Dissertations / Theses on the topic '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.
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.
Full textMultidrug 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.
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.
Full textThe 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.
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.
Full textHuchton, Scott. "Secure mobile distributed file system (MDFS)." Thesis, Monterey, California. Naval Postgraduate School, 2011. http://hdl.handle.net/10945/5758.
Full textThe 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.
Barry, Jennifer L. (Jennifer Lynn). "Fast approximate hierarchical solution of MDPs." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/53202.
Full textCataloged 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.
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.
Full textSimultaneous 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.
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.
Full textDias, 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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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.
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.
Full textCruz, 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.
Full textThis 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
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.
Full textZheng, Zhaohua. "Intracellular delivery of MDR drugs." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492718.
Full textEdwards, 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.
Full textAlfaris, 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.
Full textIncludes 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.
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.
Full textP-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
Watanabe, Takashi. "Regret analysis of constrained irreducible MDPs with reset action." Kyoto University, 2020. http://hdl.handle.net/2433/253371.
Full text0048
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
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.
Full textTatsis, 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.
Full textLeocadio, Marcelo Augusto. "Código MDS com a métrica POSET." Universidade Federal de Viçosa, 2013. http://locus.ufv.br/handle/123456789/4927.
Full textFundação 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.
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.
Full textHoffman, 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.
Full textCardell, Sara D. "Constructions of MDS codes over extension alphabets." Doctoral thesis, Universidad de Alicante, 2012. http://hdl.handle.net/10045/27320.
Full textSukhai, 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.
Full textZobair, 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.
Full textLau, 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.
Full textHafstad, 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.
Full textBackground: 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.
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.
Full textTitle 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).
El, Amrani Nora. "Codes additifs et matrices MDS pour la cryptographie." Thesis, Limoges, 2016. http://www.theses.fr/2016LIMO0034/document.
Full textThis 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
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/.
Full textSani, Lorenzo. "Unsupervised clustering of MDS data using federated learning." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2022. http://amslaurea.unibo.it/25591/.
Full textFróes, 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.
Full textBalakrishnan, 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.
Full textWohlfarth, 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.
Full textSpencer, 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.
Full textGupta, 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.
Full textGonzalez, 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.
Full textP-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.
BAUDARD, MARION. "Transduction et transfection in vitro et in vivo de vecteurs aav-mdr1." Paris 7, 1999. http://www.theses.fr/1999PA077018.
Full textOh, 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.
Full textThesis advisor(s): Young W. Kwon, James H. Luscombe. Includes bibliographical references (p. 53-57). Also available online.
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.
Full textThis 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.
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.
Full textJunior, 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.
Full textCauchois, Victor. "Couches de diffusion linéaires à partir de matrices MDS." Thesis, Rennes 1, 2018. http://www.theses.fr/2018REN1S077/document.
Full textThis 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
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.
Full textBento, 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.
Full textVeterinary 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.
Kioka, Noriyuki. "STUDIES ON THE MECHANISM OF ACQUIRING RESISTANCE BY HUMAN MULTIDRUG-RESISTANCE GENE MDR1." Kyoto University, 1991. http://hdl.handle.net/2433/78251.
Full text0048
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
FERRANDIS, ERIC. "Etude de la regulation de l'expression du gene mdr1 dans le neuroblaste humain." Paris 6, 1993. http://www.theses.fr/1993PA066364.
Full textPourquier, Philippe. "Recherche et quantification de l'expression du gène mdr1 dans les tumeurs digestives humaines." Bordeaux 2, 1992. http://www.theses.fr/1992BOR2P026.
Full textOlasoji, 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/.
Full textAdebanjo, 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.
Full textBackground: 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.