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Tang, Fung Michael, i 鄧峰. "Sequence classification and melody tracks selection". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B29742973.
Pełny tekst źródłaTang, Fung Michael. "Sequence classification and melody tracks selection /". Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?B25017470.
Pełny tekst źródłaHoffman, Michael M. "Quantifying evolution and natural selection in vertebrate noncoding sequence". Thesis, University of Cambridge, 2008. https://www.repository.cam.ac.uk/handle/1810/245947.
Pełny tekst źródłaGarske, Tini. "Mutation-selection models of sequence evolution in population genetics". Thesis, Open University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.412399.
Pełny tekst źródłaBuxton, David. "The impact of striatal neuropeptides and topography on action sequence selection". Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/22081/.
Pełny tekst źródłaBesenmatter, Werner. "Protein engineering with genetic selection : tolerance of enzyme activity to sequence change /". Zürich : ETH, 2007. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=16912.
Pełny tekst źródłaIbeh, Neke. "Inferring Viral Dynamics from Sequence Data". Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35317.
Pełny tekst źródłaSherborne, Amy Louise. "Balancing selection at the major histocompatibility complex (MHC) : sequence diversity and inbreeding avoidance". Thesis, University of Liverpool, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501605.
Pełny tekst źródłaAl-Ouran, Rami. "Motif Selection: Identification of Gene Regulatory Elements using Sequence CoverageBased Models and Evolutionary Algorithms". Ohio University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1449003717.
Pełny tekst źródłaNiu, Jia. "Translation of DNA into Evolvable Sequence-Defined Synthetic Polymers". Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11351.
Pełny tekst źródłaChemistry and Chemical Biology
Berglund, Lisa. "Selection of antigens for antibody-based proteomics". Doctoral thesis, Stockholm : School of Biotechnology, Royal Institute of Technology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4706.
Pełny tekst źródłaMurrel, Benjamin. "Improved models of biological sequence evolution". Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71870.
Pełny tekst źródłaENGLISH ABSTRACT: Computational molecular evolution is a field that attempts to characterize how genetic sequences evolve over phylogenetic trees – the branching processes that describe the patterns of genetic inheritance in living organisms. It has a long history of developing progressively more sophisticated stochastic models of evolution. Through a probabilist’s lens, this can be seen as a search for more appropriate ways to parameterize discrete state continuous time Markov chains to better encode biological reality, matching the historical processes that created empirical data sets, and creating useful tools that allow biologists to test specific hypotheses about the evolution of the organisms or the genes that interest them. This dissertation is an attempt to fill some of the gaps that persist in the literature, solving what we see as existing open problems. The overarching theme of this work is how to better model variation in the action of natural selection at multiple levels: across genes, between sites, and over time. Through four published journal articles and a fifth in preparation, we present amino acid and codon models that improve upon existing approaches, providing better descriptions of the process of natural selection and better tools to detect adaptive evolution.
AFRIKAANSE OPSOMMING: Komputasionele molekulêre evolusie is ’n navorsingsarea wat poog om die evolusie van genetiese sekwensies oor filogenetiese bome – die vertakkende prosesse wat die patrone van genetiese oorerwing in lewende organismes beskryf – te karakteriseer. Dit het ’n lang geskiedenis waartydens al hoe meer gesofistikeerde waarskynlikheidsmodelle van evolusie ontwikkel is. Deur die lens van waarskynlikheidsleer kan hierdie proses gesien word as ’n soektog na meer gepasde metodes om diskrete-toestand kontinuë-tyd Markov kettings te parametriseer ten einde biologiese realiteit beter te enkodeer – op so ’n manier dat die historiese prosesse wat tot die vorming van biologiese sekwensies gelei het nageboots word, en dat nuttige metodes geskep word wat bioloë toelaat om spesifieke hipotesisse met betrekking tot die evolusie van belanghebbende organismes of gene te toets. Hierdie proefskrif is ’n poging om sommige van die gapings wat in die literatuur bestaan in te vul en bestaande oop probleme op te los. Die oorkoepelende tema is verbeterde modellering van variasie in die werking van natuurlike seleksie op verskeie vlakke: variasie van geen tot geen, variasie tussen posisies in gene en variasie oor tyd. Deur middel van vier gepubliseerde joernaalartikels en ’n vyfde artikel in voorbereiding, bied ons aminosuur- en kodon-modelle aan wat verbeter op bestaande benaderings – hierdie modelle verskaf beter beskrywings van die proses van natuurlike seleksie sowel as beter metodes om gevalle van aanpassing in evolusie te vind.
Chakravorty, Hirak. "Equilibrium and non-equilibrium analysis of folding and sequence selection in mean field random heteropolymers". Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399162.
Pełny tekst źródłaMoilanen, J. (Jukka). "Non-neutral sequence variation in human mitochondrial DNA: selection against deleterious mutations and haplogroup-related polymorphisms". Doctoral thesis, University of Oulu, 2003. http://urn.fi/urn:isbn:9514271661.
Pełny tekst źródłaGreen, Michael C. "An Efficient Primer Selection Process Combining Progressive and Iterative Multiple Sequence Alignment Strategies: ClustalW and HMMER". DigitalCommons@CalPoly, 2011. https://digitalcommons.calpoly.edu/theses/547.
Pełny tekst źródłaIslas, Anguiano Jose Angel. "Optimal Strategies for Stopping Near the Top of a Sequence". Thesis, University of North Texas, 2015. https://digital.library.unt.edu/ark:/67531/metadc822812/.
Pełny tekst źródłaShimagaki, Kai. "Advanced statistical modeling and variable selection for protein sequences". Electronic Thesis or Diss., Sorbonne université, 2021. http://www.theses.fr/2021SORUS548.
Pełny tekst źródłaOver the last few decades, protein sequencing techniques have been developed and continuous experiments have been done. Thanks to all of these efforts, nowadays, we have obtained more than two hundred million protein sequence data. In order to deal with such a huge amount of biological data, now, we need theories and technologies to extract information that we can understand and interpret.The key idea to resolve this problem is statistical physics and the state of the art of machine learning (ML). Statistical physics is a field of physics that can successfully describe many complex systems by extracting or reducing variables to be interpretable variables based on simple principles. ML, on the other hand, can represent data (such as reconstruction and classification) without assuming how the data was generated, i.e. physical phenomenon behind of data. In this dissertation, we report studies of protein sequence generative modeling and protein-residue contact predictions using statistical physics-inspired modeling and ML-oriented methods. In the first part, we review the general background of biology and genomics. Then we discuss statistical modelings for protein sequence. In particular, we review Direct Coupling Analysis (DCA), which is the core technology of our research. We also discuss the effects of higher-order statistics contained in protein sequences and introduces deep learning-based generative models as a model that can go beyond pairwise interaction
Gamble, Christopher Thomas. "A Bayesian chromosome painting approach to detect signals of incomplete positive selection in sequence data : applications to 1000 genomes". Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:e1f3b484-59b9-4703-ae09-67079408c424.
Pełny tekst źródłaZhang, Nan. "Feature selection based segmentation of multi-source images : application to brain tumor segmentation in multi-sequence MRI". Phd thesis, INSA de Lyon, 2011. http://tel.archives-ouvertes.fr/tel-00701545.
Pełny tekst źródłaKudella, Patrick [Verfasser], i Dieter [Akademischer Betreuer] Braun. "Sequence self-selection by the network dynamics of random ligating oligomer pools / Patrick Kudella ; Betreuer: Dieter Braun". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2021. http://d-nb.info/123264546X/34.
Pełny tekst źródłaSchwarb, Hillary. "The importance of stimulus-response rules in sequence learning". Thesis, Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/28221.
Pełny tekst źródłaKabir, Mitra. "Prediction of mammalian essential genes based on sequence and functional features". Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/prediction-of-mammalian-essential-genes-based-on-sequence-and-functional-features(cf8eeed5-c2b3-47c3-9a8f-2cc290c90d56).html.
Pełny tekst źródłaBrandström, Mikael. "Bioinformatic Analysis of Mutation and Selection in the Vertebrate Non-coding Genome". Doctoral thesis, Uppsala University, Department of Evolution, Genomics and Systematics, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8240.
Pełny tekst źródłaThe majority of the vertebrate genome sequence is not coding for proteins. In recent years, the evolution of this noncoding fraction of the genome has gained interest. These studies have been greatly facilitated by the availability of full genome sequences. The aim of this thesis is to study evolution of the noncoding vertebrate genome through bioinformatic analysis of large-scale genomic datasets.
In a first analysis we addressed the use of conservation of sequence between highly diverged genomes to infer function. We provided evidence for a turnover of the patterns of negative selection. Hence, measures of constraint based on comparisons of diverged genomes might underestimate the functional proportion of the genome.
In the following analyses we focused on length variation as found in small-scale insertion and deletion (indel) polymorphisms and microsatellites. For indels in chicken, replication slippage is a likely mutation mechanism, as a large proportion of the indels are parts of tandem-duplicates. Using a set of microsatellite polymorphisms in chicken, where we avoid ascertainment bias, we showed that polymorphism is positively correlated with microsatellite length and AT-content. Furthermore, interruptions in the microsatellite sequence decrease the levels of polymorphism.
We also analysed the association between microsatellite polymorphism and recombination in the human genome. Here we found increased levels of microsatellite polymorphism in human recombination hotspots and also similar increases in the frequencies of single nucleotide polymorphisms (SNPs) and indels. This points towards natural selection shaping the levels of variation. Alternatively, recombination is mutagenic for all three kinds of polymorphisms.
Finally, I present the program ILAPlot. It is a tool for visualisation, exploration and data extraction based on BLAST.
Our combined results highlight the intricate connections between evolutionary phenomena. It also emphasises the importance of length variability in genome evolution, as well as the gradual difference between indels and microsatellites.
Wagner, Brandie D. "Permutation based microarray gene selection methods with covarience adjustment applicable to complex diseases /". Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
Znajdź pełny tekst źródłaTypescript. Includes bibliographical references (leaves 57-60). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
Beane, Melinda. "Development of response strategy selection during sequence-based learning and performance to manage attention and to facilitate behavioral flexibility /". view abstract or download file of text, 2006. http://proquest.umi.com/pqdweb?did=1251836221&sid=1&Fmt=2&clientId=11238&RQT=309&VName=PQD.
Pełny tekst źródłaTypescript. Includes vita and abstract. Includes bibliographical references (leaves 81-89). Also available for download via the World Wide Web; free to University of Oregon users.
Ali, Isse. "Analysing and predicting differences between methylated and unmethylated DNA sequence features". Thesis, De Montfort University, 2015. http://hdl.handle.net/2086/12616.
Pełny tekst źródłaBebber, Michelle Rae. "UNDERSTANDING TEMPER SELECTION IN THE PREHISTORIC CERAMIC SEQUENCE OF THE SCIOTO RIVER VALLEY, ROSS COUNTY, OHIO (500 B.C. – AD 1400)". Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1479821741762486.
Pełny tekst źródłaPegard, Marie. "New models for implementation of genome-wide evaluation in black poplar breeding program". Thesis, Orléans, 2018. http://www.theses.fr/2018ORLE2058/document.
Pełny tekst źródłaForest species are unique in many ways compared to other domesticated species. Forest trees have long juvenile phases, leading to long and costly selection cycles and requiring selection in several independent stages. Even if this method is operationally effective, it remains costly in terms of time and resources, resulting in a diluted intensity and accuracy of selection.In view of these constraints, trees are good candidates for the implementation of genomic evaluation. Genomic selection (SG) is based on the classification and selection of individuals from the information contained in their genome without using a phenotypic evaluation step and thus accelerating the selection process, in order to identify the situations, criteria and factors in which SG could be a feasible option for poplar. Our study showed that the benefits of genomic evaluation are context-dependent. Genomic evaluation is most effective in theless-advantageous situations, it also benefits from low to medium density genetic information following a high-quality imputation step. Genomic selection could be an interesting option at an early stage, when the accuracy of selection is generally low and genetic variability is abundant.Our work has also shown that it is important to evaluate performance with alternative criteria,such as those related to ranking, especially when these criteria fit the operational context of the breeding programme under study
Walsh, Capdevila Sandra 1991. "Insights into the adaptative history of African human populations from whole-genome sequence data". Doctoral thesis, Universitat Pompeu Fabra, 2019. http://hdl.handle.net/10803/668469.
Pełny tekst źródłaÀfrica és la font d'origen dels humans moderns. Malgrat que les poblacions Africanes són les que contenen la major diversitat genètica al món, estan molt poc representades en estudis genètics. Així doncs, per poder plenament entendre la història evolutiva humana és fonamental incloure més poblacions Africanes en estudis genètics. Aquesta tesi és una petita contribució en l'estudi de la història evolutiva humana a l'Àfrica. Ens hem centrat en dos localitzacions diferents, a l'est i al sud de l'Àfrica. Hem intentat dilucidar les possibles senyals de selecció positiva (o adaptativa) a través de l'anàlisi de seqüències completes de genomes de cinc poblacions d'Etiòpia i una KhoeSan. A més a més, en l'última part de la tesi s'ha intentat entendre a nivell funcional la relació entre el genotip i el fenotip d'un candidat de selecció adaptativa descobert en una població d'Etiòpia.
Borukhovich, Ian. "Intrinsic Local Balancing of Hydrophobic and Hydrophilic Residues in Folded Protein Sequences". Diss., The University of Arizona, 2015. http://hdl.handle.net/10150/596407.
Pełny tekst źródłaYin, Pei. "Segmental discriminative analysis for American Sign Language recognition and verification". Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/33939.
Pełny tekst źródłaYenihayat, Guven. "Opportunistic Multiple Relaying In Wireless Ad Hoc Networks". Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613334/index.pdf.
Pełny tekst źródłaTucker, Dominic M. "Mapping and Characterization of Phytophthora sojae and Soybean Mosaic Virus Resistance in Soybean". Diss., Virginia Tech, 2009. http://hdl.handle.net/10919/79598.
Pełny tekst źródłaPh. D.
Künstner, Axel. "Birds as a Model for Comparative Genomic Studies". Doctoral thesis, Uppsala universitet, Evolutionsbiologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-159766.
Pełny tekst źródłaCook, Kevin Michael Brooks. "Probability of Belonging to a Language". BYU ScholarsArchive, 2013. https://scholarsarchive.byu.edu/etd/4023.
Pełny tekst źródłaBorge, Thomas. "Genetics and the Origin of Two Flycatcher Species". Doctoral thesis, Uppsala University, Evolutionary Biology, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3919.
Pełny tekst źródłaIn this thesis, different genetic tools are used to investigate pre- and postzygotic barriers to gene exchange and their role in speciation in the pied flycatcher (Ficedula hypoleuca) and the collared flycatcher (F. albicollis). This species complex consists of four genetically distinct clades that apparently diverged in allopatry (I). Sequencing of introns from autosomal and Z-linked genes from the two species reveals signs of selection on the Z-chromosome. Sexual selection acting on Z-linked genes might explain this pattern (II). By using large-scale genotyping of single nucleotide polymorphisms (SNPs), introgression is observed at autosomal- but not Z-linked loci, mostly from the pied- to the collared flycatcher. Male plumage characters and genes involved in hybrid fitness are largely mapped to the Z-chromosome (III). By studying mate choice of female hybrids I show that there is a link between female preferences and the Z chromosome (IV). The rate of introgression in island versus clinal hybrid zones is consistent with regional differences in hybrid fertility. Asymmetric gene flow from allopatry on the islands may oppose reinforcement, leading to introgression and a partial breakdown of postzygotic isolation. Adaptive introgression may explain the high rate of introgression observed at one of the genetic markers (V). For late breeding female collared flycatchers it appears to be adaptive to use pied flycatchers as social fathers but conspecific males as genetic fathers. Additionally, females in mixed species pairs may reduce hybridization costs by producing an excess of male hybrid offspring that are more fertile than females (VI).
In conclusion, the Z-chromosome appears to play a major role in flycatcher speciation. Sexual selection and reinforcement are important mechanisms in the divergence of these birds. However, gene flow from allopatry, introgression of adaptive genes and adaptive hetrospecific pairing by late breeding collared flycatcher females may work in the opposite direction.
Mondal, Mayukh 1989. "New insights into human migration, demography and adaptation of Indian and South Asian populations from genome analyses". Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/511362.
Pełny tekst źródłaEl projecte del genoma humà va publicar la primera seqüència completa del genoma humà el 2001 amb un cost de milers de millions de dòlars. Després d'això, el cost de la seqüenciació està disminuint més ràpid que la llei de Moore. Actualment no només tenim la seqüència de del genoma humà, sinó que tenim la de molts humans i d’homínids extingits amb una qualitat relativement bona. L’estudi de les seqüències de molts genomes humans varen proporcionar la base per postular que els humans moderns es varen originar a Àfrica, i en la sortida d’Àfrica (Out Of Africa) varen poblar la resta del món, amb una certa barreja amb diferents poblacions d'homínids. La base del treball en biologia i en genòmica evolutiva ha estat fonamentalment empírica (a diferència de la física), però actualment la disponibilitat de moltes dades permet empenyer la recerca cap a aspectes molt més analítics: aquest és l’enfocament del nostre treball en seqüències de DNA. Aquí, en aquesta tesi, hem proporcionat un coneixement més profund sobre l’origen i l'ascendència de poblacions indígenes, d’Àsia i del Pacífic, centrant-nos en la India continental i especialment en les Illes Andaman. També hem estat capaços de revelar l’existència d’una població d'homínids desconeguts que es va barrejar amb els ancestres d’aquestes poblacions. A més, hem demostrat que una forta selecció natural pot canviar dràsticament la morfologia humana en un curt període de temps i que explicaria la morfologia pigmea del pobladors de les illes Andaman.
Soldevila, Trepat Marta. "Genetic variation in humans and chimpanzees in the prion protein gene". Doctoral thesis, Universitat Pompeu Fabra, 2005. http://hdl.handle.net/10803/7189.
Pełny tekst źródłaIn the prion gene or PRNP, we have observed that the particular pattern of variation that we have found in this gene based on sequencing data in humans is due to positive selection, and that the method and the approach used to detect this selection critical. Ascertainment bias can be introduced by using SNP data and applying neutrality tests based on sequence diversity, therefore leading to anomalous conclusions being drawn. Moreover, we have seen that polymorphisms in codon 129 and 219 have big differences in frequency in different human populations and we have also seen that these positions are fixed in chimpanzees. The normal variation that we found in controls have been then compared with patients for the same region. The resequencing of PRNP in a very large sample of humans and chimpanzees has provided a great deal of information on this gene.
Pfeifer, Susanne. "Statistical challenges in the detection of mutation and variation using high throughput sequencing". Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:e49ce2fa-aa2c-42d7-bb54-c63e50d14afb.
Pełny tekst źródłaKhoo, Choon-Kiat. "Chicken genome variations and selection : from sequences to consequences". Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28934.
Pełny tekst źródłaTaleb, Robin I. "Preparation, optimisation and characterisation of sequence selective compounds". Thesis, View thesis, 2008. http://handle.uws.edu.au:8081/1959.7/38214.
Pełny tekst źródłaTaleb, Robin I. "Preparation, optimisation and characterisation of sequence selective compounds". View thesis, 2008. http://handle.uws.edu.au:8081/1959.7/38214.
Pełny tekst źródła"A thesis presented to the University of Western Sydney, College of Health and Science, School of Biomedical and Health Sciences in fulfilment of the requirements for the degree of Doctor of Philosophy." Includes bibliography.
Tonidandel, Sandra Maria Rudella. "Superando obstáculos no ensino e na aprendizagem da evolução biológica: o desenvolvimento da argumentação dos alunos no uso de dados como evidências da seleção natural numa sequência didática baseada em investigação". Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/48/48134/tde-18122014-100501/.
Pełny tekst źródłaThe scientific education has focused on pedagogical activities that use students investigative practice. One of the objectives is so that students not only obtain the scientific concepts, but also the specific practices of science activity. It is a pretention that students develop their scientific argumentation competence. This investigation aims at understanding how students develop their written argumentation, analyzing their use of data as evidence of natural selection in order to sustain their conclusions about biological evolution investigative questions. We made a didactic sequence, which architecture establishes the foundation to the teachers pedagogical actions, and promotes students investigative actions. The sequence lies on two integrative bases: a) an investigation based scientific education and b) Darwins investigation on the natural selection as a mechanism of the historical construction matrix of biological evolution. In order to examine how would it be the biological evolution teaching based in Darwins investigative structure, our problem question was built with two main focuses: a) how could we articulate conceptual and methodological intentions, characteristic to biological sciences, with the approach of the main historical obstacles of natural selection in evolving into the concept of the mechanism of biological evolution in a didactic sequence based upon inquiry and b) how it is the use of data as evidence of natural selection in the high school students written argumentative structure during the application of Inquiry Based Biology Teaching Sequence (SEEBI, in Portuguese) to biological evolution teaching. To investigate our task, we developed a SEEBI that was applied by a public networks teacher to 125 high schools senior year students in a public school of São Paulo. Our methodology has qualitative and quantitative approaches. Our data consists of: a) materials (textbooks, experimental models, audio-visual resources used in class) and b) booklets with answers written by the students after the proposed activities. The data analyses were based upon these booklets, with students written answers, materials elaborated and posted in the SEEBI and also in the transcription we did. The results show that SEEBI has its foundation lied on conceptual and methodological intentions, characteristic to Biology. Furthermore, the results indicate an overcoming of conceptual obstacles as well, such as cosmic teleology and fixism, therefore, building the concept of natural selection as a mechanism of biological evolution. The study of the consequences presents an improvement in students argumentative ability, a strong correlation between the use of data from biological evolution with the construction of higher quality arguments by the students, using justifications (warranty and theoretical support) grounded in scientific knowledge. Theres evidence of an expansion of the arguments construction, both increasing the number of used components as well as the field-dependent components of sciences quality, such as support and evidence. The arguments constructed shall provide support based on specific conceptual assistance in paradigms of Biology, like natural selection, validating the findings from the use of data (Toulmin, 2006) in researches conducted by students.
Margolin, Yelena 1977. "Analysis of sequence-selective guanine oxidation by biological agents". Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/42381.
Pełny tekst źródłaVita.
Includes bibliographical references.
Oxidatively damaged DNA has been strongly associated with cancer, chronic degenerative diseases and aging. Guanine is the most frequently oxidized base in the DNA, and generation of a guanine radical cation (G'") as an intermediate in the oxidation reaction leads to migration of a resulting cationic hole through the DNA n-stack until it is trapped at the lowest-energy sites. These sites reside at runs of guanines, such as 5'-GG-3' sequences, and are characterized by the lowest sequence-specific ionization potentials (IPs). The charge transfer mechanism suggests that hotspots of oxidative DNA damage induced by electron transfer reagents can be predicted based on the primary DNA sequence. However, preliminary data indicated that nitrosoperoxycarbonate (ONOOCO2"), a mediator of chronic inflammation and a one-electron oxidant, displayed unusual guanine oxidation properties that were the focus of present work. As a first step in our study, we determined relative levels of guanine oxidation, induced by ONOOCO2 in all possible three-base sequence contexts (XGY) within double-stranded oligonucleotides. These levels were compared to the relative oxidation induced within the same guanines by photoactivated riboflavin, a one-electron reagent. We found that, in agreement with previous studies, photoactivated riboflavin was selective for guanines of lowest IPs located within 5'-GG-3' sequences. In contrast, ONOOCO2" preferentially reacted with guanines located within 5'-GC-3' sequences characterized by the highest IPs. This demonstrated that that sequence-specific IP was not a determinant of guanine reactivity with ONOOCO2". Sequence selectivities for both reagents were double-strand specific. Selectivity of ONOOCO2 for 5'-GC-3' sites was also observed in human genomic DNA after ligation-mediated PCR analysis.
(cont.) Relative yields of different guanine lesions produced by both ONOOCO2" and riboflavin varied 4- to 5-fold across all sequence contexts. To assess the role of solvent exposure in mediating guanine oxidation by ONOOCO2", relative reactivities of mismatched guanines with ONOOCO2" were measured. The majority of the mismatches displayed an increased reactivity with ONOOCO2 as compared to the fully matched G-C base-pairs. The extent of reactivity enhancement was sequence context-dependent, and the greatest levels of enhancement were observed for the conformationally flexible guanine- guanine (G-G) mismatches and for guanines located across from a synthetic abasic site. To test the hypothesis that the negative charge of an oxidant influences its reactivity with guanines in DNA, sequence-selective guanine oxidation by a negatively charged reagent, Fe+2-EDTA, was assessed and compared to guanine oxidation produced by a neutral oxidant, y-radiation. Because both of these agents cause high levels of deoxyribose oxidation, a general method to quantify sequence-specific nucleobase oxidation in the presence of direct strand breaks was developed. This method exploited activity of exonuclease III (Exo III), a 3' to 5' exonuclease, and utilized phosphorothioate-modified synthetic oligonucleotides that were resistant to Exo III activity. This method was employed to determine sequence-selective guanine oxidation by Fe+2-EDTA complex and y-radiation and to show that both agents produced identical guanine oxidation pattems and were equally reactive with all guanines, irrespective of their sequence-specific IPs or sequence context.
(cont.) This showed that negative charge was not a determinant of Fe+2-EDTA-mediated guanine oxidation. Finally, the role of oxidant binding on nucleobase damage was assessed by studying sequence-selective oxidation produced by DNA-bound Fe+2 ions in the presence of H202. We found that the major oxidation targets were thymines located within 5'-TGG-3' motifs, demonstrating that while guanines were a required element for coordination of Fe+2 to DNA, they were not oxidized. Our results suggest that factors other than sequence-specific IPs can act as major determinants of sequence-selective guanine oxidation, and that current models of guanine oxidation and charge transfer in DNA cannot be used to adequately predict the location and identity of mutagenic lesions in the genome.
by Yelena Margolin.
Ph.D.
Serres-Giardi, Laurana. "Diversité et évolution des paysages nucléotidiques des plantes". Thesis, Montpellier, SupAgro, 2012. http://www.theses.fr/2012NSAM0045/document.
Pełny tekst źródłaThe nucleotide landscape – the way base composition varies along a genome – is a striking feature of genome organization and is highly variable between species. The evolutionary causes of such heterogeneity in GC content have been much debated. Biased gene conversion towards G and C (BGC) and selection on codon usage (SCU) are thought to be main forces. BGC is a neutral process associated with recombination favouring G and C alleles over A and T ones. SCU is a selection process favouring the so-called “preferred” codons, i.e., those whose translation is the most efficient. Contrary to vertebrates, plant nucleotide landscapes are still poorly known. Most studies focused on the GC-poor and homogeneous Arabidopsis thaliana genome and on the GC-rich and heterogeneous rice genome. The contrast between these two genomes was often generalized as a dicot/monocot dichotomy but this vision is clearly phylogenetically biased.The objectives of this study are to characterize angiosperm nucleotide landscapes on a wide phylogenetic scale and to better understand the evolutionary mechanisms acting upon the evolution of nucleotide landscapes. To what extent do nucleotide landscapes vary across angiosperm phylogeny? Are nucleotide landscapes shaped by BGC and SCU? Are taxa affected with the same intensity?To tackle these issues, I used a comparative genomic approach relying on EST data analysis on over 230 angiosperm and gymnosperm species. Through the nucleotide landscape survey for such a wide range of species I found a continuum of GC-heterogeneity patterns across phylogeny, some taxa such as Poaceae being strikingly GC-rich and heterogeneous. My results suggest that nucleotide landscapes could have been shaped by BGC and, to a lesser extent, by SCU. GC-content enrichment and impoverishment are likely to have occurred several times independently during plant evolution and could be explained by intensity variations of BGC and SCU. Using a proxy for EST expression level, I also characterized the diversity of preferred codons between species. Codon usage preferences were shown to be evolutionarily more unstable for four- and six-fold degenerate codon families. Finally, I could link the evolution of codon usage preferences to the evolution of genome base composition. My results suggest that genome base composition, partially shaped by BGC, seems to drive the coevolution between codon usage preferences and tRNAs
Vázquez, García Ignacio. "Molecular evolution of biological sequences". Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/284174.
Pełny tekst źródłaMillan, Kelly M. "The development and application of a sequence-selective DNA sensor". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq25910.pdf.
Pełny tekst źródłaWaterloh, Kerstin. "The effects of sequence selective antitumour antibiotics on DNA structure". Thesis, University of Southampton, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385333.
Pełny tekst źródłaDoherty, Aidan Joseph. "Studies on the sequence-selective nuclease, bovine pancreatic DNase I". Thesis, University of Southampton, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359221.
Pełny tekst źródłaLin, S. "Molecular and cellular evaluation of novel DNA sequence selective polyamides". Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1403138/.
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