Dissertations / Theses: 'MDRS'

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Costa, Cesar Augusto Sam Tiago Vilanova. "Avaliação da expressão de genes de resistência às múltiplas drogas (MDRs) e de metabolização em diferentes linhagens celulares tratadas com complexos metálicos de rutênio." Universidade Federal de Goiás, 2013. http://repositorio.bc.ufg.br/tede/handle/tede/3769.

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Foi com a descoberta da atividade antimitótica da cisplatina por Rosenberg na década se 1960 e 70, em seu célebre estudo com bactérias Escherichia coli, que surgiu o interesse em sintetizar e entender as bases moleculares responsáveis pelo mecanismo de ação biológica dos compostos metálicos, visto que a própria cisplatina foi inicialmente sintetizada por Peyrone nos idos de 1840. Os primeiros estudos envolvendo o uso de complexos metálicos de rutênio como agentes antitumorais foram realizados por Tochter no final dos anos 1980 (Dale et al., 1992). Àquela época, foi inferido que todos os compostos de rutênio apresentavam como mecanismo de ação, a sua ligação com o DNA, formando adutos e desencadeando processos celulares de natureza deletéria que, por fim, levariam a morte celular. É interessante lembrar que esse é o mesmo mecanismo de ação dos compostos de platina mais aceitos nos dias atuais. Sadler e Dyson (2003) estudando compostos de rutênio que continham cloro em sua estrutura, como o cloreto de cis-(dicloro)tetraaminorutênio(III) [cis-[RuCl2(NH3)4]Cl], observaram que estes compostos apresentavam mecanismos de ação biológica muito parecidos com os apresentados pela cisplatina [Pt(NH3)2Cl2], onde a hidrólise da ligação Ru–Cl pode ser fortemente influenciada pela natureza dos coligantes presentes na estrutura do rutenato, como grupamentos amino ou até mesmo pela presença de átomos de carbono. A alta concentração de cloretos no sangue permite a esses compostos metálicos, levados por proteínas séricas, chegar até as células e atravessar sua membrana celular e nuclear. Uma vez no interior do núcleo, a ligação Ru–Cl é hidrolisada, devido a queda abrupta da concentração de cloretos (que é cerca de 25 vezes menor), levando o composto a se ligar ao DNA, mais especificamente à posição N7 da base nitrogenada guanina. Por outro lado, compostos que não possuem cloro em sua estrutura, parecem apresentar mecanismos de ação diferentes ao padrão "ligação ao DNA". Sabe-se que compostos que apresentam carboxilatos em sua molécula, como a carboplatina, oxaliplatina e o próprio ditionato de cis-tetraammino(oxalato)rutênio(III) [Cis-[Ru(C2O2)(NH3)4]2(S2O6)], uma vez no interior das células, são hidrolisados muito mais lentamente do que os compostos ricos em cloretos, o que leva a um acúmulo desses compostos no citoplasma, diminuindo sua migração até o núcleo e, assim reduzindo a sua capacidade de se ligar ao DNA. Mas se o DNA não é o alvo desses compostos, então, quem poderia ser? Essa pergunta está sendo respondida com recentes estudos, que revelaram a interação desses compostos, ricos em carboxilatos, com uma miríade de proteínas e enzimas, que vão desde catepsinas, chegando até mesmo à Pgp (Melchart & Sadler, 2008). Estudos realizados por Dyson e colaboradores (2007), utilizando alguns inibidores da proteína Pgp, como fenoxazinas e antracenos, coordenados com compostos de rutênio, observaram que estes novos complexos não somente inibiram a ação da enzima, como também induziram morte celular, demonstrando uma multifuncionalidade. Seguindo essa linha de pensamento, acreditamos que a capacidade do composto ditionato de cistetraammino(oxalato)rutênio(III) em induzir apoptose nas células tumorais, assim como os baixos níveis de expressão de Pgp apresentados pelas células tratadas, corroboram os resultados previamente observados por outros grupos, utilizando compostos de rutênio similares. A resistência a fármacos mediada por Pgp é o mecanismo de MDR mais estudado atualmente. Apesar do desenvolvimento de novos agentes antitumorais, a MDR mediada pela Pgp protege as células de possíveis agentes citotóxicos, limitando a eficácia dos tratamentos quimioterápicos em pacientes com câncer. Atualmente, a extensa maioria dos inibidores da Pgp disponíveis estão associados a vários inconvenientes, que limitam o seu uso no reestabelecimento da eficácia da quimioterapia antineoplásica, após o aparecimento do fenótipo MDR. A procura de inibidores de Pgp alternativos, com um processo sintético exequível e efeitos secundários reduzidos, continua a ser um desafio para os químicos, farmacêuticos e pesquisadores. É nesse contexto que estão sendo desenvolvidos e estudados novos agentes antitumorais que possam agir como inibidores de Pgp, apresentando um efeito dual, ou até mesmo multifuncional, no tratamento clínico das neoplasias malignas. Muito tem se discutido que a próxima geração de fármacos antitumorais poderá ser formada por substâncias que se ligam a mais do que um único alvo terapêutico, o que poderia acelerar tratamento contra a doença, reduzindo o número e a concentração de fármacos que deveriam ser administrados, como os coquetéis atualmente utilizados, e até mesmo aumentando a adesão ao tratamento por parte do paciente. No presente trabalho, estudamos dois complexos de rutênio, o cloreto e o ditionato de rutênio(III), que se apresentam como promissores no possível desenvolvimento de um novo fármaco antitumoral. Essa promessa transparece no fato de ambos serem de síntese química relativamente simples (processo sintético exequível) e, principalmente, por apresentarem efeito biológico de interesse em células tumorais, como citotoxicidade e indução de morte celular, especialmente por apoptose. Pelo que foi observado nos resultados de nossa pesquisa, os complexos aqui estudados, podem constituir um modelo para o estudo de novos agentes anticancerígenos com concomitante capacidade de não induzir MDR. Esta característica se mostrou muito evidente sobre a linhagem leucêmica K-562, onde os níveis de expressão de MDR1, após o tratamento com os rutenatos, foram muito inferiores aos apresentados pelas células tumorais tratadas com o fármaco controle Cisplatina. Ainda, é importante pontuar que o composto ditionato de cistetraammino(oxalato)rutênio(III) apresentou efeito citotóxico em ambas as linhagens tumorais K-562 e A549, sem contudo induzir altos níveis de expressão de Pgp (MDR1), apresentados pelos fármacos platinados. Assim, estudos mais aprofundados sobre a estrutura e funcionamento biológico desses complexos de rutênio, representam um ponto de partida interessante para o desenvolvimento de fármacos multifuncionais e de efeito desejável, auxiliando na delineação de estudos clínicos dirigidos a grupos selecionados de pacientes que reúnam características genotípicas e fenotípicas preditivas de máxima resposta terapêutica com mínima toxicidade. Posteriormente, estes estudos podem levar às realizações de testes diagnósticos e farmacológicos mais eficazes que poderão ser estabelecidos como rotina voltada para uma melhor definição de tratamentos. Isso traria um maior sucesso no teste de novos medicamentos e reduziria os custos e riscos, minimizando o tempo gasto para aprovação de um novo medicamento e a sua disponibilização para a sociedade.

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Stege, Alexandra Eva. "Überwindung der P-Glykoprotein (MDR1)-abhängigen Multidrugresistenz mittels RNA-Interferenz." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2007. http://dx.doi.org/10.18452/15578.

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P-Glykoprotein als Produkt des MDR1-Gens stellt einen gut untersuchten Mediator der Multidrugresistenz (MDR) in humanen Malignomen dar. Die Überexpression dieses ABC-Transporters steht in Korrelation zu einer erniedrigten Tumorremission und einer kürzeren Überlebensrate der Patienten. Bisherige Versuche, das Protein über niedermolekulare Substanzen (MDR-Modulatoren) zu inhibieren, vermochten in allen bisherigen klinischen Studien nicht zu überzeugen, so daß diese bis heute keinen Eingang in Standardtherapieschemata gefunden haben. Ziel dieser Arbeit war es, mittels RNA-Interferenz Strategien die Expression von MDR1 zu hemmen und eine Reversion der zellulären Chemoresistenz sowohl im Zellkultur- als auch im Tiermodell zu erreichen. Für die in vitro Untersuchungen an drei humanen multidrug-resistenten Karzinomzellinien wurden verschiedene siRNA (short interfering) Duplexe und shRNA (short hairpin)-exprimierende Vektoren gegen die MDR1 mRNA entwickelt. Die Behandlung der Zellen mit siRNAs führte zu einer bis zu 91 %igen Inhibition der MDR1 mRNA-Expression und zu einer Sensitivierung der Zellen gegenüber dem Anthrazyklin um 89 %. Diese Effekte konnte über einen Zeitraum von drei bis fünf Tagen aufrechterhalten werden. Die stabile Expression von anti-MDR1 shRNAs führte in zwei der untersuchten Zellmodelle zu einer dauerhaften und kompletten Überwindung des MDR1-abhängigen Resistenzphänotyps. Im Mausmodell konnte durch intratumorale Applikation des anti-MDR1 shRNA-kodierenden Vektors mittels low-volume Jet-Injektion eine komplette Reversion der MDR1-Überexpression sowie eine Wiederherstellung der Chemosensitivität gegenüber Doxorubicin in dem resistenten Tumormodell erreicht werden. Die Effizienz der kombinierten Gen- und Chemotherapie wird durch die Verminderung des in vivo Tumorwachstums auf das Volumen des von der sensiblen Zellinien-abgeleiteten Tumors reflektiert.
Multidrug resistance (MDR) is the major cause of failure of effective chemotherapeutic treatment of disseminated neoplasms. The "classical" MDR phenotype of human malignancies is mediated by drug extrusion by the adenosine triphosphate binding cassette (ABC)-transporter P-glycoprotein (MDR1/P-gp). For stable reversal of "classical" MDR in three human cancer cell lines by RNA interference (RNAi) technology, two small interfering RNA (siRNA) constructs and four H1-RNA gene promoter-driven expression vectors encoding anti-MDR1/P-gp short hairpin RNA (shRNA) molecules were constructed. In all cellular systems, siRNAs could specifically inhibit MDR1 expression up to 91% at the mRNA and protein levels. Resistance against daunorubicin was decreased to a maximum of 89%. The introduction of anti-MDR1/P-gp shRNA expression vectors leads in two of the three human cancer cell lines to a complete reversion of the MDR phenotype. The reversal of MDR was accompanied by a complete suppression of MDR1/P-gp expression on mRNA and protein level, and by a considerable increased intracellular anthracyline accumulation in the anti-MDR1/P-gp shRNA-treated cells. In a mouse xenograft model a complete in vivo restoration of MDR1 overexpression and chemosensitivity to doxorubicin could be obtained by intratumorally jet-injected anti-MDR1 shRNA in a multidrug resistant human cancer tumor model.

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Baja, Karine Gehlen. "Farmacocinética do cloridrato de tramadol administrado por via oral em cães com a mutação nt230(del4) no gene MDR1." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/79520.

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A P-glicoproteína (P-gp) é uma transportadora transmembrana de múltiplos fármacos, produto do gene MDR1 (ABCB1). A P-gp contribui para a função de barreira de vários tecidos e órgãos, funcionando como uma bomba de efluxo para muitos substratos. Diminuição na expressão desta proteína é associada à sensibilidade a fármacos. Cães da linhagem dos Collies possuem uma alta incidência de uma mutação no gene MDR1, denominada nt230(del4). Animais homozigotos para a mutação apresentam a supressão total de uma P-gp funcional e um animal heterozigoto apresenta uma maior sensibilidade para substratos da P-gp, devido a uma diminuição na expressão da mesma. Alguns fármacos opioides, como a morfina e a metadona, foram identificados como substratos da P-gp. O tramadol é um dos analgésicos opioides mais utilizados em cães. No presente trabalho, a mutação MDR1 nt230(del4) foi analisada em vinte cães Collie, utilizando reação em cadeia de polimerase (PCR). A identificação foi realizada por eletroforese em gel de poliacrilamida de alta resolução, sendo o resultado confirmado por análise de sequênciamento de DNA. Como resultado, seis cães apresentaram normalidade nos dois alelos e 14 apresentaram heterozigose para a mutação. Estes animais foram submetidos à segunda fase do experimento, quando se administrou uma dose única de 100 mg de tramadol oral de liberação prolongada (SR), objetivando investigar o tramadol como sendo substrato da P-gp. Outro objetivo foi avaliar a farmacocinética deste tipo de formulação, pois ainda não foi estabelecida para cães. A análise farmacocinética do tramadol foi realizada utilizando cromatografia líquida de alta eficiência (CLAE) com detecção por espectrometria de massas para a determinação e quantificação de tramadol no soro canino. O analito e o padrão interno foram extraídos do soro por método líquido-líquido. A separação cromatográfica foi obtida a partir de uma coluna analítica C18, mantida a 30°C, sob condições isocráticas de uma fase móvel constituída por uma mistura de acetonitrila e ácido fórmico a 0,1% (80:20). A concentração de tramadol no soro foi maior do que o limite de quantificação (LOQ), em 17 cães. Os cães foram divididos em dois grupos, cães normais (MDR1 +/+) e heterozigotos (MDR1 +/-). Os cálculos farmacocinéticos para o tramadol oral SR obtiveram valores médios de concentração máxima no soro (Cmax) de 63,12 ng/mL ± 33,35 para o grupo normal e 58,00 ng/mL ± 27,29 para o grupo heterozigoto. Tmax (tempo de concentração plasmática maxima) foi de 4 h para ambos os grupos e t ½ (meia-vida) foram 2,85 h ± 1,61 e 2,81 ± 1,46 h para os cães normais e heterozigotos, respectivamente. A área sob a curva (AUC) média para o tramadol oral SR para o grupo normal e heterozigoto foram 350,20 ± 216,61 e 312,15 ± 155,43 ng.h/mL, respectivamente. A biodisponibilidade foi de 22% e 23% para os cães normais e heterozigotos, respectivamente. Não houve diferença estatística entre os grupos em todos os parâmetros farmacocinéticos. Os resultados sugerem que o tramadol não é um substrato da Pgp. A quantidade de dados farmacocinéticos do tramadol oral na formulação de liberação prolongada (SR) em cães é escassa, sendo necessários mais estudos farmacocinéticos e farmacodinâmicos para o tramadol oral de liberação prolongada em cães para estabelecer adequada dose e frequência de administração em cães.
The P-glycoprotein (P-gp) is a transmembrane multidrug transporter, product of the MDR1 (ABCB1) gene. P-gp contributes to the barrier function of several tissues and organs, acting as an efflux pump for many substrates. Decreased expression of this protein is associated with sensitivity to drugs. Collie dogs have a high incidence of a mutation in MDR1 gene, denominated MDR1 nt230 (del4). In homozygosis, this mutation results in the total absence of a functional P-gp and a heterozygote animal presents a greater sensibility to P-gp substrates, probably due to a decrease in the expression thereof. Some opioid drugs such as morphine and methadone were identified as P-gp substrates. Tramadol is one of the most commonly opioid used in dogs. In the present work MDR1nt230 (del4) mutation was analyzed in 20 healthy Collie dogs using allele-specific polymerase chain reaction (PCR) method. Thereby, 6 homozygous intact and 14 heterozygous mutated MDR1 genotypes can be differentiated by high resolution polyacrylamide gel electrophoresis, confirmed by DNA sequence analysis. These animals underwent the second phase of the experiment, when a single oral administration of 100 mg of sustained release (SR) tramadol was administrated to investigate the tramadol as P-gp substrate. In addition, another aim was evaluate the pharmacokinetics of sustained release formulation, which has not been established for dogs. Pharmacokinetic analysis of tramadol was evaluated using high performance liquid chromatography (HPLC) with tandem mass spectrometry for determination and quantification of tramadol in canine serum. The analyte and internal standard (IS) were extracted from serum using liquid-liquid method. Chromatographic separation was achieved on a C18 analytical column, kept at 30°C, under isocratic conditions of a mobile phase consisted by a mixture of acetonitrile and water contained 0,1% formic acid (80:20). Serum tramadol concentration was greater than the limit of quantification (LOQ) in 17 dogs. The dogs were divided into two groups, normal dogs (MDR1 +/+) and heterozygous (MDR1 +/-) according to the MDR1 genotype. The median values of maximum serum concentration (Cmax) were 63.13 ng/mL ± 33.35 for the normal group and 58.01 ng/mL ± 27.29 for the heterozygous group. Tmax (time to maximum serum concentration) was 4 h for both groups and t ½ (half-life) were 2,85h ± 1,61 e 2,81h ± 1,46 for normal and heterozygous dogs, respectively. The mean area-under-the-curve (AUC) values for the sustained release tramadol compounds for the normal and heterozygous group were 350,20 ±216,61 and 312,15 ± 155,43 ng.h/mL, respectively. The bioavailability was 22% and 23% for normal and heterozygous dogs respectively. There was no statistic difference between groups in all pharmacokinetics parameters. The findings suggest that tramadol is not a P-gp substrate. The amount of pharmacokinetics data of SR formulation of tramadol in dogs is sparse. Therefore, more studies of oral SR tramadol in dogs are needed to establish appropriate dose and frequency of administration in dogs.

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Xie, Song [Verfasser], and Ulrich [Akademischer Betreuer] Landgraf. "A gas monitoring chamber for ATLAS MDTs = Eine Gas Monitoring Chamber für ATLAS MDTs." Freiburg : Universität, 2011. http://d-nb.info/1123464561/34.

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Huchton, Scott. "Secure mobile distributed file system (MDFS)." Thesis, Monterey, California. Naval Postgraduate School, 2011. http://hdl.handle.net/10945/5758.

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Approved for public release; distribution is unlimited
The goal of this research is to provide a way for frontline troops to securely store and exchange sensitive information on a network of mobile devices with resiliency. The first portion of the thesis is the design of a file system to meet military mission specific security and resiliency requirements. The design integrates advanced concepts including erasure coding, Shamir's threshold based secret sharing algorithm, and symmetric AES cryptography. The resulting system supports two important properties: (1) data can be recovered only if some minimum number of devices are accessible, and (2) sensitive data remains protected even after a small number of devices are compromised. The second part of the thesis is to implement the design on Android mobile devices and demonstrate the system under real world conditions. We implement and demonstrate a functional version of MDFS on Android hardware. Due to the device's limited resources, there are some issues that must be explored before MDFS could be deployed as a viable distributed file system.

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Barry, Jennifer L. (Jennifer Lynn). "Fast approximate hierarchical solution of MDPs." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/53202.

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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2009.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 89-91).
In this thesis, we present an efficient algorithm for creating and solving hierarchical models of large Markov decision processes (MDPs). As the size of the MDP increases, finding an exact solution becomes intractable, so we expect only to find an approximate solution. We also assume that the hierarchies we create are not necessarily applicable to more than one problem so that we must be able to construct and solve the hierarchical model in less time than it would have taken to simply solve the original, flat model. Our approach works in two stages. We first create the hierarchical MDP by forming clusters of states that can transition easily among themselves. We then solve the hierarchical MDP. We use a quick bottom-up pass based on a deterministic approximation of expected costs to move from one state to another to derive a policy from the top down, which avoids solving low-level MDPs for multiple objectives. The resulting policy may be suboptimal but it is guaranteed to reach a goal state in any problem in which it is reachable under the optimal policy. We have two versions of this algorithm, one for enumerated-state MDPs and one for factored MDPs. We have tested the enumerated-state algorithm on classic problems and shown that it is better than or comparable to current work in the field. Factored MDPs are a way of specifying extremely large MDPs without listing all of the states. Because the problem has a compact representation, we suspect that the solution should, in many cases, also have a compact representation. We have an implementation for factored MDPs and have shown that it can find solutions for large, factored problems.
by Jennifer L. Barry.
S.M.

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Kaszubiak, Alexander. "Adenoviraler Transfer von anti-MDR1 shRNAs." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2007. http://dx.doi.org/10.18452/15644.

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Tumoren entwickeln während einer Chemotherapie häufig Resistenzen gegen strukturell und funktionell unabhängige Zytostatika - ein Phänomen, das als Multidrug-Resistenz (MDR) bezeichnet wird und die Hauptursache für das Scheitern einer Chemotherapie ist. Die klassische MDR ist mit einer Überexpression des ABC-Transporters MDR1/P-gp assoziiert. Der vorliegende gentherapeutische Ansatz beinhaltet eine selektiv gegen MDR1/P-gp gerichtete und vor allem effiziente Strategie zur Überwindung des MDR-Phänotyps humaner Tumorzellen. Basierend auf der Integration verschiedener anti-MDR1 shRNA Expressionskassetten in adenovirale Gentherapievektoren, konnte mit Hilfe der RNA-Interferenz Technologie (RNAi) die MDR1/P-gp Expression selektiv inhibiert werden. Mittels des hoch effizienten Adenovirus Ad5U6/MDR-C wurde die MDR1 mRNA- sowie Protein-Expression soweit reprimiert, dass eine vollständige Aufhebung der biologischen Aktivität der Effluxpumpe MDR1/P-gp und eine Reversion des Resistenz Phänotyps gegenüber den typischen MDR1/P-g-Substraten Daunorubicin (87 % in EPP85-181RDB bzw. 66 % in EPG85-257RDB) sowie Vincristin (96 % bzw. 82 %) resultierte. Zudem wurde gezeigt, dass E1-deletierte und damit replikationsinkompetente Adenoviren in multidrug-resistenten Tumorzellen replizieren können. Damit wirkt Ad5U6/MDR-C in MDR-Tumorzellen onkolytisch. Zwar konnte die Adenovirusreplikation mit dem DNA-Synthese-Hemmer Hydroxyurea (HU) zu 94 % inhibiert werden, die anti-MDR1 Effizienz von Ad5U6/MDR-C wurde dennoch erhöht (+5 % in HeLaRDB, +12 % in EPG85-257RDB), was für eine erfolgreiche und niedrig dosierte Ad-Gentherapie multidrug-resistenter Tumoren in Kombination mit HU ausgenutzt werden kann. Außerdem wurde der entscheidende Einfluss des regulatorischen Proteins YB-1 auf die selektive Replikation von Ad5U6/MDR-C in MDR1/P-gp überexprimierenden Tumorzellen gezeigt. Eine 90 %ige Inhibition von YB-1 bedingt eine Hemmung der Adenovirusreplikation um 70 % und damit eine verringerte Effizienz der RNAi-vermittelten Inhibition von MDR1/P-gp um 40 %. Mit diesem gentherapeutischen Ansatz können die Effekte der YB-1-abhängigen und der die Zelllyse bedingenden Adenovirusreplikation sowie der anti-MDR1 shRNA vermittelten Chemosensitivierung kombiniert und zu einer verbesserten Eliminierung von MDR-Tumorzellen führen.
Simultaneous resistance of cancer cells to multiple cytotoxic drugs, multidrug resistance (MDR), is the major limitation to the successful chemotherapeutic treatment of disseminated neoplasms. The ‘classical’ MDR phenotype is conferred by MDR1/P-glycoprotein (MDR1/P-gp) that is expressed in almost 50% of human cancers. Recent developments in the use of small interfering RNAs for specific inhibition of gene expression have highlighted their potential use as therapeutic agents. DNA cassettes encoding RNA polymerase III promoter-driven siRNA-like short hairpin RNAs (shRNAs) allow long-term expression of therapeutic RNAs in targeted cells. A variety of viral vectors have been used to deliver such cassettes to mammalian cells. In this study, the construction of different adenoviruses for anti- MDR1/P-gp shRNA delivery in different human multidrug-resistant cancer cells was investigated. It could be demonstrated that MDR1/P-gp mRNA and protein expression could be completely inhibited by adenoviral delivery of anti-MDR1/P-gp shRNAs. This down regulation in mRNA and protein expression was accompanied by a complete inhibition of the pump activity of MDR1/P-gp and a reversal of the multidrug-resistant phenotype. Moreover, it could be demonstrated that MDR-tumour cells facilitate adenoviral replication of originally E1- and E3-deleted and thus replication deficient adenoviral vectors through stable relocation of the fundamental regulatory factor YB-1 to the nucleus. To analyse the impact of YB-1 on adenoviral replication, two specific in vitro MDR models were used which stably trigger YB-1 posttranscriptional gene-silencing via the RNA interference (RNAi) pathway, i.e. the MDR cell line EPG85-257RDB well as its drug-sensitive counterpart EPG85-257P. The YB-1 gene-silencing effects of 90 % were accompanied by a reduction of adenoviral gene expression of 70 %. In conclusion, the data demonstrate that an highly efficient adenoviral delivery of shRNAs can chemosensitise human cancer cells and that YB-1 is involved in the regulation of adenoviral gene expression of originally replication deficient Ad-vectors in MDR cancer cells.

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Marthinet, Eric. "Modulation du phénotype typique de multichimiorésistance (MDR) des cellules cancéreuses humaines par des leurres transcriptionnels et étude de la régulation transcriptionnelle du gène MDR1 au niveau de la région MED-1." Lyon 1, 2001. http://www.theses.fr/2001LYO10021.

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Le phenotype de multichimioresistance mdr est une cause majeure de l'echec de la chimiotherapie anticancereuse. Le phenotype dit typique s'explique entre autres par la surexpression de proteines membranaires parmi lesquelles la plus importante est la glycoproteine-p (p-gp) codee par le gene mdr1 chez l'homme. La modulation du phenotype mdr est une priorite majeure du traitement clinique anticancereux. Dans cette optique, nous developpons au laboratoire des strategies innovantes et efficaces pour moduler le phenotype mdr en agissant non pas sur la proteine elle-meme mais sur son gene. Ces approches sont basees sur l'utilisation de leurres transcriptionnels (destines a devier la fixation de proteines regulatrices sur ces leurres plutot que sur leur region regulatrice) et de ribozymes (petits arn capables de cliver l'arn messager du gene mdr1) pour reduire l'expression de la p-gp. Les resultats positifs de modulation obtenus avec les leurres transcriptionnels sur les modeles cellulaires construits au laboratoire ont ete transposes avec succes a des cellules tumorales mdr in vitro et seront testees prochainement sur des cellules in situ. L'issue de ces tests permettra d'envisager serieusement l'usage de ces approches pour le traitement clinique des cancers. De plus, afin de mieux comprendre la regulation de la transcription du gene mdr1, nous avons isole et identifie une proteine qui interagit specifiquement avec une region regulatrice specifique du gene mdr1, appelee med-1. Le role de cette region consisterait a initier correctement la transcription du gene. Nous avons identifie cette proteine par spectrometrie de masse maldi-tof comme etant la proteine lrp130. Nous avons egalement entrepris l'etude du role de cette region

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Dias, Michele Carrett. "Mecanismo de ação do ácido acetilsalicílico em linhagens celulares leucêmicas MDR e não MDR." reponame:Repositório Institucional da FURG, 2007. http://repositorio.furg.br/handle/1/229.

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Dissertação (mestrado)-Universidade Federal do Rio Grande, Programa de Pós-Graduação em Ciências Fisiológicas – Fisiologia Animal Comparada, Instituto de Ciências Biológicas, 2007.
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As estatísticas com relação ao câncer são impiedosas. Uma em cada cinco pessoas desenvolverá uma forma de câncer em determinado momento de sua vida e ainda é importante considerar que tumores malignos já foram constatados também em plantas e em outros animais. Além das ferramentas convencionais para o tratamento do câncer, que incluem radioterapia, quimioterapia e cirurgia, outras terapias alternativas têm sido propostas, como a terapia fotodinâmica. Uma outra tentativa promissora no combate ao câncer vem sendo demonstrada com o uso do ácido acetilsalicílico (AAS). O AAS, o salicilato mais importante da família de drogas antiinflamatórias não-esteróides (NSAIDs), adquiriu popularidade em 1899, quando foram reconhecidas suas propriedades antiinflamatórias. Dados experimentais sugerem que AAS e outros membros da família de NSAIDs inibem o crescimento de células cancerosas in vitro e in vivo. É atribuído às prostaglandinas o poder de iniciar e promover o câncer por causar a proliferação celular, inibição da apoptose (morte celular programada), estimulação da angiogênese ou supressão da resposta imune. Inibir a enzima Cox está relacionado com a ini bição da produção de prostaglandinas, sugerindo assim a inibição do processo de cancerização. O AAS inibe irreversivelmente a enzima Cox em determinados tipos celulares, sendo que esta inibição é não -seletiva para ambas as isoformas da Cox; Cox-1 (isoforma constitutiva) e Cox-2 (isoforma induzida). Entretanto, estudos sugerem que o efeito antiproliferativo de AAS não está correlacionado exclusivamente com a ação inibitória da enzima Cox, já que existem relatos mostrando que NSAIDs podem induzir apoptose em células de câncer de cólon que não expressam a proteína Cox-2. Neste sentido, alguns autores demonstraram uma inibição no crescimento in vitro de células tumorais do endométrio humano pelo AAS, de uma maneira dose-dependente, sendo a apoptose um dos mecanismos envolvidos nesta resposta, mediada em parte pela “downregulation” do gene bcl-2. A redução no número de apoptoses contribui para o desenvolvimento do câncer sendo o gene bcl-2 o primeiro membro de uma família de genes que regulam este processo. Foi demonstrado que a superexpressão do gene bcl-2 aumenta a sobrevida das células tumorais protegendo-as da toxicidade causada pelos quimioterápicos, não permitindo que a apoptose ocorra. Por outro lado, a indução da apoptose é uma das ações centrais pela qual a proteína P53 exerce função na supressão do tumor. Esta proteína previne a transmissão da informação genética defeituosa para a geração das células seguintes, sendo denominada “a guardiã do genoma” e a perda desta função é um achado freqüente em câncer. A mutação do gene p53 provavelmente inativa a função supressora da proteína P53, conferindo vantagem de crescimento celular, podendo contribuir para o desenvolvimento de tumores, dentre eles, as leucemias. Também a propriedade antioxidants das NSAIDs tem si do investigada, sendo que alguns autores também atribuem a isso os efeitos antitumorais do AAS. Também é de extrema relevância considerar a possibilidade de que determinadas células tumorais podem adquirir resistência a múltiplas drogas, caracterizando o f enótipo MDR. Atualmente, a procura de novas drogas capazes de vencer o mecanismo MDR e conduzir a morte de células tumorais é de extrema importância para a terapia do câncer. Assim, criar um modelo biológico que permita estudos comparativos entre uma linhagem tumoral MDR e uma não MDR é pertinente. Com base nas informações levantadas sobre a possível atividade antitumoral do AAS, objetivamos analisar como parâmetros de estudo sua citotoxicidade (em células tumorais e não tumorais); morte celular; atividade antioxidante e alterações de expressão nos genes cox-2, bcl2 e p53, utilizando como modelos biológicos linhagens celulares normais e tumorais MDR e não MDR. AAS inibiu a proliferação celular ou induziu toxicidade nas linhagens celulares K562 e Lucena desco nsiderando o fenótipo MDR. O tratamento com AAS provocou morte, nas células K562, principalmente por apoptose inicial e por necrose, nas células Lucena. Também AAS mostrou uma capacidade antioxidante em ambas linhagens. A expressão do gene bcl-2 não apresentou diferenças significativas, considerando as células controle e tratadas com AAS, bem como as duas linhagens celulares. Para os genes p53 e cox-2, a expressão foi concentração dependente para as células K562. Já para as células Lucena, a expressão de ambos os genes foi aumentada nas menores concentrações e, para o gene p53, diminuída na maior concentração quando comparadas as células controle. Como o perfil das expressões foi similar para os genes p53 e cox-2 foi possível sugerir um fator de transcrição comum, justificando esta resposta. Por outro lado, os linfócitos normais tratados com as mesmas concentrações de AAS foram mais resistentes do que as linhagens tumorais. Os resultados deste trabalho mostraram que as duas linhagens celulares foram sensíveis ao tratamento com AAS, mas permitem sugerir que o mecanismo de ação foi diferenciado nas linhagens MDR e não MDR.

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Garnier, France. "Study of transcription regulation of the gene mdr1." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56986.

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In order to characterize cis-acting sequences and trans-acting factors important in regulating the expression of the mouse mdr1 gene, in vitro DNAsel footprinting experiments were carried out on a mdr1 promoter segment between positions $-$245 and +84, using nuclear protein extracts prepared from cell lines expressing different endogenous amounts of mdr1 mRNAs. Three footprinted sequences were detected on the non-coding strand of the $-$245 to +84 mdr1 promoter fragment (between -77 to -56, between -46 to -24, and between +5 and +15) with nuclear extracts from mdr1 expressing cells (CMT-93, LTA, and Y-1 cells). In addition, a specific footprinted sequence ($-$14 to +5) was detected on both strands only with nuclear extracts from the mdr1 non-expressing cell line (RAG cells) suggesting the presence and binding of a putative negative regulatory factor in these cells. However, replacement of this sequence in the mdr1 basal promoter ($-$93 to +84) by a heterologous, although similar positioned SV40 sequence did not restore promoter activity in RAG cells. The basal mdr1 promoter was further characterized in bidirectional deletion mutants, in order to identify cis-acting elements important for general transcriptional regulation. These studies further localized the mdr1 basal promoter between positions $-$74 and +84, and also suggested the presence of possible positive and negative cis-acting sequence elements modulating the activity of this basal promoter.

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Cruz, Gabriel M. Eng Massachusetts Institute of Technology. "Solving Dec-MDPs with options and intention recognition." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/106028.

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Thesis: M. Eng. in Computer Science and Engineering, Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2016.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 31-32).
In this thesis, we designed and implemented an algorithm to find approximate solutions to multi-agent systems. We model the problems with a Decentralized Markov Decision Process, and we make use of options and intention recognition to solve the problem. Rather than directly solving the Dec-MDP, which is NEXP-Complete, we instead solve a set of single-agent MDPs, that we can solve in P-Complete, and combine these solutions during execution time. We tested our algorithm on several instances of the Bribed Package Retrieval Problem and we were able to handle problems as large as our MDP solver would allow, which is a big improvement over what optimal Dec-MDP solvers can handle.
by Gabriel Cruz.
M. Eng. in Computer Science and Engineering

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Wingate, David. "Solving Large MDPs Quickly with Partitioned Value Iteration." Diss., CLICK HERE for online access, 2004. http://contentdm.lib.byu.edu/ETD/image/etd437.pdf.

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Zheng, Zhaohua. "Intracellular delivery of MDR drugs." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492718.

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One of the most important mechanisms for multidrug resistance (MDR) phenotype is believed be the P-gp-mediated drug efflux. The consequent lowering of the intracellular concentrations of many commonly-used chemotherapeutic drugs, such as doxorubicin (Dox), has been addressed by P-gp inhibition via covalent attachment of MDR drugs to carriers.This project aimed to develop new drug binding peptide structures able to traverse cell membranes and to investigate their potential in the 'non'-covalent' deiivery of Dox in drug-resistant (KD30) cells.

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Edwards, Helen Jane. "Transcriptional and post-transcriptional regulation of MDR1 expression during oxidative stress and recovery : a spatial and temporal study of MDR1 mRNA localization." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438197.

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Alfaris, Anas (Anas Faris). "Emergence through conflict : the Multi-Disciplinary Design System (MDDS)." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/49718.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Architecture, 2009.
Includes bibliographical references (p. 413-430).
This dissertation proposes a framework and a group of systematic methodologies to construct a computational Multi-Disciplinary Design System (MDDS) that can support the design of complex systems within a variety of domains. The way in which the resulting design system is constructed, and the capabilities it brings to bare, are totally different from the methods used in traditional sequential design. The MDDS embraces diverse areas of research that include design science, systems theory, artificial intelligence, design synthesis and generative algorithms, mathematical modeling and disciplinary analyses, optimization theory, data management and model integration, and experimental design among many others. There are five phases to generate the MDDS. These phases involve decomposition, formulation, modeling, integration, and exploration. These phases are not carried out in a sequential manner, but rather in a continuous move back and forth between the different phases. The process of building the MDDS begins with a top-down decomposition of a design concept. The design, seen as an object, is decomposed into its components and aspects, while the design, seen as a process, is decomposed into developmental levels and design activities. Then based on the process decomposition, the architecture of the MDDS is formulated into hierarchical levels each of which comprises a group of design cycles that include design modules at different degrees of abstraction. Based on the design object decomposition, the design activities which include synthesis, analysis, evaluation and optimization are modeled within the design modules.
(cont.) Subsequently through a bottom-up approach, the design modules are integrated into a data flow network. This network forms MDDS as an integrated system that acts as a holistic structured functional unit that explores the design space in search of satisfactory solutions. The MDDS emergent properties are not detectable through the properties and behaviors of its parts, and can only be enucleated through a holistic approach. The MDDS is an adaptable system that is continuously dependent on, and responsive to, the uncertainties of the design process. The evolving MDDS is thus characterized a multi-level, multi-module, multi-variable and multi-resolution system. Although the MDDS framework is intended to be domain-independent, several MDDS prototypes were developed within this dissertation to generate exploratory building designs.
by Anas Alfaris.
Ph.D.

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Barroso, Maria Cristina Tenreiro Pereira Rodrigues. "Detection of the MDR1 mutation in Portuguese dog breeds." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2020. http://hdl.handle.net/10400.5/19292.

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Dissertação de Mestrado Integrado em Medicina Veterinária
P-glycoprotein is an ATP-driven drug efflux carrier, encoded by the multidrug resistance gene MDR1, also been referred as ABCB1, that is responsible for the transport of a broad variety of compounds, including drugs commonly used in veterinary medicine, out of the cell against the concentration gradient. The influence of P-gp on drug disposition has been demonstrated in Collies and in other herding dog breeds since a severe intoxication in response to treatment with the antiparasitic drug ivermectin and other avermectins has been reported in a subpopulation of these breeds. This adverse reaction is related to a 4-bp deletion in the ABCB1 gene. To our knowledge, no study was conducted in portuguese dog breeds to detect this gene mutation and there is no available information for the clinicians about this fact and consequently, about the safety of the administration of drugs that are P-gp substrates. Thus, it is important to know the status about the presence of MDR1 in dog breeds in Portugal. The main objective of this project was to implement the genetic test to identify the gene mutation on MDR1 gene and to perform this analysis in several animals from dog breeds in Portugal to obtain their MDR1 genotype. For that, we performed biological samples of saliva in animals from the dog breeds belonging to Group 1 and from the ones already identified as affected. The diagnosis technique used was adapted from the ones utilized by other authors, namely Mealy and collaborators. We analyzed 105 animals, 21.9% of which are Barbado da Terceira, 9.5% are Cão da Serra d’Aires, 52.4% belonging to breeds known to carry the mutation and 16.2% to other breeds. With this study we were able to establish the analysis in our laboratory, we identified the mutation in dogs of breeds already signalized as having the mutation and we evidenced that the mutation already is in Barbado da Terceira - carriers.
RESUMO - DETEÇÃO DA MUTAÇÃO MDR1 NAS RAÇAS CANINAS PORTUGUESAS - A glicoproteína P é um transportador dependente de ATP, codificado pelo gene de resistência a fármacos MDR1, também conhecido como ABCB1, que é responsável pelo transporte contra o gradiente de concentração (para o espaço extracelular) de vários substratos, incluindo fármacos comummente utlizados em Medicina Veterinária. A influencia deste transportador na reação a fármacos foi demonstrada em Collies e outras raças pastoras devido ao desenvolvimento de sinais neurológicos, de intoxicação grave, após o tratamento destes animais com antiparasitários do grupo das avermectinas, nomeadamente, a ivermectina. Esta reação está relacionada com a deleção de 4 pares de base no gene canino ABCB1, descoberta em 2001, em cães com fenótipo sensível à ivermectina. Até à data, não temos conhecimento de nenhum estudo feito em Portugal para detetar esta mutação genética e não existe informação disponível para os clínicos sobre este facto e, consequentemente, sobre a segurança de administração de medicamentos que sejam substratos da gp-P. É, por isso, importante saber-se o estatuto MDR1 em raças caninas em Portugal. O principal objetivo deste trabalho foi implementar o teste genético para identificação da mutação genética no gene MDR1 e realizar esta análise em vários exemplares de raças caninas em Portugal para obter o seu genótipo MDR1. Para o efeito foram realizadas colheitas de amostras biológicas de saliva em exemplares das raças caninas pertencentes ao grupo I e das raças já identificadas como afetadas. A técnica de diagnóstico utilizada foi adaptada das técnicas utilizadas por outros autores, nomeadamente Mealey e colaboradores. Foram analisados 105 animais, 21.9% dos quais são Barbados da Terceira, 9.5% são Cão da Serra d’Aires, 52.4% pertence a raças já identificadas como portadoras da mutação e 16.2% a outras raças. Com a realização deste estudo, conseguimos estabelecer a técnica no nosso laboratório, identificámos a mutação em cães de raças já sinalizadas como tendo a mutação e detetámos evidências que a mutação também circula na raça Barbado da Terceira - portadores.
N/A

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Watanabe, Takashi. "Regret analysis of constrained irreducible MDPs with reset action." Kyoto University, 2020. http://hdl.handle.net/2433/253371.

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Kyoto University (京都大学)
0048
新制・課程博士
博士(人間・環境学)
甲第22535号
人博第938号
新制||人||223(附属図書館)
2019||人博||938(吉田南総合図書館)
京都大学大学院人間・環境学研究科共生人間学専攻
(主査)准教授櫻川貴司, 教授立木秀樹, 教授日置尋久
学位規則第4条第1項該当

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Bettin, Bettina [Verfasser]. "MDR1-Polymorphismen als Suszeptibilitätsfaktor für das Harnblasenkarzinom / Bettina Bettin." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023464918/34.

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Tatsis, Nikolaos. "Constructions for efficient MDS diffusion layers." Thesis, KTH, Skolan för informations- och kommunikationsteknik (ICT), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-215728.

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Matrices are widely used in Block Cipher Diffusion layers, usually chosen for offering maximal branch numbers, and allowing lightweight hardware implementations through their low XOR Count. When implemented in software however, is XOR Count the only metric? This project will utilize the parallelism provided by modern SIMD vector instructions to evaluate metrics, by implementing different algorithmic approaches. Timing their executions will hopefully provide some insight into the effect of the immense complexity of modern architectures and software tools on the expected outcome of an algorithm. A further focus will be the construction of matrices with interesting properties over large extension fields, which can apply in recent white-box cipher designs[BIT16]. This involves implementing a 1979 paper[Mac71], and the translation from mathematical paper to working implementation will involve many coding challenges. Both having an evaluation of matrix diffusion software implementation approaches and another method for finding matrices can ultimately help with the design of more efficient block ciphers.

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Leocadio, Marcelo Augusto. "Código MDS com a métrica POSET." Universidade Federal de Viçosa, 2013. http://locus.ufv.br/handle/123456789/4927.

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Fundação de Amparo a Pesquisa do Estado de Minas Gerais
A poset metric is the generalization of the Hamming metric. In this work we make a detailed study of poset spaces, hierarchy of I -weights and I -distribution of P P weights, emphasizing the non-degenerate poset codes. We verify the duality relation between the hierarchy weights of poset code and its dual. In the sequel two new parameters are defined to a class of poset codes non-degenerate with dual code is too non-degenerate in the environment. As a result enunciated in the Minimality Theorem, the Variance Theorem and the Minimality Identity in the poset spaces.
Uma generalização da métrica de Hamming é a métrica poset. Faremos um estudo detalhado dos espaços poset, hierarquia de I-pesos e a I-distribuição de pesos, dando ênfase aos códigos poset não degenerados. Verificamos a relação de dualidade poset entre as hierarquias de um código e seu dual. Definimos dois novos parâmetros para a classe de códigos dualmente não degenerados no ambiente poset. Como consequência, enunciamos e mostramos o Teorema da Minimalidade, o Teorema da e Variância e a Identidade de Minimalidades no espaço poset.

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Kwan, Tony 1972. "Structural and functional analysis of the mouse Mdr3 P-glycoprotein." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38069.

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Multidrug resistance in certain tumours in vivo and in cultured cells in vitro is caused by the overexpression of P-glycoprotein. Pgps are encoded by a small family of three genes in rodents (mdr1, mdr2, mdr3 ) and two in humans (MDR1, MDR2), and belong to the larger superfamily of ABC transporters, characterized by their ability to transport various substrates at the expense of ATP. Pgps are comprised of 12 transmembrane (TM) domains, some of which are involved in the binding of these drugs, and two intracellular nucleotide-binding (NB) domains that catalyze ATP hydrolysis. Communication occurs between these two regions as drug binding can significantly activate the ATPase activity, and the signalling is thought to occur through the highly conserved intracellular (IC) loops linking the individual TM domains. Using a random mutagenesis approach, mutations were identified in IC1 affecting both substrate specificity and drug-stimulated ATPase activity of Pgp. The finding that mutations in IC1 can modulate the activities of two separate and distinct regions supports the proposed role for the IC loops. Purification of Pgp mutants to a high degree allowed for the further biochemical characterization of selected mutants in IC1. The findings support a role for IC1 in signalling between the two regions: (1) from the TM domains to the NB sites to activate ATPase activity, and (2) in the opposite direction to effect drug release. The analysis of mutations in TM11 provides more support that this helix is involved in protein-substrate interactions and forms part of the drug-binding site. The formation and maintenance of an active drug-binding site through the proper organization and orientation of TM helices are critical to the function of Pgp. Despite the large body of functional data through the characterization of the many naturally occurring and genetically engineered mutants of Pgp, high-resolution structural information of the drug binding site and the overall structur

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Hoffman, Mary M. "Mechanism of MDR protein mediated multidrug resistance /." Access full-text from WCMC, 1997. http://proquest.umi.com/pqdweb?did=733008491&sid=6&Fmt=2&clientId=8424&RQT=309&VName=PQD.

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Cardell, Sara D. "Constructions of MDS codes over extension alphabets." Doctoral thesis, Universidad de Alicante, 2012. http://hdl.handle.net/10045/27320.

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24

Sukhai, Mahadeo A. "Cytokine-mediated pathways of mdr1 gene regulation in cultured rat hepatocytes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ58862.pdf.

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Zobair, Md Hasan. "Modeling and formal verification of a telecom system block using MDGs." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ59312.pdf.

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Lau, Yvonne [Verfasser]. "Untersuchung der Knochen bei hepatischer Osteodystrophie am MDR2-/--Mausmodell / Yvonne Lau." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1058360728/34.

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Hafstad, Ulrika, and Amanda Lundén. "Jämförelse av CKD-EPI och MDRD ekvationsformler för estimerad glomerulär filtrationshastighet." Thesis, Luleå tekniska universitet, Institutionen för hälsovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-72648.

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Bakgrund: Inom yrket som röntgensjuksköterska används dagligen kontrastmedel i samband med undersökningar. För att räkna ut hur mycket kontrastmedel som patienter ska erhålla för att förebygga kontrastinducerade njurskador används ekvationsformler för att räkna ut njurfunktionens glomerulära filtrationshastighet. Två formler som jämfördes var CKD-EPI och MDRD. Syfte: I denna litteraturstudie var syftet att jämföra vilken av de två mest förekommande ekvationsformler är mest optimal att använda för att räkna ut estimerat GFR. Metod: Denna studie genomfördes i form av en litteraturstudie där 11 artiklar kvalitetsgranskades och sammanställdes. Resultat: CKD-EPI-formeln uppvisade generellt bättre prestationsförmåga för noggrannhet, precision och avvikelse än MDRD-formeln för estimering av GFR. Dock hade båda ekvationerna svagheter och är inte universella då MDRD och CKD-EPI-formlerna inte är lämpliga att använda på alla individer. Slutsats: I dagsläget är CKD-EPI-formeln den som ter sig vara mest användbar, dock behövs det mer forskning för att kunna utveckla ekvationsformler som passar för alla typer av patienter.
Background: In the profession as radiology nurse contrast media is used daily in radiologic examinations. In order to determine the volume of contrast media that patients should be administered and to prevent contrast-induced nephropathy equation formulas are applied to calculate the kidney function glomerular filtration rate. Two formulas were compared the CKD-EPI and MDRD. Aim: In this literature study the aim was to compare which of the two most commonly used equation formulas is the most optimal for calculating estimated GFR. Methods: This study was conducted as a literature study, where 11 articles were quality assessed and compiled. Results: The CKD-EPI formula generally showed better performance for estimating GFR in accuracy, precision and bias than the MDRD formula. However, both equation formulas present inadequacies and are not universal as they are not applicable to all individuals. Conclusions: At the moment the CKD-EPI formula appears to be the most applicable, although more research is required in order to develop equation formulas which cater to all types of patients.

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Bhuma, Venkata Deepti Kiran. "Bidirectional LAO algorithm a faster approach to solve goal-directed MDPs /." Lexington, Ky. : [University of Kentucky Libraries], 2004. http://lib.uky.edu/ETD/ukycosc2004t00187/VBThesis.pdf.

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Thesis (m.s.)--University of Kentucky, 2004.
Title from document title page (viewed Jan. 5, 2005). Document formatted into pages; contains vii, 32p. : ill. Includes abstract and vita. Includes bibliographical references (p. 30-31).

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El, Amrani Nora. "Codes additifs et matrices MDS pour la cryptographie." Thesis, Limoges, 2016. http://www.theses.fr/2016LIMO0034/document.

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Cette thèse porte sur les liens entre les codes correcteurs d'erreurs et les matrices de diffusion linéaires utilisées en cryptographie symétrique. L'objectif est d'étudier les constructions possibles de codes MDS additifs définis sur le groupe (Fm2, +) des m-uplets binaires et de minimiser le coût de l'implémentation matérielle ou logicielles de ces matrices de diffusion. Cette thèse commence par l'étude des codes définis sur un anneau de polynômes du type F[x]/f(x), qui généralisent les codes quasi-cycliques. Elle se poursuit par l'étude des codes additifs systématiques définis sur (Fm2, +) et leur lien avec la diffusion linéaire en cryptographie symétrique. Un point important de la thèse est l'introduction de codes à coefficient dans l'anneau des endomorphismes de Fm2. Le lien entre les codes qui sont des sous-modules à gauche et les codes additifs est mis en évidence. La dernière partie porte sur l'étude et la construction de matrices de diffusion MDS ayant de bonnes propriétés pour la cryptographie, à savoir les matrices circulantes, les matrices dyadiques, ainsi que les matrices ayant des représentations creuses minimisant leur implémentation
This PhD focuses on the links between error correcting codes and diffusion matrices used in cryptography symmetric. The goal is to study the possible construction of additives MDS codes defined over the group (Fm2, +) of binary m-tuples and minimize cost of hardware or software implementation of these diffusion matrices. This thesis begins with the study of codes defined over the polynomial ring F[x]/f(x), these codes are a generalization of quasi-cyclic codes, and continues with the study of additive systematic codes over (Fm2, +) and there relation with linear diffusion on symmetric cryptography. An important point of this thesis is the introduction of codes with coefficients in the ring of endomorphisms of Fm2. The link between codes which are a left-submodules and additive codes have been identified. The last part focuses on the study and construction of efficient diffusion MDS matrices for the cryptographic applications, namely the circulantes matrices, dyadic matrices, and matrices with hollow representation, in ordre to minimize their implementations

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Salek-Ardakani, S. "Investigating the molecular basic of AMKL and MDS." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1445038/.

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Malignant haematopoiesis is usually associated with various genetic lesions such as chromosomal translocations or mutations in individual genes. This thesis investigates the genetic basis of two such syndromes, acute megakaryoblastic leukaemia (AMKL) and myelodysplastic syndrome (MDS). The most common constitutional aneuploidy with predisposition to leukaemia is trisomy 21, also known as Down Syndrome (DS). DS children have a 500-fold increased risk for AMKL. Somatic mutations acquired during foetal haematopoiesis in the GATA1 transcription factor are detected in megakaryoblasts from all the DS patients with AMKL. Here we show that the Gatal mutation co-operates with the chromosome 21 gene, ERGS, to immortalize foetal megakaryocyte progenitors with the phenotype of AMKL megakaryoblasts. We show that ERG-3 promotes megakaryopoiesis and acts as an oncogene and that progenitor cells harbouring a Gatal mutation plus ERG-3 or ERG-3 alone lead to rapid development of leukaemia in vivo. Our data support a model where trisomy 21 overexpressed genes, that promote foetal megakaryopoiesis, co-operate with mutations that arrest development and lead to DS-AMKL. This is also the first direct demonstration of the leukaemogenic activity of full length ERG protein, possibly explaining the poor prognosis of the acute myeloid leukaemias with high expression of ERG. DS patients are also predisposed to TMD (transient myeloproliferative disorder) and MDS (myelodysplastic syndrome) prior to AMKL development. Myelodysplastic syndromes are a group of clonal haematopoietic disorders, characterised by aberrant proliferation and differentiation of cells of the myeloid lineage resulting in severe cytopenia and dysplasia of myeloid, erythroid and megakaryocytes. The most common chromosomal translocation associated with MDS is the t(3 5)(q25q35) translocation. This rearrangement results in a fusion transcript comprised of nucleophosmin (NPM) gene and myeloid leukaemia factor 1 (MLF1) gene. To determine the importance of the NPM-MLF1 fusion protein in the development and progression of MDS to AML, its role in myelopoiesis and megakaryopoiesis was investigated. Our results show that NPM-MLF1 affects the differentiation of myeloid cells. Our preliminary data predicts that NPM may have a role in megakaryopoiesis and its interaction with NPM-MLF1 may affect the function of the fusion protein.

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Sani, Lorenzo. "Unsupervised clustering of MDS data using federated learning." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2022. http://amslaurea.unibo.it/25591/.

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In this master thesis we developed a model for unsupervised clustering on a data set of biomedical data. This data has been collected by GenoMed4All consortium from patients affected by Myelodysplastic Syndrome (MDS), that is an haematological disease. The main focus is put on the genetic mutations collected that are used as features of the patients in order to cluster them. Clustering approaches have been used in several studies concerning haematological diseases such MDS. A neural network-based model was used to solve the task. The results of the clustering have been compared with labels from a "gold standard'' technique, i.e. hierarchical Dirichlet processes (HDP). Our model was designed to be also implemented in the context of federated learning (FL). This innovative technique is able to achieve machine learning objective without the necessity of collecting all the data in one single center, allowing strict privacy policies to be respected. Federated learning was used because of its properties, and because of the sensitivity of data. Several recent studies regarding clinical problems addressed with machine learning endorse the development of federated learning settings in such context, because its privacy preserving properties could represent a cornerstone for applying machine learning techniques to medical data. In this work will be then discussed the clustering performance of the model, and also its generative capabilities.

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Fróes, Renata de Sá Brito. "Estudo dos polimorfismos C1236T, G2677T e C3435T do gene MDR1 em pacientes portadores de doenças inflamatórias intestinais." Universidade do Estado do Rio de Janeiro, 2013. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=6380.

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Estudos recentes têm avaliado a presença de polimorfismos do gene multidroga resistente 1 (MDR1), que codifica o transportador de membrana de efluxo chamado de P-glicoproteína, seu potencial papel na suscetibilidade das doenças inflamatórias intestinais (DII) e suas possíveis correlações com aspectos clínicos das DII. Dados conflitantes podem resultar da análise genética de populações distintas. Investigamos se os polimorfismos do gene MDR1 estão associados com as DII em população do sudeste do Brasil e suas possíveis correlações com fenótipos, atividade de doença, resposta ao tratamento e efeitos colaterais. Como métodos, a presente pesquisa trabalhou com 146 pacientes com Doença de Crohn (DC) e 90 com Retocolite Ulcerativa Idiopática (RCUI), que foram recrutados através de critérios diagnósticos estabelecidos. Os polimorfismos do MDR1 mais comumente descritos na literatura, C1236T, G2677T e C3435T, foram avaliados por PCR. As frequências genotípicas de pacientes com RCUI e DC foram analisadas na população de estudo. Associações de genótipo-fenótipo com características clínicas foram estabelecidas e riscos estimados para as mutações foram calculados. Nenhuma diferença significativa foi observada nas freqüências genotípicas para os polimorfismos G2677T/A e C3435T do MDR1 na DC ou na RCUI. O polimorfismo C1236T foi significativamente mais comum na DC do que na RCUI (p = 0,036). Na RCUI foram encontrados mais homens nos polimorfismos C1236T e G2677T no grupo de heterozigotos. Foram encontradas associações significativas entre o polimorfismo C3435T do gene MDR1 em pacientes com fenótipo estenosante na DC (OR: 3,16, p = 0,036), em oposição ao comportamento penetrante (OR: 0,31, p = 0,076). Na DC, associações positivas também foram encontradas entre o polimorfismo C3435T, à atividade moderada/severa da doença (OR: 3,54, p = 0,046), e à resistência / refratariedade ao corticosteróide (OR: 3,29, p = 0,043) nos homozigotos polimórficos. Nenhuma associação significativa foi encontrada entre os polimorfismos do MDR1 e categorias fenotípicas, atividade de doença ou resposta ao tratamento da RCUI. Em conclusão, os resultados do presente estudo sugerem que os polimorfismos do gene MDR1 poderiam estar implicados na susceptibilidade a DC e no seu fenótipo estenosante, como também estarem associados com uma resposta inadequada ao tratamento em um grupo de pacientes com DC. A forte relação com a DC suporta a existência de papéis adicionais para o MDR1 em mecanismos específicos subjacentes na patogênese da DC, como o controle da microbiota intestinal, mediação e regulação da fibrose. Além disso, compreender os efeitos de vários fármacos associados a estas variantes do MDR1 pode contribuir para a prescrição personalizada de regimes terapêuticos.

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Balakrishnan, Subhashini. "A hierarchical approach to the formal verification of embedded systems using MDGs." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0018/MQ47823.pdf.

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Wohlfarth, Melanie. "Vergleich der In-vitro-Transportcharakteristik genetischer Varianten des ABC-Transmembrantransporters MDR1 (ABCB1)." [S.l.] : [s.n.], 2006. http://www.diss.fu-berlin.de/2007/60/index.html.

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Spencer, Erick. "Sequence and tissue expression of the ABCB4 (MDR3) gene in the canine." Online access for everyone, 2008. http://www.dissertations.wsu.edu/Thesis/Summer2008/e_spencer_072308.pdf.

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Gupta, Arun. "Failure detection and diagnosis in a multi-module deployable manipulator system (MDMS)." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/5742.

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This thesis focuses on the study of failure detection and identification of an innovative multi-modular robot that has been designed and developed in our laboratory. The interest in this class of manipulators developed after Canada's participation in the development of the international space station. All the existing space based manipulators have exclusively revolute joints, providing rotational motions. However, our laboratory manipulator has combined revolute (rotational) and prismatic (translational) joints in each module. Several such modules are connected in series to form the multi-modular deployable manipulator system (MDMS), as desired. This innovative design has several advantages when compared with its counterparts; for example, reduced singular configurations, reduced dynamic interactions, and improved obstacle avoidance capability for a specified number of degrees of freedom. Structural failures of a robotic system are critical in remote and dangerous surroundings such as space, radioactive sites or areas of explosion or battle. During the course of a robotic undertaking if there is a malfunction or failure in the manipulator, still one would wish to have the task completed autonomously, without human intervention. A manipulator that accomplishes such tasks has to be highly reliable, safe, and cost effective, and must possess good maintainability and survival rate. In the present thesis, methodology is developed for identification of structural failures in the multi-modular manipulator system MDMS, which through the use of a decision-making strategy, effective control and kinematic redundancy is capable of satisfactorily executing the intended task in the presence of joint malfunction or failure. The Bayes hypothesis testing method is used to identify the failure. First, a possible set of failure modes is defined, and a hypothesis is associated with each considered failure mode. The most likely hypothesis is selected depending on the observations of the response of the manipulator and a suitable test. This test minimizes the maximum risk of accepting a false hypothesis and thus the identification methodology is considered as most optimal. This failure identification methodology is general and can be used for any failure detection strategy. In the present thesis, the physical MDMS is subjected to several critical failure scenarios in our laboratory. In particular we consider failure due to locked joint, freewheeling of the joint and the sensor failure. The results are studied to evaluate the effectiveness of the methodology for fault-tolerant operation of a class of robotic manipulators.

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Gonzalez, Tatiana Pereira. "Polimorfismos moleculares do gene MDR1/ABCB1 em pacientes com Lupus Erimatoso Sistêmico." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2006. http://hdl.handle.net/10183/12141.

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A Glicoproteína P (Pgp), produto do gene MDR1 (ABCB1), é um transportador de efluxo que age sobre uma grande variedade de substratos e constitui um mecanismo de proteção do organismo contra xenobióticos. O gene MDR1 apresenta um grande número de polimorfismos e um número cada vez maior de estudos mostra que alguns destes podem afetar a expressão e atividade da Pgp, além de apresentarem implicações no desenvolvimento e susceptibilidade a algumas doenças e também na resposta a tratamento farmacológico. No entanto, ainda existem controvérsias. A Pgp tem sido estudada em algumas doenças autoimunes, como lupus eritematoso sistêmico (SLE), onde foi detectado aumento de atividade deste transportador. Neste trabalho, os polimorfismos C1236T, G2677T/A e C3435T foram analisados em uma amostra de Brasileiros de origem Européia e em uma amostra de pacientes com SLE. Não foram detectadas diferenças estatisticamente significantes entre as duas amostras quanto às distribuições alélicas e genotípicas destes polimorfismos. Foi observada uma maior freqüência do alelo 3435C em pacientes afrodescendentes em relação aos eurodescendentes. A análise de características clínicas mostrou que (1) pacientes com eritema malar apresentaram menor freqüência do alelo 2677A em comparação com pacientes sem eritema malar; e (2) pacientes com pleurite apresentam maior freqüência do alelo 2677A e do genótipo 2677TA em comparação com aqueles sem pleurite. Estes dados indicam um possível envolvimento destes polimorfismos na resposta imunológica, especialmente do alelo 2677A, uma vez que eritema malar e pleurite envolvem respostas imunológicas contrastantes, respectivamente, tipos Th2 e Th1.
P-glycoprotein (Pgp), the MDR1 (ABCB1) gene product, is an efflux pump that transports a huge variety of substrates and is a mechanism of xenobiotic protection. MDR1 gene presents a great number of polymorphisms and an increasing number of studies show that some of those may affect Pgp expression and activity, besides affecting the development and susceptibility of diseases and pharmacological response. However, there are still controversies. Pgp has been studied in some autoimmune diseases, such as systemic lupus erythematosus (SLE), where high activity of this transporter was detected. In the present work, C1236T, G2677T/A, and C3435T polymorphisms were analyzed in a sample of Brazilian individuals with European ancestry and in a sample of SLE patients. No statistically significant differences were detected between these samples concerning allelic or genotypic frequencies of these polymorphisms. It was observed a higher frequency of the 3435T allele in patients with African ancestry than in patients with European ancestry. Clinical characteristics analysis showed that (1) patients developing malar rash presented lower frequency of the 2677A allele than patients without malar rash; and (2) patients with pleuritis presented higher frequency of the 2677A allele and 2677TA genotype in comparison with those without pleuritis. These data indicate possible involvement of these polymorphisms in immunological response, specially the 2677A allele, as rash malar and pleuritis are consequence of contrasting immune responses, respectively, Th2 and Th1 types.

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BAUDARD, MARION. "Transduction et transfection in vitro et in vivo de vecteurs aav-mdr1." Paris 7, 1999. http://www.theses.fr/1999PA077018.

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Nous avons clone des plasmides (aav-mdr1) dans lesquels l'adnc du gene mdr1 humain (codant pour le transporteur membranaire pgp) est place sous la dependance de sequences de l'extremite 5 du genome aav. Le phenotype de resistance confere par l'expression de pgp a ete utilise pour selectionner les cellules humaines ou murines transfectees avec ces plasmides. L'importante activite transcriptionnelle du promoteur aav p5 (equivalente a celle du ltr du virus de sarcome murin harvey du plasmide controle) et des sequences aav situees en amont de p5 a ete demontree. L'utilisation de ces promoteurs de taille reduite a permis la production de particules aavr contenant l'adnc mdr1 dont la taille est proche de la limite pour un empaquetage efficace. L'analyse par southern blot des adns genomiques et de bas poids moleculaire extraits des cellules nih3t3 transfectees a revele la persistance de formes non integrees intactes des plasmides aav-mdr1. Par ailleurs, l'integration des sequences transfectees dans le genome de la cellule hote a ete demontree par hybridation in situ. L'expression de pgp est restee stable a la surface des cellules mdr1 transfectees maintenues en culture en presence continue d'un agent cytotoxique de pgp, mais a disparu de la surface des cellules transduites. L'expression de l'adnc codant pour la glucocerebrosidase humaine a ete observee dans des cellules transfectees avec un plasmide bicistronique contenant une cassette transcriptionnelle adnc hmdr1 - sequence ires virale - adnc hgc, et selectionnees par le phenotype de resistance. Apres injection intraveineuse de ce plasmide bicistronique complexe a des liposomes cationiques a des souris, les sequences hmdr1 et hgc ont ete retrouvees dans la plupart des organes des souris analyses. Des formes non integrees du plasmide bicistronique ont ete detectees par analyse par southern blot d'adns extraits des foies et l'expression de pgp a pu etre mise en evidence par analyse en cytometrie de flux de suspensions de cellules hepatiques pour de rares souris sacrifiees a des temps precoces post-injection.

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Oh, Jung Joo. "Determination of Young's modulus of carbon nanotube using molecular dynamics (MDSS) simulation." Thesis, Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 2003. http://library.nps.navy.mil/uhtbin/hyperion-image/03Dec%5FOh.pdf.

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Thesis (M.S. in Applied Physics)--Naval Postgraduate School, December 2003.
Thesis advisor(s): Young W. Kwon, James H. Luscombe. Includes bibliographical references (p. 53-57). Also available online.

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Čeikauskaitė, Dalia. "Daugiamačių duomenų vizualizavimo metodų internetinės realizacijos ir jų tyrimas." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2007. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2007~D_20070816_170819-29832.

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Šiame magistro darbe aptarsime keletą projekcijos metodų: tai pagrindinių komponenčių analizė (Principal Component Analysis (PCA)), daugiamačių skalių (Multidimensional Scaling (MDS)) ir santykinės perspektyvos (relational perspective map (RPM)). Tirsime, kuris iš trijų pradinių projekcijos taškų parinkimo būdų - atsitiktinis, pagrindinių komponenčių ar didžiausių dispersijų garantuoja mažesnę paklaidą RPM algoritme. Atliksime paprasto RPM algoritmo, pasiūlyto autoriaus James Xinzhi Li modifikaciją. Taip pat tirsime parametrus r,a (mokymo greičiai), nustatysime, kaip jie įtakoja RPM algoritmo konvergavimą. Integruosime MDS ir RPM algoritmus į internetinę terpę. Vizualiai vaizduosime daugiamačių duomenų projekcijas.
This paper deals with a methods, called the relational perspective map and multidimentional scaling. Relational perspective map that visualizes multidimensional data onto two-dimensional closed plane. It tries to preserve the distances between the multidimensional data in the lowerdimensional space. But the most important feature of the relational perspective map is the ability to visualize data in a non-overlapping manner so that it reveals small distances better than other known visualization methods. In the methods are In this paper, the features of relational perspective map are explored experimentally and some disadvantages are noticed. We have proposed a modification of this method, which enables us to avoid them. Also we have stored RPM and MDS algorithms in php language and included them in web site for testing these methods online. But allow testing only small data, because algorithms in php language works longer that stored in c++ language.

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Pradhan, Anjala Vinayak. "Genes differentially expressed in adult familial myelodysplastic syndromes (MDS)." Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418063.

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Junior, Moacyr Machado Cardoso. "Incorporação da incerteza nos mapas perceptuais obtidos via MDS." Instituto Tecnológico de Aeronáutica, 2014. http://www.bd.bibl.ita.br/tde_busca/arquivo.php?codArquivo=2939.

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Os mapas perceptuais obtidos via escalonamento multidimensional representam uma poderosa ferramenta estatística para análise de dados multivariados. São aplicados em várias áreas do conhecimento humano por permitir ao pesquisador comprovar ou validar um modelo idealizado do comportamento humano frente a julgamentos subjetivos obtidos utilizando escalas ordinais. Sua utilização nas ciências sociais, marcadamente psicologia, sociologia, política e na percepção de riscos são destacadas pois estas ciências tomam por base a subjetividade do julgamento humano. Neste contexto, essa tese tem por objetivo incorporar a incerteza do posicionamento dos objetos após o escalonamento multidimensional, para que o modelo conceitual imposto possa ser testado levando em conta a variabilidade inerente a um grupo de julgadores. O modelo proposto parte da premissa de que as funções de distribuição de probabilidade não são conhecidas para as coordenadas dos objetos no mapa perceptual e que os julgadores e os objetos estudados são estatisticamente independentes entre si. A ferramenta explora uma característica do escalonamento multidimensional, que é a representação gráfica do conjunto de dados em baixa dimensão, e além disso, a análise dos diferentes objetos representados no mapa perceptual é realizada à luz da inferência estatística. O modelo para geração do mapa perceptual de 3-vias, denominado extbf{MDSvarext}, é obtido em 3 fases: i) Redução de dimensão e geração de agrupamentos; ii) Alinhamento das configurações, e iii) Obtenção das regiões de confiança. Como resultado verifica-se que a incorporação da geração de agrupamentos, utilizando o método extbf{K-médias} ao extbf{MDSvarext}, mostra-se viável pois permite produzir agrupamentos que reduzem a variabilidade e consequentemente as regiões de confiança nos mapas gerados, além da obtenção de mais de um mapa. Finalmente com a redução da variabilidade torna-se possível a representação das regiões de confiança que mostram visualmente nos mapas gerados quais objetos diferem estatisticamente entre si.

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Cauchois, Victor. "Couches de diffusion linéaires à partir de matrices MDS." Thesis, Rennes 1, 2018. http://www.theses.fr/2018REN1S077/document.

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Cette thèse s’intéresse à deux aspects de la cryptologie symétrique liés à l’utilisation de matrices MDS dans les couches de diffusion linéaires de primitives. Une première partie se fonde sur les conceptions de couches de diffusion linéaires de schémas de chiffrement symétrique à partir de matrices MDS. Les associations entre matrices récursives, respectivement circulantes, et polynômes sont calquées pour construire de nouvelles associations entre d’autres structures de matrices et des éléments d’anneaux de polynômes non commutatifs de Ore. À l’instar des matrices récursives et circulantes, ces structures bénéficient d’implémentations matérielles légères. Des codes de Gabidulin dérivent des méthodes de construction directe de telles matrices, optimales en termes de diffusion, proches d’involutions pour l’implémentation. La seconde partie développe une attaque par différenciation de permutations dont l’architecture s’inspire de l’AES. L’utilisation d’une couche de diffusion linéaire locale avec une matrice MDS induit une description macroscopique de la propagation de valeurs de différences à travers les étapes du chiffrement. Des chemins différentiels tronqués apparaissent, qui servent de point de départ à la conception d’attaques rebond. Les travaux présentés généralisent les attaques rebond connues à l’exploitation de chemins différentiels tronqués structurés non issus d’avalanches libres. Cette structure permet de ne pas consommer tous les degrés de libertés au cours d’une seule étape algorithmique mais de les répartir en trois étapes. Une attaque sur 11 tours d’une permutation de Grostl-512 est alors déployée
This thesis focuses on two aspects of symmetric cryptology related to the use of MDS matrices as building blocks of linear layers for symmetric primitives. A first part handles designs of linear layers for symmetric ciphers based upon MDS matrices. Associations between recursive, respectively circulant, matrices and polynomials are reproduced between other matrix structures and elements in non-commutative polynomial rings of Ore. As for recursive and circulant matrices, those structures come along with lightweight hardware implementations. From Gabidulin codes are derived direct constructions of MDS matrices with properties close to involution from hardware perspectives. The second part is about distinguishing attacks on an exemple of AES-like permutations. The use of some MDS matrix to build the linear layer induces a macroscopic description of differential trails through the different steps of the algorithm computing the permutation. Truncated differential path appears, from which rebound attack are built. Original work here generalizes rebound attack applied on permutations of GROSTL-512 from structured differential path not raised from free propagations of differences. This structure allows not to consume all degrees of freedom in a simple algorithmic step but to divide this comsumption into three algorithmic steps. An attack of a reduced-round version with 11 rounds of one permutation of GROSTL-512 can then be mounted

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Philipp, Ute Elisabeth. "Hundegenomik am Beispiel von MLPH und MDR1 sowie Kandidatengenen für die dilatative Kardiomyopathie." Hannover Bibliothek der Tierärztlichen Hochschule Hannover, 2009. http://d-nb.info/1001223195/34.

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Bento, Rita Isabel Costa. "Veterinary pharmacovigilance, from regulation to scientific explanation : case studies of canine MDR1 mutation." Master's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2012. http://hdl.handle.net/10400.5/5082.

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Dissertação de Mestrado Integrado em Medicina Veterinária
Veterinary pharmacovigilance is the science and activities related to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem associated to veterinary medicinal products. It seems that some breeds are more sensitive than others to this type of events and understanding this sensitivity is permitted by the pharmacogenetics discipline. Nowadays, there is a national legislation for all countries of EU to implement a veterinary pharmacovigilance system. However, situations and philosophy vary from one country to another and, for example, in France the system works very differently. The Collie breed is known for having a special sensitivity to the ivermectin drug and this will be taken as an example to explain the existence of genetic particularities among breeds, such as, in this case, a mutation in the multidrug resistance gene 1 that encodes a large transmembrane protein cell, namely P-glycoprotein. Using data from the Sentinel-Vet software, it was investigated the existence of a superior number of adverse drug reactions reported to CPVL (Veterinary Pharmacovigilance Center of Lyon) related with breeds which have present the referent mutation within their population. It was also made a study with an innovative treatment based on intravenous lipid emulsions, applied in 7 cases after intoxication with avermectins.
RESUMO - FARMACOVIGILÂNCIA VETERINÁRIA, DA REGULAMENTAÇÃO À SUA APLICAÇÃO CIÊNTIFICA. ESTUDO DE CASO DA MUTAÇÃO CANINA MDR1 - A farmacovigilância veterinária é definida como uma ciência que envolve as atividades relacionadas com a deteção, avaliação, compreensão e prevenção de efeitos adversos ou quaisquer problemas relacionados com o uso de medicamentos veterinários. Nos diferentes indivíduos da mesma espécie parecem existir raças mais sensíveis que outras a este tipo de eventos, e a compreensão desta sensibilidade é abordada pela farmacogenética. Atualmente existe uma legislação nacional para a implementação de um sistema de farmacovigilância em todos os países da EU. Contudo, este pode variar conforme a filosofia do país. A raça canina Collie é conhecida por ter uma sensibilidade especial à ivermectina, e este facto é tomado como exemplificativo para a existência de particularidades genéticas dentro de determinadas raças, tais como, neste caso, uma mutação no gene da multiresistência 1 que codifica uma grande proteína transmembranar, a glicoproteína P. Através da análise dos dados do programa Sentinel-Vet foi investigada a existência de um número superior de reações adversas, reportadas ao CPVL (Centro de Farmacovigilância Veterinária de Lyon), relacionadas com as raças que têm presente na sua população a mutação referida. Foi realizado, igualmente, um estudo para o tratamento de intoxicações através do uso de emulsificações lipídicas intravenosas, tendo sido analisados 7 casos após intoxicação por avermectinas.

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46

Kioka, Noriyuki. "STUDIES ON THE MECHANISM OF ACQUIRING RESISTANCE BY HUMAN MULTIDRUG-RESISTANCE GENE MDR1." Kyoto University, 1991. http://hdl.handle.net/2433/78251.

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Kyoto University (京都大学)
0048
新制・課程博士
博士(農学)
甲第4925号
農博第696号
新制||農||609(附属図書館)
学位論文||H3||N2389(農学部図書室)
UT51-91-X96
京都大学大学院農学研究科農芸化学専攻
(主査)教授駒野徹, 教授大山莞爾, 教授佐々木隆造
学位規則第4条第1項該当

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FERRANDIS, ERIC. "Etude de la regulation de l'expression du gene mdr1 dans le neuroblaste humain." Paris 6, 1993. http://www.theses.fr/1993PA066364.

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Tumeur embryonnaire du tissu sympathique, le neuroblaste (nb) est l'un des cancers pediatriques les plus frequents. Le nb metastatique, au pronostic generalement severe, est traite par chimiotherapie mais manifeste souvent une chimioresistance a laquelle sont associes des taux eleves de transcrit du gene mdr1, gene implique dans le phenomene de resistance multiple aux drogues (mdr). D'autre part, l'oncogene n-myc, qui code pour une proteine nucleaire agissant comme un facteur transcriptionnel, est frequemment active par amplification genique dans ces formes disseminees de la maladie. Cette these etudie la regulation de l'expression du gene mdr1 humain et la compare a celle de l'oncogene n-myc dans des neuroblastes humains differencies, proliferatifs et metastatiques

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Pourquier, Philippe. "Recherche et quantification de l'expression du gène mdr1 dans les tumeurs digestives humaines." Bordeaux 2, 1992. http://www.theses.fr/1992BOR2P026.

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Olasoji, Motunrayo Olutoyin Remy. "Modelling of the relationships between Mobile Device Technologies (MDTs) and UK educational practices." Thesis, University of East London, 2014. http://roar.uel.ac.uk/4177/.

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This study investigates the state of the art of the concept and practice of Mobile Learning (ML) and the integration of Mobile Device Technologies (MDTs) in educational processes. Using a combination of techniques from Requirement Engineering (RE) and Agent Oriented Software Engineering (AOSE), the domain is explored and analysed for ongoing effectiveness and sustainability. Impressive advances in MDTs have made them pervasive and entrenched in many cultures, systems and in everyday living. In the last decade, the emergent of mobile / handheld devices, and subsequently, wireless technology standards have given rise to the concept of ML. Although MDT was seen by many early on as part of the solutions for learning transformation, quantifying benefits and placement in teaching and learning, either to achieve learning objectives or enhance the process remain problematic. In spite of efforts in the last decade by researchers and educators, expected potentials for learning mobility and adaptability resulting from their use are largely unfulfilled. Rapid changes in development and manufacture also continue to present additional challenges. Most research studies typically employ the approach of evidencing benefits through usage implementations and experimentation. In the review of this thesis, application of techniques provided in domain neutral RE and AOSE disciplines for specifying goals and requirements for complex systems is proposed. Alignment with teaching and learning strategies as well as institutional goals and strategies is considered essential for successful integration in any learning institution. Consequently, this review advocate strategies for alignment through elicitation and modelling techniques of RE and AOSE disciplines. Requirement elicitation is carried out using a mixed methods of inquiry comprising of four phases in sequential & parallel investigations. Phase I involves literature / citation report analysis / systematic review and quantitative survey. Secondary quantitative data is also sought during this phase. Phase II includes further in-depth quantitative and qualitative study. Questions used during this phase are designed from issues arising in Phase I. Phase III comprises of targeted studies among stakeholders in Higher Educational Institutions (HEIs), allowing for comparison of underpinning policies, cultures and practices; gaining an understanding of the concept and influential factors. Data gathering techniques include surveys, observations, interviews and focus group sessions. Using both sequential and parallel mixed method of enquiry afford opportunities to establish a frame of reference and analyse opinions within the domain among relevant stakeholders: students, academics / educators, those in the role of learning support and governance and IT support personnel. The survey is analysed using descriptive statistical analysis techniques, also involving comparison of responses from all participating groups. Qualitative data is analysed using thematic methods The review of this thesis contributes to the body of knowledge on ML as a concept and practice, evaluating definitions, frameworks and practices as relating to HEIs for the most part. Approaches to integration by selected HEIs are explored and analysed for effectiveness. A series of models is created illustrating the use of RE and AOSE techniques to align ML system requirements with organisational goals and strategies. Outcomes from the review will make it possible to advance research and knowledge forward for the practice of ML and integration of MDTs in educational processes.

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Adebanjo, Omotayo David. "Knowledge, attittudes and practices of healthcare workers about prevention and control of multidrug-resistant tuberculosis at Botsabelo Hospital Maseru, Lesotho." Thesis, University of Limpopo ( Medunsa Campus), 2011. http://hdl.handle.net/10386/423.

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Thesis (MPH)--University of Limpopo, 2011.
Background: Tuberculosis is one of the major public health problems in Lesotho. With the occurrence of multi-drug resistant tuberculosis, little is known about the views of health care workers on this disease. The aim of this study was to investigate the knowledge, attitudes, and practices of healthcare professionals about prevention and control of MDR-TB at Botsabelo hospital, situated in Maseru, Lesotho. Methods: This study was conducted by means of a semi-structured, anonymous, and self-administered questionnaire that was sent to health care workers. Returned questionnaires were collected through designated boxes stationed at selected places at the study site from 23rd September to 13th October 2010. The investigator and his assistants collected the returned questionnaires on the 15th October 2010. Results: The results of this study indicate that, overall, less than half (47.3%) of respondents had good level of knowledge about MDR-TB; but the overwhelming majority of them held negative attitude towards patients with MDR-TB. Further analysis showed that the level of knowledge did not affect the attitude towards patients suffering from MDR-TB but it influenced their practices. Having good level of knowledge about MDR-TB was associated with good practices such as the use of protective masks and MDR-TB guidelines and involvement in educating patients about MDR-TB. Moreover, the findings of this study showed also that the attitude of respondents towards patients suffering from MDR-TB did not influence their practices. Conclusion: In conclusion, less than half of respondents had good level of knowledge about MDR-TB, but over 85.5% of them held negative attitude towards patients suffering from MDR-TB. Although the level of knowledge about MDR-TB was found not to have influenced the attitude of respondents towards patients suffering from MDR-TB; and that xi their attitude did not influence practices, good level of knowledge was positively associated with safer practices such as using protective masks, educating patients on MDR-TB, and referring to the MDR-TB guidelines manual. An educational remedial intervention is recommended.

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Dissertations / Theses on the topic 'MDRS'

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