativa para uma utilização eficiente e sustentável das águas, procede-se à organização metódica, coerente e integrada dos procedimentos de licenciamento no âmbito da utilização dos recursos hídricos para captação de águas existentes nas regiões hidrográficas do Sado e Mira (RH6) e do Guadiana (RH7), afectas à Administração da Região Hidrográfica do Alentejo, I.P. Esta estrutura de procedimentos sistematiza os trâmites associados aos procedimentos legais e técnicos, desde a formalização da instrução de pedido, à decisão e consequente emissão de título. Adoptando uma perspectiva de consistência na tramitação dos processos de licenciamento, pretende-se formalizar nesta metodologia, uma ferramenta, para utilizadores e técnicos superiores da administração pública, que possibilite maior celeridade e eficácia na apreciação processual, bem como minimizar constrangimentos ao desenvolvimento das actividades associadas e/ou dependentes de captações de água; ABSTRACT: Nowadays water is an ecological and social heritage with functions determined by its use. This model requires natural resources integrated management, where freshwater plays a decisive role. The portuguese present institutional and legislative framework, regulations that transpose the Water Framework Directive, lead to protection and sustainable use of inland surface waters, transitional waters, coastal waters and groundwater. Hence, in order to improve official services for a simpler and more modern administration, aiming efficient and sustainable use of water, this procedures establishes a coherent and methodical organization of water use permit procedures for Sado and Mira (RH6) and Guadiana (RH7) river basin districts, in the Administração de Região Hidrográfica do Alentejo, I.P. area. This methodology gathers water permit legal and technical procedures, from the request to permit issuance. This guide to both water users and permit writers will ensure consistency in procedures in order to create a faster and effective review instrument and minimize water abstraction dependent activities constraints.
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Hoover, Ashtyn. "The Role of Small GTPase RhoG in Focal Adhesion Dynamics and Contractility." University of Toledo / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1556712457014336.
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Rodrigues, Artemis Socorro do Nascimento. "Caracterização molecular dos antigenos RhD, (RhD fraco e RhD parcial) e sua aplicação na pratica transfusional." [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310418.
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Orientador: Lilian Maria de CastilhoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Considerando a imunogenicidade e importância clínica do antígeno RhD bem como o grande número de variantes RhD identificadas, estudos que possam esclarecer sua expressão e mecanismos moleculares envolvidos são importantes para a padronização de técnicas moleculares e sorológicas em diferentes populações. Assim foram nossos objetivos: padronizar técnicas moleculares para realização da genotipagem RHD fraco e determinar sua ocorrência na população brasileira; associar os tipos de RhD fracos encontrados com os haplótipos Rh presentes; e avaliar a aplicação da determinação do antígeno RhD na prática transfusional. Estudamos 503 amostras de DNA de doadores voluntários de sangue fenotipados como RhD ftaco. Destas amostras de DNA estudadas, 415 (82,5%) foram caracterizadas como RhD ftaco, 65 (12,9%) como RhD parcial, 15 (3%) apresentaram associações de RhD parcial e RhD ftaco e 8 (1,6%) foram RhD normal. I Os antígenos RhD fraco tipos 1, 3 e 4 foram os mais fteqüentes em nossa população. Como estes três tipos de RhD fraco não apresentam risco de aloimunização anti-D, pacientes assim classificadospodem ser transfundidos com sangue RhD-positivo. Nossos resultados demonstraram que 12,~A>das amostras fenotipadas como RhD fraco eram na verdade RhD parcial. Os antígenos RhD parciais encontrados em nosso estudo foram D~ DHMi e DVI. Quarenta (7,9%) amostras de DNA foram caracterizadas como D~ 16 (3,2%) como DHMi e 9 (1,8%) como DVI. A caracterização dos antígenos RhD parciais que reagem sorologicamente como RhD ftaco, tais como D DHMi e RhD categoria VI pode ser de grande auxilio na prevenção da aloimunização anti-D em pacientes politransfundidos e gestantes. A freqüência dos antígenos RhD parciais D~ DHMi e DVI encontrada em nossas amostras sugere um elevado risco de aloimunização ao antígeno RhD em pacientes fenotipados como RhD ftaco. - Das 503 amostras estudadas, 15 apresentaram mutações responsáveis pela expressão do antígeno RhD fraco e ao mesmo tempo mutações características de antígenos RhD parciais, ou seja, estas amostras possuíam os antígenos RhD fraco e RhD parcial associados. Estudamos quatro amostras de DNA de pacientes fenotipados como RhD :fraco que apresentavam anti-D. Nosso estudo demonstrou que a aloimunização anti-D nestes pacientes estava relacionada à presença de um antígeno RhD parcial e não a um antígeno RhD :fraco como diagnosticado sorologicamente. Duas amostras foram classificadascomo RhD parcial DAR, 1 como RhD parcial DHMi e 1 como DVI. Os resuhados demonstraram que os tipos de RhD fraco 1, 2, 3 e 4 que foram detectados à TA ou à 3'te e apresentaram grau de aglutinação superior a 1+ na AGH podem ser considerados como RhD positivo, pois não foram associados ao antígeno RhD parcial. Apesar deste trabalho ter sido o único que relacionou os tipos de RhD ftaco com o grau de aglutinação, a literatura revela que ainda não foi demonstrada aloimunização anti-D em pacientes portadores dos antígenos RhD fraco tipos 1,2 e 3. De acordo com os nossos resultados pode-se concluir que: 1. A transfusão com sangue RhD-positivo pode ser recomendada para todos os pacientes que apresentam os tipos do antígeno RhD :ftaco 1, 3 e 4 identificados por técnicas moleculares e para aqueles que apresentarem grau de aglutinação superior a 1+ na fenotipagem RhD. 2. A utilização de métodos de fenotipagem mais sensíveis em combinação com reagentes anti-D de alta afinidade é recomendada na detecção de antígenos RhD ftaco com baixa densidade antigênica em doadores de sangue; 3. Há necessidade da utilização de dois anti-soros monoc1onais (IgM e IgG) na determinação do antígeno RhD :ftacoem pacientes; 4. As genotipagens RHD, RHD ftaco e RHD parcial devem ser rea1i73dasquando os resuhados sorológicos não forem claros ou quando o paciente for politransfundido. 5. A biologia molecular associada à hemaglutinação pode aumentar consideravelmente a segurança transfusional pela mellior caracterização dos antígenos RhD em nossa população
Abstract: The purpose of this study was to characterize by molecular studies theRhD antigens (weak D and partial D) in Brazilian blood donors. DNA samples ftom 503 blood donors phenotyped as weak D were tested by two different sequence-specific primers (pCR-SSP) assays to determine the presence or absence of RHD gene (PCR-SSP intron 4 and exon 10) and to detect the common weak D types. Ofthe 503 weak D samples studied, 415 (82,5%) were identified as weak D, 65 (12,9%) as partial D, 15 (3%) showed association ofweak D and partial D and 8 (1,6%) were normal D. Weak D types 1, 3 and 4 contributed more than 85% of alI molecular weak D types. For these 3 types, D-positive transfusion can be considered safe because no immunization events have been documented yet. These findings show for the first time the frequency of weak D types in Brazilians. Molecular analysis showed that 12,9% of the weak D phenotype samples studied carried a partia! D alIele. The partial Ds found in our study were DAR, DVI and DHMi. Forty (7,9%) DNA samples were characterized as DAR, 16 (3,8%) as DHMi and 9 (1,8%) as DVI. The characterization of the partia! D antigens DAR, DHMi and DVI may avoid alIoimmunization in patients phenotyped as weak D. Fiffeteen patients showed mutations to weak D and partia! D showing that these samples had the weak D and partia! D antigens associated. We also studied 4 DNA samples of patients phenotyped as weak D who had developed anti-D. Our study showed that anti-D alIoimmunization in these patients was associated with the presence of partia! D antigens. Two samples were classified as partia!, D DAR, 1 as DHMi and 1 was DVI.AlI the weak D types identified in our study were associated with the intensity of agglutination obtained at room temperature (RT), 3'fC and AGH. The sensitivity of detecting weak D depends on the anti-D reagent and on the exact conditions of the methods. Our results showed that the weak D types 1, 2, 3 and 4 were frequently detected at RT and 3'fC and therefore could be considered as D-positive for transfusion. According to our results we could recommend the use ofmonoclonal anti-DIgM with high avidity to detect weak D antigen with low antigen density in blood donors and two monoclonals, one IgM and one IgG in combination with AGT to detect the weak D antigen in patients
Doutorado
Ciencias Basicas
Doutor em Clínica Médica
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Axelsson, Lena. "Karakterisering av blodgruppsgenen RHD hos patienter med svagt RhD-antigenuttryck." Thesis, Malmö högskola, Fakulteten för hälsa och samhälle (HS), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-24168.
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Rh-blodgruppssystemet är mycket komplext med 54 blodgruppsantigen som kodas av två nära varandra belägna gener på kromosom 1 – RHD och RHCE. RHD-genen kodar för RhD-proteinet, ett membranbundet protein på erytrocyter vars antigen utgör de kliniskt viktigaste och mest immunogena efter ABOsystemets, och som kan ge upphov till transfusionskomplikationer och hemolytisk sjukdom hos foster och nyfödda. Vissa individer har varianter av RhD-protein som uttrycks svagare än normalt (”svaga D”), eller där vissa epitoper saknas (”partiella D”), och för vilka serologiska metoder inte kan ge enhetliga resultat. Detta orsakar problem vid blodtransfusion, graviditet och bloddonation, och leder ofta till användning av det redan knappa lagret av RhD-negativa blodenheter för att skydda patienten. I detta projekt har åtta prover med svaga RhD-antigenuttryck sekvenserats med avseende på RHD-genen i syfte att fastställa individernas RhDfenotyp. I sex av proverna hittades sex nukleotidpolymorfismer och två deletioner, som alla är sällsynta men dock är kända sedan tidigare. I två prover kunde inga mutationer i exon eller intilliggande intron påvisas som förklaring till de svaga uttrycken av RhD hos dessa individer.The Rh blood group system is very complex with 54 blood group antigens encoded by two adjacent genes on chromosome 1 – RHD and RHCE. The RHD gene encodes the RhD protein, a membrane bound protein on erythrocytes whose antigens are the most clinically important and immunogenic after those of the ABO system, and which can result in transfusion complications and haemolytic disease of the fetus and newborn. Some individuals have variants of the RhD proteins that are expressed more weakly than normal (“weak D”), or have some of the epitopes missing (“partial D”), and for which serological methods cannot give a uniform result. This provides a problem in blood transfusion, pregnancy, and blood donation, and often results in the use of the already sparse supply of RhDnegative blood units for the safety of the patient. In this project, eight samples with weak RhD antigen expression have been sequenced with regard to the RHD gene in order to determine the RhD phenotype of the individuals. In six of the samples, six single nucleotide polymorphisms and two deletions were found, all of which are rare but are previously known. For two of the samples, no mutations in exons or adjacent introns could be detected to explain the weak expression of RhD in those individuals.
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Fauré, Julien. "Régulation des GTPases de la famille RHO par RHO-GDI." Université Joseph Fourier (Grenoble), 1999. http://www.theses.fr/1999GRE10006.
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Les membres de la famille RHO de GTPpases monomériques sont des interrupteurs moléculaires impliqués dans la transduction de nombreux signaux aboutissant notamment à la motilité cellulaire et à la transcription de gènes. Notre travail a porté sur le complexe formé entre la protéine G RHO et RHO-GDI, son régulateur naturel. Les deux protéines sont associées dans le cytosol mais il est nécessaire qu'elles soient séparées pour que RHO puisse exercer sa fonction. Nous nous sommes intéressés aux stimuli permettant d'activer leur protéine G à partir de son complexe avec RHO-GDI. Nous avons d'abord mis au point dans un système d'expression eucaryote la production de complexes formés in vivo entre les GTPases de la famille RHO et RHO-GDI. La purification de ces complexes a abouti à la production de cristaux et devrait permettre l'étude de leurs structures tridimensionnelles. Nous avons utilisé ces complexes pour étudier l'effet des phosphoïnositides sur l'état d'association de RHO avec RHO-GDI. Nous avons montré que ces lipides induisaient une conformation pré-activée du complexe, sans toutefois dissocier les deux partenaires. La méthode double-hybride nous a permis de cloner par interaction avec RHO-GDI l'ensemble des membres de la famille RHO ainsi que plusieurs régulateurs potentiels. Cette methode a ensuite servi à étudier les zones de RHO susceptibles d'interagir avec RHO-GDI grâce à la production de mutants de RHOA. L'interaction entre la GTPase RHO et RHO-GDI met en oeuvre un résidu isoprène lié à l'extrémité c-terminale de RHO. Les mutants de RHOA ne portant pas ce résidu sont cependant toujours capables d'interagir avec RHO-GDI, vraissemblablement grâce à la zone d'insertion de RHO. Enfin, une technique d'overlay a été utilisée pour mettre en évidence des partenaires membranaires du complexe RHO/RHO-GDI activé par les phosphoïnositides. Une protéine de 32kda, lâchement attachée à la membrane, a ainsi été isolée comme régulateur potentiel du complexe RHO/RHO-GDI.
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Carrot, Laurent. "Rayon [rhô]-numérique." Lyon 1, 2003. http://www.theses.fr/2003LYO10190.
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Dans un premier temps, on s'intéressera aux propriétés du rayon [rhô] -numérique dans les espaces de Hilbert, notion initialement introduite par Sz. -Nagy et Foias à l'aide de la [rhô]-dilatation unitaire. Puis, l'étude du shift tronqué sur l(2n) permettra d'évaluer la constante dans une inégalité de Von Neumann avec contraintes, donnée par Badea et Cassier. Ensuite, à l'aide d'une condition sur la croissance de la résolvante, nous étendrons cette notion aux espaces de Banach. L'usage de la résolvante pour les définir assurera des classes C(p)"solides", qui conserveront de nombreuses propriétés. De plus, elles permettront de passer continuement de la classe des contractions à celle des opérateurs de rayon spectral inférieur à 1. Ces classes seront donc très riches, et elles pourraient fournir une alternative à la notion de [rhô]-dilatation unitaire pour les espaces de Banach. Enfin, nous étudierons des classes particulières d'opérateurs, dont notamment les shifts à poids sur l(1) et les nilpotents.
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Bucic, Ida. "Pollard's rho method." Thesis, Linnéuniversitetet, Institutionen för matematik (MA), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-85886.
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In this work we are going to investigate a factorization method that was invented by John Pollard. It makes possible to factorize medium large integers into a product of prime numbers. We will run a C++ program and test how do different parameters affect the results. There will be a connection drawn between the Pollard's rho method, the Birthday paradox and the Floyd's cycle finding algorithm. In results we will find a polynomial function that has the best effectiveness and performance for Pollard's rho method.
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Grim, Rebekah. "Rig to flip." Thesis, University of Iowa, 2018. https://ir.uiowa.edu/etd/6430.
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This manuscript tells the story of seven years as a whitewater raft guide on Brown’s Canyon in Colorado, one of the most rafted sections of river in the country. The title is a rafting term that means prepare for the worst. I’m interested in the rush of moving water, raptors overhead, the hardened rhythms of lava, navigating a raft by reading currents, care for each other.
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Vanhoefer, Pit. "Study of B0->rho rho decays with the belle experiment." Diss., Ludwig-Maximilians-Universität München, 2015. http://nbn-resolving.de/urn:nbn:de:bvb:19-183537.
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Nguyen, Dinh Huu. "On [rho]-generic splitting varieties for Milnor K-symbols mod [rho]." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1905631291&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Tsipolitis, George. "[Omega omega] and [rho]+[rho-] production in two photon interactions at ARGUS." Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74351.
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The reactions $ gamma gamma$ $ to$ 2$ pi sp+2 pi sp-2 pi sp0$ and $ gamma gamma to pi sp+ pi sp- pi sp0 pi sp0$ have been studied by using the ARGUS detector at the $e sp+e sp-$ storage ring DORIS II at DESY.In the $2 pi sp+2 pi sp-2 pi sp0$ final state the production of $ omega$-mesons is observed and in particular the reaction $ gamma gamma$ $ to$ $ omega omega$ is seen for the first time. The cross section for $ gamma gamma to omega omega$ is found to have an enhancement at $ sim$1.9GeV/c$ sp2$ of about 12 nb. The topological cross sections for the reactions $ gamma gamma$ $ to$ 2$ pi sp+2 pi sp-2 pi sp0$ and $ gamma gamma$ $ to$ $ omega pi sp+ pi sp- pi sp0$ are also measured.
The production of charged $ rho$-mesons is observed in the $ pi sp+ pi sp- pi sp0 pi sp0$ final state. The cross section for the reaction $ gamma gamma$ $ to$ $ rho sp+ rho sp-$ is measured for the first time. The cross section did not show a threshold enhancement similar to that found in the reaction $ gamma gamma$ $ to$ $ rho sp0 rho sp0$ and is about a factor of four smaller. A spin parity analysis of the $ rho sp+ rho sp-$ system shows that the cross section is dominated by the two amplitudes $J sp{P}$ = 0$ sp+$ and $J sp{P}$ = 2$ sp+$ with helicity 2.
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Yeshaya, Joachim J. M. S. "Moses ben Abraham Dari︠: a Karaite poet and physician from twelfth-century Egypt selective edition of the Dĩwãn on the basis of manuscript Firkovicz Heb. I 802, with introduction and commentary /." [S.l. : s.n.], 2009. http://irs.ub/rug/nl/ppn/316.
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Rafat, Neysan. "The endothelium in sepsis: inflammatory response and progenitor cell involvement." Groningen : [Groningen : Rijksuniversiteit Groningen ; University Library Groningen] [Host], 2009. http://irs.ub/rug/nl/pp/316.
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Hakanen, Eva. "Återbrukets estetik - Uppländska trasryor : Förekomst, tillverkning, funktion och värde." Thesis, Uppsala universitet, Textilvetenskap, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-439775.
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Since the beginning of the early 20th century bed rugs have been interesting research objects, but only in passing researchers have paid attention to rugs woven with rags. Noone has taken a closer look upon the reasons why people have woven these rugs. What does the materials of the rag – like recycled garments and interior textiles in the form of clothing rags – have to tell about the times when these rugs were woven? Did the rag rugs have any specific function or were the materials available and therefore used? The main sources of information are 21 rag rugs from Roslagen in Uppland, with a varied amount of rags. They were woven during the latter half of 19th century, and estate inventories from Väddö- and Häverö Ship District have altogether given some answers to the primary question of this paper: in wich way can the examined bed rugs bear witness to the use and value of recycled textile materials and the view of these in the context of the community where they were manufactured and used? This research doesn´t give an answer to whether these rugs have any particular function or not. Instead these rag rugs can be looked upon as representing a general development of the society towards an increasing amount of textiles surplus material. This being due an increasing consumption of factory-made clothing and textiles, manufactured in factories, as well as the paper mills development from producing paper made of cellulose rather than textile waste. To this we can add a principle lingering on from the 19th century, of domestic production and a thrift of resources. This resulted in an obvious recycling of discarded textiles. The home weaving of interior textiles was still strong by the end of the 19th century, and in Rosagen there was also a long tradition of weaving and of using rugs in the beds. At the same time there was, in the coastal regions of Roslagen, a local need for warming covers in boats and boat houses. This demand was related to the shooting of seals and other hunting in the coastal areas, as well as in the fishing- and maritime trades.
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Tichy, Eva [Verfasser]. "Ilias diachronica Rho (17)." Freiburg : Universität, 2015. http://d-nb.info/1119327490/34.
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Ashcroft, Felicity Jayne. "The physiology of Reg." Thesis, University of Liverpool, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288281.
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Nuernberger, Kathryn L. "Rag and Bone: Poems." Ohio University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1312926732.
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Bennet, Scott Alan. "A jury-rig heritage." The Ohio State University, 1989. http://rave.ohiolink.edu/etdc/view?acc_num=osu1299778394.
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Kavarana, Farokh H. "Cracked shaft detection rig." Thesis, This resource online, 1994. http://scholar.lib.vt.edu/theses/available/etd-03142009-040531/.
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Verkoczy, Laurent Karl. "Regulation studies of the human recombination activating genes, RAG-1 and RAG-2." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1995. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ51544.pdf.
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Silver, Daniel P. (Daniel Peter). "Studies of the structure and function of the RAG-1 and RAG-2 genes." Thesis, Massachusetts Institute of Technology, 1992. http://hdl.handle.net/1721.1/12587.
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Blumenstein, Lars. "Rho-Effektor-Interaktion Struktur-Funktionsbeziehungen /." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=971971897.
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Mohammadi, Peyman. "DLE burner water rig simulations." Thesis, Mälardalen University, Department of Computer Science and Electronics, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-626.
Full textAbstract:
In today’s industrial world, there are high demands on the environmental aspects.
Siemens Industrial Turbomachinery AB (SIT AB) is a company that is keen about the environment, and therefore spends a lot of effort in developing combustion processes in order to reduce NOx (nitrogen oxides) emissions on their engine products. They are also researching in optional fuels, which are more environment-friendly.
In order to provide lower emissions the SIT designed a water rig to study the flow dynamics in a DLE (Dry Low Emission) burner.
An analyze program (GUI horizontal) was developed with new functions and the existing functions were improved. The program’s function was to evaluate different experimental tests of the flow dynamics in the 3rd generation DLE burners, of the SGT-800 gas turbine engine.
The aim was to ensure repeatability to enhance reliability, of the experimental test results for further comparison, for upcoming projects concerning future DLE burners.
When repeatability was achieved, implementations of different geometrical modifications were performed in the 3rd generation DLE burner.
The reason of the geometrical alterations was to look over if better fuel air mixture could be obtained and accordingly (thus) to reduce hotspots in the burner and in that case reduce NOx emissions.
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Amundsen, Siren Carstens. "Wet Gas Compression : Impeller Rig." Thesis, Norwegian University of Science and Technology, Department of Energy and Process Engineering, 2009. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-9976.
Full textAbstract:
Wet gas compression technology is of great value to the oil and gas industry for boosting of unprocessed well stream and to reduce investment costs related to equipment and personnel. The growing interest in wet gas compression leads to a general request for accurate performance calculation procedures and proper measurement techniques for multiphase flow metering in compressors. An impeller rig for examination of single-phase and multiphase performance and aerodynamic stability is under construction at the test facility at NTNU. The construction of the compressor rig is behind time due to late deliveries of the compressor components and instrumentation. The performance calculations are therefore based upon one compressor test conducted with dry gas at part-load. The thermodynamic equation of state for ambient air is verified to be consistent with the ideal gas law in the compressor pressure and temperature range. The calculated polytropic performance is calculated with ideal gas assumptions and compared to values estimated by PRO/II. By analyzing the results the sensitivity of the calculation procedures is identified and the suitability for the ideal polytropic performance calculations is validated for the actual compressor test and operating range. A sensitivity analysis is conducted in order to determine the effect of measurement uncertainties on performance calculations. Due to the low pressures involved for the compressor test, the performance calculation procedures are highly sensitive to uncertainties in the pressure measurements. Uncertainties in the temperature measurements will only slightly influence the polytropic head, but have great influence on the polytropic efficiency. The efficiency and operating range of a compressor are constrained by aerodynamic instabilities. This thesis describes the different flow phenomena associated with compressor instability and presents recommendations for suitable instrumentation and measuring techniques. Various visualization techniques are in addition evaluated to determine the suitability for multiphase compressors. Dynamic pressure transducers installed in the inlet and discharge piping are recommended for detection of pressure pulsation throughout the compressor system. Unsteady internal pressure measurements can be obtained from circumferentially distributed pressure transducers at various locations within the compressor components. Vibration probes installed at each end of the rotor are recommended for the vibration measurements. By analyzing the frequency spectrum for the pressure fluctuation and radial vibrations one can identify the type of instability phenomenon that occur. Laser measurement techniques are recommended for the flow visualization in order to obtain information on the main features of the multiphase flow field.
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McGrath, J. D. "Maximal-#rho#-extensions and irreducibility." Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235015.
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Schubert, Susanne, Sandra Heller, Birgit Löffler, Ingo Schäfer, Martina Seibel, Gaetano Villani, and Peter Seibel. "Generation of rho zero cells." Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-167888.
Full textAbstract:
Human mitochondrial DNA (mtDNA) is located in discrete DNA-protein
complexes, so called nucleoids. These structures can be easily visualized in living cells by utilizing the fluorescent stain PicoGreen®. In contrary, cells devoid of endogenous mitochondrial genomes (ρ0 cells) display no mitochondrial staining in the cytoplasm. A modified restriction enzyme can be targeted to mitochondria to cleave the mtDNA molecules in more than two fragments, thereby activating endogenous nucleases.
By applying this novel enzymatic approach to generate mtDNA-depleted cells the destruction of mitochondrial nucleoids in cultured cells could be detected in a time course. It is clear from these experiments that mtDNA-depleted cells can be seen as early as 48 h post-transfection using the depletion system. To prove that mtDNA is degraded during
this process, mtDNA of transfected cells was quantified by real-time PCR. A significant decline could be observed 24 h post-transfection. Combination of both results showed that mtDNA of transfected cells is completely degraded and, therefore, ρ0 cells were generated within 48 h. Thus, the application of a mitochondrially-targeted restriction endonuclease proves to be a first and fast, but essential step towards a therapy for mtDNA disorders.
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Abbas, Leila. "Rho GTPases and zebrafish development." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249330.
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Cocks, Stuart Peter. "Rho prime electroproduction at HERA." Thesis, University of Liverpool, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366427.
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