Дисертації: "Rfc1"

1

Breitenbücher, Frank. "Allgemeine und funktionelle Untersuchungen zur grossen Untereinheit des humanen Replikationsfaktors C (RFC1), sowie initiale Untersuchungen zur Regulation der Expression von RFC1 durch das BCR-ABLp210-Onkogen." [S.l.] : [s.n.], 2005. http://archiv.ub.uni-marburg.de/diss/z2005/0114/.

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2

Hinken, Matthias. "Gewebeverteilung und Lokalisation des Transportproteins für reduzierte Folate (RFC1) der Ratte." Doctoral thesis, Universitätsbibliothek Leipzig, 2007. http://nbn-resolving.de/urn:nbn:de:bsz:15-20071107-143055-8.

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Der Folsäureantagonist Methotrexat (MTX) wird zur Behandlung onkologischer und rheumatoider Erkrankungen eingesetzt. Die Aufnahme des Methotrexats in die Zielzelle ist dabei Vorraussetzung für die Bindung an seine intrazellulären Zielstrukturen und erfolgt über verschiedene Transportsysteme. In diesem Zusammenhang ist bei entsprechenden Plasma-konzentrationen von MTX der Reduced Folate Carrier (RFC1) von besonderer Bedeutung. 1994 konnte erstmals die cDNA dieses Transporters aus Maus- und Hamstergewebe isoliert werden. Die cDNA für einen mit dem RFC1 identischen hepatozellulären MTX-Transporter der Ratte wurde 2000 kloniert. Vorhergehende Gen-Expressionsstudien zeigten, dass die RFC1-mRNA ubiquitär gebildet wird. Die Proteinexpression wurde jedoch bisher nur in ausgewählten Geweben der Maus untersucht. Systematische Arbeiten, in denen in vergleichender Weise sowohl die RFC1 Gen- als auch die Proteinexpression in allen Geweben mit einer möglichen Relevanz für die Folat- und Antifolataufnahme, Speicherung und Eliminierung untersucht werden, fehlten bisher. Insbesondere die Expression des RFC1-Proteins der Ratte (rRFC1) mittels immunologischer Verfahren ist bisher nicht beschrieben worden. Ziel dieser Arbeit war es daher, die Gen- und Proteinexpression des rRFC1 in ausgewählten Geweben der Ratte darzustellen. Dieses schließt die Generierung spezifischer Antiseren gegen den rRFC1 als ersten Schritt mit ein. Es wurden geeignete antigene Aminosäuresequenzen des rRFC1 bestimmt und die entsprechenden cDNA Sequenzen wurden amplifiziert und in einen geeigneten Expressionsvektor kloniert. Rekombinante rRFC1 Fusionsproteine konnten mittels E. coli Zellen hergestellt und anschließend aufgereinigt werden. Nachfolgend wurden entweder die rRFC1 Fusionsproteine oder die rRFC1 spezifischen Peptide, welche von dem Affinitätspeptid separiert worden waren, für die Immunisierung von Kaninchen verwendet Drei Antiseren mit ausreichender Reaktivität und Spezifität konnten gewonnen und mittels Affinitätschromatographie aufgereinigt werden. Die erhaltenen Antiseren sind gegen die intrazellulären N- und C-terminalen Regionen (ID1, ID7) bzw. gegen die erste extrazelluläre Schleife (OD1) gerichtet. In Western-Blot Studien konnte mittels dieser Antiseren für den rRFC1, der in transfizierten Nierenepithelzellen (MDCK-rRFC-HA) stabil exprimiert wurde, ein Molekulargewicht von 71 kD für die glykosylierte Form und von 53 kD für die unglykosylierte Form ermittelt werden. Weiter konnte belegt werden, dass das Protein in MDCK-rRFC1-HA Zellen überwiegend in der glycosylierten Form vorliegt. Mittels RT-PCR Analysen wurde die Genexpression des rRFC1 in allen untersuchten Geweben nachgewiesen. Besonders hohe mRNA-Gehalte waren in Thymus, Niere und Milz vorhanden, während in Herz- und Muskelgewebe sowie in Leukozyten nur ein Signal nahe der Nachweisgrenze detektierbar war. Durch immunhistologische Untersuchungen konnten die rRFC1 Proteinexpression und beträchtliche Unterschiede in der Signalintensität bestätigt werden. Zusätzlich konnten neue Informationen über die unterschiedliche subzelluläre Lokalisation gewonnen werden: so konnte eine starke Expression des Transporters in der apikalen Membran von Dünn- und Dickdarmmukosa dargestellt werden, während die ebenfalls starke Färbung in der Niere auf den Bereich der basolateralen Membran der Tubuli beschränkt war. In der Leber war eine Expression mittlerer Intensität im Bereich der Lebertrias erkennbar. Während in der Milz nur in der roten Pulpa das RFC1-Protein detektiert wurde, konnten im Thymus sowohl in der Rinde als auch im Mark positive Zellen nachgewiesen werden. Im Hoden konnte der Transporter in den Sertoli-Zellen dargestellt werden. Eine starke Expression des Transporters wurde im Gehirn im Bereich der apikalen Membran der Ependymzellen des Plexus choroideus nachgewiesen. In der Skelettmuskulatur und im Herzgewebe beschränkte sich die Expression des rRFC1 auf das Perimysium des Muskelgewebes und auf kleinere Gefäße des Muskel- und Herzgewebes. In dieser Arbeit konnte somit gezeigt werden, dass der RFC1 der Ratte ubiquitär exprimiert wird, wobei die Expressionsstärke jedoch stark variiert. Die beobachtete Gewebslokalisation des RFC1 belegt sowohl dessen zentrale Rolle in der Folathomöostase als auch in der MTX vermittelten Organtoxizität und Pharmakokinetik, insbesondere bei der intestinalen Resorption sowie der hepatischen und renalen Exkretion.

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3

Chazelas, Pauline. "Syndrome de CANVAS – Analyse moléculaire des répétitions pentanucléotidiques du gène RFC1 et étude de leurs conséquences physiopathologiques." Electronic Thesis or Diss., Limoges, 2024. http://www.theses.fr/2024LIMO0006.

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Le syndrome de CANVAS définie un ensemble d’entités cliniques que sont l’ataxie cérébelleuse, la neuronopathie sensitive et l’aréflexie vestibulaire, responsable conjointement ou individuellement de différents symptômes dont le plus majoritaire est un trouble de l’équilibre. De façon intéressante, il est maintenant établi que la majorité des patients présentent, des dizaines d’années avant les troubles neurologiques, une toux chronique réfractaire. En 2019, la cause génétique de ce syndrome a été décrite. Elle intéresse le gène RFC1 au sein duquel une expansion biallélique de répétitions du pentanucléotide AAGGG situé dans l’intron 2 du gène a pu être mise en cause chez les patients cliniquement atteint. Ce motif AAGGG de grande taille remplace la conformation AAAAG classiquement répétée 11 fois en population générale. La cause physiopathologique responsable de cette maladie n’est pas encore connue. Plusieurs études ont montré une variabilité de la zone répétée qu’elles soient en termes de conformations du motif qu’en termes de nombre de répétitions. Leurs implications dans la pathologie ne sont pas toujours évidentes.Dans ce travail, nous nous sommes intéressés à trois axes concernant ce syndrome : (a) décrire la variabilité de la zone répétée dans une cohorte de témoins et dans une cohorte de patients adressée pour neuropathie, (b) étudier histologiquement l’atteinte nerveuse périphérique en particulier celle des petites fibres nerveuses, non décrites antérieurement, (c) étudier la prévalence de l’expansion biallélique du pentanucléotide AAGGG dans une cohorte de patients tousseurs chroniques réfractaires.Nos résultats ont permis de mettre en évidence de nouveaux motifs répétés complexes à la fois chez des témoins mais aussi chez des patients avec neuropathie. L’atteinte des petites fibres nerveuses dans le CANVAS a pu être objectivée pour la première fois. Notre étude de cohorte de 68 patients tousseurs chroniques réfractaires a permis de mettre en évidence 16% des patients porteurs d’une expansion biallélique AAGGG pathogène et nous conduit à suggérer que la toux des patients CANVAS serait une toux neurogène.L’ensemble de ces résultats de thèse a permis une avancée dans les connaissances moléculaires et physiopathologiques du syndrome de CANVAS. Des travaux complémentaires permettront de comprendre les mécanismes physiopathologiques sous-jacents afin d’envisager in fine d’éventuelles thérapeutiques personnalisées The CANVAS syndrome defines a group of clinical entities - cerebellar ataxia, sensory neuronopathy and vestibular areflexia - that together or separately are responsible for a variety of symptoms, the most common of which is a disturbance of balance. Interestingly, it has now been shown that the majority of patients present with a chronic refractory cough decades before the onset of neurological disorders. In 2019, the genetic cause of this syndrome was described. It involves the RFC1 gene, in which a biallelic expansion of AAGGG pentanucleotide repeats in intron 2 of the gene has been implicated in clinically affected patients. This large AAGGG motif replaces the AAAAG conformation, which is classically repeated 11 times in the general population. The pathophysiological cause of the disease is still unknown. Several studies have shown variability in the repeat zone, both in terms of motif conformation and number of repeats. The implications for pathology are not always clear.In this study, we focused on three aspects of this syndrome: (a) description of the variability of the repeated zone in a cohort of controls and in a cohort of patients referred for neuropathy, (b) histological study of peripheral nerve damage, particularly that of small nerve fibers, which has not been previously described, (c) study of the prevalence of biallelic expansion of the pentanucleotide AAGGG in a cohort of refractory chronic cough patients.Our results revealed novel complex repeats in both controls and patients with neuropathy. The involvement of small nerve fibers in CANVAS was objectified for the first time. Our cohort study of 68 patients with refractory chronic cough identified 16% of patients with a pathogenic AAGGG biallelic expansion, leading us to suggest that the cough of CANVAS patients is neurogenic.Taken together, the results of this thesis represent a breakthrough in the molecular and pathophysiological knowledge of CANVAS syndrome. Further work is required to understand the underlying pathophysiological mechanisms with a view to developing personalized therapies

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4

Halwachs, Sandra. "Regulation des Reduced Folate Carrier (RFC1) in HPCT-1E3-Ratten-Hepatocytoma-Zellen durch Cytochrom P450-Induktoren vom Phenobarbital-Typ." Doctoral thesis, Universitätsbibliothek Leipzig, 2006. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-34397.

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The sodium dependent reduced folate carrier (Rfc1; Slc19a1) provides the major route for cellular uptake of antifolate chemotherapeutic drugs such as methotrexate (MTX) and reduced folates into liver, kidneys and other tissues. Despite its essential role in cancer treatment and for the body’s folate homeostasis, little is known about Rfc1 regulation. In rat hepatocytes, the 5´ untranslated region of this carrier exhibits, amongst other regulatory elements, a barbiturate recognition box which as yet has only been found in the promotor region of xenobiotic metabolizing enzymes, particularly those of the CYP450 enzyme family. We have therefore investigated the issue of Rfc1 regulation by phenobarbital (PB)-type CYP450 inducers on the functional, transcriptional and translational level using an adequate in vitro model for rat liver. A significant decrease in Rfc1 activity was observed following treatment (48 h) with 1-10 times therapeutic plasma concentrations of PB-type CYP450 inducers like PB, carbamazepine, chlorpromazine, clotrimazole and with the constitutive androstane receptor agonist TCPOBOP. This was not associated with reduced mRNA and protein levels. Further mechanistic investigations revealed that short-term treatment (2 h) of cells with protein phosphatase 2A inhibitor okadaic acid and proteinkinase C inductor PMA was related to a significant reduction of Rfc1 mediated MTX uptake. Finally, the reduction in Rfc1 activity caused by PB, TCPOBOP and PMA was almost completely reversed by simultaneous incubation with the specific PKC inhibitor bisindolylmaleimide. These results demonstrate, that clinical relevant concentrations of PB-type CYP450 inducers cause a significant PKC-dependent reduction in Rfc1 uptake activity on the posttranscriptional level.

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5

Lopes, Tairine Zara. "Avaliação de polimorfismos nos genes MTHFR, MTR, RFC1 e CßS envolvidos no metabolismo do folato em pacientes com câncer de tireoide." Faculdade de Medicina de São José do Rio Preto, 2015. http://hdl.handle.net/tede/272.

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Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2016-06-21T19:17:07Z No. of bitstreams: 1 tairinezaralopes_dissert.pdf: 1511634 bytes, checksum: 2203122e0b39cf1687115059c3e19447 (MD5) Made available in DSpace on 2016-06-21T19:17:07Z (GMT). No. of bitstreams: 1 tairinezaralopes_dissert.pdf: 1511634 bytes, checksum: 2203122e0b39cf1687115059c3e19447 (MD5) Previous issue date: 2015-10-29 Introduction: Thyroid cancer is the most common malignancy of the endocrine system and has been presenting continuous increase in the last years. Studies suggest that folate deficiency in the body decrease DNA repair, resulting in malignant cells changes that alter expression of genes, and may induce several kinds of cancer development. Polymorphisms in genes involved in folate pathway have been investigated as risk factors for susceptibility to cancer, among them MTHFR, MTR, RFC1 and CßS. Objectives: To investigate association of polymorphisms in the MTHFR (C677T), MTR (A2756G), RFC1 (A80G) and CßS (844ins68) genes in risk thyroid cancer in a case-control study; to evaluate the association of polymorphisms with gender, age, alcohol and tobacco consumption, body-mass index in thyroid cancer development; and to evaluated the association between polymorphisms and clinical-histopathological parameters. Methods: This study included 462 individuals (151 patients with thyroid cancer and 311 controls). The peripheral blood was collected and genomic DNA was extracted. The MTHFR (C677T), MTR (A2756G) and RFC1 (A80G) were evaluated by PCR-RFLP and CßS (844ins68) by conventional PCR without enzymatic digestion. For statistical analysis chi-square and multiple logistic regression were used. Results: The results showed that MTHFR C677T (OR=2.87, 95% CI=1.50-5.48, p< 0.01, codominant model), (OR=1.76, 95% CI=1.18-2.64, p< 0.01, dominant model), (OR=2.37, 95% CI=1.28-4.39, p< 0.01, recessive model) and RFC1 A80G (OR: 1.55; 95% CI: 1.02-2.38; p=0.04, recessive model) were associated with thyroid cancer. The alcohol (OR=1.56, 95% CI=1.36-1.89, p< 0.01) and tobacco consumption (OR=1.97, 95% CI=1.28-3.04, p< 0.01) were statistically significant, being associated with increased risk. The MTR A2756G is associated with tumor extension (OR=2.69, 95% CI=1.27-5.71, p< 0.01) and aggressiveness (OR= 4.51, 95% CI=1.67-12.1, p< 0.01). Conclusions: The MTHFR (C677T) and RFC1 (A80G) polymorphisms were involved in risk for thyroid cancer. Additionally, alcohol and tobacco consumption increase risk for disease development. Introdução: O câncer de tireoide é a neoplasia maligna mais comum do sistema endócrino e vem apresentando contínuo aumento nos últimos anos. Estudos sugerem que a deficiência de folato no organismo diminui a reparação do DNA, resultando em alterações celulares malignas que modulam a expressão gênica, podendo levar ao desenvolvimento de vários tipos de câncer. Polimorfismos em genes envolvidos na via do folato têm sido investigados como fatores de risco para suscetibilidade ao câncer, entre eles, polimorfismos nos genes MTHFR, MTR, RFC1 e CßS. Objetivos: Investigar a associação dos polimorfismos nos genes MTHFR (C677T), MTR (A2756G), RFC1 (A80G) e CßS (844ins68) no risco de câncer de tireoide em um estudo caso-controle; Avaliar a associação dos polimorfismos com o gênero, idade, consumo de álcool e tabaco, índice de massa corpórea (IMC) no desenvolvimento do câncer de tireoide; Avaliar a associação entre os polimorfismos e os parâmetros clínico-histopatológicos do câncer de tireoide. Casuística e Método: Este estudo incluiu 462 indivíduos (151 pacientes com câncer de tireoide e 311 indivíduos controles). Foi coletado sangue periférico e extraído o DNA genômico. Os polimorfismos MTHFR (C677T), MTR (A2756G) e RFC1 (A80G) foram avaliados por meio da PCR-RFLP e o polimorfismo CßS (844ins68) foi analisado por PCR convencional sem corte enzimático. Para análise estatística utilizou-se o teste do qui-quadrado e regressão logística múltipla. Resultados: Os resultados mostraram que os polimorfismos MTHFR C677T (OR=2.87, 95% IC=1.50-5.48, p< 0.01, modelo codominante), (OR=1.76, 95% IC=1.18-2.64, p< 0.01, modelo dominante), (OR=2.37, 95% IC=1.28-4.39, p< 0.01, modelo recessivo) e RFC1 A80G (OR: 1.55; 95% IC: 1.02-2.38; p=0.04, modelo recessivo) estão associados ao câncer de tireoide. O consumo de álcool (OR=1.56, 95% IC=1.36-1.89, p< 0.01) e tabaco (OR=1.97, 95% IC=1.28-3.04, p< 0.01) foram estatisticamente significantes, sendo associados ao aumento do risco. O polimorfismo MTR A2756G está associado à extensão do tumor (OR=2.69, 95% IC=1.27-5.71, p< 0.01) e à agressividade (OR= 4.51, 95% IC=1.67-12.1, p< 0.01). Conclusões: Os polimorfismos MTHFR (C677T) e RFC1 (A80G) estão envolvidos no risco de câncer de tireoide. Adicionalmente, o consumo de álcool e tabaco aumenta o risco de desenvolvimento da doença.

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Tomida, Junya. "DNA damage induced ubiquitylation of RFC2 subunit of RFC complex." Kyoto University, 2008. http://hdl.handle.net/2433/135870.

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7

Ng, Chin Chin. "Performance analysis of the mobile IP protocol (RFC 3344 and related RFCS)." Thesis, Monterey, Calif. : Naval Postgraduate School, 2006. http://bosun.nps.edu/uhtbin/hyperion.exe/06Dec%5FNg%5FChin.pdf.

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Thesis (M.S. in Computer Science)--Naval Postgraduate School, December 2006. Thesis Advisor(s): George W. Dinolt, J. D. Fulp. "December 2006." Includes bibliographical references (p. 121-125). Also available in print.

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Hakim, Chantal DDS MSD, Marie M. MD PhD DrSc Tolarová, and Miroslav MD PhD Tolar. "Association of Type and Severity of Nonsyndromic Orofacial Clefts with Combined Genotypes of RFC1 80 GA, MTHFR 677 CT, IRF6 (rs642961) and IRF6 (rs2235371) Gene Polymorphisms in an Indian Population." Scholarly Commons, 2020. https://scholarlycommons.pacific.edu/dugoni_etd/2.

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Association of type and severity of nonsyndromic OROFACIAL CLEFTS with combined genotypes of RFC1 80 GA, MTHFR 677 CT, IRF6 rs642961 and rs2235371 gene polymorphisms in an Indian population Abstract By Chantal Hakim University of the Pacific. Arthur Dugoni School of Dentistry 2020 Introduction. Genetic etiology of nonsyndromic orofacial clefts comprises many genes acting together. However, little is known about their interactions. The purpose of our study was to analyze associations of phenotypic subtypes of nonsyndromic orofacial clefts with combinations of four genotypes involving candidate gene polymorphisms. Materials and Methods. We analyzed a large dataset of cases and controls collected in one location (Karaikal in India) and genotyped for four gene polymorphisms: RFC1 G80A, MTHFR C677T, IRF6 GA rs642961 and IRF6 CT rs2235371 (IRB approval Nr. 17-118 for existing data). The samples were tested for Hardy-Weinberg genetic equilibrium. Combinations of genotypes in cleft subsamples were compared with controls using Odds Ratio and Confidence Interval (95% significance level) calculations. Results. The Hardy-Weinberg equilibrium test showed that all samples were in genetic equilibrium. Some combinations of RFC1 G80A, MTHFR C677T, IRF6 GA rs642961 and IRF6 CT rs2235371 yielded increased or decreased Odds Ratio (OR>1 or OR<1).This means that subtypes of orofacial clefts were differentially determined by genotype combinations of four gene polymorphisms. Conclusions. Our results suggest that combinations of gene polymorphisms may modulate genetic risk in subtypes of nonsyndromic orofacial clefts. Such studies seem to be important for development of a general procedure and how a prevention plan for a specific location needs to be prepared, which data needs to be collected and which analyses need to be performed.

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Giusti, Kelma Cordeiro da Silva. "Associação entre polimorfismos em genes relacionados ao metabolismo de folato (RFC1, GCP2, MTHFR e MTHFD1) e alterações nas concentrações de folato, cobalamina e homocisteína em mulheres com história de abortos espontâneos recorrentes." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-08032013-115754/.

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O aborto espontâneo recorrente (AER) é caracterizado pela ocorrência de três ou mais abortos consecutivos e acomete 2-4% das mulheres em idade fértil. A etiologia está associada a vários fatores de risco, tais como anomalias uterinas, aberrações cromossômicas, autoimunidade, trombofilias, elevação na concentração de homocisteína (tHcy), porém cerca de 40% dos casos permanece sem causa definida. O metabolismo de unidades de carbono desempenha papel fundamental na disponibilidade de folato na célula, sendo essencial para o desenvolvimento placentário e fetal. Deficiência de vitaminas que regulam este metabolismo, como o ácido fólico, e polimorfismos em genes que codificam enzimas relacionadas ao metabolismo de folato (MTHFR, RFC1, GCP2 e MTHFD1) podem levar à redução das concentrações desta vitamina e ao aumento das concentrações de tHcy. Objetivo foi avaliar a associação entre polimorfismos em genes relacionados ao metabolismo do folato (RFC1, GCP2, MTHFR e MTHFD1) e o risco de se ter AER, bem como avaliar a associação entre estes polimorfismos e as alterações nas concetranções de folato, cobalamina e homocisteína. Foram constituídos três grupos: AER primário: 117 mulheres com AER e nenhum feto viável; AER secundário: 139 mulheres com AER e pelo menos um feto viável; e Controle: 264 mulheres sem história de aborto espontâneo. Nenhuma das mulheres estava grávida no momento da coleta do sangue. Amostras de sangue foram obtidas para dosagens bioquímicas (folato, Cbl, tHcy, entre outras), imunológicas e extração de DNA genômico. As genotipagens foram feitas por PCR-RFLP ou PCR em tempo real. As concentrações séricas de folato e Cbl foram maiores no AER primário e secundário (p<0,05). A distribuição dos genótipos de todos os polimorfismos foi semelhante nos três grupos. O aumento nas concentrações de folato sérico (OR: 1,05, 95% IC: 1,03 - 1,07, p<0,001), Cbl (OR: 1,00, 95% IC: 1,00 - 1,00, p= 0,016), tHcy (OR: 1,03, 95% IC: 0,97 - 1,11, p= 0,033) e T4 (OR: 1,02, 95% IC: 1,00 - 1,03, p= 0,006) e a presença de FAN reagente (1:160) (OR: 2,90, 95% IC: 1,25 - 6,75, p= 0,013) foram considerados fatores de risco para aborto primário. Para o aborto secundário, foram considerados fatores de risco o aumento nas concentrações de folato sérico (OR: 1,04, 95% IC: 1,02 - 1,05, p<0,001), Cbl (OR: 1,00, 95% IC: 1,00 - 1,00, p= 0,019) e tHcy (OR: 1,05, 95% IC: 1,00 - 1,09, p= 0,039), maiores idades (OR: 1,02, 95% IC: 0,98 - 1,06, p= 0,031), hábito de fumar (OR: 2,54, 95% IC: 1,41 - 4,60, p= 0,002) e ter maior IMC (OR:1,42, 95% IC: 1,07 - 1,88, p= 0,015). Os polimorfismos estudados não foram associados ao maior risco de se ter AER, quando analisados isoladamente, e também não foram associados a alterações nas concentrações séricas de folato, Cbl e tHcy, com exceção do genótipo MTHFR 677TT, cujas portadoras apresentaram maior concentração de tHcy, quando comparadas com as portadoras de genótipos 677CC e 677CT nos três grupos. As variáveis concentrações de folato, Cbl, tHcy e T4 e presença de FAN reagente foram associadas ao maior risco de se ter aborto primário. As variáveis idade, IMC, tabagismo, concentrações de folato, Cbl e tHcy foram associadas ao maior risco de aborto secundário. The recurrent spontaneous abortion (RSA) is characterized by the occurrence of three or more consecutive miscarriages and affects 2-4% of women of childbearing age. The etiology is associated with several risk factors such as uterine abnormalities, chromosomal aberrations, autoimmunity, thrombophilia, increased concentration of homocysteine (tHcy). About 40% of cases remains unknown cause. The units of carbon metabolism plays an essential role in the availability of the cell folate, is essential for the placental and fetal development. A deficiency of the vitamins that regulate this metabolism, like folic acid, and polymorphisms in genes encoding enzymes related to folate metabolism (MTHFR, RFC1, and GCP2 MTHFD1) may lead to decreased concentrations of this vitamin and increased concentrations of tHcy. Objective was to evaluate the association between polymorphisms in genes related to folate metabolism (RFC1, GCP2, MTHFD1 and MTHFR) and the risk of having AER, and to evaluate the association between these polymorphisms and changes in concetranções folate, cobalamin, and homocysteine. Three groups were divided: AER primary: 117 women with RSA and no viable fetus, AER secondary: 139 women with RSA and at least one viable fetus and Control: 264 women with no history of miscarriage. None of the women was pregnant at time of blood collection. Blood samples were taken for biochemical (folate, Cbl, tHcy, etc.), immunological and genomic DNA extraction. The genotyping were carried out by PCR-RFLP or real time PCR. Serum concentrations of folate and Cbl were higher in groups 1 and 2 (p <0.05). The distribution of genotypes of MTHFR c.677C> T, MTHFR c.1298A> C, MTHFD1 c.1958G> A, RFC1 c.80G>GCP2 A and c.1561C> T was similar among the three groups. The increased concentrations of serum folate (OR: 1.05, 95% CI: 1.03 - 1.07, p <0.001), Cbl (OR: 1.00, 95% CI: 1.00 to 1.00, p = 0.016), tHcy (OR: 1.03, 95% CI: 0.97 to 1.11, p = 0.033) and T4 (OR: 1.02, 95% CI: 1.00 to 1.03, p = 0.006) and the presence of ANA (1:160) (OR: 2.90, 95% CI: 1.25 - 6.75, p = 0.013) were considered risk factors primary for abortion. For secondary abortion, were considered risk factors increased the concentrations of serum folate (OR: 1.04, 95% CI: 1.02 - 1.05, p <0.001), cobalamin (OR: 1.00, 95 % CI: 1.00 to 1.00, p = 0.019) and tHcy (OR: 1.05, 95% CI: 1.00 to 1.09, p = 0.039), higher age (OR: 1.02, 95% CI: 0.98 to 1.06, p = 0.031), cigarette smoking (OR: 2.54, 95% CI: 1.41 to 4.60, p = 0.002) and had a higher BMI (OR : 1,42,95% CI: 1.07 to 1.88, p = 0.015). The studied polymorphisms were not associated with increased risk of having RSA when analyzed separately, and were not associated with changes in serum folate, Cbl and tHcy, with the exception of the MTHFR 677TT genotype, whose patients had a higher concentration of total tHcy compared with those with 677CC and 677CT genotypes in the three groups. The variable concentrations of folate, Cbl, tHcy, and T4, presence of ANA and have been associated with increased risk for miscarriage primary. The variables age, BMI, smoking, concentrations of folate, Cbl and tHcy were associated with increased risk of secondary miscarriage.

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10

Alata, Jimenez Nagif. "La deficiencia en los transportadores de folato (FOLR1 y RFC1) causa cambios epigenéticos que afectan el desarrollo neural y de las células de la cresta neural en embriones de pollo Gallus gallus." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2019. https://hdl.handle.net/20.500.12672/10342.

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El desarrollo neural ocurre mediante el proceso de neurulación originando el sistema nervioso central y la médula espinal. Durante este proceso las células de la cresta neural (CCN) son especificadas en la región más dorsal del tubo neural; posteriormente, las CCN delaminan del epitelio neural, migran a diferentes regiones del embrión y se diferencian en diversos tipos celulares. Defectos en el desarrollo del tubo neural y de las CCN generan desórdenes congénitos como espina bífida, encefalocelia, y neurocristopatías (paladar-labio hendido, albinismo, entre otras). Una vitamina importante durante el desarrollo embrionario temprano es el folato, el cual se encuentra en el sistema circulatorio en forma de 5-metiltetrahidrofolato (5-MTHF) e ingresa a la célula por medio del receptor de membrana FOLR1 y el transportador RFC1. El 5-MTHF participa en la síntesis de nucleótidos y en la generación de Sadenosilmetionina (SAM) para la metilación de ácidos nucleicos y proteínas. La metilación de ácidos nucleicos y proteínas son importantes mecanismos de regulación epigenética durante el normal desarrollo embrionario de los vertebrados. Considerando lo dicho se plantea determinar el efecto epigenético de la deficiencia del folato en el desarrollo del tubo neural y de las CCN. Para esto realizamos la pérdida de función del receptor FOLR1 y transportador RFC1 mediante el uso de los morfolinos FolR1spMO y RFC1spMO en embriones de pollo. Posteriormente se evalúan los niveles de 5mC en el ADN y 6mA en el ARN mediante dot blots, observando una clara disminución en ambas marcas epigenéticas. El análisis de expresión del marcador de CCN Sox10 en embriones inyectados evidenció una disminución en el número de CCN. Adicionalmente, el marcador neural Sox2 presentó una expresión ectópica en el territorio de las CCN. Estos resultados muestran que la deficiencia de folato afecta la metilación global del ADN y ARN generando un cambio en el destino celular de los progenitores de las CCN hacia un destino neural. Los resultados obtenidos pueden sentar las bases para un mejor entendimiento y desarrollo de tratamientos capaces de prevenir o disminuir las anomalías ocasionadas por la deficiencia de folato en mujeres embarazadas. Tesis

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11

Kim, Jiyoung. "Functional analysis of RFC and RFC-like complexes in fission yeast." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/12375.

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RFC plays an essential role in DNA replication by loading the sliding clamp PCNA onto DNA in order to tether DNA polymerase δ to DNA. RFC consists of five subunits, one large subunit and four small subunits. The large subunit of RFC contains an extended C-terminal domain that is not present in the small subunits and whose function remains unknown. In addition to RFC, eukaryotic cells contain two more putative PCNA loaders known as RLCs. These other PCNA loaders have similar structures to RFC and contains the RFC small subunits, however the large subunit is replaced with a different protein, either Elg1 or Ctf18. The function of the three PCNA loaders is not clear. In this work the function of the Rfcl C-terminal domain (CTD) was examined. The analysis of an Rfcl CTD deletion mutant showed that the domain is essential for cell viability. rfcl-44, a temperature-sensitive mutant with a mutation in the C-terminal domain, displayed sensitivity to DNA damaging agents, abnormal chromosome structure and a synthetic lethal phenotype when combined with DNA replication mutants. rfc5 mutants were isolated as suppressors of rfcl-44 suggesting that the defect in rfcl-44 may be in the Rfcl-Rfc5 interaction. Ctf18, Dccl and Ctf8, components of Ctf18-RLC, were required for the viability of rfc1-44 whilst Elg1 was not. Deletion of Elg1 restored the viability of rfc1-44 ctf18Δ double mutant cells, suggesting that Elg1 plays a negative role. The negative role of Elg1 was confirmed by over-expression of Elg1 in rfc1-44 cells showing a lethal phenotype at permissive temperature. These results suggest that RFC plays a key role in DNA replication and that Elg1-RLC and Ctf18-RLC can play negative and positive roles respectively when RFC function is impaired.

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12

Silva, Alan Castro. "Implementação inicial da RFC 6897." Universidade Federal de São Carlos, 2016. https://repositorio.ufscar.br/handle/ufscar/8806.

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Submitted by Milena Rubi (milenarubi@ufscar.br) on 2017-06-01T14:58:47Z No. of bitstreams: 1 SILVA_Alan_2016.pdf: 14722594 bytes, checksum: 0c8346924c434318f6c349f7ed8112d9 (MD5) Approved for entry into archive by Milena Rubi (milenarubi@ufscar.br) on 2017-06-01T14:58:54Z (GMT) No. of bitstreams: 1 SILVA_Alan_2016.pdf: 14722594 bytes, checksum: 0c8346924c434318f6c349f7ed8112d9 (MD5) Approved for entry into archive by Milena Rubi (milenarubi@ufscar.br) on 2017-06-01T14:58:59Z (GMT) No. of bitstreams: 1 SILVA_Alan_2016.pdf: 14722594 bytes, checksum: 0c8346924c434318f6c349f7ed8112d9 (MD5) Made available in DSpace on 2017-06-01T14:59:06Z (GMT). No. of bitstreams: 1 SILVA_Alan_2016.pdf: 14722594 bytes, checksum: 0c8346924c434318f6c349f7ed8112d9 (MD5) Previous issue date: 2016-12-06 Não recebi financiamento The Multipath TCP (MPTCP) protocol allows applications to better explore the network resources available to multi-connected devices such as mobile phones or multi-homed systems. Here, some advantages are envisioned: bandwidth aggregation, the ability to maintain the connection, if one of the network path fails and the use of multiple paths. To extend these capabilities to the application, RFC 6897 defines an API to better control each of MPTCP’s subflows, so that these can be added or removed as needed. This work presents an initial API implementation as defined in RFC 6897. We implemented some functions described in the document, such as protocol on/o, check existent subflows and add new subflows. To test the API and validate our implementation we built an HTTP application that detects elephant flows and uses the API for open new subflows using the original TCP connection. Some tests were performed in a network using a cubic topology and showed that the API utilization decreased the Flow Completion time of TCP connections. O protocolo Multipath TCP (MPTCP) permite que as aplicações possam explorar melhor os recursos de rede disponíveis para dispositivos multiconectados como os telefones móveis ou sistemas multi-homed. Aqui, algumas vantagens são previstas: agregação de banda, a habilidade de manter a conexão estabelecida se houver falha em um dos caminhos de rede e a utilização de múltiplos caminhos. Para estender essas capacidades para a aplicação, a RFC 6897 define uma API que permite um melhor controle de cada subfluxo MPTCP, de modo que esses possam ser adicionados ou removidos conforme necessário. Este trabalho apresenta uma implementação inicial da API descrita na RFC 6897 para o protocolo MPTCP. Sendo assim, implementamos algumas das funções de manipulação do protocolo MPTCP descritas no documento, quais sejam: ligar e desligar o protocolo, verificar subfluxos existentes e adicionar novos subfluxos. Para testar a API e validar a nossa implementação, nós desenvolvemos uma aplicação HTTP que detecta fluxos elefantes e utiliza a API para abrir novos subfluxos a partir da conexão TCP original. Testes de desempenho foram realizados em uma topologia cúbica e mostraram que a utilização da API pela aplicação diminuiu o Flow Completion Time das conexões TCP.

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13

Mankelow, Rowena Chemistry Faculty of Science UNSW. "Creating mesophorous materials by liquid crystal templating of readily available materials." Awarded by:University of New South Wales, 2003. http://handle.unsw.edu.au/1959.4/38346.

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14

Zhao, Min Chemistry Faculty of Science UNSW. "A fill and flow channel enzyme biosensor." Awarded by:University of New South Wales, 2004. http://handle.unsw.edu.au/1959.4/38333.

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15

Perez-Bercoff, Danielle. "L'activation des macrophages via les RFcγ inhibe la réplication du VIH-1". Paris 7, 2002. http://www.theses.fr/2002PA077144.

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16

Siberil, Sophie. "Etude des interactions moléculaires entre RFcγ et IgG : implications fonctionnelles et thérapeutiques". Paris 6, 2005. http://www.theses.fr/2005PA066549.

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17

Bruhns, Pierre. "Bases moleculaires des proprietes inhibitrices des rfc ii b." Paris 6, 2001. http://www.theses.fr/2001PA066039.

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Les recepteurs de faible affinite pour la portion fc les igg (rfciib) regulent negativement la proliferation et l'activation de cellules du systeme immunitaire. Ces recepteurs inhibiteurs possedent un immunoreceptor tyrosine-based inhibition motif (itim) dans leur domaine intracytoplasmique qui, lorsqu'il est phosphoryle lors la coagregation des rfciib a des recepteurs activateurs, recrute les inositol 5-phosphatase a domaine sh2, ship1 et ship2. Comme la majorite des autres recepteurs a itim, les kir2dl3, des killer cell inhibitory receptors with a long intracytoplasmic domain capables d'inhiber la cytotoxicite des cellules nk, possedent plusieurs itim et recrutent les proteines tyrosines phosphatases shp-1 et shp-2. L'etude comparative de deux types de recepteurs inhibiteurs, rfciib et kir2dl3, nous a permis d'identifier les residus permettant la fixation specifique de ship1 et de ship2 par l'itim unique des rfciib et de reconnaitre un role differentiel des deux itim dans le recrutement de shp-1 et de shp-2 par les kir2dl3. L'etude, par mutation dirigee, de l'itim des rfciib a revele que des recepteurs mutes, incapables de recruter l'une ou l'autre des 4 phosphatases a domaine sh2 cytoplasmiques connues, restent capables d'inhiber l'activation cellulaire. Nous avons montre que deux sequences differentes, situees hors de l'itim, etaient responsables de l'inhibition conservee dans un rfciib dont l'itim n'est plus fonctionnel. L'ensemble de ce travail indique que les proprietes inhibitrices des rfciib ne peuvent pas se reduire a la seule presence dans leur domaine intracytoplasmique d'un itim capable de recruter ship1 et ship2. Trois regions du domaine transmembranaire et du domaine intracellulaire des rfciib, codees par trois exons differents, sont donc impliquees dans l'inhibition de l'activation cellulaire, via des mecanismes differents et additifs, permettant aux rfciib de reguler efficacement l'activation de cellules du systeme immunitaire.

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18

Bartoš, Patrik. "Testování přenosových parametrů internetového připojení." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2021. http://www.nusl.cz/ntk/nusl-442361.

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This thesis deals with methodology for measuring transmission parameters of internet connection. The aim of the thesis is to cover and compare known methods used for testing. Based on the research then design and realize an application that will provide those kind of measurements.

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19

Watson, Joni. "Identification of Transcription Factors GZF3, RFX1, Orf19.3928 as Being Implicated in Candida-Bacterial Interactions." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/honors/261.

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Candida albicans is an opportunistic pathogen that is present in the normal flora in a majority of individuals. One key factor in C. albicans virulence is the ability to change its morphology from yeast to an elongated or hyphal form. The regulation of this morphogenesis relies in part upon quorum sensing (QS) molecules. C. albicans often exists as part of a mixed culture alongside other microbes and is influenced by their presence as well as the presence of QS molecules that they produce. In this study, a library of diploid homozygous transcriptional regulator knockout (TRKO) mutants were screened to identify strains capable of forming hyphae in the presence of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. We identified three strains that showed increased hyphae development compared to wild type C. albicans. The strains identified had deletions of the transcriptional regulating genes Orf19.3928, Orf19.2842 (GZF3), and Orf19.3865 (RFX1). These strains were tested for alterations of filamentation in liquid media, and biofilm formation. All three strains showed increased rates of biofilm formation compared to the wild type. Orf19.3928 showed altered response to farnesol, a marked in biofilm formation and no inhibition of filamentation when farnesol was present in liquid media. The GZF3 deletion strain showed enhanced filamentation with all three bacterial species while the RFX1 deletion strain showed increased filamentation only with E. coli and S. aureus. In spent media, GZF3 showed slight increases in filamentation in E. coli and S. aureus while RFX1 had moderate increases in filamentation in E. coli and S. aureus and slight increases with P. aeruginosa.

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20

Schrader, Stephanie. "Molekularbiologische und zellbiologische Charakterisierung alternativer Splicing- Varianten des Methotrexat- Carriers (RFC)." Doctoral thesis, Universitätsbibliothek Leipzig, 2009. http://nbn-resolving.de/urn:nbn:de:bsz:15-20090429-113312-2.

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Die Chemotherapie hat in letzten Jahren in der Veterinärmedizin zunehmend an Bedeutung gewonnen. Das Zytostatikum Methotrexat (MTX) wird in der Veterinärmedizin vorwiegend zur Behandlung von Lymphomen und lymphatischen Leukämien eingesetzt. In der Humanmedizin findet es aufgrund seiner immunsuppressiven Wirkung auch bei nicht neoplastischen Erkrankungen wie der rheumatoiden Arthritis Anwendung. Die Aufnahme von reduzierten Folaten und MTX wird vornehmlich als aktiver Transport über den Reduced folate carrier (Rfc) vermittelt. Inzwischen konnte die für das Transportprotein codierende cDNA aus Maus (mRfc) und Hamster (haRfc) und Mensch (hRFC) isoliert und das jeweilige Gen identifiziert werden. Ein orthologes Transportsystem für MTX (MTX-Carrier) wurde auch für die Ratte beschrieben. Die full-length cDNAs des MTX-Carriers wurden aus Leber und Niere isoliert und die Proteine funktionell charakterisiert. Während die cDNAs der MTX-Carrier aus Leber und Niere im codierenden Sequenzbereich identisch waren und für ein Protein bestehend aus 512 Aminosäuren codierten, wiesen die cDNAs im 5´-untranslatierten Bereich unterschiedliche Sequenzen auf. Aus der Leber wurde zudem eine cDNA Variante des MTX-Carriers isoliert, die sich im Sequenzvergleich mit der cDNA des MTX-Carriers durch eine Insertion von 203 bp auszeichnete und als MTX-2 bezeichnet wurde. Die Varianz ist möglicherweise auf alternatives Spleißen der Prä-mRNA zurückzuführen. Alternatives Spleißen ist ein wichtiger Mechanismus, verschiedene Proteine aus einem Gen zu generieren. Während in den letzten Jahren zwar zunehmend alternativ gespleißte Transkripte auch für den RFC entdeckt wurden, wurden nur verhältnismäßig wenige dieser Transkripte weiterführend charakterisiert. In dieser Arbeit wurden Splicing-Varianten des MTX-Carrier der Rattenniere molekularbiologisch und zellbiologisch charakterisiert. Für die Niere wurden mittels RT-PCR vier mögliche Splicing-Varianten des MTX-Carriers (RK-MTX-1, RK-MTX-2, RK-MTX-5 und RK-MTX-6) identifiziert. Dabei wies die Variante MTX-2 im Vergleich zum MTX-1 eine Insertion von 203 bp auf und war in der 5´-UTR identisch mit dem renalen MTX-1. Die Varianten MTX-5 und MTX-6 wiesen eine Deletion von 119 bp und 116 bp auf. Ein Vergleich der Sequenzen dieser renalen Varianten und der bekannten Sequenzen der Varianten aus der Leber (RL-MTX-1, RL-MTX-2) mit den Daten des Rat Genome Project führte zur Identifizierung des MTX-Gens auf dem Rattenchromosom 20 (NCBI AABR01066371) sowie zur Aufklärung seiner genomischen Organisation. Insgesamt wurden auf diese Weise 7 Exons und 6 Introns erkannt. Gleichzeitig konnten die Varianten als Splicing-Varianten des MTX-Carriers definiert werden. Die ersten beiden Exons werden alternativ in Leber und Niere genutzt, daher ist anzunehmen, dass der Prozess des alternativen Spleißens der Exons I und Ia gewebsspezifisch erfolgt und wahrscheinlich regulatorisch von Bedeutung ist. Die Insertion von 203 bp des MTX-2 in Leber und Niere erklärt sich durch die Retention des Intron III. Die Varianten MTX-5 und MTX-6 entstehen durch die verkürzten alternativen Exons IIIa und IVa durch die Nutzung alternativer Splice-Sites. Während die unterschiedlichen 5´-UTR des renalen und hepatozelluären MTX-1 keine Auswirkungen auf die Proteinstruktur haben, ergeben sich für die Varianten MTX-2, MTX-5 und MTX-6 laut Proteinvorhersage weitreichende Konsequenzen. Das alternative Spleißen führt in allen Varianten zu einem vorzeitigen Stopp-Codon in der codierenden Region und in der Folge zu C-terminal verkürzten Proteinvarianten. Während für den MTX-1 12 TMD vorausgesagt sind, codieren die cDNAs der Varianten nur noch für ein Protein mit 7 TMD (MTX-2, MTX-6) bzw. 6 TMD (MTX-5). Studien mit Deletionskonstrukten des RFC/Rfc anderer Spezies zeigten, dass in den C-terminalen TMD 7-12 bedeutsame Strukturen funktioneller und struktureller Art lokalisiert sind. Insbesondere fehlen den Varianten damit die Substratbindungsdomäne, sowie noch nicht identifizierte Strukturen oder Sequenzen, die für das Protein-Targeting zur Zellmembran erforderlich sind. Funktionelle Untersuchungen am RK-MTX-2 zu einer Aufnahmeaktivität von MTX in stabil transfizierten MDCK führten zu keinem eindeutigen Ergebnis. Während die mRNA-Expression nachgewiesen werden konnte, wurde mittels indirekter Immunfluoreszenz und Westernblot keine Proteinexpression des RK-MTX-2 ermittelt. Die Proteinexpression der Splicing-Varianten MTX-1, MTX-2, MTX-5 und MTX-6 konnte jedoch anhand von GFP-Fusionsproteinen in transienter Transfektion in ihrem zeitlichen Verlauf dargestellt und die subzelluläre Lokalisation der Proteine bestimmt werden. Im Ergebnis zeigte sich, dass die Proteine MTX-2, MTX-5 und MTX-6 geringer als MTX-1 und das ungekoppelte GFP exprimiert wurden. Im Gegensatz zum MTX-1 blieb die für ein Transportprotein notwendige Lokalisation in der Zellmembran aus. Stattdessen kam es über einen Zeitraum von 72 h zur Akkumulation in subzellulären Strukturen im Zytoplasma, möglicherweise dem endoplasmatischen Retikulum. Es ist anzunehmen, dass den Varianten aufgrund ihrer verkürzten Proteinstruktur die notwendigen Strukturen für das Protein-Targeting fehlen und sie somit nicht korrekt zur Zellmembran transportiert und folglich abgebaut werden. Nach stabiler Transfektion war im Gegensatz zum GFP und GFP-MTX-1 keine Proteinexpression nachweisbar. Die RNA hingegen wurde bei allen Varianten stabil exprimiert. Die Resultate dieser Arbeit zeigen, dass den Varianten als mögliche Proteinisoformen des MTX-Carriers zumindest in vitro keine funktionelle Bedeutung zugesprochen werden kann. Durch die vorzeitigen Stopp-Codons (PTC) in den Varianten, die durch das alternative Spleißen entstehen, sind sie als mögliche Substrate für den „Nonsense Mediated Decay“ (NMD) klassifiziert. Der NMD dient einerseits dem Abbau fehlerhafter und fehlgespleißter mRNA. Möglicherweise sind die Splice-Sites des Intron III nicht eindeutig und stellen einen Schwachpunkt der DNA des MTX-Gens (rat slc19a1) dar. Andererseits könnte die Kopplung vom alternativen Spleißen und NMD auch eine große Bedeutung in der Regulation der Proteinexpression einnehmen. In Bezug auf den MTX-Carrier könnte der MTX-Transport über die Steuerung der Menge der Transkripte der Splicing-Varianten reguliert sein. Die Ergebnisse dieser Arbeit zeigen deutlich die Notwendigkeit einer sowohl molekularbiologischen als auch funktionellen Untersuchung möglicher alternativer Splicing-Varianten.

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Bossard, Florian. "La mucoviscidose : correction de la mutation [delta]F508 par sur-expression de NHE-RF1 : modifications d'expression de NHE-RF1 et des récepteurs [béta]-adrénergiques dans les poumons humains." Nantes, 2007. http://archive.bu.univ-nantes.fr/pollux/show.action?id=6c13703c-0312-4f63-9879-11bdd9fd3d9a.

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Ces travaux de thèse se sont organisés autour de deux projets. Premièrement, nous avons étudié l'impact d'une protéine partenaire de CFTR, NHE-RF1, sur la protéine mutée la plus fréquente dans la mucoviscidose : deltaF508. NHE-RF1 était décrite jusque là pour son implication dans l'adressage apical et la stabilité membranaire de la protéine CFTR sauvage. Nos travaux démontrent que la surexpression de NHE-RF1 corrige le défaut d'adressage de deltaF508 et restaure une activité partielle de canal chlorure. Deuxièmement, nous nous sommes intéressés à l'expression des récepteurs beta-adrénergiques (beta-AR) et NHE-RF1 dans les poumons humains témoins et mucoviscidosiques. En effet, les beta1 et beta2-AR sont présents dans les poumons où ils régulent diverses fonctions biologiques. Mais dans la mucoviscidose, la réponse beta-adrénergique globale est altérée. Par ailleurs, notre équipe a démontré que le troisième sous-type de beta-AR, beta3, est capable d'activer CFTR. Mais aucune étude ne démontre la présence de beta3-AR dans les poumons humains. Ces données nous ont conduits à analyser l'expression des trois beta-AR ainsi que NHE-RF1 dans des bronches humaines contrôles et mucoviscidosiques. Nous avons ainsi démontré : 1) l'expression du beta3-AR dans les poumons humains et 2) une modification d'expression des beta-AR et de NHE-RF1 dans la mucoviscidose (surexpression des beta1 et beta3-AR, sous-expression des beta2-AR et NHE-RF1). L'implication physiopathologique de ce remodelage dans la mucoviscidose reste à définir. Enfin, la sous-expression de NHE-RF1 devra être prise en compte pour les possibilités de restauration pharmacologique des mutations chez les patient The present work encompasses two projects. Firstly, we studied the impact of a protein partner of CFTR, NHE-RF1, on the most frequent mutant in cystic fibrosis (CF): deltaF508. NHE-RF1 has been described up to now for its involvement in apical trafficking and membrane stability of wild-type CFTR. Our study showed that NHE-RF1 overexpression rescued the trafficking defect of deltaF508 and rehabilitated a partial channel chloride activity. Secondly, we focused on the expression of the beta-adrenergic receptors (beta-AR) and NHE-RF1 in control and CF human lungs. Indeed, the beta1 and beta2-AR are largely expressed in the lungs where they control various biological functions. But the beta-AR stimulation leads to a faded response in CF. In addition, our team has previously shown that the third beta-AR subtype, beta3-AR, can activate CFTR. But no study has shown the presence of the beta3-AR in human lungs. These data encouraged us to analyze the three beta-AR and NHE-RF1 expressions in human control and CF bronchi samples. We thus showed that: 1) beta3-AR were expressed in human lungs and 2) a remodeling was observed in CF (beta1 and beta3-AR overexpression, beta2-AR and NHE-RF1 under-expression). The physiological relevance of this remodeling remains to be defined. However, NHE-RF1 under-expression should be taken into account for the pharmacological rescue of the patients' mutants

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22

Vehera, Vladyslav. "Přenosové technologie VDSL2 vplus a G.fast a jejich testování." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2020. http://www.nusl.cz/ntk/nusl-413049.

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This semester work focuses on the basic characteristics of the VDSl2 and G.fast technologies that allow to transfer data using old telephone lines. The theoretical part of the work describes the main parameters of all currently known profiles for VDSL and G.fast. There is also a description of DMT modulation, used in both types of DSL connections. Moreover, the theoretical part presents a vectoring technique that helps to increase the data transfer rate using a twisted pair. The work also provides methods for testing networks using the recommendations of RFC 2455, ITU-T Y.1564 and RFC6349. The practical part of this thesis contains all conducted tests and measuring, which were described in detail. The results od these tests were presented in the format of graphs and tables.

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23

Silva, Dênis [UNESP]. "Purificação e caracterização bioquímica de poligalacturonases produzidas pelo fungo Penicillium viridicatum RFC3 em fermentação em estado sólido e submersa." Universidade Estadual Paulista (UNESP), 2006. http://hdl.handle.net/11449/103949.

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Made available in DSpace on 2014-06-11T19:32:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-09-22Bitstream added on 2014-06-13T20:24:23Z : No. of bitstreams: 1 silva_d_dr_rcla.pdf: 1167994 bytes, checksum: eca15b5bfad71b8173fe9d808385fd94 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) A poligalacturonase (PG) é uma pectinase que degrada a molécula de pectina atuando internamente , ao acaso, liberando oligossacarídeos (Endo-PG) ou por ataque a partir da extremidade não redutora da cadeia, liberando moléculas de ácido galacturônico (Exo-PG). As pectinases, como várias outras enzimas, têm sido obtidas a partir de microrganismos, em processos fermentativos em estado sólido (FES) e fermentação submersa (FSM). A purificação e caracterização destas enzimas podem possibilitar o estudo das diferenças de suas propriedades funcionais, bem como, permitem avaliar suas possibilidades de aplicação, em diferentes condições, em processos industriais. Este trabalho teve por objetivos estudar a produção, purificação e caracterização da PG produzida por Penicillium viridicatum RFC3 através de FES e FSM. Para FSM foram testados os resíduos agroindustriais (farelo de trigo, bagaço de laranja, uma mistura de ambos) a 3% (p/v) além da água amarela (resíduo do processamento da indústria cítrica) no seu estado bruto e com diluições (2, 4 e 10x). Os pHs iniciais foram corrigidos para 4,5, 5 e 5,5 e a fermentação ocorreu por 24 - 96 h. A ANOVA mostrou que o extrato do bagaço de laranja (pH 5,5 e 96 h) foi o melhor meio para a produção da PG em FSM. A purificação da PG produzida em FSM iniciou-se pela ultrafiltração do extrato bruto (membranas de 50 e 10 kDa, repectivamente) seguida pela aplicação da amostra em uma coluna de filtração em gel Sephadex G75 e posterior aplicação em uma Q Sepharose. A fração isolada e desorvida revelou, após 2 eletroforese (PAGE-SDS) a homogeneidade da banda cuja massa molar foi estimada em 92,24 kDa e pI de 5,4. A enzima mostrou ser uma exopoligalacturonase (Exo-PG) com pH e temperatura ótimos em 5,0 e 50-55ºC. The polygalacturonase (PG) is a pectinase that degrade pectin acting internally, releasing olygossacharide (Endo-PG) or by atack to a non reducing chain extremity, releasing galacturonic acid (Exo-PG). The pectinases, like many others enzymes, have been obtained from microorganisms by solid state fermentation (SSF) and submerged fermentation (SMF). The purification and characterization of these enzymes besides the study of differences of its functional properties permit its application on industrial process, on different conditions. This work aimed the study of production, purification and characterization of PG from Penicillium viridicatum RFC3 by SSF and SMF. In SMF they were assayed agroindustrial wastes (wheat bran, orange bagasse and a mixture of both) at 3% (w/v 1:1) and citric industry liquid waste (yellow water) in crude state and with dilutions (2, 4 and 10x). It was also evaluated the variation of the initial pH of the medium (4.5, 5.0 nd 5.5) and the time of fermentation (24 96 h). The ANOVA test revealed that the culture medium composed by orange bagasse extract, at pH 5.5 and 96 h, was the best condition for production of PG in SMF. The purification process of PG from SMF was carried out by the ultrafiltration of the crude extract (50 and kDa membranes, respectively) and by gel filtration in Sephadex G75 and Q Sepharose columns. The fraction with PG activity show by eletrophoresis (SDSPAGE), an homogeinity of a band with estimated molar mass of 92.24 KDa and pI 5.4. The enzyme revealed to be an Exo-PG with optimal pH and temperature of 5.0 and 50-55 °C. It also revealed to be Ca2+ dependent, which increased its 4 activity and stability. The Km of the enzyme was 1.30 and 1.16 mg/ml on Ca2+ presence. The Vmax was 1.76 and 2.07 ?mol/min/mg when Ca2+ was added. The better fermentation conditions in SSF was wheat bran mixed with orange bagasse (1:1 w/w) at 80% moisture as an culture medium and 336h of fermentation.

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24

Silva, Dênis. "Purificação e caracterização bioquímica de poligalacturonases produzidas pelo fungo Penicillium viridicatum RFC3 em fermentação em estado sólido e submersa /." Rio Claro : [s.n.], 2006. http://hdl.handle.net/11449/103949.

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Orientador: Eleni Gomes Banca: Eleonora Cano Carmona Banca: Rubens Monti Banca: Iracema de Oliveira Moraes Banca: Márcia Luzia Rizzatto Resumo: A poligalacturonase (PG) é uma pectinase que degrada a molécula de pectina atuando internamente, ao acaso, liberando oligossacarídeos (Endo-PG) ou por ataque a partir da extremidade não redutora da cadeia, liberando moléculas de ácido galacturônico (Exo-PG). As pectinases, como várias outras enzimas, têm sido obtidas a partir de microrganismos, em processos fermentativos em estado sólido (FES) e fermentação submersa (FSM). A purificação e caracterização destas enzimas podem possibilitar o estudo das diferenças de suas propriedades funcionais, bem como, permitem avaliar suas possibilidades de aplicação, em diferentes condições, em processos industriais. Este trabalho teve por objetivos estudar a produção, purificação e caracterização da PG produzida por Penicillium viridicatum RFC3 através de FES e FSM. Para FSM foram testados os resíduos agroindustriais (farelo de trigo, bagaço de laranja, uma mistura de ambos) a 3% (p/v) além da água amarela (resíduo do processamento da indústria cítrica) no seu estado bruto e com diluições (2, 4 e 10x). Os pHs iniciais foram corrigidos para 4,5, 5 e 5,5 e a fermentação ocorreu por 24 - 96 h. A ANOVA mostrou que o extrato do bagaço de laranja (pH 5,5 e 96 h) foi o melhor meio para a produção da PG em FSM. A purificação da PG produzida em FSM iniciou-se pela ultrafiltração do extrato bruto (membranas de 50 e 10 kDa, repectivamente) seguida pela aplicação da amostra em uma coluna de filtração em gel Sephadex G75 e posterior aplicação em uma Q Sepharose. A fração isolada e desorvida revelou, após 2 eletroforese (PAGE-SDS) a homogeneidade da banda cuja massa molar foi estimada em 92,24 kDa e pI de 5,4. A enzima mostrou ser uma exopoligalacturonase (Exo-PG) com pH e temperatura ótimos em 5,0 e 50-55ºC Abstract: The polygalacturonase (PG) is a pectinase that degrade pectin acting internally, releasing olygossacharide (Endo-PG) or by atack to a non reducing chain extremity, releasing galacturonic acid (Exo-PG). The pectinases, like many others enzymes, have been obtained from microorganisms by solid state fermentation (SSF) and submerged fermentation (SMF). The purification and characterization of these enzymes besides the study of differences of its functional properties permit its application on industrial process, on different conditions. This work aimed the study of production, purification and characterization of PG from Penicillium viridicatum RFC3 by SSF and SMF. In SMF they were assayed agroindustrial wastes (wheat bran, orange bagasse and a mixture of both) at 3% (w/v 1:1) and citric industry liquid waste (yellow water) in crude state and with dilutions (2, 4 and 10x). It was also evaluated the variation of the initial pH of the medium (4.5, 5.0 nd 5.5) and the time of fermentation (24 96 h). The ANOVA test revealed that the culture medium composed by orange bagasse extract, at pH 5.5 and 96 h, was the best condition for production of PG in SMF. The purification process of PG from SMF was carried out by the ultrafiltration of the crude extract (50 and kDa membranes, respectively) and by gel filtration in Sephadex G75 and Q Sepharose columns. The fraction with PG activity show by eletrophoresis (SDSPAGE), an homogeinity of a band with estimated molar mass of 92.24 KDa and pI 5.4. The enzyme revealed to be an Exo-PG with optimal pH and temperature of 5.0 and 50-55 °C. It also revealed to be Ca2+ dependent, which increased its 4 activity and stability. The Km of the enzyme was 1.30 and 1.16 mg/ml on Ca2+ presence. The Vmax was 1.76 and 2.07 ?mol/min/mg when Ca2+ was added. The better fermentation conditions in SSF was wheat bran mixed with orange bagasse (1:1 w/w) at 80% moisture as an culture medium and 336h of fermentation Doutor

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25

Walter, Aaron Joseph. "Approximate Thermal Modeling of Radiofrequency Cardiac Ablation." Diss., CLICK HERE for online access, 2005. http://contentdm.lib.byu.edu/ETD/image/etd1002.pdf.

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26

SILVA, Rafaela Maria Seabra. "Polimorfismos em genes envolvidos no metabolismo do ácido fólico e o risco de desenvolvimento da leucemia infantil." Universidade Federal de Pernambuco, 2010. https://repositorio.ufpe.br/handle/123456789/19894.

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Submitted by Luiza Maria Pereira de Oliveira (luiza.oliveira@ufpe.br) on 2017-07-20T16:29:24Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Rafaela Maria Seabra Silva.pdf: 1206163 bytes, checksum: 40c5b3e504a66706b66919d7543260cc (MD5) Made available in DSpace on 2017-07-20T16:29:24Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Rafaela Maria Seabra Silva.pdf: 1206163 bytes, checksum: 40c5b3e504a66706b66919d7543260cc (MD5) Previous issue date: 2010-03-05 Leucemia é a neoplasia hematológica mais comum na infância. Sua etiologia não está elucidada sendo provável uma interação gene-ambiente. O ácido fólico é uma vitamina do complexo B transportado para a célula pela proteína carreadora de folato reduzido. Enzimas importantes no metabolismo do ácido fólico são: A metilenotetrahidrofolato redutase, metionina sintase, e timidilato sintase. Este foi um estudo exploratório com caso-controle. A população amostral foi diferente para cada um dos polimorfismos estudados sendo constituída de amostras oriundas do CEONHPE/HUOC e INCa. A detecção dos genótipos foi realizada através PCR–RFLP para os polimorfismos MTHFR 677, MS 2756 e RFC1, seguida de digestão enzimática, por PCR para as repetições em tandem no gene TS e PCR alelo-específica para o polimorfismo MTHFR 1298. Não observamos diferença estatisticamente significante na freqüência genotípica dos polimorfismos A2756G MS e nas repetições em tandem 2R/3R no promotor do gene TS. O genótipo mutante RFC 80AA foi relacionado a diminuição do risco de desenvolvimento de leucemias agudas e LLA no CEONHPE, LMA no INCa e leucemias agudas e LMA, na análise CEONHPE e INCa. A presença do alelo 677T foi associada ao aumento do risco de leucemias agudas e LLA. Enquanto a presença do genótipo MTHFR 1298CC foi associado a uma significativa redução do risco. O resultado deste estudo sugere a associação dos polimorfismos RFC G80A, MTHFR A1298C e MTHFR C677T com a susceptibilidade a LA infantil. Leukemia is the most common hematologic malignancy in childhood. Its etiology is not elucidated and is likely a gene-environment interaction. Folic acid is a vitamin B complex transported to the cell by binding protein of reduced folate. Important enzymes in the metabolism of folic acid are: The methylenetetrahydrofolate reductase, methionine synthase, and thymidylate synthase. This was an exploratory study with case-control. The sample population was different for each of the polymorphisms studied was made up of samples from CEONHPE / HUOC and Cancer Institute. Genotype detection was performed by PCR-RFLP for the polymorphisms MTHFR 677, MS 2756 and RFC1, followed by enzymatic digestion, by PCR for the tandem repeats in the TS gene and allele-specific PCR for the MTHFR 1298 polymorphism. No statistically significant difference in genotype frequency of polymorphisms A2756G MS and tandem repeats in the 2R/3R TS gene promoter. The mutant RFC 80AA genotype was related to decreased risk of developing acute leukemia and in CEONHPE ALL, AML and INCa in acute leukemias and AML, and the analysis CEONHPE Cancer Institute. The presence of 677T allele was associated with increased risk of acute leukemia and ALL. While the presence of the MTHFR 1298CC genotype was associated with a significant reduction in risk. The result of this study suggests the association of polymorphisms G80a RFC, MTHFR A1298C and MTHFR C677T with susceptibility to AL's.

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Mancardi, David. "Rôles pro-inflammatoires des RFcγIV murins, et de leurs deux équivalents fonctionnels humains, les RFcγI et les RFcεI(αγ)". Paris 6, 2009. http://www.theses.fr/2009PA066504.

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Un nouveau RFc, nommé RFcγIV, a été récemment cloné. Ce sont des RFc activateurs murins pour les IgG2 exprimés par les macrophages et les neutrophiles. Ils n’existent pas chez l’homme. Nous avons caractérisé des propriétés biologiques de ces RFc et recherché s’ils avaient des équivalents fonctionnels humains. Nous avons mis en évidence une interaction de faible affinité entre les RFcγIV et les IgE. Cette interaction participe à l’induction d’une inflammation pulmonaire. Dans des modèles d’inflammation dépendante des IgG, les RFcγIV sont capables d’induire une arthrite auto-immune et des chocs anaphylactiques systémiques. L’ensemble de ce travail met en évidence de nouvelles fonctions des RFcγIV, et des cellules qui les expriment, dans des réactions in vivo induites à la fois par des IgE et par des IgG. Deux RFc humains, les RFcγI et les RFcεI(αγ) pourraient, chez l’homme, jouer le rôle que jouent les RFcγIV chez la souris.

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28

LAUNAY, PIERRE. "Fonctions et signalisations alternatives du rfc alpha dependantes de l'association avec la chaine gamma (doctorat : immunologie)." Paris 5, 1999. http://www.theses.fr/1999PA05N039.

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29

Compaleo, Joshua. "Accurate Clutter Power Modeling Technique for Very LowGrazing Angles with RFC Capable Radar Design and Demonstration." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1595563370860726.

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30

Decraene, Maud. "Mise en place de la réponse immunitaire orchestrée par les cellules dendritiques humaines : caractérisation et étude fonctionnelle du rôle des RFcγ". Paris 6, 2005. http://www.theses.fr/2005PA066130.

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31

Ibrahim, Isak Georgina. "Studies on Translation Initiation and Termination in Escherichia coli." Doctoral thesis, Stockholms universitet, Institutionen för genetik, mikrobiologi och toxikologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-69954.

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Translation initiation factor 1 (IF1) has been shown to be an RNA chaperone. In order to find functional interactions that IF1 may have with rRNA, we have isolated second-site suppressors of a cold-sensitive IF1 mutant. Joining of the ribosomal subunit seems to be affected in the IF1 mutant strain and the suppressive effect is a consequence of decreasing the available pool of mature 50S subunits. The results serve as additional evidence that IF1 is an RNA chaperone and that final maturation of the ribosome takes place during translation initiation. In this study we have also investigated the effect of a cold-sensitive mutant IF1 or kasugamycin addition on gene expression using a 2D gel electrophoresis technique. The effect is much more dramatic when cells are treated with kasugamycin compared to mutant IF1. The ybgF gene is uniquely sensitive to the IF1 mutation as well as the addition of kasugamycin. This effect on the native gene could be connected with some property of the TIR sequence of ybgF and supports the notion that kasugamycin addition and the IF1 cold-sensitive mutation have a similar TIR-specific effect on mRNA translation. Finally we have isolated a suppressor of a temperature-sensitive mutation in ribosomal release factor 1 (RF1) to shed more light on the translation termination process. The suppressor mutation is linked to an IS10 insertion into the cysB gene and results in a Cys- phenotype. Our results suggest that suppression of the thermosensitive growth is a consequence of the mnm5s2U hypomodification of certain tRNA species. The ability of mnm5s2U hypomodified tRNA to induce frameshifting may be responsible for the suppression mechanism and it supports the hypothesis that modified nucleosides in the anticodon of tRNA act in part to prevent frameshifting by the ribosome. At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 2: Manuscript.

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32

Grossetête-Pedron, Béatrice. "Role du rfc alpha (cd89) dans la physiopathologie de la maladie de berger et de l'infection a vih." Paris 5, 1999. http://www.theses.fr/1999PA05N115.

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33

Abrisqueta, Costa Pau. "Tratamiento de primera línea con rituximab combinado con fludarabina, ciclofosfamida y mitoxantrone (RFCM) y mantenimiento con rituximab en pacientes con leucemia linfática crónica." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/283529.

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La leucemia linfática crónica (LLC) es la leucemia más frecuente en la edad adulta en los países occidentales, y se caracteriza por la acumulación y proliferación de linfocitos clonales B maduros CD5+ en la sangre, médula ósea, y ganglios linfáticos. La mediana de supervivencia de los pacientes es de alrededor de 10 años aunque su curso clínico es heterogéneo. Durante varias décadas el tratamiento de esta enfermedad se había basado en el empleo de agentes alquilantes como el clorambucilo, en los análogos de la purinas, o en la asociación de ambos, como la combinación de fludarabina y ciclofosfamida (FC). Posteriormente las combinaciones de rituximab, un anticuerpo monoclonal anti-CD20, con quimioterapia, en general FC, lo que ha pasado a denominarse tratamiento inmunoquimioterápico, revolucionaron el tratamiento de esta enfermedad al alcanzar intervalos de supervivencia libre de progresión (SLP) superiores a cinco años, lo que se tradujo en una mayor supervivencia de los enfermos. Sin embargo, a pesar de estos buenos resultados, los pacientes siguen recayendo de su enfermedad y la LLC continúa siendo incurable más allá del trasplante de progenitores hematopoyéticos. Con el fin de mejorar estos resultados se han diseñado nuevas combinaciones de quimioterapia como la asociación de FC con mitoxantrone (FCM), una anthracenedione con capacidad de inhibir la topoisomerasa II. Por otro lado, las estrategias de mantenimiento o las terapias de consolidación dirigidas a controlar la enfermedad mínima residual (EMR) persistente tras el tratamiento inicial, podrían derivar en una mejora en la evolución de los pacientes con LLC. Con estos antecedentes, diseñamos un ensayo clínico multicéntrico fase II en pacientes jóvenes (= 70 años) con LLC previamente no tratados que consistió en un tratamiento inicial con rituximab 500 mg/m2 (día 1) (375mg/m2 en el primer ciclo), fludarabina 25mg/m2 (días 1-3), ciclofosfamida 200mg/m2 (días 1-3), y mitoxantrone 6mg/m2 (día 1), (R-FCM), cada cuatro semanas, hasta un total de seis ciclos. Posteriormente, aquellos pacientes que obtuvieron al menos una respuesta parcial (RP) tras el tratamiento inicial fueron elegibles para la fase de mantenimiento, que consistió en 375mg/m2 de rituximab cada tres meses durante dos años. Además, se analizó la EMR mediante citometría de flujo de forma simultánea en sangre periférica y médula ósea. El objetivo principal del estudio fue el determinar la eficacia de R-FCM medida a través de la tasa de respuestas, incluyendo la tasa de respuestas con EMR negativa. Como objetivos secundarios se planteó el determinar la duración de la respuesta y la SLP, el análisis de las variables clínico-biológicas que influyen en la respuesta, y el perfil de toxicidad del tratamiento. Se incluyeron 81 pacientes en el estudio, con una mediana de edad de 60 años (rango, 40 a 70 años). La tasa de respuesta global obtenida tras el tratamiento inicial con R-FCM fue del 93%, con una tasa de respuesta completa (RC) con EMR negativa, tasa de RC con EMR positiva y de RP del 46%, 36% y 11%, respectivamente. Los factores que se correlacionaron con una menor tasa de RC fueron el estadio clínico avanzado al inicio del tratamiento, la deleción de 17p, y un valor elevado de ß2-microglobulina. En general, el tratamiento con R-FCM fue bien tolerado y aunque se observó algún grado de neutropenia en un 41% de los ciclos administrados, ésta fue grave únicamente en una 13% de los ciclos. En cuanto a la toxicidad infecciosa, se observó un evento infeccioso mayor en un 8% de los ciclos administrados. Sesenta y siete pacientes recibieron el tratamiento de mantenimiento con rituximab. Al finalizar el mantenimiento, un 40.6% de los pacientes presentaban una RC con EMR negativa, un 40.6% una RC con EMR positiva, un 4.8% un RP, y un 14% se consideraron como fallo de tratamiento. Seis de los 29 pacientes (21%) que se hallaban en RC con EMR positiva o en RP tras R-FCM mejoraron su respuesta mediante el tratamiento de mantenimiento. La SLP y la supervivencia global estimada a los cuatro años fueron del 74.8% y 93.7%, respectivamente. El nivel de EMR obtenido tras el tratamiento con R-FCM fue la variable con mayor poder predictivo de la SLP. Se observó neutropenia grave en el 8.5% de los ciclos de mantenimiento y 16 pacientes tuvieron un episodio infeccioso grado 3–4. En conclusión, la combinación de R-FCM es un tratamiento de primera línea altamente eficaz en pacientes jóvenes con LLC. Esta combinación obtuvo una alta tasa de RC, consiguiendo en gran parte de ellas la negativización de la EMR. El tratamiento de mantenimiento con rituximab tras R-FCM consiguió una SLP prolongada y mejoró la calidad de las respuestas en un porcentaje de pacientes, particularmente en aquellos con persistencia de enfermedad detectable tras R-FCM. Chronic lymphocytic leukemia (CLL) is a frequent malignancy composed of CD5+ B-lymphocytes, is predominant in older people, and has a variable clinical course. The median survival of patients with CLL is approximately 10 years, but the individual prognosis is extremely variable. The addition of monoclonal antibodies to chemotherapy has significantly improved treatment of CLL. Based on excellent results with the chemotherapy-only regimen fludarabine, cyclophosphamide, and mitoxantrone (FCM), we built a new chemoimmunotherapy combination—rituximab plus FCM (R-FCM). The effectiveness of R-FCM followed by rituximab maintenance therapy as first-line treatment for younger patients with CLL (age = 70) has been investigated in a phase 2 clinical trial that included an initial treatment with rituximab 500 mg/m2 on day 1 (375 mg/m2 the first cycle), fludarabine 25 mg/m2 on days 1 to 3, cyclophosphamide 200 mg/m2 on days 1 to 3, and mitoxantrone 6 mg/m2 on day 1 (R-FCM), for 6 cycles. Patients achieving response received maintenance with rituximab 375 mg/m2 every 3 months for 2 years. Eighty-one patients (median age, 60 years; range, 40 to 70 years) were enrolled in the study. The overall response, minimal residual disease (MRD)–negative complete response (CR), MRD positive CR, and partial response (PR) rates were 93%, 46%, 36%, and 11%, respectively. Severe neutropenia developed in 13% of patients. Major and minor infections were reported in 8% and 5% of cycles, respectively. Advanced clinical stage, del(17p), or increased serum ß2-microglobulin levels correlated with a lower CR rate. Sixty-seven patients having achieved CR or PR with R-FCM were given maintenance therapy. At the end of maintenance, 40.6% of patients were in CR MRD-negative, 40.6% were in CR MRD-positive, 4.8% remained in PR, and 14% were considered failures. Six of 29 patients (21%) who were in CR MRD-positive or in PR after R-FCM improved their response upon rituximab maintenance. The 4-year progression-free survival (PFS) and overall survival rates were 74.8% and 93.7%, respectively. MRD status after R-FCM induction was the strongest predictor of PFS. R-FCM is highly effective in previously untreated CLL, with an 82% CR rate and a high proportion of MRD-negative CRs (46%). Treatment toxicity is acceptable. Maintenance with rituximab after R-FCM improved the quality of the response, particularly in patients MRD-positive after initial treatment, and obtained a prolonged PFS.

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34

Díaz, Puentes Alfredo Andrés. "Integración de SAP y Aplicaciones Legadas a Través de SOA." Tesis, Universidad de Chile, 2008. http://repositorio.uchile.cl/handle/2250/104945.

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El objetivo general del presente trabajo de título es un caso real de integración entre el ERP de SAP y los legacy del área de logística de una compañía distribuidora de combustible en Chile utilizando los principios que el patrón de diseño SOA ofrece y con la ayuda de herramientas comerciales que implementan y facilitan la integración entre sistemas computacionales heterogéneos. El área de logística de la compañía cuenta con una variedad de aplicaciones legacy Web del tipo J2EE que utilizan de manera independiente y que les permiten realizar la programación de los pedidos de combustible que sus clientes efectúan, asignación de los pedidos a los distintos camiones tanques, modificaciones y cancelaciones que se deban realizar a los pedidos, medición de eficiencia de los transportes y viajes efectuados, etc. La integración se basó en los conceptos que el patrón SOA indica como mejor práctica con la ayuda de plataformas tecnológicas de la línea WebSphere de IBM tales como MessageBroker, MQ, Adaptadores del MessageBroker para comunicarse con el ERP y con el sistema operativo sobre el cual funciona que es Os/400 sobre iSeries, etc. Las principales decisiones tomadas durante el proyecto dicen relación con casos en los cuales se decidió hacer pasar el flujo de datos por la plataforma SOA instalada y cuando no hacerlo porque entregaba mejores prestaciones, tiempos de respuesta y seguridad. Durante todo el proyecto estos fueron temas de discusión y análisis dado que cada caso en la práctica trae un análisis individual que debe ser enfrentado bajo la mirada de conveniencia para la empresa, entendiéndose que estas conveniencias podrían ser tiempos de respuesta, puntos de falla, servicio e imagen al cliente. En el detalle del trabajo se tomaron decisiones relacionadas con el tipo y formato de mensajes que transportan los datos entre las aplicaciones que participan del proceso de despacho de combustibles. Detalles como saber cuántos campos de datos son necesarios por mensaje, que separadores debían acordarse y ser utilizados, como serían tratados los encolamientos de los mensajes según si prioridad, los mensajes devuelta que deben ser enviados para cerrar los ciclos de cada proceso que se gatillen, etc. Cada una de estas decisiones en los distintos mensajes de datos que se gatillan en cualquier sentido dentro del proceso de despacho de combustible muestra los esfuerzos principales sobre los cuales se concentró el presente trabajo de título. El resultado final fue un conjunto de aplicaciones del tipo Web y legacy que se comunican con el ERP de SAP para lograr de manera exitosa el despacho de combustible desde las plantas de la compañía; todo esto con la ayuda de una infraestructura conformada por filesystem y carpetas compartidas, plataformas de integración de IBM, flujo de mensajes que transmiten los datos, etc. Se concluye que los proyectos de integración si bien logran el objetivo principal sobre el cual se basan, carecen aún de la madurez necesaria en su diseño o bien en los productos comerciales que existen hoy en el mercado, dado que muchas decisiones se debieron tomar descartando lo que eran las mejores prácticas de SOA en beneficio de obtener una solución acorde a las necesidades de la compañía. La mirada de performance y eficiencia de los procesos es muy difícil dimensionarla y considerarla durante este tipo de proyectos y deben ser enfrentados, por lo general, posteriormente a su puesta en marcha, cuando los datos cuantitativos del funcionamiento entregan muchos más antecedentes que ayuden a encontrar las oportunidades de mejoras y los cuellos de botella que deben ser solucionados.

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35

Nieke, Franziska. "Beeinflussung der intestinalen Folatresorption durch Umweltkontaminanten am Beispiel eines humanen in vitro Modells." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-154886.

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Folate sind als Überträger von C1-Fragmenten verschiedener Oxidationsstufen direkt an der Nukleinsäuresynthese beteiligt und spielen somit eine entscheidende Rolle im Zellstoffwechsel. So kann ein suboptimaler Folatstatus zur Ausprägung einer klinischen Symptomatik führen, die sich primär in Zellen mit hoher Teilungsrate manifestiert. Dabei gilt die megaloblastäre Anämie als Leitsymptom für einen akuten Folatmangel. Herausragende Bedeutung besitzen Folate in der Schwangerschaft, wo ihnen bei der Entwicklung des fetalen Nervensystems eine besondere Rolle zukommt. Bei einem zu niedrigen Serumfolatspiegel der Mutter steigt das Risiko für embryonale Missbildungen wie Neuralrohrdefekte stark an. Die weitere medizinische Relevanz der Folate steht momentan im Fokus der Forschung, wie z. B. der protektive Effekt in Bezug auf bestimmte Krebsformen, die Risikoreduktion für verschiedene kardiovaskuläre Erkrankungen sowie Zusammenhänge zwischen dem Folatstatus und neurologischen Störungen (Alzheimer, Depressionen). Allerdings kann Folat als essentielles Vitamin von Säugetieren nicht selbst synthetisiert werden, sondern muss aus externen Quellen über den Verdauungstrakt aufgenommen werden. Die Resorption aus dem Darm erfolgt nach aktuellem Kenntnisstand insbesondere über den Reduced Folate Carrier (RFC, SLC19A1) und den Proton-Coupled Folate Transporter (PCFT, SLC46A1). Trotz der Existenz dieser spezifischen Transporter ist der Folatmangel des Menschen der häufigste Vitaminmangel in Mitteleuropa. Er lässt sich durch eine ausschließlich ernährungsphysiologische Problematik nur unzureichend erklären. Interessanterweise besitzen sowohl das PCFT-Gen als auch das RFC-Gen in ihrer Promoterregion verschiedene Regulationselemente, unter anderem auch funktionell aktive DREs (Dioxin Response Element), die als Bindungsstelle für einen ligandenaktivierten Transkriptionsfaktor, den nukleären Arylhydrocarbon-Rezeptor (AhR), dienen. DREs wurden bisher hauptsächlich bei fremdstoffmetabolisierenden Enzymen wie z. B. Cytochrom P450-Isoenzymen gefunden und vermitteln bekanntermaßen die toxischen und karzinogenen Effekte von AhR-Liganden. Von besonderem Interesse sind in diesem Zusammenhang ubiquitär verbreitete Umweltkontaminanten wie die polyzyklischen und die halogenierten aromatischen Kohlenwasserstoffe (PAK, HAK), da sie in der Umwelt sehr persistent sind und sich dadurch in der Lebensmittelkette anreichern. Infolgedessen wurde im Rahmen dieser Studie der mögliche Einfluss von AhR-Liganden wie TCDD (2,3,7,8-tetrachlordibenzo-p-dioxin) und B[a]P (Benzo[a]pyren) auf die carriervermittelte intestinale Folatresorption beim Menschen untersucht sowie die Regulation der Transportproteine RFC und PCFT auf transkriptioneller Ebene experimentell überprüft. Als adäquates in vitro Modell diente dabei die humane Kolonzelllinie LS180, für die zunächst eine Charakterisierung erfolgte. Mittels RT-PCR wurde der Nachweis erbracht, dass alle am Folattransport beteiligten Import-und Exportcarrier auf mRNA-Ebene exprimiert werden. Für die Transportproteine RFC und PCFT erfolgte über den Western Blot auch der Nachweis auf Proteinebene. Die Funktionalität der AhR-Signalkaskade, die über methylcholanthrenartige Induktoren wie TCDD zur Induktion von Cytochrom P450 führt, konnte im Folgenden mittels Ethoxyresorufin-O-deethylase-Assay (EROD) überprüft werden. Es zeigte sich nach Induktion mit TCDD (0,01 - 10 nM) oder B[a]P (0,01 - 1 μM) über 12 – 96 h ein hochsignifikanter, dosis- und zeitabhängiger Effekt auf die Cyp1A1 vermittelte Enzymaktivität der Ethoxyresorufin-O-deethylase in den LS180-Zellen. Dabei konnten ligandenabhängige Unterschiede im Induktionsmuster ermittelt werden. Im Anschluss wurde im intestinalen Zellmodell die initiale konzentrations- und zeitabhängige Folataufnahme bei pH 5.5 über funktionelle Aufnahmeversuche mit Tritium-markierter Folsäure untersucht und charakterisiert. Sie stellte sich als aktiver, sättigbarer Prozess dar, wobei in den unbehandelten LS180-Zellen ca. eine Verdreifachung der intrazellulären Radioaktivität über einen Zeitraum von 2,5 min beobachtet werden konnte. Als kinetische Parameter wurden ein Km-Wert von 27,91 μM sowie ein Vmax-Wert von 281,2 pmol/min berechnet. Nachfolgende Untersuchungen mit den spezifischen Inhibitoren Raltitrexed (RTX) und Pemetrexed (PMX) konnten zeigen, dass sowohl PCFT als auch RFC an der funktionellen Folsäureaufnahme bei einem pH-Wert von 5.5 in dem gewählten Versuchsaufbau beteiligt sind. Der RFC scheint jedoch einen etwas höheren Anteil an der Gesamtaufnahme zu haben als der PCFT. In LS180-Zellen, die vorher mit den Modellsubstanzen TCDD (1 bzw. 10 nM) oder B[a]P (0,1 bzw. 1 μM) über 24 - 120 h inkubiert wurden, konnte eine zeit- und dosisabhängige, statistisch signifikante Reduktion der carriervermittelten Folatresorption beobachtet werden, wobei die maximale Verminderung der Aufnahmerate ca. 75 % betrug. Da sich dieser Effekt durch die AhR-Antagonisten Salicylamid (SAL) und CH-223191 (CH) dosisabhängig umkehren ließ, erfolgt die Regulation vermutlich über den AhR-Signalweg. Um den Mechanismus der Regulation zu klären, wurde mit Hilfe der quantitativen qRT-PCR unter Verwendung von TaqMan-Sonden die Genexpression von RFC und PCFT nach Vorbehandlung mit 1 - 10 nM TCDD oder 0,1 – 1 μM B[a]P über 12 - 120 h untersucht. Analog zu den Aufnahmeversuchen konnte hier eine zeit- und dosisabhängige Reduktion beider Transporter auf transkriptioneller Ebene beobachtet werden. Auch führte eine Vorbehandlung mit CH und SAL wiederum zu einer Umkehr des Effektes, wobei CH wahrscheinlich einen ligandenselektiven AhR-Antagonisten darstellt. Zusammenfassend konnte durch die vorliegende Arbeit nachgewiesen werden, dass Cytochrom P450-Induktoren über die AhR-Signalkaskade die carriervermittelte Folatresorption in humanen Kolonzellen herabregulieren. Es erscheint anhand der gewonnen Erkenntnisse möglich, dass die Folathomoöstase durch verschiedene Umweltkontaminanten wie z. B. TCDD negativ beeinflusst werden kann und als Folge daraus auch eventuell der Folatmangel der Bevölkerung in Industrienationen zumindest teilweise erklärbar wird. Es ist darüber hinaus denkbar, dass auch andere Fremdstoffe die Folataufnahme beeinflussen, da große planare Strukturen häufig über den AhR-Weg wirken. Weiterführende Studien sind notwendig, um das Verständnis für den Einfluss von Umweltkontaminanten auf die intestinale Folataufnahme zu verbessern.

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36

Pujol, F. (François). "Experiments on fatty acids chain elongation and glycan flipping in the ER membrane." Doctoral thesis, University of Oulu, 2009. http://urn.fi/urn:isbn:9789514290695.

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Abstract Very long chain fatty acids (VLCFA) are essential molecules that take part in many different cellular processes such as membrane pore stabilization, membrane trafficking and signaling pathways. The fatty acid elongation pathway in yeast has been studied for about a decade. As part of our work on cellular VLCFA elongation, we identified and characterized the condensing enzyme as well as ketoacyl reductases of the elongation pathway in cotton. In order to identify the yeast 3-hydroxyacyl-CoA dehydratase, we introduced a redundancy in this function by engineering a chimera consisting of the two first predicted transmembrane domains of Elo3p and the hydratase2 domain of Candida tropicalis Mfe2p. Yeast harboring the chimeric construct were subjected to random mutagenesis, and screened for mutants whose survival was dependent on the chimera. The mutants isolated contained RFT1 mutations and exhibited a defect in protein glycosylation, but no VLCFA deficiencies. The N-linked glycosylation pathway is well conserved in eukaryotes. Glycan synthesis occurs on the ER membrane; first on the cytoplasmic side up to Dol-PP-GlcNAc2Man5, which is then translocated to the ER luminal side in an Rft1p-dependent flipping process. The core glycan is further extended to Dol-PP-GlcNAc2Glc3Man9, and then transferred to an asparagine side chain of the nascent polypeptide to be glycosylated. It was found that the Elo3'-hydratase2 chimera acts as a multicopy suppressor of the Rft1p deficiency. The subsequent studies elucidated new aspects of Rft1p function, as well as a hitherto under-appreciated role of the ER associated protein degradation process in the maintenance of ER integral membrane complexes and the physical integrity of the membrane. The functionality of the human Rft1p homologue was demonstrated using a yeast complementation assay. A mutant variant from a patient was analyzed, aiding in the identification and characterization of the first reported case of a glycosylation deficiency in humans caused by a defective RFT1 allele.

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37

Veronesi, Junior José Ronaldo. "A eficácia da reeducação postural global através do reequilíbrio funcional corporal (RPG/RFC) na correção postural e no reequilíbrio muscular." reponame:Repositório Institucional da UnB, 2006. http://repositorio.unb.br/handle/10482/5219.

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Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2006. Submitted by wesley oliveira leite (leite.wesley@yahoo.com.br) on 2009-11-02T17:05:11Z No. of bitstreams: 1 DISSERTACAO FINAL JOSE RONALDO VERONESI JUNIOR.pdf: 1474934 bytes, checksum: 0bb8299fd305b81a21573e89cfa4b04d (MD5) Approved for entry into archive by Gomes Neide(nagomes2005@gmail.com) on 2010-07-12T19:42:18Z (GMT) No. of bitstreams: 1 DISSERTACAO FINAL JOSE RONALDO VERONESI JUNIOR.pdf: 1474934 bytes, checksum: 0bb8299fd305b81a21573e89cfa4b04d (MD5) Made available in DSpace on 2010-07-12T19:42:18Z (GMT). No. of bitstreams: 1 DISSERTACAO FINAL JOSE RONALDO VERONESI JUNIOR.pdf: 1474934 bytes, checksum: 0bb8299fd305b81a21573e89cfa4b04d (MD5) Previous issue date: 2006 A presente pesquisa teve como objetivo geral investigar o potencial terapêutico da Reeducação Postural Global através do Reequilíbrio Funcional Laboral RPG/RFL no reequilíbrio muscular e na correção postural em indivíduos hígidos. A amostra foi randomizada e estratificada em dois grupos – controle e tratamento - com 48 participantes cada (n=96). Os testes estatísticos demonstram que a amostra foi homogênea. No grupo tratamento foi realizada uma Reeducação Postural Global através do Reequilíbrio Funcional Corporal, com uma postura inicial e três variantes de membros superiores e seis de membros inferiores durante cinco sessões diárias. O grupo controle não recebeu nenhuma intervenção. Todos os indivíduos foram analisados através de exame de eletromiografia de superfície e fotogrametria computadorizada, antes e após intervalo de cinco dias. No grupo tratamento todos os músculos estudados reequilibraram-se, e no controle todos os músculos desequilibraram-se (p<0,001). No grupo tratamento, 47,92% melhoram todos os segmentos, 41,67% melhoraram dois segmentos, 10,4% melhoraram um segmento apenas. No grupo controle apenas 4,2% melhoraram os três segmentos, 47,92% melhoraram apenas um segmento, e 31,25% não melhoraram nenhum segmento (p<0,001). Estes resultados indicam que o tratamento com o método RPG/RFL foi eficaz no reequilíbrio neuro-muscular e na correção _________________________________________________________________________________________ ABSTRACT The goal of this research was to investigate the potential therapeutic value of Global Postural Reeducation through re-equilibrium functional labour RPG/RFL on the muscular and the posture correction in normal individuals. The sample was randomized and separated in two groups of 48 participants (n=96). The statistic tests showed that the sample was homogeneous. The treatment group received GPR through Corporal Functional Re-equilibrium, with a first posture and three variants of superior members and six of inferior members during five daily sessions. The control group did not receive any intervention. All participants were examined using surface electromyography and computerized photogrammetry before and after treatment. In the treatment group all muscles investigated showed a re-equilibrium, whereas in the control individuos no a such difference was observed. In the treatment group 47,92% of the individuals improved all segments, 41,67% improved two segments, and 10,4% only one segment. On the other hand, in control group, only 4,2% improved the three segments, 47,92% showed only one segment improved, and 31,25% did not showed any difference. These results indicate that treatment with a Global Posture Reeducation using the Functional labour Re-equilibrium method was efficient it mussel reequilibrium and in the posture correction.

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38

Amigorena, Sebastian. "Activation, proliferation et differenciation des lymphocytes b murins : flux ioniques, expression des rfc gamma de type deux et regulation isotypique." Paris 7, 1990. http://www.theses.fr/1990PA077004.

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Le travail presente dans cette these concerne l'etude de certains aspects du developpement des lymphocytes b quiescents en plasmocytes. D'une part, nous avons etudie l'expression des recepteurs de type deux pour la portion fc des igg (rfc gamma deux), ainsi que l'expression et le role de canaux k#+ lors de l'activation et de la proliferation de lymphocytes b murins. Nous avons montre que: 1) la forme beta 1 des rfc gamma deux est exprimee majoritairement dans les lymphocytes b quiescents et actives; 2) l'expression membranaire des rfc gamma deux augmente lorsque les lymphocytes b entrent en phase g1 du cycle cellulaire et 3) differents inhibiteurs des canaux k#+ bloquent la proliferation des lymphocytes b en bloquant le passage entre les phases g1a et g1b du cycle cellulaire. D'autre part, nous avons analyse la regulation de la production des differentes sous-classes d'igg par les immunoglobulin bidding factors (ibf), par l'il2 et par les cellules natural killer. Nous avons montre que: 1) les ibf inhibent la secretion d'igg par des cellules d'hybridomes b, ainsi que la proliferation de ces cellules; 2) l'il2 provoque une augmentation de la secretion d'igg2a par des lymphocytes b actives et 3) des cellules nk activees par l'il2 exercent le meme effet; cette induction d'igg2a necessite la production endogene d'ifn gamma par les cellules spleniques

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39

Martel, Velasquez Victor Ronald. "Diseño de una red de comunicación VPN sobre internet para un Distribuidor Autorizado de Claro basado en el RFC 2764." Bachelor's thesis, Universidad Peruana de Ciencias Aplicadas (UPC), 2019. http://hdl.handle.net/10757/625693.

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El presente proyecto sobre redes de comunicación VPN sobre internet nos muestra una guía de configuraciones necesarias por requisitos en base al RFC 2764 incluyendo las funcionalidades de la red que permitirá ejecutar las acciones requeridas para agilizar los procesos de negocio mediante un eficiente uso de los recursos TI para la disponibilidad de la información. Actualmente las empresas desean tener presencia en nuevos mercados, por lo que se expanden a nuevas sucursales en distintos distritos y hasta en el interior del país lo que origina la necesidad de mantenerse conectados en todo momento de manera segura, confiable, y sobre todo a un costo aceptable entre todos sus locales con el fin de compartir información que les permita tomar decisiones en tiempo real. La solución consiste en el diseño de una red de comunicación mediante redes privadas virtuales entre sus locales con el fin de optimizar recursos y agilizar las transacciones diarias propias del giro del negocio, para lo cual el eje principal de la solución es la interconexión de la sede principal y sus sucursales, es así que se consideraron diversas soluciones de comunicación entre locales, las cuales se explicaran y analizaran. En dicho análisis se buscara que la solución responda a criterios como: escalabilidad, seguridad de datos, disponibilidad de información, y sobre todo economía. The present project on VPN communication networks over the Internet shows us a guide of necessary configurations by requirements based on RFC 2764 including the functionalities of the network that will allow executing the actions required to streamline business processes through an efficient use of IT resources for the availability of information. Currently companies want to have a presence in new markets, so they expand to new branches in different districts and even in the interior of the country which causes the need to stay connected at all times in a safe, reliable, and especially at a Acceptable cost among all its premises in order to share information that allows them to make decisions in real time. The solution consists of the design of a communication network through virtual private networks between its premises in order to optimize resources and streamline the daily transactions of the business, for which the main focus of the solution is the interconnection of the headquarters principal and its branches, so that various communication solutions between the premises were considered, which will be explained and analyzed. In this analysis we will look for the solution to respond to criteria such as: scalability, data security, availability of information, and above all economy. Tesis

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40

Ťápal, Tomáš. "Zefektivnění analýzy počítačové sítě 10Gbit/s." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2013. http://www.nusl.cz/ntk/nusl-220194.

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The master’s thesis consists of several parts. Describes the technology 10 Gbps Ethernet. Analyzer Ixia and Endace presents, especially their use for traffic analysis and stress testing the network devices. It deals with documents RFC concerning the routers and switch testing. Thesis includes the reports of tests switches and router performed by RFC 2544 and RFC 2889 documents. Part of the thesis is dedicated to COMBO FPGA cards. Documentations to the analyzers is created in this thesis and macro is on the CD for presentation of measurement results.

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41

Pilčík, Jan. "Metody měření přenosových rychlostí na Internetu." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2008. http://www.nusl.cz/ntk/nusl-217279.

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Due to a signifikant development of computer networks in the last few years the demands for measurement of network metrics increased. This master´s thesis is dealing with standards for testing and test techniques used for the measurement of network metrics. Further it compares the existing free accessible measurement tools and metrics measures them. Finaly the thesis draws up a web application for measurement of the basic network metrics.

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42

Martin-Verdeaux, Sophie. "Mécanismes moléculaires de l'exocytose mastocytaire médiée par le RFc[epsilon]I : rôle du complexe SNARE et des protéines régulatrices MUNC18 et RAB3D." Paris 5, 2002. http://www.theses.fr/2002PA05P609.

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Les mastocytes sont des cellules du système immunitaire hautement spécialisées, impliquées dans des réactions inflammatoires et allergiques. Suite à l'agrégation des récepteurs de haute affinité pour les IgE(RFc[epsilon]I)présents à la surface membranaire, les mastocytes sécrètent massivement et rapidement leur contenu granulaire. Cette dégranulation, mettant en jeu des mécanismes Ca2+- et PKC-dépendants, mobilise presque tous les granules intracellulaires par un mécanisme d'exocytose cumulative, impliquant, d'une part la fusion hétérotypique des granules avec la membrane plasmique et d'autre part la fusion homotypique des granules entre eux. Alors que les événements de signalisation permettant la dégranulation ont fait l'objet de nombreuses études, l'identité de la machinerie moléculaire contrôlant ces événements, et particulièrement la propagation de la fusion membranaire à la population granulaire, reste peu connue. Les mécanismes généraux du trafic intracellulaire vers la membrane plasmique dépendent de l'interaction de protéines SNAREs, situées d'une part sur la membrane cible (t-SNAREs) et d'autre part sur les vésicules sécrétoires (v-SNAREs), capables de former un complexe catalysant la fusion membranaire. En utilisant des mastocytes de rat de la lignée RBL-2H3, nous avons caractérisé certaines de ces protéines. Les complexes mis en évidence sont composés des t-SNAREs Syntaxine 2,3,4 et SNAP-23 et des V-SNAREsVAMP-2,-3, et -8. Le développement d'un test unicellulaire permettant de mesurer l'exocytose nous a permis de révéler le rôle fonctionnel de Syntaxine 2,3 et 4 dans la dégranulation mastocytaire. Certaines protéines comme les protéines Sec1/Munc18, capables de lier les SNAREs Syntaxines, ou les GTPases Rab3 peuvent réguler spécifiquement la formation de ce complexe [. . . ] Le lien entre la dégranulation mastocyrtaire médiée par le FRc[epsilon]I et la GTPase Rab3d a été révélé par la caractérisation d'une activité kinase associée, régulée par le Ca2+ et capable de phosphoryler Syntaxine 4 dans les mastocytes non activés, ce qui a pour effet d'empêcher sa liaison à son partenaire SNAP-23. Rab3D pourrait ainsi réguler la formation du complexe SNARE par des mécanismes de phosphorylation.

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43

Knoll, Thomas Martin. "BGP Extended Community Attribute for QoS Marking." Universitätsbibliothek Chemnitz, 2008. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-200800767.

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This document specifies a simple signalling mechanism for inter-domain QoS marking using a BGP Extended Community QoS Attribute. Class based packet forwarding for delay and loss critical services is currently performed in an individual AS internal manner. The new QoS marking attribute makes the QoS class setup within the IP prefix advertising AS known to all access and transit ASes. This enables individual (re-)marking and forwarding treatment adaptation to the original QoS class setup of the respective IP prefix. The attribute provides the means to signal QoS markings on different layers, which are linked together in QoS class sets. It provides inter-domain and cross-layer insight into the QoS class mapping of the source AS with minimal signalling traffic.

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44

Brunati, Silvana. "Régulation de la production des IgG par les lymphocytes T RF#c gamma positifs." Paris 6, 1990. http://www.theses.fr/1990PA066058.

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Dans ce travail, nous avons analysé l'action suppressive des cellules d'un hybridome T exprimant des récepteurs FC gamma, producteur d'IgG-BF, (T2D4. C1) sur la production d'IgG par des cellules d'hybridomes B. Le système expérimental consiste en la co-culture de différents clones d'hybridomes B (producteurs soit d'IgG (H et L) (UN2. C3), soit uniquement de chaines L (UN2. C17. K1) avec T2D4. C1 ou avec D10C5 (ce dernier est un hybridome T n'exprimant pas de récepteurs FC gamma et ne produisant pas d'IgG-BF). Nous avons montré que seul T2D4. C1 inhibe la sécrétion des IgG par les cellules UN2. C3, par l'intermédiaire d'un facteur soluble ; cette inhibition résulte d'une diminution de la stabilité des ARNM codant pour les chaines H et L d'IGG. Les cellules de l'hybridome B variant (UN2. C17. K1) n'exprimant plus de chaines H d'IgG, sont par contre insensibles à l'action suppressive des cellules T2D4. C1 : dans les mêmes conditions expérimentales, leur production de chaines L reste inchangée. Ces résultats suggèrent qu'une molécule d'IgG complète est nécessaire pour observer l'action suppressive des cellules T2D4. C1. Les modalités de l'inhibition, dépendante donc de la présence de cellules exprimant des récepteurs FC gamma et productrices d'IgG-BF, en tant qu'effectrices, et de la production d'IgG par les cellules-cibles, suggèrent que le facteur soluble responsable de l'inhibition est un IgG-BF

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45

Metz, Josué Claudio. "Avaliação do uso combinado de pó de aciaria elétrica (PAE) com resíduo do forno de cal (RFC) na hidratação de pastas de cimento." Universidade do Vale do Rio dos Sinos, 2016. http://www.repositorio.jesuita.org.br/handle/UNISINOS/5991.

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Submitted by Silvana Teresinha Dornelles Studzinski (sstudzinski) on 2016-12-22T12:03:13Z No. of bitstreams: 1 Josué Claudio Metz_.pdf: 3580473 bytes, checksum: 4bb7f81d4d0a95ef4e39a7d4dffb0599 (MD5) Made available in DSpace on 2016-12-22T12:03:13Z (GMT). No. of bitstreams: 1 Josué Claudio Metz_.pdf: 3580473 bytes, checksum: 4bb7f81d4d0a95ef4e39a7d4dffb0599 (MD5) Previous issue date: 2016-09-19 Nenhuma A concepção de desenvolvimento sustentável tem resultado no aumento de pressões ambientais para a melhoria da eficiência na utilização de recursos, e para a redução das emissões e da geração de resíduos. No processo de fabricação de aço, nas siderúrgicas com fornos elétricos a arco (FEA), ocorre a geração do resíduo sólido denominado pó de aciaria elétrica (PAE). O PAE é constituído por diferentes óxidos metálicos. Contém os elementos químicos cromo (Cr), chumbo (Pb) e cádmio (Cd) e, por isso, é classificado como resíduo classe I – Perigoso pela NBR 10004. Gerado em grandes quantidades diariamente em todo o país, o PAE ainda tem como principal destinação final o aterro industrial. A indústria de papel e celulose, outra atividade de destaque na indústria nacional, gera uma grande quantidade de resíduos em diferentes etapas do processo, entre os quais está o resíduo do forno de cal (RFC), cuja geração está associada a interrupções no funcionamento do forno de cal. A indústria da construção civil, devido a quantidade de matérias-primas consumida e variedade de materiais empregados – cimento, concreto, agregados, cerâmica, entre outros – apresenta-se como alternativa para a reciclagem de resíduos gerados em outros setores da economia. A incorporação do PAE no cimento e concreto produz retardo no tempo de pega em razão da presença de zinco (Zn) no resíduo. Estudos sugerem que em quantidades próximas a 1%, a incorporação de PAE não afeta de forma significativa as propriedades do cimento. O objetivo deste trabalho foi avaliar a influência do uso combinado de PAE e RFC no processo de endurecimento e evolução da hidratação de pastas de cimento. Para tanto, foi realizada a caracterização dos resíduos através dos ensaios de distribuição granulométrica, perda ao fogo, massa específica, área superficial específica, análise química elementar, difração de raios X com refinamento por Rietveld e microscopia eletrônica de varredura. A influência dos resíduos nas pastas de cimento foi avaliada através do ensaio de tempo de pega de acordo com a NBR NM 65 (ABNT, 2003b) e evolução da temperatura semi-adiabática das pastas em estado fresco, além de DRX, com refinamento por Rietveld, e microscopia eletrônica de varredura nas pastas de cimento com diferentes teores de substituição de resíduos (REF, 1%, 2%, 3%, 5% e 10%) em diferentes idades (1, 4 e 7 dias). Os resultados de tempo de pega e evolução da temperatura semi-adiabática indicaram a influência do PAE na hidratação das pastas de cimento. Nas pastas de cimento com substituição de 1% de PAE combinado ou não com RFC, não foram verificados retardos significativos no tempo de pega, demonstrando o potencial do uso de PAE e do RFC na produção de artefatos de cimento. The sustainable development conception has resulted in increased environmental pressures to improve the efficient use of resources and reduction of emissions and waste generation. In the steelmaking process through electric arc furnaces (EAF), dust generation occurs which is called electric arc furnace dust (EAFD). EAFD is composed by different metal oxides. Some common elements those constitute this dust is chromium, lead and cadmium, and therefore, waste is classified as class I – hazardous by NBR 10004. EAFD has been generated in large quantities every day across the country and it still has mainly landfilled. The pulp and paper industry, another important activity in the domestic industry, generates a lot of waste in different stages of the process, among which is the lime kiln waste (LKW), whose generation is associated with disruptions in the lime oven. Due to expressive amount of raw materials consumed in civil construction industry and also the variety of products available - cement, concrete, aggregates, ceramics, among others - this seems to be an alternative for waste recycling generated in other sectors. The incorporation of EAFD in the cement and concrete produces delayed setting time due to the presence of zinc (Zn) in the waste. Studies suggest that in amounts up to 1%, EAFD incorporation does not affect significantly cement properties. The aim of this work was to evaluate the influence of the combined use of EAFD and LKW in the process of hardening and evolution of the cement pastes hydration. Therefore, were evaluated the characterization of the waste performed through the grain size distribution, loss on ignition, specific gravity, specific surface area, elemental chemical analysis, pH, X ray powder diffraction with refinement by Rietveld and scanning electron microscopy.. The influence of the waste on the cement pastes was evaluated through the setting time tests in accordance with the NBR NM 65 (ABNT, 2003b) and evolution of semi-adiabatic temperature in fresh conditions, XRD with refinement by Rietveld, and SEM in cement pastes with different levels of waste substitution (REF, 1%, 2%, 3%, 5% e 10%) at different ages (1, 4 and 7 days). The setting time results and evolution of semi-adiabatic temperature indicated an increase in the setting time with the increase of the EAFD in cement pastes. In cement pastes with replacement of 1% EAFD combined or not with LKW, significant delays were not verified in the setting time, demonstrating the potential use of EAFD in the production of cement artifacts.

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Dutertre, Charles-Antoine. "De l'importance de la caractérisation des différentes isoformes de RFC gamma des cellules NK pour l'optimisation fonctionnelle des anticorps monoclonaux à usage thérapeutique." Paris 7, 2008. http://www.theses.fr/2008PA077132.

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De gros efforts ont été faits pour optimiser les propriétés cytotoxiques des anticorps monoclonaux (AcM) à usage thérapeutique, en particulier leur capacité d'engagement du RFcγIIIA (CD16) activateur exprimé à la surface des cellules NK capables d'induire une cytotoxicité cellulaire dépendante d'anticorps (ADCC). La première partie de nos travaux a visé à déterminer l'expression de RFcγll par les cellules NK, ainsi que leur rôle dans le contrôle de l'ADCC, et nous a permis de mettre en évidence une nouvelle sous-population de cellules NK CD56dim/CD3ˉ/NKp46⁺/RFcγlllAbright/RFcγllbright exprimant fortement le RFcγllB inhibiteur. Nous avons montré que les cellules NK RFcγllBbright, détectée chez tous les donneurs sains, présentent un profil d'expression de récepteurs NK (NKR) différent de celui des cellules NK RFcγll'°/ˉ(exprimant majoritairement le RFcγIIC activateur), ainsi qu'une dégranulation réduite au cours de leur activation RFcγ-dépendante. La seconde partie de nos travaux a permis de démontrer qu'un AcM anti-CD20 développé par le Laboratoire français du Fractionnement et des Biotechnologies, l'EMAB-6, présente in vitro une activité cytotoxique contre les cellules de leucémie lymphoïde chronique B (LLC-B) beaucoup plus élevée que celle du rituximab, grâce a sa capacité de fixation au RFcγlllA beaucoup plus importante que le rituximab. Nos études ont permis de confirmer qu'un faible taux de fucosylation de l'AcM EMAB-6 était responsable de cette propriété et qu'un meilleur engagement du RFcylllA donne un avantage cytotoxique d'autant plus important à cet AcM par rapport au rituximab que la densité de molécules CD20 à la surface des cellules cibles était plus faible Important efforts have been devoted to the optimization of cytotoxic therapeutic monoclonal antibodies (mAb), in particular to the improvement of their capacity to engage the activating RFcγIIIA (CD16) expressed on NK cells that are capable of antibody-dependent cellular cytotoxicity (ADCC). In the present work, we examined the expression of FcγRIl by human NK cells, as well as their role in the control of ADCC, which made it possible to define a novel NK cell subpopulation, CD56dim/CD3ˉ/NKp46⁺/RFcγlllAbright/RFcγllbright that strongly expresses inhibitory FcyRIlB. We showed that FcYRMBbright NK cells, detected in all the donors tested, exhibit an expression profile of NK cell receptors (NKR) different from that of NK RFcγll'°/ˉ cells (that predominantly express the activating FcγRIIC), as well as a reduced degranulation following FcγR-dependent activation. The second part of our work allowed the demonstration that an anti-CD20 EMAB-6 antibody developed by the Laboratoire français du Fractionnement et des Biotechnologies, presents a much higher cytotoxic activity against B cell chronic lymphocytic leukemia (B-CLL) cells in vitro than rituximab, a marketed anti-CD20 therapeutic mAb. This increased activity was linked to a much higher binding capacity to FcyRIIIA as compared to its non-optimized counterpart or to rituximab. Our studies also confirmed that the low fucose level of the EMAB-6 mAb is essential to its increased FcγRIIIA binding and efficacy. Finally, the better cytotoxic activity of this antibody as compared to rituximab was found even increased when the density of CD20 on target cells was lower

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Malbec, Odile. "La trans-inhibition : une nouvelle propriété inhibitrice des RFcγIIB". Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00833016.

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L'engagement des récepteurs de forte affinité pour les IgE (RFcγI), qui contiennent des motifs d'activation nommés ITAM, induit l'activation des mastocytes et des basophiles. Les récepteurs de faible affinité pour les IgG (RFcγIIB) contiennent des motifs d'inhibition nommés ITIM et inhibent l'activation cellulaire lorsqu'ils sont coagrégés aux récepteurs à ITAM. Les RFcγIIB inhibent également la prolifération cellulaire induite par les récepteurs à activité tyrosine kinase comme Kit. Les propriétés inhibitrices des RFcγIIB reposent sur le recrutement de l'inositol phosphatase SHIP1, qui dégrade le Phosphatidyl Inositol tri-phosphate PI(3,4,5)P3, une molécule impliquée dans de nombreuses voies de signalisation. Au cours de ma thèse, j'ai montré que lorsqu'ils sont coagrégés avec les RFcγI, les RFcγIIB, inhibent non seulement l'activation induite par ces RFcγI (cis-inhibition), mais aussi l'activation induite par d'autres RFcγI et la prolifération induite par Kit. Nous avons appelé cette nouvelle propriété, la trans-inhibition. De même, la coagrégation de Kit avec les RFcγIIB inhibe l'activation des mastocytes induite par les RFcγI. La trans-inhibition peut être également induite dans les basophiles murins et humains. Finalement, la coagrégation de Kit et des RFcyIIB inhibe la prolifération, dépendante de l'oncogène Abl, d'un mastocytome murin. En conclusion, la trans-inhibition est un nouveau mécanisme de régulation, dépendant de SHIP1, qui induit un état d'anergie de la cellule, l'empêchant de répondre à des signaux d'activation et de prolifération

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Fornůsek, Jan. "Návrh softwarového prostředí pro zpracování dat z měření telekomunikačních sítí." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2012. http://www.nusl.cz/ntk/nusl-219465.

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This document introduces the reader with measurements related to optical networks. This is not a list of all measurements. There are only mentioned selected measurements related to input files into the developed application. The practical part describes the application's documentation.

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Horváth, Tomáš. "Simulace a měření služeb Triple Play v sítích FTTx." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2013. http://www.nusl.cz/ntk/nusl-220307.

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The aim of this thesis was to ascertain with the measurement methods of passive optical networks and the creation of a simulation model that corresponds to the measured network and comparison of results. The first chapter deals with Triple Play services, which are focused on different services (transmission of television signals, voice and data transmission). Each service consists of a subchapter and presents a detailed description of the parameters associated with the transmission. The second chapter of the theoretical part consists of an analysis of passive optical networks according to termination method of FTTx optical fiber. Partial part of this chapter consists of description of standard passive optical networks APON, BPON, GPON and EPON. The EPON standard is explained in detail. The theoretical part of the thesis is concluded with a description of active elements that will form the laboratory measured network. Testing of designed passive optical network is performed in the practical part of the thesis. The measurement is divided into two chapters. The first chapter consist of measuring of the „inanimate network“, as there are missing active elements in the nominated net. Network measurements were done by a direct measuring method and reflectometric method. The second chapter of the practical part consists of measuring the parameters of quality of service (QoS). This chapter is divided into subchapters, such as: the measurement using RFC 2544 standard, the measurement using ITU-T standard Y.156 (EtherSam) and bit error rate testing (BERT). The practical part ends with a designed simulation network model, which was proposed in OptSim 5.2. The aim of the simulation model was to maximally resemble a real network, due to result comparison.

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Nwup, Emineimo Kennedy, and Adesola Idris Akande. "Evaluation of the pre IEEE 802.11s RFC : Aspects of the Design and Implementation of the Mesh Station with RA-OLSR in the C-Core." Thesis, Blekinge Tekniska Högskola, Avdelningen för telekommunikationssystem, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-3883.

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The demand for ubiquitous networks has pushed the designs of networks all the way. The requirement for access point to be integrated into IEEE 802.3 standard and other networks has always been a sore point in the limitation of wireless coverage of IEEE 802.11 standard networks. Wireless Mesh Network (WMN) is expected to be the future of the next generation wireless network. It is experiencing a fast growing development due to its attractive features which includes high reliable connectivity, easy deployment, self healing, self configuring, flexible network expansion etc. Hence the mobility of the WMN nodes has been of paramount importance, which would make it independent of wired infrastructure and flexible interoperability with various networks and devices. The requirements like mobility, transparency etc. have led to the amendment of the WMN standard by the Institute of Electronics and Electrical Engineering (IEEE) 802.11 Working Group (WG), Task Group (TG) “S. The IEEE 802.11s standard tackles these issues by its operation on layer 2 of Open Systems Interconnection (OSI) reference model and creates a transparent IEEE 802 broadcast domain that supports any higher layer protocol. In our work we give the evaluation of the upcoming IEEE 802.11s standard based on its features some of which include routing at layer 2 and medium access control to enable its design and implementation in the existing mesh frame work of Communication Research Labs (CRL) using the proposed IEEE 802.11s routing protocols with focus on RA-OLSR and HWMP. We concentrate on how to integrate these features into the existing CRL’s C-CORE which runs other layer 3 routing protocols and complex functions as Application Programming Interface (API) modules. The implementation of the IEEE 802.11s standard creates major challenges as we have to create a roadmap on integrating the new wireless kernel interfaces like the nl80211, cfg80211 and the Wireless Extension (Wext) into the CRL’s C-CORE framework for communication between user space and kernel space, especially taking into consideration of the existing HAL and madwifi wireless drivers of the CRL’s framework. To support the evaluation of the features like the layer 2 routing and the modified MAC performance, we compare results of the CRL’s real time mesh network test with our simulation result of the IEEE 802.11s standard using the Qualnet 4.5 simulator with focus on the basic network parameters like delay, jitter and throughput. The comparison shows that the CRL’s network has higher throughput running its existing layer 3 protocols. The analysis also proves that the 802.11s is flexible, scalable and efficient in delivering multi hop capabilities to clients that cannot afford the deployment time or the cost for wired networks that use access points. With the complete integration, of the 802.11s standard specifications the CRL’s C-CORE framework can be much more capable of supporting more diverse network scenario deployments. +46-736318897

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