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1
Murphy, Christopher. "Control of DNA Replication by the Nucleus to Cytoplasm Ratio." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10129.
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Xenopus embryos begin development by undergoing a series of extremely rapid cell divisions that occur without growth, gap phases, or cell cycle checkpoints. This cell cycle program, which allows the fertilized egg to rapidly subdivide its contents into many separate cells, is made possible by the extraordinary ability of these embryos to replicate DNA quickly. After a dozen such divisions, the time required to complete S phase and complete the cell cycle increases sharply amidst other embryonic changes during the midblastula transition (MBT). Successful completion of the MBT is essential for viability, but the mechanism responsible for actuating these changes remains unknown. Previous work has shown that the onset of the MBT is dependent upon the embryo reaching a critical nucleus to cytoplasm (N/C) ratio, but it is unclear how this controls cell cycle lengthening. Here, we use Xenopus egg extracts to investigate the mechanism responsible for S phase lengthening at the MBT. As in embryos, high N/C extracts exhibit lengthened S phases, and this is due to both reduced utilization of origins of replication and reduced replication fork progression. Although recent work has suggested that developmental activation of the ATR/Chk1 pathway may provide the stimulus for cell cycle remodeling at the MBT, we find that this pathway is not activated more efficiently at high N/C ratio. Rather, the Chk1 phosphorylation observed at high N/C is simply the aggregated, basal checkpoint activity associated with normal replication in a large number of nuclei. Instead, we provide evidence that the reduced replication rates at high N/C ratio are the result of the depletion of maternal factors by the increased number of nuclei, and these factors are involved in both the initiation of replication and replication fork progression. We provide evidence that protein phosphatase 2A (PP2A) activity is the limiting factor for origin firing in high N/C extracts. Likewise, partial depletion of PP2A is sufficient to prevent the high levels of origin firing observed in low N/C extracts. These results suggest a mechanism by which PP2A levels control the rate of origin firing in Xenopus egg extracts and in Xenopus embryos at the MBT.
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Yang, Lanjian 1976. "Effect of DNA methyltransferase 1 on transmission ratio distortion and epigenetic inheritance." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116080.
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Epigenetic modification of DNA plays an important role in gene regulation. During gametogenesis and early embryogenesis epigenetic states are reset to ensure embryonic-specific gene expression patterns after fertilization. However, certain genomic regions may resist epigenetic reprogramming. This may result in transgenerational epigenetic inheritance. Earlier, a grandparental origin dependent (GPO) transmission ratio distortion (TRD) of alleles in the distal region of mouse chromosome 12 had been found (Croteau et al ., 2002). The distorted region overlaps with the imprinted region of chromosome 12. The mechanism underlying this TRD is unknown, and we hypothesized that it was due to failure to reset imprints in the imprinted region in a proportion of germ cells. Such an imprint resetting failure would represent a particular case of transgenerational epigenetic inheritance. DNA (Cytosine-5) methyltransferase 1 (DNMT1) plays a key role in the maintenance of epigenetic states in mammalian genomes. To test the role of DNA methylation and DNMT1 in the genesis of TRD and its relationship to epigenetic inheritance we investigated the effect of Dnmt1 loss-of-function mutations using two mouse models: GPO (grandparental origin dependent)-TRD (transmission ratio distortion) and epigenetic inheritance at the agouti locus. Here, we report that Dnmt1 mutations have a modifying parental effect on the transmission of grandparental chromosome 12 alleles. However, the same Dnmt1 mutation did not affect the agouti coat color inheritance patterns in mice that inherited the Avy (agouti viable yellow) mutant allele from the father. Our results suggest that Dnmt1 is a trans-acting modifier of allelic transmission and support the role of epigenetic states in the genesis of TRD.
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Dungey, Fiona A. "Targeting replication-specific DNA repair pathways to enhance the therapeutic ratio of brain tumour radiotherapy." Thesis, University of Sussex, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506947.
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Glioblastoma multiforme is associated with poor prognosis and resistance to standard therapy. However the non-dividing nature of normal brain provides an opportunity for enhancing the therapeutic ratio by combining radiation with inhibitors of replication-specific DNA repair pathways. KU-0059436, an inhibitor of the base excision repair (BER) protein poly(ADP-ribose) polymerase (PARP), was demonstrated to specifically radiosensitise glioma cells during S-phase and to increase lonising radiation (IR)-induced γH2AX and Rad51 foci. This radiosensitisation was enhanced using fractionated radiation, possibly because more cells were exposed to IR whilst in S-phase. A model is proposed whereby PARP inhibition decreases repair of radiation-induced single strand breaks (SSB) which are converted at collapsed replication forks to double strand breaks (DSB) requiring homologous recombination (HR) for repair. To investigate whether inhibition of downstream HR repair potentiates the radiosensitising effect of KU-0059436, and in the absence of specific HR inhibitors, the heat shock protein 90 (HSP90) inhibitor 17-AAG was used. This compound exhibits tumour-specific cytotoxic and radiosensitising properties and downregulates the HR proteins BRCA2 and Rad5l. Work in this thesis confirmed that 17-AAG inhibits HRR and radiosensitises glioma cells. Radiosensitisation was replication-dependent and was increased in the presence of KU-0059436. The combined effect was at least partially replication-dependent, was associated with increased γH2AX foci in G2 cells, and was absent in non-malignant CHO cells. Since Rad5l-depleted cells were also radiosensitised by 17-AAG, this effect could not be attributed entirely to HRR inhibition. 17-AAG inhibits multiple tumour survival and DNA repair pathways that may contribute to its enhancement of the replication-dependent effects of KU-0059436. These multiple mechanisms may be difficult to elucidate but are likely to be therapeutically beneficial. In summary, the combination of HSP90 and PARP inhibitors may potentially improve brain tumour radiotherapy by mechanisms that include but are not restricted to inhibition of the BER and HRR DNA repair pathways.
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Catarino, Ana Isabel dos Ramos. "Effects of field metal contamination on sperm motility and RNA/DNA ratio in two echinoderm species." Master's thesis, Universidade de Évora, 2006. http://hdl.handle.net/10174/16151.
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Este estudo teve como objetivo verificar o efeito da acumulação de metais pesados na motilidade do esperma e na razão ARN/ADN em indivíduos de duas populações de equinodermes: Asterias rubens e Echinus acutus. Estas espécies ocorrem naturalmente ao longo de um gradiente de contaminação de cádmio, cobre, chumbo e zinco, num fiorde norueguês (Sørfjord). A motilidade do esperma foi quantificada com o auxílio de um sistema informático especializado (CASA). A razão ARN/ADN foi determinada através de ensaios utilizando brometo de etídio como corante fluorescente. Embora se tenha verificado acumulação de metais pesados nos tecidos dos indivíduos, não se registaram diferenças significativas na motilidade do esperma e na razão ARN/ADN do tegumento em função do grau de contaminação do ambiente. Apenas os valores da razão ARN/ADN do ceco pilórico de A. rubens foram significativamente maiores na estação mais contaminada. Estas populações parecem então tolerar os níveis de contaminantes existentes no Sørfjord. /ABSTRACT - Effects of field metal contamination on sperm motility and RNA/DNA ratio in two echinoderm species this study aimed to assess the effects of field metal contamination on sperm motility and RNA/DNA ratio in two populations of echinoderms: Asterias Rubens and Echinus acutus. These species occur naturally along a contamination gradient of cadmium, copper, lead and zinc, in a Norwegian fjord (Sørfjord). Sperm motility was quantified with the help of a computer assisted sperm analysis system (CASA). The RNA/DNA ratios were assessed based on a 1-dye, (Ethidium bromide)/1-enzyme (RNase) 96-well microplate fluorometric assay. Although both species appeared to readily accumulate metals, neither sperm motility parameters in A. Rubens nor RNA/DNA in the body wall of both species were affected. The RNA/DNA ratios in A. Rubens pyloric caeca were significantly higher in the most contaminated station. Even though this fjord is considered a highly contaminated place, these populations seem to tolerate these metal contamination levels.
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KIKOSADA, Yasutomi, Hisatoshi MAEDA, Manabu ANDOH та ін. "異数倍数体を示す上咽頭腫瘍におけるmagnetization transfer ratio". 日本磁気共鳴医学会, 1996. http://hdl.handle.net/2237/19431.
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Yeung, Wai-yin Jamius. "Evaluation of RNA/DNA ratio in the green-lipped mussel Perna viridis as a potential biomonitoring tool." View the Table of Contents & Abstract, 2009. http://sunzi.lib.hku.hk/hkuto/record/B44212963.
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Muttray, Annette Friederike. "Population and metabolic activity dynamics of resin-acid-degrading bacteria as determined by the RNA, DNA ratio." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ61150.pdf.
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Yeung, Wai-yin Jamius, and 楊慧賢. "Evaluation of RNA/DNA ratio in the green-lipped mussel Perna viridis as a potential biomonitoring tool." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B44236153.
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Hedell, Ronny. "Rarities of genotype profiles in a normal Swedish population." Thesis, Linköpings universitet, Matematiska institutionen, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-59708.
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Investigation of stains from crime scenes are commonly used in the search for criminals. At The National Laboratory of Forensic Science, where these stains are examined, a number of questions of theoretical and practical interest regarding the databases of DNA profiles and the strength of DNA evidence against a suspect in a trial are not fully investigated. The first part of this thesis deals with how a sample of DNA profiles from a population is used in the process of estimating the strength of DNA evidence in a trial, taking population genetic factors into account. We then consider how to combine hypotheses regarding the relationship between a suspect and other possible donors of the stain from the crime scene by two applications of Bayes’ theorem. After that we assess the DNA profiles that minimize the strength of DNA evidence against a suspect, and investigate how the strength is affected by sampling error using the bootstrap method and a Bayesian method. In the last part of the thesis we examine discrepancies between different databases of DNA profiles by both descriptive and inferential statistics, including likelihood ratio tests and Bayes factor tests. Little evidence of major differences is found.
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Manabe, Sho. "Development and validation of open-source software for DNA mixture interpretation based on a quantitative continuous model." Kyoto University, 2018. http://hdl.handle.net/2433/232301.
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Procházka, Ondřej. "Metody detekce selekce v DNA sekvencích." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2016. http://www.nusl.cz/ntk/nusl-242086.
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The topic of semestral thesis is methods to detect selection in DNA sequences. In the begining of the thesis we will describe molecular evolution. It will be written what made the evolution and how the evolution is shown. Moreover there are gen mutations and mechanisms of diffuse and fixation. It will be defined what pozitive, negative and neutral selection is. The thesis is focused on evolution distance of synonymous and nonsynonymous substitution. There will be described three methods – Nei-Gojobori, Li-Wu-Luo and Comeron. All these methods will be described with mathematic formulas. There will be statistic test to decide what kind of selection ti is – there will be used z-test. In the practical part, there will be information about developed software what counts selection pressure from sequences from databazes in format GenBank and it shows parts where selection is. The software will be used for two data sets with two different genetic codes. The result will be discussed. We will discuss results of all three methods of selection pressure and influence of input parametrs.
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Mondaini, Federico. "Valutazione statistica della ripetibilità di esperimenti di sequenziamento del DNA in specie batteriche." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2017. http://amslaurea.unibo.it/13516/.
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I progressi della biologia molecolare assieme alle nuove tecnologie di sequenziamento applicate su scala genomica alla genetica molecolare, hanno notevolmente elevato la conoscenza sulle componenti di base della biologia e delle patologie umane. All’interno di questo contesto, prende piede lo studio delle sequenze genetiche dei batteri, consentendo dunque, una migliore comprensione di ciò che si nasconde dietro le malattie legate all’uomo.
Il seguente lavoro di tesi si propone come obiettivo l’analisi del DNA del batterio Listeria monocytogenes, un microrganismo presente nel suolo e in grado di contaminare l’acqua e gli alimenti. Lo scopo principale è quello di confrontare la variabilità tecnica e biologica, al fine di capire quali siano gli SNPs reali (Single Nucleotide Polymorphism) e quali artefatti tecnici.
La prima parte, quindi, comprende una descrizione del processo di individuazione degli SNPs presenti nel DNA dei campioni in esame, in particolare di tre isolati diversi e tre copie.
Nella seconda parte, invece, sono effettuate delle indagini statistiche sui parametri relativi agli SNPs individuati, ad esempio il coverage o il punteggio di qualità assegnato alle basi. Il fine ultimo è quello di andare a verificare se sussistano particolari differenze tra gli SNPs dei vari isolati batterici.
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Pearson, Mary Elizabeth. "The Interaction of Radio Frequency and Lambda DNA." Thesis, North Dakota State University, 2016. https://hdl.handle.net/10365/28004.
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By exposing an aqueous DNA solution to a spectrum of radio frequency (RF) energy this research identifies frequencies, if any, where DNA interacts with RF energy. Interaction is determined by the amount of RF energy either absorbed or reflected by the DNA solution. Previous studies have shown that RF energy at high power levels causes destruction of DNA. The method outlined in this thesis will radiate a DNA solution at a low power level of non-ionizing RF energy. This will determine if DNA behavioral changes can be induced without heating the DNA solution. Any frequencies interacting with DNA within the frequency band areas will be identified as potential frequencies to induce change in genetic function. This thesis sets a foundational experimental protocol to test RF energy interaction with a variety of biological molecules.
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Mohapatra, Susovan. "ARTEMIS AND METNASE MEDIATED PROCESSING OF 3΄-BLOCKED DNA LESIONS: ROLE IN RADIO/CHEMORESISTANCE AND DNA REPAIR." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/331.
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DNA double-strand breaks (DSB) with chemically modified end-termini are the most significant lesions resulting from radio/chemotherapeutic intervention of cancer and non homologous end-joining (NHEJ) factor Artemis nuclease has been implicated in the repair of such breaks. To examine whether the resolution of terminally blocked DNA DSBs is the biologically relevant function of Artemis, Artemis deficient fibroblasts were stably complemented with wild type or an endonuclease deficient D165N mutant Artemis. Physiological levels of wild type (WT) Artemis completely restored DSB repair proficiency and resistance to γ-radiation, bleomycin, and neocarzinostatin. Cells expressing the D165N mutants remained as chemo/radiosensitive and as repair deficient as parental cells, with persistent γ H2AX and 53BP1 foci that increased in size 6-18 hour post irradiation. These persistent foci co-localized with DNA double strand break repair factor Mre11 and also with promyelocytic leukemia protein (PML). Further, in vitro studies have revealed that DNA-PK dependent Artemis endonucleolytic activity may play a role in the repair of commonly found oxidative base damage; 8-oxoguanine (8-oxoG), a hallmark of complex DSBs. However, majority of DNA DSBs are repaired in an Artemis independent manner, and recently discovered, DNA end-specific nuclease, Metnase is a candidate enzyme for repair of such breaks. To study the role of Metnase in resolution of 3ʹ-blocked termini, several substrates mimicking such breaks were constructed. A 3ʹ-phosphoglycolate moiety on longer overhangs (4 and 6 bases) altered specificity and stimulated Metnase-mediated cleavage of the terminal 3 nucleotides. However, an 8-oxoG residue at the single-strand/double-strand border did not affect specificity or extent of cleavage. Metnase preferentially cleaved ssDNA-overhang of a partially duplex substrate, and the cleavage increased with increase in length of 3ʹ-overhangs. A D483A mutation in Metnase completely abrogated Metnase cleavage activity towards DNA ends. These results suggest that Metnase may resolve oxidatively damaged DNA ends to facilitate repair while Artemis is required for the resolution of more complex DNA DSBs that persist for longer times and are not amenable to repair by other NHEJ factors.
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Delucchi, Anthony Benjamin. "Bacterial expression of radio-labeled recombinant proteins for studying AHR signalling." Scholarly Commons, 2001. https://scholarlycommons.pacific.edu/uop_etds/550.
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The ligand activated transcription factor Aryl Hydrocarbon Receptor (AHR) forms a DNA binding heterodimer with the Aryl Hydrocarbon Nuclear Translocator (ARNT) in response to planar aromatic hydrocarbons. In addition to AHR and ARNT there are at least three other proteins involved in AHR signaling. These proteins are the co-chaperone p23, Ara-9 and two molecules of Heat Shock Protein-90 (HSP-90). This study documents the production of Ara-9 and C∆418 (an ARNT deletion construct) in a modified thioredoxin fusion system. These proteins were expressed in a system that allowed for removal from the fusion partner via a thrombin recognition site as well as the incorporation of an in vitro phosphorylation site. The proteins were then expressed and column purified from E. coli. Once the proteins were expressed and purified they were cleaved from the thioredoxin fusion partner and radioloabeled. Following optimization of the proteolytic digest and radio-labeling each protein was subject to two methods of functional analysis. C∆418 function was assessed by electrophoretic mobility shift assay (EMSA) and proved to effectively form a DNA binding heterodimer with ARNT. In addition the functionality of C∆418 was assessed by co-precipitation showing that the ThioHis-produced C∆418 was indeed able to dimerize with C∆553 (an AHR deletion construct). The ThioHisproduced Ara-9 was also assessed for functionality by EMSA and showed that it was able to restore AHR/ ARNT/DRE complex formation as effectively as Ara-9 produced in a baculovirus system. In addition the function of ThioHis-Ara-9 was also assessed through Far-Western blotting for its ability to associate with renatured HSP-90. These studies involving C∆418 and Ara-9 show that these proteins can be efficiently produced in a functional manner utilizing an inexpensive bacterial system In addition this study documents the production of a plasmid (pCMV-Ara-9) for transfection into the HepG2 cell line to monitor the effects of increased cellular Ara-9 on AHR.
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Dahlke, Markus [Verfasser]. "Radio- und Chemosensitivität stammzellähnlicher Gliomzellen und Aspekte der strahleninduzierten DNA-Schadensantwort / Markus Dahlke." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2018. http://d-nb.info/1168946204/34.
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Barros, Andréa Coelho de [UNESP]. "Estudos estruturais com a importina-σ de mamíferos e peptídeos de sequências de localização nuclear (NLS) de proteínas envolvidas no reparo de DNA". Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/144038.
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000869160_20200801.pdf: 948171 bytes, checksum: b1b99c6dc56613330126eb9e2d642cff (MD5)<br>Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)<br>Danos no DNA, podem ocorrer tanto por agentes genotóxicos endógenos quanto agentes exógenos, que podem promover a instabilidade do genoma e levar diretamente a doenças, como por exemplo, o câncer, alterações neurológicas, imunodeficiências e envelhecimento prematuro. Auxiliando na manutenção da estabilidade, as células apresentam uma série de vias de reparo de DNA, as quais realizam o processo em múltiplas etapas para resolver lesões específicas no DNA e manter a integridade do genoma. A importação nuclear é um pré-requisito para as funções das proteínas de reparo do DNA e dentre os mecanismos responsáveis pela regulação da importação nuclear, a via clássica constituída pelo heterodímero Importina-α/β é um dos principais mecanismos de deslocamento. A Importina-β (Impβ) atua como o transportador enquanto a Importina-α (Impα) atua como adaptador, reconhecendo as sequências de localização nuclear (NLS) presentes nas proteínas que possuem função no núcleo. Esse trabalho trata especificamente dos estudos estruturais de complexos da Impα peptídeos NLSs de proteínas relacionadas ao reparo de DNA utilizando técnicas de cristalografia e ensaios de afinidade pela técnica de calorimetria de titulação isotérmica (ITC). A expressão e purificação da Impα de Mus musculus truncada em sua porção N-terminal foi realizada, bem como a co-cristalização da Impα peptídeos NLSs de proteínas relacionadas ao reparo de DNA, correspondentes as sequências MLH1, PMS2, XPG1 e XPG2. Peptídeos mutados em regiões importantes de reconhecimento nuclear para os peptídeos MLH1 e PMS2 também foram selecionados para o desenvolvimento deste projeto. Dados de difração de raios-X foram coletados dos cristais obtidos e processados no intervalo de 2,0-2,8 Å de resolução. Com esses resultados, as estruturas contendo cNLSs MLH1, PMS2, XPG1 e XPG2 foram elucidadas. As proteínas do complexo MutLα, a MLH1 e...<br>DNA damage can occur by endogenous and exogenous genotoxic agents, which may promote instability of the genome and directly lead to diseases such as cancer, neurological disorders, immunodeficiencies and even premature aging. Helping in the maintenance of the stability, the cells display a number of DNA repair pathways, which carry out the process in multiple steps to resolve specific DNA damage, and maintain the integrity of the genome. The nuclear import is a pre-requisite for the functions of DNA repair proteins and, among the mechanisms responsible for regulation of nuclear import, the classical pathway constituted by the heterodimer importin-α / β is a major shift mechanisms. Importin-β (Impβ) acts as the carrier while the importin α-(Impα) acts as an adapter recognizing the nuclear localization sequence (NLS) present in proteins that have function into the nucleus.This work concerns specifically the structural studies of complexes with Imp and NLSs peptides from proteins related to DNA repair using crystallographic techniques and binding assays by isotermal titration calorimetry technique (ITC). The expression and purification of Mus musculus Impα truncated at its N-terminal portion was performed, as well as co-crystallization with Impα NLSs peptides of proteins related to DNA repair, the corresponding sequences MLH1, PMS2, XPG1 and XPG2. Peptides mutated in key regions of nuclear recognition for MLH1 and PMS2 peptides were also selected for this project. X-ray diffraction data collected from crystals were obtained and processed in the range of 2.0-2.8 Å resolution. With these results, the structures containing cNLSs MLH1, PMS2, XPG1 and XPG2 were elucidated. The MutLα complex proteins, MLH1 and PMS2, related to the mismatch repair (MMR), bound to the Impα similarly to the T antigen NLS of SV40 in the major binding site. ITC experiments corroborate the crystallographic results, which suggest that both NLSs are classic...<br>FAPESP: 2011/09905-0
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Barros, Andréa Coelho de. "Estudos estruturais com a importina-σ de mamíferos e peptídeos de sequências de localização nuclear (NLS) de proteínas envolvidas no reparo de DNA". Botucatu, 2015. http://hdl.handle.net/11449/144038.
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Orientador: Marcos Roberto de Mattos Fontes<br>Coorientador: Agnes Alessandra Sekijima Takeda<br>Banca: Maria Célia Bertolini<br>Banca: Rafael Lemos Miguez Counãgo<br>Banca: Valber de Albuquerque Pedrosa<br>Banca: Lucilene Delazari dos Santos<br>Resumo: Danos no DNA, podem ocorrer tanto por agentes genotóxicos endógenos quanto agentes exógenos, que podem promover a instabilidade do genoma e levar diretamente a doenças, como por exemplo, o câncer, alterações neurológicas, imunodeficiências e envelhecimento prematuro. Auxiliando na manutenção da estabilidade, as células apresentam uma série de vias de reparo de DNA, as quais realizam o processo em múltiplas etapas para resolver lesões específicas no DNA e manter a integridade do genoma. A importação nuclear é um pré-requisito para as funções das proteínas de reparo do DNA e dentre os mecanismos responsáveis pela regulação da importação nuclear, a via clássica constituída pelo heterodímero Importina-α/β é um dos principais mecanismos de deslocamento. A Importina-β (Impβ) atua como o transportador enquanto a Importina-α (Impα) atua como adaptador, reconhecendo as sequências de localização nuclear (NLS) presentes nas proteínas que possuem função no núcleo. Esse trabalho trata especificamente dos estudos estruturais de complexos da Impα peptídeos NLSs de proteínas relacionadas ao reparo de DNA utilizando técnicas de cristalografia e ensaios de afinidade pela técnica de calorimetria de titulação isotérmica (ITC). A expressão e purificação da Impα de Mus musculus truncada em sua porção N-terminal foi realizada, bem como a co-cristalização da Impα peptídeos NLSs de proteínas relacionadas ao reparo de DNA, correspondentes as sequências MLH1, PMS2, XPG1 e XPG2. Peptídeos mutados em regiões importantes de reconhecimento nuclear para os peptídeos MLH1 e PMS2 também foram selecionados para o desenvolvimento deste projeto. Dados de difração de raios-X foram coletados dos cristais obtidos e processados no intervalo de 2,0-2,8 Å de resolução. Com esses resultados, as estruturas contendo cNLSs MLH1, PMS2, XPG1 e XPG2 foram elucidadas. As proteínas do complexo MutLα, a MLH1 e...<br>Abstract: DNA damage can occur by endogenous and exogenous genotoxic agents, which may promote instability of the genome and directly lead to diseases such as cancer, neurological disorders, immunodeficiencies and even premature aging. Helping in the maintenance of the stability, the cells display a number of DNA repair pathways, which carry out the process in multiple steps to resolve specific DNA damage, and maintain the integrity of the genome. The nuclear import is a pre-requisite for the functions of DNA repair proteins and, among the mechanisms responsible for regulation of nuclear import, the classical pathway constituted by the heterodimer importin-α / β is a major shift mechanisms. Importin-β (Impβ) acts as the carrier while the importin α-(Impα) acts as an adapter recognizing the nuclear localization sequence (NLS) present in proteins that have function into the nucleus.This work concerns specifically the structural studies of complexes with Imp and NLSs peptides from proteins related to DNA repair using crystallographic techniques and binding assays by isotermal titration calorimetry technique (ITC). The expression and purification of Mus musculus Impα truncated at its N-terminal portion was performed, as well as co-crystallization with Impα NLSs peptides of proteins related to DNA repair, the corresponding sequences MLH1, PMS2, XPG1 and XPG2. Peptides mutated in key regions of nuclear recognition for MLH1 and PMS2 peptides were also selected for this project. X-ray diffraction data collected from crystals were obtained and processed in the range of 2.0-2.8 Å resolution. With these results, the structures containing cNLSs MLH1, PMS2, XPG1 and XPG2 were elucidated. The MutLα complex proteins, MLH1 and PMS2, related to the mismatch repair (MMR), bound to the Impα similarly to the T antigen NLS of SV40 in the major binding site. ITC experiments corroborate the crystallographic results, which suggest that both NLSs are classic...<br>Doutor
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Deckmann, Ana Carolina. "Busca por genes diferencialmente expressos em resposta a indução de hipertrofia ventricular em rato (Rattus norvegicus) atraves da tecnica de microarranjos de DNA." [s.n.], 2004. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314283.
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Orientador: Gonçalo Amarante Guimarães Pereira<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-03T21:29:47Z (GMT). No. of bitstreams: 1
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Previous issue date: 2004<br>Resumo: Myocardial hypertrophy is one of the major responses to hemodynamic overload imposed by arterial hypertension. This elicits several histological and physiological alterations that affect the performance of the cardiac muscle as a whole. However, little is known about the molecular basis of the process, mainly because its multifactorial and polygenic trait. In this study, the DNA microarrays technique was adopted to identify genes directly involved in the establishment of myocardial hypertrophy. The experiments were based on the production of microarrays from 2304 clones of unknown identity derived from a non-normalized rat heart library. The microarrays were hybridized against cDNA targets synthesized after samples collect at short intervals (1, 3, 6, 12 and 48 hours) following hypertrophy induction by aorta constriction in rats (Rattus norvegicus). The results had confirmed the great potential of microarray technique for identification of differentially expressed genes in response to arterial hypertension, identifying the genes a-MHC, b-MHC and cardiac a-actin, previously described as involved in the process. More interesting, the gene of synaptopodin-2, protein associated with actin cytoskeleton and involved in stress fiber formation in response to mechanical stimuli in podocytes, and the gene of a precursor protein of amyloid beta A4, which is important because of its interaction with a protein that promotes the aggregation of components of MAPK (mitogen-activated protein kinase) cascade in a functional signaling module, were also identified. However, we concluded that it will be essential to utilize normalized libraries to reduce the redundancy of the selected genes, increasing the possibility to find novel genes<br>Abstract: A hipertrofia do miocárdio é uma das principais respostas à sobrecarga hemodinâmica imposta ao coração em um quadro de hipertensão arterial, gerando diversas modificações histofisiológicas que afetam o desempenho do músculo cardíaco como um todo. Entretanto, pouco se sabe sobre a base molecular deste processo, uma vez que esta fisiopatologia possui um caráter poligênico e multicausal. O presente estudo utilizou a técnica de microarranjos de DNA para tentar identificar genes diretamente envolvidos no estabelecimento da hipertrofia cardíaca. Os experimentos basearam-se na produção de microarranjos a partir de 2304 fragmentos de DNA de seqüência desconhecida, provenientes de uma biblioteca não normalizada de ESTs (expressed sequence tags) de coração controle de rato. Esses microarranjos foram hibridados contra amostras de cDNAs sintetizadas a partir do mRNA coletado a intervalos curtos de tempo (1, 3, 6, 12 e 48 horas) após a indução de hipertrofia em ratos (Rattus norvegicus). Os resultados demonstraram que a técnica tem grande potencial para a identificação de genes diferencialmente expressos em resposta à hipertensão cardiovascular, tendo sido identificados os genes a-MHC, _bMHC e a-actina cardíaca, previamente descritos como envolvidos neste processo, bem como os genes da sinaptopodina-2, proteína associada à actina e envolvida na formação de fibras de estresse em resposta à estímulo mecânico em podócitos, não descrito anteriormente como expresso neste tecido, e da proteína precursora de amilóide beta A4, importante porque atua sobre uma proteína que promove a agregação de componentes da cascata das MAPKs (mitogen activated protein kinase) para formar um módulo sinalizatório funcional. Entretanto, observou-se que será essencial usar bibliotecas normalizadas para reduzir a redundância dos genes selecionados e aumentar a possibilidade de encontrar genes novos<br>Mestrado<br>Bioquimica<br>Mestre em Biologia Funcional e Molecular
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Tang, Nicolas. "Évaluation, à partir de modélisations nanodosimétriques, de l'influence de la compaction de la chromatine sur les effets radio-induits précoces et extension aux effets tardifs (réparation des dommages à l’ADN et mort cellulaire)." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0160/document.
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Ce travail de thèse s'inscrit dans le cadre d'une recherche fondamentale visant à améliorer la compréhension des mécanismes d'interaction des rayonnements ionisants avec la matière biologique en s’intéressant à la prédiction par simulations numériques des dommages précoces radio-induits à l’ADN. Dans un premier temps, une étude sur le rôle des différents niveaux de compaction de la chromatine (hétérochromatine et euchromatine) dans l’induction de ces premiers effets, à savoir les cassures de brins de l’ADN, est proposée. De nouveaux modèles géométriques réalistes de noyaux cellulaires intégrant la compaction de la chromatine ont donc été créés et utilisés dans une chaîne de calcul, basée sur le code Monte Carlo ouvert et généraliste Geant4 et son extension Geant4-DNA, permettant de simuler les étapes physique, physico-chimique et chimique menant aux cassures de brin. Les développements effectués dans cette thèse ont également permis d’étudier l’impact de plusieurs types de rayonnement (protons, alphas, photons) sur les dommages radio-induits. Les différents résultats ont été confrontés à des données expérimentales et en particulier à celles obtenues par l’équipe de radiobiologistes de l’IRSN. Enfin, une étude portant sur les effets plus tardifs comme la réparation de l’ADN et la mort cellulaire a été réalisée par l’utilisation conjointe de la chaîne de calcul et de certains modèles paramétriques issus de la littérature. Ainsi, les résultats obtenus dans cette thèse ont permis d’acquérir de nouvelles connaissances et de développer des outils de calcul qui seront bientôt disponibles en accès libre à la communauté scientifique afin de prédire des effets biologiques de plusieurs types de rayonnement dans la perspective d’améliorer les modèles de risque<br>This thesis work is part of a fundamental research aimed at improving the understanding of the mechanisms of interaction of ionizing radiation with biological matter by focusing on the prediction of early radiation-induced DNA damage by numerical simulations. As a first step, a study on the role of the different levels of chromatin compaction (heterochromatin and euchromatin) in the induction of these early effects, namely DNA strand breaks, is proposed. New realistic geometric models of cell nuclei integrating chromatin compaction have therefore been created and used in a calculation chain, based on the open source and general purpose Monte Carlo code Geant4 and its extension Geant4-DNA, to simulate the physical, physico-chemical and chemical stages leading to strand breaks. Developments in this thesis have also allowed studying the impact of several types of radiation (protons, alphas, photons) on radiation-induced damage. The various results were compared with experimental data and in particular those obtained by the IRSN team of radiobiologists. Finally, a study on later effects such as DNA repair and cell death was carried out using both the calculation chain and some parametric models from the literature. Thus, the results obtained in this thesis have made it possible to acquire new knowledge and to develop calculation tools that will soon be delivered in free access to the scientific community in order to predict the biological effects of several types of radiation with the aim of improving risk models
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Costa, Filho João. "Relações da taxa RNA/DNA e parâmetros morfológicos no crescimento de juvenis de robalo-flecha (Centropomus undecimalis) cultivados." Universidade do Estado de Santa Catarina, 2013. http://tede.udesc.br/handle/handle/869.
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Previous issue date: 2013-07-09<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior<br>The marine fish farming and culture of snook, Centropomus
undecimalis, have good prospects for commercial development in Brazil.
In this regard, there is a need to expand studies on the evaluation of
growth on snook, which can be realized by morphological or
biochemical methods. The nutritional status and growth of fish can be
influenced by several factors and their interactions, including genetic and
environmental conditions, such as diet, different temperatures and
salinities. Morphological analysis allows an investigation of the
biometric data obtained from the body dimensions which are analyzed
based on a mathematical relationship through correlation and linear
regression equation. Regarding the biochemical methods, the most used
are the quantification of DNA, RNA, proteins and determination of the
RNA/DNA, protein/DNA ratios. Once the cell metabolism is usually
associated with the nutritional status of the organism higher amounts of
these components indicate greater biochemical activity of cells and
protein synthesis. The results from this study will provide useful
information related to the biology and cultivation of snook, promoting
the application of biometric analysis and promoting a jumpstart for the
application of biochemical analysis, cellular metabolism involved in the
culture snook<br>A piscicultura marinha e o cultivo do robalo-flecha possuem boas
perspectivas para o desenvolvimento comercial no Brasil. Neste sentido,
existe a necessidade da ampliação de estudos relacionados com a
avaliação do crescimento em robalos, que pode ser realizado por
métodos morfológicos ou bioquímicos. A condição nutricional e o
crescimento dos peixes podem ser influenciados por vários fatores e suas
interações, incluindo a genética e as condições ambientais, como a
alimentação, diferentes temperaturas e salinidades. A análise
morfológica permite uma investigação das características biométricas,
obtidas por meio das dimensões corporais, com base na sua relação
matemática pela correlação e equação de regressão linear. Em relação
aos métodos bioquímicos, os mais utilizados são a quantificação do
DNA, RNA, proteínas e determinação das razões RNA/DNA,
proteína/DNA. Uma vez que o metabolismo celular normalmente está
relacionado com a situação nutricional do organismo, maiores
quantidades desses componentes indicam maior atividade bioquímica
das células e síntese proteica. Os resultados deste estudo permitem
incrementar informações relacionadas à biologia e ao cultivo dos robalos
aperfeiçoando a aplicação das análises biométricas e promovendo um
salto inicial para a aplicação de análises bioquímicas, envolvidas com o
metabolismo celular, no cultivo do robalo-flecha
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Roddick, Dale L. "The use of RNA/DNA ratios as an index of health for the sea scallop (Placopecten magellanicus)." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq24903.pdf.
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Tran, Ngoc Hoang. "Extension et validation de l’outil Geant4 dans le cadre du projet Geant4-DNA pour la prédiction des dommages biologiques radio-induits à l’échelle cellulaire." Thesis, Bordeaux 1, 2012. http://www.theses.fr/2012BOR14575/document.
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L’étude des effets biologiques des radiations ionisantes à l’échelle de la cellule individuelle et en particulier sur l’ADN du noyau cellulaire reste un enjeu majeur de la radiobiologie actuelle. L’objectif principal des recherches actuelles est de déterminer quels peuvent être les effets biologiques délétères des radiations ionisantes pour la santé humaine, en particulier dans le domaine des faibles doses de radiation. Afin d’étudier précisément la réponse des cellules aux radiations ionisantes, de nombreuses études expérimentales des effets des radiations ionisantes sur les cellules, tissus et organismes biologiques aux basses énergies ont accumulées de grandes quantités de données de qualité sur la réponse de cellules aux radiations. Il existe également de nombreux modèles semi-empiriques de survie cellulaire qui incorporent des paramètres biologiques et physiques. En parallèle, des stochastiques basées sur la technique « Monte Carlo » pour modéliser les processus élémentaires en physique, chimie et biologie sont en cours de développement. L’outil Geant4 développé dès 1993 (CERN et KEK) en utilisant des techniques informatiques de dernière génération (C++) permet à l’utilisateur de construire une simulation complète grâce à de nombreuses fonctionnalités : formes géométriques, matériaux, particules élémentaires, processus physiques électromagnétiques et hadroniques, visualisation, analyse de données, interactivité et extensibilité… Cependant, Geant4 présente un certain nombre de limitations pour la simulation des effets biologiques des radiations ionisants à l’échelle subcellulaire : les modèles standard ne prennent pas compte le technique « pas-à-pas », les modèles physique sont limités à basse énergie, il n’a pas des descriptions des cibles moléculaires et Geant4 n’est pas capable de simuler les étapes physico-chimique et chimique nécessaire pour déterminer l’oxydation des bases et les éventuelles cassures d’ADN.Dans ce contexte, le projet Geant4-DNA propose d’étendre Geant4 afin de modéliser les interactions des radiations ionisantes à l’échelle de la cellule biologique et la molécule d’ADN et aux basses énergies. Au cours du travail de thèse, j’ai tout d’abord validé les modèles physiques en comparant les résultats de simulation à une grande collection de données expérimentales disponibles dans la littérature. L’accord entre les valeurs de sections efficaces totales et différentielles et les mesures expérimentales a été quantifié à l’aide du test statistique Kolmogorov-Smirnov. J’ai par la suite amélioré les classes des processus de diffusion élastique des électrons et travailler sur les calculs théoriques du modèle de diffusion élastique des protons et des alphas dans l’eau liquide auparavant inexistant dans Geant4-DNA. J’ai effectué une combinaison des processus multi-échelles des modèles de Geant4-DNA (à l’échelle microscopique) avec les modèles électromagnétiques disponibles dans l’outil Geant4 (les processus d’interaction des photons et autres modèles de Geant4). A la fin de mon travail, j’ai participé à l’estimation des performances de Geant4-DNA pour la dosimétrie dans des géométries de petite taille (jusqu’à l’échelle du nanomètre) dans l’eau liquide à l’aide des distributions « Dose Point Kernel ». J’ai ensuite calculé les fréquences de dépôts d’énergie dans des petits cylindres de dimensions nanométriques correspondant à des cibles biologiques et des modèles de noyau cellulaire humain simplifié pour l’estimation des cassures directes simple et double. Mon travail de thèse a fournit les premiers résultats de Geant4-DNA pour la prédiction de cassure de brin d’ADN combinant physique et géométries à l’échelle de l’ADN. Enfin, nous avons développé des classes de processus et modèles basés sur l’approche CTMC-COB (Classical Trajetory Monte Carlo avec critère d’Over Barrier) spécifique aux bases de la molécule d’ADN et à l’eau liquide<br>A large experimental and modeling activity is currently taking place, aimed at better understanding the biological effects of ionizing radiation at the molecular scales. Considerable amounts of experimental data have been accumulated over the past decades in order to measure quantities such as macroscopic cellular survival curves and DNA strand damages after irradiation. In parallel, computer codes have been proposed to use a stochastic approach based on Monte Carlo technique to model physical interaction in the irradiated medium. The Geant4 toolkit uses the object-oriented technology (C++) to describing particle-matter interactions, such as bio-medical physics and space physics, from sub-micrometer cells up to planetary scales. Geant4-DNA project is included in the Geant4 toolkit and benefits from the easy accessibility of the Geant4 code for the development of a computing platform allowing estimation effects of ionizing radiations. In my thesis, firstly, I have contributed in the project the validation of various models with the experimental data collections extracted from the recent literature. A good agreement between total and differential cross section values corresponding to each available Geant4-DNA model and experimental data is validated by Kolmogorov-Smirnov testing. Secondly, I have improved elastic scattering process and working on the calculation of the DDCS for proton elastic scattering in water in the Geant4-DNA. In addition, I have combined Geant4 electromagnetic processes with the Geant4-DNA. This combination brought additional Geant4 simulation capabilities in complement of the possibility to combine Geant4-DNA models with other Geant4 electromagnetic models at different sizes and energy scales in a single simulation application. Finally, we have presented the usage of Geant4-DNA physics processes in nanometer-size targets fully implemented in a single Geant4 application. The frequencies of the deposited energy and number of direct DNA single strand break and double strand break in the simplified nucleus model are compared with other codes results and with a collection of experimental data on direct DNA dimensions on plasmid DNA. Furthermore I have implemented in Geant4-DNA theoretical cross sections of physics processes based on a Classical Trajectory Monte Carlo (CTMC) approach for modeling the detailed transport of protons and neutral hydrogen atoms in liquid water and in DNA nucleobases
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Berthod, Thomas. "Synthèse d'oligonucléotides comportant des lésions radio- et photo-induites des bases pyrimidiques." Université Joseph Fourier (Grenoble ; 1971-2015), 1996. http://www.theses.fr/1996GRE10224.
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De nombreuses modifications des bases de l'adn peuvent etre generees par divers facteurs comme les agents oxydants ou cancerigenes, les rayonnements afin d'evaluer les consequences biologiques et physico-chimiques de ces dommages, il est necessaire de posseder des modeles plus complexes de ceux-ci qui peuvent etre obtenus par leur incorporation dans des oligonucleotides par voie chimique. Ce travail est consacre a la preparation de fragments d'adn contenant des derives de la 2'-desoxyuridine. Le premier volet de ce travail a consiste a preparer un synthon phosphoramidite de la 5-formyl-2'-desoxyuridine et a l'incorporer dans des oligonucleotides de synthese. La suite de ce travail concerne la mise en evidence et la caracterisation d'une nouvelle lesion, resultant de l'oxydation de la thymidine: la 5-carboxy-2'-desoxyuridine. Par ailleurs, la preparation d'oligonucleotides comportant cette lesion a ete realisee. La troisieme partie de ce travail correspond a l'incorporation d'un troisieme defaut dans des oligonucleotides: la 5,6-dihydro-2'-desoxyuridine (dhdu). Une etude plus complete sur les produits de degradation de cette lesion, susceptibles de se former en milieu alcalin, a ete ensuite menee avec le monomere et avec un trinucleotide, d(gdhdut). Dans une derniere partie, la recherche de conditions analytiques de separation de produits d'oxydation de la thymidine par electrophorese capillaire est presentee
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Gayet-Ageron, Angèle. "L’utilisation de la technique d’amplification de Treponema pallidum dans le diagnostic des ulcères oro-génitaux liés à la syphilis." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA11T005/document.
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CONTEXTE La syphilis est une maladie ré-émergente depuis 2000. Son traitement est simple, mais son diagnostic est complexe. La technique d’amplification génique de Treponema pallidum (Tp-PCR) existe depuis 1990 mais le CDC l’a incluse dans sa définition de cas en janvier 2014. OBJECTIFS 1) Evaluer la performance diagnostique de la Tp-PCR à différents stades cliniques et milieux biologiques. 2) Mesurer la sensibilité, spécificité et les valeurs prédictives de la Tp-PCR en fonction de 3 groupes de référence dans des ulcères récents. 3) Comparer les performances des 2 principales cibles de Tp-PCR.MATÉRIEL ET MÉTHODES Premièrement, une revue systématique et méta-analyse des études publiées depuis 1990 ont été menées. Ensuite une étude multicentrique prospective a été conduite dans 5 villes européennes pendant 2 ans chez des patients avec un ulcère oro-génital. Tous ont reçu le test de référence local et 2 Tp-PCRs dans l’ulcère (gène tpp47 vs. polA). Les valeurs de sensibilité, spécificité et valeurs prédictives de la Tp-PCR ont été calculées comparativement au fond noir (FN), à la sérologie et à un gold standard amélioré. La concordance des 2 cibles a été évaluée par un coefficient kappa.RÉSULTATS PRINCIPAUX La méta-analyse conclut que la Tp-PCR a une meilleure performance dans les ulcères récents. L’étude clinique montre que la Tp-PCR décrit une meilleure performance comparativement au gold standard amélioré et a même une meilleure sensibilité que le FN. Les 2 cibles ont la même valeur diagnostique et une concordance quasi parfaite. CONCLUSIONS La Tp-PCR ciblant tpp47 ou polA est cliniquement utile pour diagnostiquer une syphilis primaire et pourrait même remplacer le FN sous certaines conditions<br>BACKGROUND Syphilis has re-emerged in at-risk populations since 2000. Although the treatment of syphilis is simple, its diagnosis remains challenging. Treponema pallidum Polymerase Chain Reaction (Tp-PCR) has been used in the diagnosis of syphilis since 1990 but it is included in the case definition of the CDC since January 2014. OBJECTIVES 1) To assess the accuracy of Tp-PCR in various biological specimens and syphilis stages. 2) To measure its diagnostic performance (sensitivity, specificity and predictive values) in ulcers from early syphilis compared to three groups of reference. 3) To compare the accuracy of the two most currently used targets: tpp47 and polA genes.METHODS We conducted a systematic review and meta-analysis of all studies published from 1990. We implemented a multicentre, prospective, observational study in 5 European cities between 09/2011 and 09/2013 among patients with an oral or genital ulcer suggestive of syphilis. All patients were tested with traditional reference tests plus 2 Tp-PCRs (tpp47 and polA). We estimated the sensitivity, specificity and predictive values of Tp-PCR compared to darkfield microscopy (DFM), serology and an enhanced gold standard. We used the kappa coefficient to assess the agreement between the 2 targets.MAIN RESULTST p-PCR had the best accuracy in ulcers from early syphilis. Tp-PCR performed better when compared to the enhanced gold standard and had a higher sensitivity than DFM. The 2 Tp-PCRs had a similar accuracy and an almost perfect agreement.CONCLUSIONS Tp-PCR targeting either tpp47 or polA is clinically useful to confirm an early syphilis in smears and could even replace DFM under specific conditions
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Rice, Owen D. "Muscle Fiber Types, DNA:RNA:Protein Ratios, and Measures of Tenderness in Various Muscles of Normal and Callipyge Lambs." DigitalCommons@USU, 1995. https://digitalcommons.usu.edu/etd/5419.
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An inherited muscle hypertrophy in sheep is caused by the callipyge gene (CLPG) located on ovine chromosome 18. It has been suggested that this gene is a single autosomal dominant gene. Animals expressing the callipyge gene show increased muscling in the pelvic and torso regions of the body and, thus, have been given the phenotype- descriptive name callipyge (from Greek calli-beautiful; pyge-buttocks). In this study 21 wether lambs, the offspring of callipyge rams (genotype CLPG /clpg) and normal Rambouillet ewes (genotype clpg/clpg), were used to determine the difference s in muscle fiber type percentages, composition, and tenderness between normal and callipyge lambs . Eleven of these lambs showed muscle hypertrophy typical of the callipyge phenotype; 10 were classified as normal . Several histochemical, biochemical , and physical measures were examined in order to study changes in the physiology and biochemistry of some economically important muscles.
When compared to normal lambs, the callipyge lambs have a larger (P < .05) average percentage of fast-twitch glycolytic (FG) muscle fibers and smaller average percentages of fast-twitch oxidative and glycolytic (FOG) and slow-twitch oxidative (SO) muscle fibers in both the longissimus and gluteus medius muscles. The diameter of the fast-twitch muscle fibers was larger in the callipyge group, but slow-twitch fibers were smaller than those of normal lambs. No differences were observed in the supraspinatus muscle of the normal and callipyge groups. Thus there is an indication of a differential effect of the callipyge gene among muscles of the callipyge lambs.
The semitendinosis muscles of both the callipyge and normal groups were dissected from the carcasses. This muscle was larger (P < .01) and contained more protein in the callipyge lambs than in the normal lambs. However, the callipyge semitendinosis muscle did not have a significantly higher content of DNA than the normal lamb semitendinosis, suggesting that the muscle hypertrophy is not associated with an increase in muscle nuclei. The protein-to-DNA ratio was larger (P < .05) in the semitendinosis muscle of callipyge lambs than in the normal lambs. Protein-to-RNA and RNA-to-DNA ratios were similar; this suggests that the semitendinosis muscle was enlarged without increased translational or transcriptional activity. Samples from the callipyge longissimus and gluteus medius muscles had RNA, DNA, and protein ratios similar to those of the semitendinosis muscle, suggesting a similar mode of action for muscle enlargement in other muscles affected by this gene.
Loin chops from the callipyge lambs had lower tenderness scores (P < .01) as measured by the Wamer-Bratzler shear force and myofibril fragmentation index (MFI). However, aging increased MFI scores and decreased shear scores (P < .0 l) of the callipyge lamb chops . The normal lamb chops also had decreased shear and increased MFI scores following the aging period. The loin chops from the callipyge lambs also tended to be less red (P < .1) than chops from normal animals as measured by Hunter 'L,' 'a,' and 'b' colorimeter scores.
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D'ham, Cédric. "Répartition de bases radio-induites de l'ADN par des glycosylases : spécificités de substrat et mécanismes." Université Joseph Fourier (Grenoble), 1998. http://www.theses.fr/1998GRE10221.
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L'adn cellulaire est soumis de facon constante a des agressions. Face a cela, la cellule possede plusieurs systemes de defense, dont la reparation par excision de base. Les glycosylases sont les enzymes clefs de ce processus. Le present manuscrit concerne l'etude des specificites de substrat et des mecanismes de coupure de trois de ces enzymes : endonuclease iii et fpg d'escherichia coli, ainsi que ogg1 de saccharomyces cerevisiae. Le manuscrit est divise en quatre parties : l'etude de l'excision par l'endonuclease iii de la 5,6-dihydrothymine et de la 5-hydroxy-5,6-dihydrothymine a ete effectuee a partir d'adn soumis a des rayonnements ionisants. L'analyse, par chromatographie gazeuse couplee a un spectrometre de masse, a ete amelioree par une etape de prepurification en chromatographie liquide. Ce systeme permet ainsi d'analyser l'excision de la 5-hydroxy-5,6-dihydrothymine en evitant la contribution des isomeres cis et trans de la 6-hydroxy-5,6-dihydrothymine. Des oligonucleotides modifies contenant un glycol de thymine, une 5,6-dihydrothymine et une 5-hydroxycytosine ont ete synthetises pour determiner les specificites de substrat de l'endonuclease iii et de la fpg. Les ordres de preference des enzymes pour ces produits ont ete etablis a partir des constantes de michaelis. De plus, le mecanisme d'action de l'endonuclease iii a ete reconsidere a partir de resultats obtenus par spectrometrie de masse maldi. Il apparait que ce mecanisme est majoritairement de type hydrolytique. A partir d'un oligonucleotide modifie, la 8-oxo-7,8-dihydroadenine a ete detectee comme etant un produit d'excision de l'enzyme yogg1. L'influence de la base complementaire a la lesion s'est revelee preponderante dans la reconnaissance et l'excision du dommage. La synthese et la caracterisation des quatre isomeres des 5(6)-hydroperoxydes de thymine qui sont des substrats potentiels de l'endonuclease iii ou de la fpg, sont finalement rapportees dans un dernier chapitre.
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Romieu, Anthony. "Synthèse d'oligonucléotides modifiés comportant des lésions radio-induites des bases puriques et pyrimidiques." Université Joseph Fourier (Grenoble), 1999. http://www.theses.fr/1999GRE10140.
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Divers facteurs comme des agents oxydants ou cancerigenes, les rayonnement ultraviolets et ionisants, peuvent engendrer des modifications des bases de l'adn. Afin d'evaluer les consequences biologiques et physico-chimiques de ces dommages, l'obtention de courts fragments d'adn (oligonucleotides), de sequence definie (20 a 50 bases de long) et comportant une ou plusieurs modifications en des sites bien precis est primordiale. La synthese oligonucleotidique est aujourd'hui la methode de choix pour preparer de tels composes modeles. Ce travail est consacre a la preparation de fragments d'adn synthetiques contenant des nucleosides modifies formes lors de la radiolyse ou de la photosensibilisation des acides nucleiques. La premiere partie de cette these concerne la preparation d'un synthon phosphoramidite de la 5-hydroxy-2-desoxycytidine et l'incorporation de ce dernier dans des oligonucleotides de synthese de 14 a 33 bases de long. La deuxieme partie (chapitres iii et iv) concerne la synthese et l'incorporation de lesions radio-induites originales : les cyclonucleosides. Les deux diastereoisomeres (5r)- et (5s)- des 5,8-cyclopurine-2-desoxyribonucleosides ont ete inseres separement dans differents oligonucleotides (3 a 22 bases de long) en utilisant la chimie phosphoramidite classique. L'incorporation de la (5s, 6s)-5,6-cyclo-5,6-dihydrothymidine a egalement ete effectuee. La structure particuliere de ce cyclonucleosides (perte du caractere aromatique de l'heterocycle azote) ainsi que sa faible reactivite (determinee au cours de nos experiences) nous ont contraint au developpement d'une strategie de synthese radicalement differente de celle utilisee pour les 5,8-cyclopurine-2-desoxyribonucleosides. La troisieme partie de ce travail est consacre a la preparation d'un synthon phosphoramidite pour la 4-hydroxy-8-oxo-7,8-dihydro-2-desoxyguanosine. Au cours de l'une des etapes de synthese de ce precurseur, nous avons pu facilement separer les deux diastereoisomeres (4r)- et (4s)- de ce nucleoside modifie. Ils ont ete incorpores separemment dans les fragments d'adn synthetiques; l'epimerisation de la position c-4 n'etant pas observee au cours de la synthese sur support solide et lors de l'etape de deprotection ammoniacale. La derniere partie de ce manuscrit concerne la preparation d'oligonucleotides (2 a 9 bases de long) contenant un nucleoside modifie precurseur du radical 5-(2-desoxyuridilyl)methyle : la 5-(phenylthiomethyl)-2-desoxyuridine. Ces substrats ont ete utilises dans des etudes mecanistiques ayant pour but de preciser la reactivite de cet intermediaire radicalaire. Pour chacun des dommages incorpores une attention toute particuliere a ete portee a l'integrite des oligonucleotides synthetises. L'utilisation de differentes methodes analytiques (spectrometrie de masse et analyses clhp et maldi-tof des digestions enzymatiques) a permis de demontrer la purete des produits obtenus.
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Zvénigorosky-Durel, Vincent. "Etude des parentés génétiques dans les populations humaines anciennes : estimation de la fiabilité et de l'efficacité des méthodes d'analyse." Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30260/document.
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L'étude des parentés génétiques permet à l'anthropologie d'identifier la place du sujet au sein des différentes structures dans lesquelles il évolue : l'individu est membre d'une famille biologique, d'un groupe social et d'une population. L'application des méthodes probabilistes classiques (établies pour répondre à des problématiques de médecine légale, comme la méthode des Likelihood Ratios (LR) ou " Rapports de vraisemblance ") aux données STR issues du matériel archéologique a permis la découverte de nombreux liens de parenté, qui ensemble constituent des généalogies parfois complexes. Notre pratique prolongée de ces méthodes nous a cependant amenés à identifier certaines limites de l'interprétation des données STR, en particulier dans les cas de parentés complexes, distantes ou consanguines, ou dans des populations isolées, méconnues ou disparues. Ce travail de thèse s'attache en premier lieu à quantifier la fiabilité et l'efficacité de la méthode des LR dans quatre situations : une population moderne avec une grande diversité allélique, une population moderne avec une faible diversité allélique, une population ancienne de grande taille et une population ancienne de petite taille. Les publications récentes font usage des marqueurs plus nombreux issus des nouvelles technologies de séquençage (NGS) pour mettre en place de nouvelles stratégies de détection des parentés, basées en particulier sur l'analyse des segments chromosomiques partagés par ascendance entre les individus (segments IBD). Ces méthodes ont rendu possible l'estimation plus fiable de probabilités de parenté dans le matériel ancien. Elles sont néanmoins inadaptées à certaines situations caractéristiques de la génétique des parentés archéologiques : elles ne sont pas conçues pour fonctionner avec une seule paire isolée d'individus et reposent, comme les méthodes classiques, sur l'estimation de la diversité allélique dans la population. Nous proposons donc une quantification de la fiabilité et de l'efficacité de la méthode des segments partagés à partir de données NGS, en s'attachant à déterminer la qualité des résultats dans les différentes situations qui correspondent à des tailles de population plus ou moins importantes et à une hétérogénéité plus ou moins grande de l'échantillonnage.[...]<br>The study of genetic kinship allows anthropology to identify the place of an individual within which they evolve: a biological family, a social group, a population. The application of classical probabilistic methods (that were established to solve cases in legal medicine, such as Likelihood Ratios, or LR) to STR data from archaeological material has permitted the discovery of numerous parental links which together constitute genealogies both simple and complex. Our continued practice of these methods has however led us to identify limits to the interpretation of STR data, especially in cases of complex, distant or inbred kinship. The first part of the present work is constituted by the estimation of the reliability and the efficacy of the LR method in four situations: a large modern population with significant allelic diversity, a large modern population with poor allelic diversity, a large ancient population and a small ancient population. Recent publications use the more numerous markers analysed using Next generation Sequencing (NGS) to implement new strategies in the detection of kinship, especially based on the analysis of chromosome segments shared due to common ancestry (IBD "Identity-by-Descent" segments). These methods have permitted the more reliable estimation of kinship probabilities in ancient material. They are nevertheless ill-suited to certain typical situations that are characteristic of ancient DNA studies: they were not conceived to function using single pairs of isolated individuals and they depend, like classical methods, on the estimation of allelic diversity in the population. We therefore propose the quantification of the reliability and efficiency of the IBD segment method using NGS data, focusing on the estimation of the quality of results in different situations with populations of different sizes and different sets of more or less heterogeneous samples.[...]
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Oliveira, Leonardo Sokolnik de. "Perfil de expressão de genes modulados pela amilina em ilhotas pancreáticas de rato." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-25062009-092443/.
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O Diabetes Mellitus tipo 2 (DM 2) é uma doença crônica na qual os pacientes apresentam capacidade secretória de insulina inadequada para suplantar a resistência insulínica concomitante e, como resultado, advém a hiperglicemia. Os mecanismos que explicam a diminuição da secreção insulínica não são completamente conhecidos e acredita-se que o depósito de amilina, um achado histopatológico freqüente nesses pacientes, esteja envolvido. A amilina humana é uma proteína co-secretada com a insulina capaz de se agregar e se depositar nas ilhotas pancreáticas. Ainda não está totalmente estabelecido se a toxicidade da amilina humana é mediada pelas fibrilas maduras, conforme demonstrado em trabalhos mais antigos, ou por oligômeros de tamanho intermediário, como tem sido aventado nos trabalhos mais recentes. O objetivo deste estudo foi avaliar o perfil de genes modulados por oligômeros, bem como por fibrilas maduras de amilina, em ilhotas pancreáticas de rato. As ilhotas foram isoladas a partir de ratos Wistar, mantidas em cultura por 24 horas e a seguir tratadas com 10 M de oligômeros ou de fibrilas maduras de amilina por 24 horas adicionais em concentração fisiológica ou suprafisiológica de glicose. O RNA total foi extraído e utilizado para análise da expressão gênica por microarranjos de DNA. O conteúdo de RNA de alguns genes modulados nas condições experimentais estudadas também foi avaliado por RT-qPCR, a fim de validar os resultados obtidos pela análise de microarranjos. A análise das vias significativamente afetadas pelas preparações de amilina demonstrou que, em ilhotas mantidas em concentração fisiológica de glicose, os oligômeros de amilina modularam, entre outros, processos relacionados à Resposta ao Estresse e à Apoptose, processos não modulados pelas fibrilas maduras de amilina. Em concentração suprafisiológica de glicose, o tratamento com oligômeros de amilina deixou de modular as vias relacionadas a Estresse e Apoptose, surgindo como moduladas vias relacionadas aos processos de Regulação da endocitose e Biossíntese de óxido nítrico. Os resultados do RT-qPCR sugeriram que somente os oligômeros (e não as fibrilas maduras) de amilina modulam genes relacionados a apoptose (Anxa1, Rab5a) e ao estresse oxidativo (Nos2 e Xdh), o que vai ao encontro dos estudos mais recentes que atribuem às fibrilas intermediárias um papel na citotoxicidade das células . Um achado novo do presente estudo foi a identificação do mRNA do Gipr (receptor de polipeptídeo inibitório gástrico) como alvo de regulação negativa pelos oligômeros de amilina, o que sugere que esse possa ser um mecanismo adicional pelo qual essas fibrilas intermediárias de amilina sejam deletérias para a célula pancreática.<br>Type 2 diabetes mellitus is a chronic disease in which there is inability of pancreatic cells to secrete sufficient insulin to overcome the insulin resistance in the peripheral tissues with resultant hyperglycemia. Mechanisms leading to diminished insulin secretion are not completely known and the amyloid deposit, a frequent histopathological finding in patients with type 2 diabetes, is believed to be involved. Human amylin, a protein co-secreted with insulin, is capable of aggregating and forming deposits in the pancreatic islets. It is not fully established whether amylin cytotoxicity is mediated by mature amylin fibrils or by soluble oligomers. The objective of this study was to evaluate the gene profiling modulated by oligomers as well as by mature amylin fibrils in rat pancreatic islets. The islets were isolated from Wistar rats, maintained in culture for 24 hours and then treated with 10 M of oligomers or mature amylin fibrils for additional 24 hour in physiologic and supraphysiologic glucose concentrations. Total RNA was extracted and used for gene expression analysis by microarray. RNA content of some modulated genes was evaluated by RT-qPCR in order to validate the results obtained from the microarray analysis. The analysis of the pathways significantly affected by the two amylin preparations demonstrated that, in islets maintained in physiological glucose concentration, amylin oligomers modulated, among others, processes related to Response to stress and to Apoptosis, which were not modulated by mature amylin fibrils. In supraphysiological glucose concentration, treatment with oligomers did not modulate the pathways related to Stress and Apoptosis, which were replaced by processes related to Endocytosis regulation and Nitric oxide biosynthesis. RT-qPCR results suggested that only amylin oligomers modulate genes related to apoptosis (Anxa1, Rab5a) and oxidative stress (Nos2 e Xdh), which is in agreement with studies indicating a role for oligomers in the cytotoxicity of cells. A new finding of the present study was the identification of the Gipr (gastric inhibitory polypeptide receptor) mRNA as a target for downregulation by amylin oligomers, which suggests that this might be an additional mechanism by which these oligomers are deleterious to the pancreatic cells.
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Bornman, Eugin. "An appraisal of warm temperate mangrove estuaries as food patches using zooplankton and RNA: DNA ratios of Gilchristella aestuaria larvae as indicators." Thesis, Nelson Mandela University, 2018. http://hdl.handle.net/10948/17908.
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Mangrove habitats are considered as the ideal fish nursery as they are known to increase the growth and survival of juvenile fishes by providing enhanced food availability and protection. However, most studies have focused on tropical mangroves with a few recent warm temperate studies finding conflicting results. Furthermore, the nursery value of South African mangroves to fishes remain understudied in subtropical areas, while warm temperate mangroves are yet to be evaluated. This study aimed to assess whether mangrove presence leads to any advantage to the larvae of an important estuarine resident fish species, Gilchristella aestuaria, by comparing the food patch quality of South African warm temperate mangrove and non-mangrove estuaries. Results indicate that larvae fed primarily on the dominant prey species, Pseudodiaptomus hessei, Paracrtia longipatella, and Acartiella natalensis. However, postflexion larvae consumed more of the larger species, P. hessei, within the two mangrove estuaries (16.09 %V in Nahoon and 13.79 %V in Xhora) than the two nonmangrove estuaries (12.20 %V in Gonubie and 7.05 %V in Qora), despite other prey species occurring at similar densities. Results indicate that mangrove habitats acted as sediment sinks, slightly reducing the turbidity of these estuaries which resulted in postflexion larvae actively selecting larger, more nutritious prey, which in turn, significantly increased their individual instantaneous growth rates (0.11 ± 0.21 Gi) when compared to postflexion larvae in non-mangrove estuaries (0.09 ± 0.12 Gi). This study found that mangrove presence was significantly related to postflexion larval densities when coupled with abiotic (such as temperature and turbidity) and biotic factors (such as predator-prey interactions). Understanding the spatial and temporal dynamics, predator-prey interactions as well as the growth and survival of G. aestuaria is particularly important as they are key zooplanktivores that are prey to other species in estuarine food webs.
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Karlevall, Jimmie. "Hur ska du investera dina PPM-pengar? : En studie om PPM-fondernas historiska avkastning." Thesis, Södertörn University College, School of Business Studies, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-3569.
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<p><strong>Purpose:</strong> The main purpose of this study is to study the 45 funds, divided into three differentdivisions, then the result will provide a greater understanding of how returns change with ahigher risk.</p><p><strong>Methodology:</strong> The study is based on a quantitative approach. The survey was conducted bygathering raw data from databases and secondary data from literature, printed and electronicsources.</p><p><strong>Theoretical perspectives:</strong> The study is based on the theory: the efficient markethypothesis, which argues that future returns can not be calculated as the market is fullyinformed. The study is therefore studying historical yields.</p><p><strong>Empirical foundation:</strong> Empirical data are acquired from www.morningstar.se, andtherefore also treated on this page. The material is then divided into documents and time axes.</p><p><strong>Conclusions:</strong> The study has shown that high-risk funds give a higher percentage returns thanmedium-and low-risk funds. However, does not imply a higher risk automatically earn ahigher return when the low-risk funds have shown a higher yield than medium-risk funds. Animportant factor to study when you are looking for the fund which generated the highest ROIis the Sharpe ratio. Although this study demonstrates that high-risk funds have a higherSharpe ratio than competing risk groups.</p>
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Dos, Santos Morgane. "Modélisation de la topologie des dépôts d’énergie créés par un rayonnement ionisant à l’échelle nanométrique dans les noyaux cellulaires et relation avec les événements précoces radio-induits." Thesis, Bordeaux 1, 2013. http://www.theses.fr/2013BOR14865/document.
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Les rayonnements ionisants sont connus pour induire des dommages critiques au sein de la matière biologique et spécialement au sein de l’ADN. Parmi ces dommages, les cassures doubles brins de l’ADN (DSB) sont considérées comme les principales responsables des effets létaux des rayonnements. Comprendre et prédire comment ces cassures sont créées et réparées dans les noyaux cellulaires demeure un défi dans la recherche en radiobiologie. Ce travail s’inscrit dans ce contexte, dans la modélisation des cassures double brin de l’ADN (DSB) à partir des dépôts d’énergie créés par l’irradiation au niveau intracellulaire. Le détail topologique au niveau nanométrique des dépôts d’énergie nécessaire à ce travail est obtenu par modélisation Monte Carlo à l’aide du code Geant4 et, en particulier son extension Geant4-DNA pour des processus à très faible énergie. Les dommages étudiés étant ceux localisés dans l’ADN, le premier objectif de ce travail a été de réaliser une géométrie détaillée de celui-ci afin de l’implémenter dans les calculs Monte Carlo. Deux types de noyaux cellulaires, représentant un fibroblaste et un endothélium, ont été décrits afin d’évaluer l’influence de la densité d’ADN dans les résultats sur la topologie des dépôts pouvant donner lieux à des cassures de la molécule. Cette géométrie nous permet d’effectuer une première sélection des dépôts d’énergie pouvant contribuer aux cassures car situées sur la chaîne sucre-phosphate. Ces dépôts sont ensuite analysés à l’aide d’un algorithme de clustérisation de manière à les regrouper sous forme d’agrégats afin d’étudier leur localisation et complexité. Néanmoins, dans cette étude, seule les interactions physiques entre les rayonnements ionisants et la cible sont modélisées, il n’est donc pas possible d’obtenir un nombre absolu de cassures de brins car cette modélisation n’inclue pas l’étape de création et de transport des radicaux libres pouvant donner lieu à des dommages indirects. Ainsi, le but de ce travail était d’évaluer la dépendance relative des dommages radio-induits directs avec la densité d’ADN, la qualité du rayonnement, la morphologie du noyau ou encore la condensation de la chromatine. Les différentes modélisations réalisées ont permis de quantifier l’influence de ces différents paramètres dans le nombre et la complexité des dommages directs induits dans l’ADN, pouvant ensuite contribuer aux effets tardifs sur le devenir cellulaire<br>Ionizing radiations are known to induce critical damages on biological matter and especially on DNA. Among these damages, DNA double strand breaks (DSB) are considered as key precursor of lethal effects of ionizing radiations. Understand and predict how DNA double and simple strand breaks are created by ionising radiation and repaired in cell nucleus is nowadays a major challenge in radiobiology research. This work presents the results on the simulation of the DNA double strand breaks produced from the energy deposited by the irradiation at the intracellular level. At the nanometric scale, the only method to accurately simulate the topological details of energy deposited on the biological matter is the use of Monte Carlo codes. In this work, we used the Geant4 Monte Carlo code and, in particular, the low energy electromagnetic package extensions, referred as Geant4-DNA processes.In order to evaluate DNA radio-induced damages, the first objective of this work consisted in implementing a detailed geometry of the DNA on the Monte Carlo simulations. Two types of cell nuclei, representing a fibroblast and an endothelium, were described in order to evaluate the influence of the DNA density on the topology of the energy deposits contributing to strand breaks. Indeed, the implemented geometry allows the selection of energy transfer points that can lead to strand breaks because they are located on the backbone. Then, these energy transfer points were analysed with a clustering algorithm in order to reveal groups of aggregates and to study their location and complexity.In this work, only the physical interactions of ionizing radiations are simulated. Thus, it is not possible to achieve an absolute number of strand breaks as the creation and transportation of radical species which could lead to indirect DNA damages is not included. Nevertheless, the aim of this work was to evaluate the relative dependence of direct DNA damages with the DNA density, radiation quality, cell nuclei morphology or also chromatin condensation. The results presented in this work have allowed the quantification of the influence of these different parameters in the number and complexity of directs DNA damages which can then contribute to the late effects on cell fate
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Costa, Ana Maria Duarte Dias. "Estudo do miocardio ventricular de ratos cujas mães foram injetadas com palmitato de vitamina A, no decimo dia de gestação." [s.n.], 1985. http://repositorio.unicamp.br/jspui/handle/REPOSIP/289959.
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Orientador: Samir Tufic Arbex<br>Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba<br>Made available in DSpace on 2018-07-14T14:27:51Z (GMT). No. of bitstreams: 1
Costa_AnaMariaDuarteDias_D.pdf: 1879485 bytes, checksum: 96212047f0f73edc92d5716eea0e229a (MD5)
Previous issue date: 1985<br>Resumo: Não informado<br>Abstract: Not informed.<br>Doutorado<br>Farmacologia<br>Doutor em Odontologia
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Cosma, Aurélien. "Modélisation de type "DFA" d'une Institution de Prévoyance : application à la détermination d'une stratégie optimale d'allocation d'actifs." Lyon 1, 2005. http://www.theses.fr/2005LYO10046.
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L'objet de cette thèse est l'optimisation de l'allocation d'actifs d'une Institution de Prévoyance, sous contraintes de risque économique et réglementaire. L'approche retenue consiste à rechercher des portefeuilles efficients dans un diagramme rentabilité - risque. On définit donc tout d'abord des mesures de rentabilité et de risque, cohérentes avec l'environnement réglementaire de la prévoyance collective. Le calcul de valeurs numériques pour ces mesures passe ensuite par la construction d'un modèle d'Analyse Financière Dynamique, ou DFA, permettant de projeter dans le temps, de manière stochastique, les flux financiers futurs générés par toutes les composantes de l'activité de Prévoyance collective : cotisations, prestations, réassurance, fluctuations des marchés financiers, etc. Il est tenu compte des corrélations existant entre ces composantes, à travers l'inflation en particulier. Outre des éléments de réponse au problème initial, le modèle DFA élaboré fournit des indications sur les caractéristiques financières et le profil de risque du passif d'une Institution de Prévoyance
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Meylan, Sylvain. "Développement d'un outil de simulation multi-échelle adapté au calcul des dommages radio-induits précoces dans des cellules exposées à des irradiations d'ions légers (proton et alpha)." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0184/document.
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Ce travail de thèse, réalisé dans le cadre des projets de recherche ROSIRIS (IRSN) et Geant4-DNA, porte sur la construction d’une simulation multi-échelle dédiée au calcul des dommages radio-induits précoces à l’ADN qui peuvent apparaître suite à l’irradiation d’un noyau cellulaire. L’outil développé s’appuie sur une version modifiée du code de Monte Carlo Geant4-DNA et est capable de simuler dans le détail le transport et les interactions physiques entre l’irradiation ionisante et la matière biologique (étape physique), la création d’espèces chimiques (étape physico-chimique) et les réactions et processus de diffusion de ces dernières (étape chimique). Durant la simulation de ces trois étapes, un modèle géométrique de l’ADN, décrivant l’ensemble du génome humain avec une précision moléculaire, est généré avec un nouveau logiciel développé dans le cadre de cette thèse : DnaFabric. Les premiers résultats obtenus pour des irradiations avec des protons et des ions alpha sont détaillés et comparés à des données de la littérature. Un bon accord est observés avec ces dernières illustrant ainsi la cohérence de l’ensemble de la simulation. L’influence très significative du critère de sélection utilisé pour identifier les dommages à l’ADN est également démontrée<br>This work was performed in the frame of the ROSIRIS (IRSN) and Geant4-DNA research projects and describes the development of a simulation tool to compute radioinduced early DNA damages in a cell nucleus. The modeling tool is based on a modified version of the Monte Carlo code Geant4-DNA and is able to simulate the physical interactions between ionizing particles and the biological target (physical stage), the creation of chemical species within the cell nucleus (physico-chemical stage) as well as the reactions and diffusion processes of these chemical species (chemical stage). During all the simulation, a geometrical model that describes the DNA content of a human diploid cell nucleus is taken into account. This model was generated with a new software (DnaFabric) developed in the frame of this work and has a molecular level of detail.The first results (in term of DNA strand breaks) obtained with this tool are detailed and compared with experimental data from the literature. The good agreement between the simulation results and those data shows the coherence of our modeling. The significant influence of the selection criteria used to identify the DNA damages is also demonstrated
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Lochet, Florian. "Design of an Emulator of Contactless Card from a Discontinued Product." Thesis, KTH, Skolan för informations- och kommunikationsteknik (ICT), 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-129302.
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Contactless cards are everywhere nowadays due to their ease to use and low price to produce. In addition, their reliability is excellent. That is why they are used in systems where security is essential within a low price. To develop the associated systems (cards, readers, terminals), efficient tools are needed. These tools can be a spy analyzing any communication or an emulator that can act and answer exactly as a real contactless card. The objective of this thesis was to develop a contactless card emulator on a product that is currently only spying, the NomadLAB of KEOLABS. The emulator feature is based on a discontinued product, the ProxiCARD, and it has for main objective to be compliant with the ISO 14443 standard. Through the analysis of its architecture and its current performance, I have developed a complete system that can be integrated into the ecosystem of the KEOLABS products. The features I developed take place into the source code of the NomadLAB, at the level of its ARM microcontroller in language C, and in its FPGA in language VHDL. The ARM is here to handle all the smart part of the transmission, while the FPGA to handle the coding and decoding process. In addition, I developed an antenna able to on one hand receive the signal from a reader and on the other hand to reply to it by modulating the magnetic field. I also developed and added my controls to the current computer software. Finally, I have written a lot of testing to make sure that this new system is reliable. The NomadLAB is now able to emulate a contactless card complying with ISO14443 standard, while keeping its spy features, and its control through a computer.
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Bourdat, Anne-Gaëlle. "Lésions tandem radio-induites de l'ADN : formation, insertion dans des oligonucléotides et réparation." Université Joseph Fourier (Grenoble), 2000. http://www.theses.fr/2000GRE10100.
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La formation de lesions simples de l'adn generees par des photosensibilisateurs excites, les radiations ionisantes, les agents chimiques ne peut expliquer a elle seule la forte letalite cellulaire. Aussi, des modifications multiples sont supposees avoir un fort impact biologique. Parmi ces lesions complexes, la n-(2-desoxy, d-erythro-pentofuranosyl)-formylamine (df)/8-oxo-7,8-dihydro-2-desoxyguanosine (8-oxodguo) a ete observee dans de courts fragments d'adn apres exposition a un rayonnement x en solution aqueuse aeree. Afin d'evaluer les consequences biologiques liees a la presence de telles lesions, les residus 8-oxodguo et df ont ete introduits dans des oligonucleotides synthetiques en position vicinale. La chimie des phosphoramidites pac sur support solide a permis de preparer les oligonucleotides modifies. La purete des fragments d'adn synthetiques et l'integrite des bases modifiees inserees ont ete confirmees par differentes techniques analytiques : clhp, page, sm ies, sm malditof et electrophorese capillaire. Ces modeles synthetiques ont ete utilises pour determiner les specificites de substrats et les mecanismes d'excision de trois adn n-glycosylases impliquees dans la reparation par excision de base : endo iii et fpg of e. Coli ainsi que yogg1 of s. Cerevisiae. Les oligonucleotides sont incises par chacune des trois enzymes etudiees. Pourtant, les lesions tandem ne sont pas completement excisees par ces enzymes. L'efficacite d'excision, determinee par le rapport des constantes cinetiques de michaelis vm/km, n'est que peu modifiee par la presence des dommages multiples. La sm maldi-tof apporte des informations interessantes quand au mecanisme d'action des enzymes. Des experiences de replication in vitro ont montre que la progression des trois polymerases taq pol, pol et le fragment de klenow exo, est arretee par la presence des lesions tandem. Enfin, nous avons mesure par lc-ms/ms le taux de lesion tandem genere dans de l'adn expose a un rayonnement. Les lesions df-8-oxodguo et 8-oxodguo-df se forme significativement dans ces conditions. Il est interessant de noter que le dommage 8-oxodguo-df est produit en plus grande quantite que la lesion de sequence inverse. De plus, les resultats de ces experiences indiquent indirectement qu'il se forme d'autres dommages multiples comportant une lesion 8-oxodguo.
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Charazac, Aurélie. "Effet de la dérégulation de la voie Sonic Hedgehog sur les réponses aux dommages de I'ADN et la prédisposition aux cancers." Thesis, Université Grenoble Alpes (ComUE), 2015. http://www.theses.fr/2015GREAV006/document.
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Le syndrome de Gorlin est une maladie rare caractérisée par de nombreuses anomalies du développement. Ces manifestations cliniques, dues à des mutations d'un acteur essentiel de la voie de signalisation sonic hedgehog, incluent aussi une hyper-radiosensibilité et une forte prédisposition à développer des carcinomes basocellulaires. Etant donné l'implication de défaut de la réparation de l'ADN au niveau des affections liées à l'hyper-radiosensibilité, nous avons décidé d'étudier l'effet des mutations du gène PTCH1 sur la réponse aux dommages de l'ADN afin de mieux comprendre les mécanismes cellulaires et moléculaires conduisant au phénotype Gorlin.Cette étude permet de mettre en évidence une défaillance globale des systèmes de réparation des dommages de l'ADN dans les fibroblastes issus de patients Gorlin par rapport à des fibroblastes normaux. Elle met notamment en exergue un écroulement de la réparation par excision de bases (BER) responsable de la réparation des dommages oxydatifs<br>The Gorlin syndrome is a rare genetic disorder characterized by several developmental abnormalities. Due to mutations in PTCH1, a key player of the sonic hedgehog signaling pathway, clinical manifestations also includes hyper-radiosensitivity and an increased predisposition to the development of basal cell carcinomas. Given the implication of DNA repair system defects in hyper-radiosensitivity pathologies, we decided to study the effect of PTCH1 mutations on the DNA damage response in order to better understand the cellular and molecular mechanisms leading to Gorlin's phenotype.This study demonstrate a global failure of the DNA damage repair systems in Gorlin fibroblasts with respect to controls. It highlights in particular the collapse of the base excision repair pathway (BER) responsible for the repair of oxidative DNA damage
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Vaurijoux, Aurélie. "Étude des conséquences génétiques et épigénétiques consécutives à la signalisation persistante des dommages radio-induits de l'ADN." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS515/document.
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Les cassures double-brin de l’ADN (CDB) sont des événements clés dans la réponse aux rayonnements ionisants qui, avec le profil génétique et épigénétique individuel, peuvent conditionner le devenir des tissus sains d’un individu exposé. À la suite des cassures de la molécule d’ADN et de la déstabilisation de la chromatine, une série de modifications post-traductionnelles des histones se produit, notamment la phosphorylation de la serine 139 de l'histone H2A.X (gamma-H2A.X), conduisant à la formation de foyers radio-induits. La réparation des CDB, et donc la disparition de ces foyers, a lieu dans les heures suivant l’exposition. Toutefois, une certaine proportion de ces foyers gamma-H2A.X persiste 24 heures après l’irradiation. La nature et le rôle de ces foyers persistants sont encore peu clairs. L’objectif de ce travail est d'explorer les caractéristiques de ces foyers persistants et leurs conséquences sur le devenir des cellules. Pour étudier la dynamique des foyers radio-induits, nous avons exposé des HUVEC synchronisées en phase G0/G1 à des doses de 1 et 5 Gy de rayons X. Les foyers radio-induits ont été étudiés à partir de 10 minutes et jusqu'à 7 jours après l'exposition par l’analyse de gamma-H2A.X et de l’association temporelle de la protéine 53BP1 et des CN-PML (corps nucléaires PML). L’impact des foyers persistants sur la prolifération cellulaire a également été exploré. Nous avons analysé en microscopie à fluorescence une moyenne de 4 000 cellules pour chaque condition à l'aide d'une analyse d’image permettant la détection automatique des noyaux et des foyers. L'analyse d'un grand nombre d‘évènements nous a permis de discriminer des sous-populations de cellules ou de foyers sur la base de différentes caractéristiques, telles que leur aire ou la phase du cycle cellulaire, et de mesurer leur représentativité dans l'ensemble de la population de cellules exposées. Ainsi, nous avons déterminé que les foyers gamma-H2A.X persistant ont une aire supérieure à 0,72 ± 0,11 µm² et qu’ils sont toujours colocalisés avec 53BP1. Plus de 70% des cellules exposées à 5 Gy ont au moins un foyer persistant 24 heures après l'exposition. De plus, ces foyers persistants sont observables au moins jusqu'à 7 jours après l’irradiation. Une association spatiale significative entre les CN-PML et les foyers gamma-H2A.X a été observée à partir de 10 minutes après l'exposition et 24 heures après l’exposition, environ 90% des foyers persistants sont associés à un CN-PML. De plus, la présence de foyers persistants ne bloque pas définitivement la prolifération des cellules. Cependant, la fréquence des foyers persistants est plus faible dans les cellules filles que dans les cellules irradiées, probablement en raison d'une certaine proportion de distribution asymétrique des foyers persistants entre les cellules filles. Nous avons également mesuré une corrélation positive entre la présence d'un foyer persistant et la probabilité de mauvaise ségrégation de l'ADN par l'observation de phénomènes de catastrophes mitotiques. Il semble donc que la structure formée après le passage d'un foyer persistant à travers les phases S et G2 soit susceptible d’empêcher la séparation correcte des chromatides sœurs du chromosome affecté. Nous suggérons donc que la nature des foyers persistants n’est pas la même avant et après la première division cellulaire due à une résolution anormale de l'anaphase. Ces assemblages chromosomiques atypiques résultants d’anaphases anormales pourraient être létaux pour la cellule ou entraîner un déséquilibre du dosage génique et une instabilité génomique accrue pouvant conduire à une mosaïque de phénotypes cellulaires<br>The DNA double-stranded breaks (DSB) are key events in the cell response to ionizing radiation that may affect, with the individual genetic and epigenetic profile, the fate of healthy tissues of people exposed. Following initial breaks and chromatin destabilization, a set of post-translational modifications of histones occurs, including the phosphorylation of serine 139 of histone H2AX (gamma-H2A.X), which leads to the formation of ionizing radiation-induced foci (IRIF). DSB repair results in the disappearance of most IRIF within hours after exposure. However, a proportion of IRIF remains 24 hours upon irradiation. The nature and role of these persistent IRIF are still unclear. The goal of this work is to explore the characteristics of these persistent IRIF and their consequences on the cell behavior. To investigate the dynamic of IRIF in our model, we exposed G0/G1-phase synchronized HUVECs to 1 or 5 Gy of X-rays. IRIF were studied from 10 minutes up to 7 days after exposure by monitoring gamma-H2A.X foci, their temporal association with 53BP1 protein and PML NBs (Promyelocytic leukemia nuclear bodies), and their impact on cell proliferation. We analyzed a mean of 4 000 cells for each condition using an automated detection of nuclei and foci. The analysis of a large number of cells and foci allowed us to screen subpopulations of cells or foci through different characteristics, such as size, shape or cell cycle phase among others, and to weight their representativeness in the whole population of exposed cells. We identified that persistent gamma-H2A.X foci after irradiation had a size superior to 0.72 ± 0.11 µm² and always collocated with 53BP1. More than 70% of cells exposed to 5 Gy had at least one persistent IRIF 24 hours after exposure and we observed these persistent IRIF up to 7 days post irradiation. A significant spatial association between PML NBs and IRIF was observed from 10 minutes after exposure; at 24h post irradiation, around 90% of persistent IRIF were associated with PML NBs. Moreover we demonstrated that persistent IRIF did not block cell proliferation definitively. The frequency of IRIF was lower in daughter cells, probably due to a certain amount of asymmetric distribution of IRIF between them. We report a positive association between the presence of an IRIF and the likelihood of DNA missegregation by observation of mitotic catastrophes. Hence, the structure formed after the passage of a persistent IRIF across the S and G2 phases may impede the correct segregation of sister chromatids of the chromosome affected. Consequently, the nature of IRIF in the nucleus of daughter cells might differ before and after the first cell division due to an abnormal resolution of anaphase. The resulting atypical chromosomal assembly may be lethal or result in a gene dosage imbalance and possible enhanced genomic instability, and could lead to a patchwork of cell phenotypes
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Ciochina, Dana [Verfasser], Marius [Akademischer Betreuer] Pesavento, Dirk [Akademischer Betreuer] Slock, Anja [Akademischer Betreuer] Klein, and David [Akademischer Betreuer] Hausheer. "Multiuser Downlink Beamforming Techniques for Cognitive Radio Networks / Dana Ciochina. Betreuer: Marius Pesavento ; Dirk Slock ; Anja Klein ; David Hausheer." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2016. http://d-nb.info/1112269541/34.
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Ciochina, Dana Silvia [Verfasser], Marius [Akademischer Betreuer] Pesavento, Dirk [Akademischer Betreuer] Slock, Anja [Akademischer Betreuer] Klein, and David [Akademischer Betreuer] Hausheer. "Multiuser Downlink Beamforming Techniques for Cognitive Radio Networks / Dana Ciochina. Betreuer: Marius Pesavento ; Dirk Slock ; Anja Klein ; David Hausheer." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2016. http://nbn-resolving.de/urn:nbn:de:tuda-tuprints-55173.
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Rausch, Jamie Ann. "Secondary Data Analysis Investigating Effects of Marine Omega-3 Fatty Acidson Circulating Levels of Leptin and Adiponectin in Older Adultswith Chronic Venous Leg Ulcers." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu158652907707218.
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Peudon, Aude. "Prise en compte de la structure moléculaire pour la modélisation des dommages biologiques radio-induits." Toulouse 3, 2007. http://www.theses.fr/2007TOU30125.
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Pour améliorer la modélisation des effets des rayonnements sur le milieu biologique, l'objectif de ce travail fût la prise en compte de la structure moléculaire. Pour cela des sections efficaces moléculaires photoniques et électroniques ont été calculées à partir des données moléculaires ab-initio (énergies de liaison des orbitales, population…). Un modèle dynamique de réorganisation moléculaire a également été développé pour évaluer l'impact des électrons Auger et des photons de fluorescence émis suite à une ionisation interne. L'influence de ces changements, sur le nombre et la répartition des dommages radio-induits, a été étudiée sur le nucléosome, élément unitaire de l'ADN. Des modifications ont ensuite été réalisées pour permettre la modélisation d'expériences in vitro. Une simulation a permis d'évaluer le nombre de cytosines mutagènes sur le plasmide P53, et une autre, la quantité de dommages provoquée par les isotopes 125 et 123 de l'iode sur le plasmide pBR322. Le bon accord entre les résultats confirme la complémentarité nécessaire du modèle et de l'expérience<br>To improve modelling of biological radio-induced damage, the aim of this work was to take into account molecular structure. Based on ab-initio molecular data (molecular binding energy, population analysis…), photonic and electronic cross sections have been calculated. An interactive model of molecular reorganization has been also developed to evaluate efficiency of Auger electrons and fluorescent photons after inner shell ionization. The improvement impact on number and distribution of SSB and DSB has been studied with one core particle. Then, modifications have been performed to model in-vitro experiments. One simulation allows mutagenic cytosines number evaluation on P53 plasmid. And another one deals with I-125 and I-123 impact on pBR322 plasmid. The good agreement in the results confirms the necessary complement of model and experiment
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Enzo, Maria Vittoria. "Analysis of blood-based markers as predicting tools of pathologic tumour response in rectal cancer patients receiving neo-adjuvant chemoradiotherapy." Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3423392.
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Neo-adjuvant chemo-radio therapy (pCRT) has been accepted as a standard care in the treatment of patients with locally advanced rectal cancer. The multimodality treatment has been established to improve tumour downstaging, pathological complete response, and local disease control. However, the response of individual tumors to the treament is not uniform and ranges from complete response to complete resistance. The discovery of new molecular markers that predict the tumour response is surely of wide interest for personalizing the therapy and reducing time, costs and side effects in the patients with resistant tumours. Many potential biomarkers have been evaluated in order to predict the response to pCRT, and to implement targeted therapeutics. However, single-marker or multi-markers analyses, based on pre-treatment tissue biopsies, often obtained conflicting results demonstrating the heterogeneity of the individual tumour response. Moreover, the prediction of histopathological response to neo-adjuvant treatment is complicated by the interaction and the involvement of the microenvironment in modulating the sensitivity to pCRT. In this study, we developed blood-based methods of biomarker analysis in order to evaluate the histopathological response to treatment in a broad contest that can take into account not only the signalling pathway of tumour cells but also the microenvironment as a part of a unique system. Indeed, the non-invasive nature and the dynamism for which different molecules could be detected according with physiological and pathological states has given us the possibility to monitor the response along the administration of the treatment. In particular, we focused on two different kind of circulating molecules: the cell-free DNA (cfDNA) and the circulating low molecular weight (LMW) peptides. In particular, we investigated the presence, the quantity of cfDNA and its integrity (cfDNA integrity = non apototic cfDNA / total cfDNA) along the chemo-radio treatment. For this purpose we measured the cfDNA concentration and cfDNA integrity in a prospective study of locally advanced rectal cancer patients plasma collected before the pCRT, after two weeks from initiation of the pCRT and after the pCRT. We evaluated the association of these markers with the histological response to the chemo-radio therapy, demonstrating a different kinetic of cfDNA integrity in association with the tumour response.
Then we studied the LMW peptidome circulating in plasma, in order to find evidences of possible differences in the peptide profile that could reflect the tumour response. To overcome the technical difficulties in harvesting LMW species, we have employed the mesoporous chip-based technology, developed by the Nanomedicine Department of The Methodist Hospital Research Institute in Houston, Texas. This mesoporous device, in combination with matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF MS), allows the isolation and the detection of small peptides from the large proteins. We analyzed plasma of rectal cancer patients, with positive or negative response to the therapy, at the same time points as the cfDNA: before, during, after the chemo-radio therapy. Multivariate analyses of the LMW peptide profile at different time points identified combinations of peptides that revealed high discriminating capacity of the different tumour responses. In particular, before the pCRT, a pattern of five ionic species showed a sensitivity and a specificity of 80% and after the pCRT, a pattern of other five specific ionic species showed a sensitivity of 80% and a specificity of 85% to cluster patients on the basis of histopathologic response to pCRT. Moreover the identification of the amino acids sequences of the response-specific ionic species revealed the presence of protein fragments that could be directly or indirectly valuable for further investigation on the resistance mechanisms of the rectal tumour to the neo-adjuvant chemo-radio therapy<br>La radiochemioterapia neoadiuvante (pCRT) è un protocollo standard accettato per il trattamento di pazienti con cancro rettale localmente avanzato. Il trattamento preoperatorio multimodale è stato introdotto per la riduzione dello stadio del tumore, per l’aumento della risposta completa patologica e per il controllo locale della malattia. Tuttavia la risposta patologica al trattamento non è uniforme e varia da una risposta completa alla resistenza totale. La scoperta di nuovi marcatori molecolari in grado di predire la risposta del tumore è sicuramente di grande interesse al fine di personalizzare la terapia, riducendo così i tempi, i costi e gli effetti collaterali nei pazienti con tumori resistenti. Molti potenziali biomarcatori sono stati valutati con l’obiettivo di prevedere la risposta alla pCRT, e di attuare terapie mirate. Finora molti studi su singolo o multi-marcatore sono stati eseguiti prevalentemente su biopsie di tessuto pre-trattamento. I risultati ottenuti, tuttavia, erano spesso contrastanti dimostrando l'eterogeneità individuale della risposta tumorale al trattamento. Inoltre, la predizione della risposta istopatologica alla pCRT è complicata dall’interazione e dal coinvolgimento del microambiente che può modulare la sensibilità del tumore al trattamento. In questo studio, abbiamo sviluppato metodi di analisi di biomarcatori su sangue, al fine di valutare la risposta del tumore al trattamento in un contesto più ampio, che rende conto non solo dell’ambiente strettamente tumorale, ma che prende in considerazione anche il microambiente come parte di un sistema unico. Infatti, la natura non invasiva del materiale biologico analizzato e il dinamismo per cui molecole differenti possono essere rilevate secondo lo stato fisiologico e patologico dell’organismo, ci hanno permesso di monitorare la risposta lungo il tempo di somministrazione del trattamento. In particolare, ci siamo concentrati su due diversi tipi di molecole circolanti: il DNA libero da cellule (cfDNA) e i peptidi a basso peso molecolare (Low Molecular Weight, LMW). In particolare, abbiamo studiato la presenza, la quantità e l’integrità del cfDNA durante il trattamento radio-chemioterapico. A questo scopo abbiamo misurato la concentrazione e l'integrità del cfDNA (cfDNA integrity=cfDNA apoptotico/cfDNA totale) in uno studio prospettico di plasma di pazienti con carcinoma rettale localmente avanzato, raccolto prima della pCRT, dopo due settimane dall'inizio del trattamento e dopo la pCRT. Abbiamo valutato l'associazione di questi marcatori con la risposta istologica alla chemio-radio terapia, dimostrando la presenza di diversa cinetica nell’integrità del cfDNA, in associazione con la risposta tumorale.
Nel plasma, abbiamo quindi studiato il peptidoma circolante a basso peso molecolare, al fine di trovare potenziali differenze nel profilo peptidico che potessero riflettere la risposta tumorale. Per superare le difficoltà tecniche nella rilevazione dei peptidi circolanti a basso peso molecolare, abbiamo utilizzato una strategia basata sull’esclusione dimensionale di un chip di silice mesoporosa (MSC), sviluppato dal Dipartimento Nanomedicina del The Methodist Hospital Research Institute di Houston, Texas. Questo dispositivo mesoporoso, in combinazione con l’utilizzo dello spettrometro di massa MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry), consente l'efficiente rimozione di grandi proteine e l'isolamento del peptidoma circolante da campioni di fluidi corporei. Abbiamo analizzato il plasma di pazienti con cancro rettale, prelevato in diversi tempi (prima, durante, dopo la chemio-radio terapia) e stratificati secondo la risposta positiva o negativa alla pCRT. L'analisi multivariata del profilo peptidico nei diversi tempi di analisi ha identificato combinazioni di peptidi che evidenziavano un’elevata capacità discriminante della risposta tumorale. In particolare, il modello di regressione logistica ha evidenziato, prima della pCRT, una combinazione di cinque specie ioniche capace di identificare i pazienti che non rispondono al trattamento, con una sensibilità e una specificità del 80%; mentre la stessa analisi con i campioni raccolti dopo la pCRT, ha identificato un'altra combinazione di cinque specie ioniche che evidenziano una sensibilità del 80% e una specificità del 85%. Inoltre, l'identificazione delle sequenze amminoacidiche di alcune tra le specie ioniche discriminanti la risposta alla pCRT, hanno rivelato la presenza di frammenti proteici che possono essere direttamente o indirettamente utili per ulteriori indagini sui meccanismi di resistenza del tumore rettale alla radio-chemio terapia neo-adiuvante
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Souza, M?rcio Fl?vio Amaral de. "An?lise de desempenho no setor banc?rio brasileiro atrav?s da An?lise Envolt?ria de Dados (DEA)." Universidade Federal Rural do Rio de Janeiro, 2006. https://tede.ufrrj.br/jspui/handle/tede/956.
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Previous issue date: 2006-12-29<br>The objective of this study is to analyze the multicriterial performance of financial institutions
in operation in Brazil during the period from 2001 to 2005. The research results searched to
show a new perception about the financial performance of the banks which is not available to
managers and the market in general, through the financial statements and traditional financial
indexes analyses. That is, from information which would not be available for the conventional
techniques, Data Envelopment Analysis (DEA) results, which is the methodology used for
this analysis, can provide a better overview of market competitiveness conditions, as much for
the top managers as for the others stakeholders. For that was conducted an analysis using
leverage indicators, operational costs, immobilization, immediate liquidity, deposits levels,
credit operations and yield. From the identification of the 100’s biggest banks showed in the
list published by Valor Financeiro Magazine between years 2002 and 2006, the study
analyzed the indicators under two aspects, plus the discussion about the modeling presented.
First of all made an analysis about the institutions efficiency distributed in four segments:
wholesale, middle market, financing and retail. Secondly searched to demonstrate the relative
performance of the 100’s biggest all along five years, with the aim to making a
competitiveness sector analysis panel. Related to the general analysis, was pointed that
immobilization was the variable with biggest need of reduction to increase the efficiency of
the sector, occurring a change of level in the period 2001 to the 2003 in comparison to last the
two years of the research. It was also noticed that efficiency was related to low operational
costs and high level yields. On the segments analysis, the wholesale banking was the most
efficient and, in a general, in each segment the performance leaders were not the institutions
with the highest assets. At end, it was noticed that, although the increase in banking
concentration of the country, the competition degree on the pointed items of this research
appear to be sufficiently high.<br>O objetivo deste estudo ? analisar o desempenho multicriterial de institui??es financeiras em
opera??o no Brasil durante o per?odo de 2001 a 2005. Os resultados desta pesquisa buscaram
mostrar uma nova percep??o sobre a performance financeira de bancos que n?o se encontram
dispon?veis aos gestores e ao mercado em geral atrav?s dos balan?os e tradicionais an?lises de
?ndices financeiros. Ou seja, a partir de informa??es que n?o estariam dispon?veis pelas
t?cnicas convencionais, os resultados da an?lise envolt?ria de dados, que ? a metodologia
utilizada para an?lise, podem proporcionar melhor vis?o das condi??es de competitividade do
mercado, tanto para a alta administra??o quanto para as demais partes interessadas. Para tanto
se conduziu uma an?lise utilizando indicadores de alavancagem, custo operacional,
imobiliza??o, liquidez imediata, n?veis de dep?sitos e de opera??es de cr?dito e rentabilidade.
A partir da identifica??o dos 100 maiores bancos que constavam da listagem publicada na
Revista Valor Financeiro entre os anos 2002 e 2006, o estudo analisou os indicadores sob dois
enfoques, al?m de discutir a modelagem apresentada. O primeiro fez uma an?lise sobre a
efici?ncia de institui??es distribu?das em quatro segmentos: atacado, middle market,
financiamento e varejo. O segundo buscou demonstrar a performance relativa dos 100
maiores ao longo de cinco anos, com a finalidade de formar um painel de an?lise da
competitividade do setor. Quanto a an?lise geral, observou-se que a imobiliza??o foi a
vari?vel com maior necessidade de redu??o para melhoria na efici?ncia do setor, ocorrendo
uma mudan?a de patamar no per?odo 2001 ? 2003 em compara??o aos ?ltimos dois anos da
pesquisa. Notou-se tamb?m que a efici?ncia estava relacionada a baixos custos operacionais e
altas rentabilidades. Na an?lise por segmentos, o atacado foi o mais eficiente e, de uma forma
geral, em cada segmento os l?deres de desempenho n?o eram as institui??es com os maiores
ativos. Por fim, observou-se que, apesar do aumento na concentra??o banc?ria do pa?s, o grau
de competi??o nos itens apontados por esta pesquisa parece bastante elevado.
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Muggiolu, Giovanna. "Deciphering the biological effects of ionizing radiations using charged particle microbeam : from molecular mechanisms to perspectives in emerging cancer therapies." Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0599/document.
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Ces dernières années, le paradigme de la radiobiologie selon lequel les effets biologiques des rayonnements ionisants ne concernent strictement que les dommages à l'ADN et les conséquences liées à leur non réparation ou à leur réparation défectueuse, a été remis en question. Ainsi, plusieurs études suggèrent que des mécanismes «non centrés » sur l'ADN ont une importance significative dans les réponses radio-induites. Ces effets doivent donc être identifiés et caractérisés afin d’évaluer leurs contributions respectives dans des phénomènes tels que la radiorésistance, les risques associés au développement de cancers radio-induits, les conséquences des expositions aux faibles doses. Pour ce faire, il est nécessaire : (i) d'analyser la contribution de ces différentes voies de signalisation et réparation induites en fonction de la dose et de la zone d’irradiation; (ii) d’’étudier les réponses radio-induites suite à l’irradiation exclusive de compartiments subcellulaires spécifiques (exclure les dommages spécifiques à l'ADN nucléaire); (iii) d’améliorer la connaissance des mécanismes moléculaires impliqués dans les phénomènes de radiosensibilité/radiorésistance dans la perspective d’optimiser les protocoles de radiothérapie et d’évaluer in vitro de nouvelles thérapies associant par exemple les effets des rayonnements ionisants et de nanoparticules d’oxydes métalliques. Les microfaisceaux de particules chargées offrent des caractéristiques uniques pour répondre à ces questions en permettant (i) des irradiations sélectives et en dose contrôlée de populations cellulaires et donc l’étude in vitro des effets « ciblés » et « non ciblés » à l'échelle cellulaire et subcellulaire, (ii) de caractériser l’homéostasie de cultures cellulaires en réponses à des expositions aux rayonnements ionisants et/ou aux nanoparticules d’oxydes métalliques (micro-analyse chimique multi-élémentaire). Ainsi, au cours de ma thèse, j'ai validé et exploité des méthodes d’évaluation qualitatives et quantitatives (i) in cellulo et en temps réel de la réponse radio-induite de compartiments biologiques spécifiques (ADN, mitochondrie, …) ; (ii) in vitro de la radiosensibilité de lignées sarcomateuses issues de patients; et (iii) in vitro des effets induits par des expositions à des nanoparticules d'oxydes métalliques afin d’évaluer leur potentiel thérapeutique et anti-cancéreux<br>Few years ago, the paradigm of radiation biology was that the biological effects of ionizing radiations occurred only if cell nuclei were hit, and that cell death/dysfunction was strictly due to unrepaired/misrepaired DNA. Now, next this “DNA-centric” view several results have shown the importance of “non-DNA centered” effects. Both non-targeted effects and DNA-targeted effects induced by ionizing radiations need to be clarified for the evaluation of the associated radiation resistance phenomena and cancer risks. A complete overview on radiation induced effects requires the study of several points: (i) analyzing the contribution of different signaling and repair pathways activated in response to radiation-induced injuries; (ii) elucidating non-targeted effects to explain cellular mechanisms induced in cellular compartments different from DNA; and (iii) improving the knowledge of sensitivity/resistance molecular mechanisms to adapt, improve and optimize the radiation treatment protocols combining ionizing radiations and nanoparticles. Charged particle microbeams provide unique features to answer these challenge questions by (i) studying in vitro both targeted and non-targeted radiation responses at the cellular scale, (ii) performing dose-controlled irradiations on a cellular populations and (iii) quantifying the chemical element distribution in single cells after exposure to ionizing radiations or nanoparticles. By using this tool, I had the opportunity to (i) use an original micro-irradiation setup based on charged particles microbeam (AIFIRA) with which the delivered particles are controlled in time, amount and space to validate in vitro methodological approaches for assessing the radiation sensitivity of different biological compartments (DNA and cytoplasm); (ii) assess the radiation sensitivity of a collection of cancerous cell lines derived from patients in the context of radiation therapy; (iii) study metal oxide nanoparticles effects in cells in order to understand the potential of nanoparticles in emerging cancer therapeutic approaches
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Smith, Matthew Alan. "Unveiling the Impact of the “-opathies”: Axonopathy, Dysferopathy, and Synaptopathy in Glaucomatous Neurodegeneration." NEOMED Integrated Pharmaceutical Medicine / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ne2mh1523282895761979.
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Antiope, Nathalie. "Radio infranationale et discursivité identitaire en milieu insulaire : Des représentations sociales aux ethnodiscours médiatiques. Le cas des Départements français d'Amérique." Phd thesis, Université de la Sorbonne nouvelle - Paris III, 2008. http://tel.archives-ouvertes.fr/tel-00422069.
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La présente recherche vise à questionner le système triadique que forment une identité culturelle, un territoire et un média au sein d'une aire géographique singulière : la Méditerranée caribéenne, et plus particulièrement les Départements français d'Amérique (DFA) que sont la Guadeloupe et la Martinique. L'essor de la société de l'information et de la communication n'ayant pas épargné ces départements, les mésocommunications et microcommunications, en tant qu'expressions alternatives aux phénomènes contemporains de globalisation, se présentent désormais comme des lieux de refondation, de (re)construction mais également de réenracinement identitaire. Dans cette dynamique, les médias infranationaux jouent un rôle central dans la matrice de construction identitaire et culturelle, et notamment la radio qui occupe une place centrale au sein de ces sociétés de l'oralité. En tant qu'objet social, nous soutenons l'hypothèse que la radio, à travers ses discours, participe à la matrice de figuration d'une identité mythifiée et au maintien de ce complexe fictionnel ayant une puissance symbolique, idéologique et sociale. Les interactions des dimensions médiatique, territoriale, culturelle et linguistique au sein d'une formation humaine donnée participant à l'élaboration d'un certain type d'énoncés médiatiques que nous avons identifiés comme étant des ethnodiscours ; des implicites communautaires d'interconnaissance manifestations médiatiques d'une conscience d'appartenance spécifique et des représentations sociospatiales, socioculturelles et sociolinguistiques que celle-ci sous-tend.
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Ngo, Cong Khanh. "Etude et amélioration de l'organisation de la production de dispositifs médicaux stériles." Phd thesis, Grenoble 1, 2009. http://tel.archives-ouvertes.fr/tel-00371165.
Full textAbstract:
Dans les établissements de santé, la stérilisation des dispositifs médicaux occupe une place primordiale dans la lutte contre l'infection. On appelle dispositif médical un instrument de chirurgie ou d'exploration utilisé lors d'une intervention ou d'un examen. Dans cette thèse nous étudions et proposons des améliorations de l'organisation de la production de dispositifs médicaux stériles en appliquant au milieu hospitalier des méthodes habituellement utilisées pour évaluer et améliorer les performances de systèmes de production industriels. Nous avons construit un modèle de simulation spécifique représentant le service de stérilisation du Centre Hospitalier Privé Saint Martin de Caen. Nous montrons les améliorations que nous avons pu obtenir en modifiant certains points de l'organisation. Par la suite nous avons cherché à dégager les spécificités des services de stérilisation de plusieurs établissements hospitaliers, dans le but d'effectuer une comparaison des différents types d'organisation et d'identifier les services les plus performants. Cette comparaison, réalisée à partir de données issues d'une enquête menée auprès d'établissements de la région Rhône-Alpes, repose sur des ratios de comparaison, sur la méthode DEA (Data Envelopment Analysis) et sur un modèle générique de simulation que nous avons élaboré. Dans cette thèse, nous proposons également des pistes pour analyser un service de stérilisation générique en utilisant des méthodes analytiques stochastiques. Nous commençons par dresser un état de l'art sur l'utilisation de modèles stochastiques analytiques pour l'analyse de systèmes de production de soins, puis nous étudions la possibilité d'utiliser une méthode analytique pour analyser notre modèle générique d'un service de stérilisation. Une modélisation par réseau de files d'attente du modèle générique est enfin présentée.