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Nicholls, Felicity K. M. "Genetic analysis of the gene Additional sex combs and interacting loci". Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/29644.
Pełny tekst źródłaScience, Faculty of
Zoology, Department of
Graduate
Mat, Wai Kin. "Genetic code mutants of bacillus subtilis /". View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?BICH%202007%20MAT.
Pełny tekst źródłaFreeland, Stephen J. "Natural selection and the genetic code". Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313922.
Pełny tekst źródłaGutfraind, Alexander. "Error-Tolerant Coding and the Genetic Code". Thesis, University of Waterloo, 2006. http://hdl.handle.net/10012/2913.
Pełny tekst źródłaThe main advance in this thesis is a set of methods for calculating the primordial evolutionary pressures that shaped the genetic code. These pressures are due to genetic errors, and hence the statistical properties of the errors and of the genome are imprinted in the statistical properties of the code. Thus, by studying the code it is possible to reconstruct, to some extent, the primordial error rates and the composition of the primordial genome. In this way, I find evidence that the fixation of the genetic code occurred in organisms which were not thermophiles.
Mateus, Denisa Daud. "Molecular reconstruction of a genetic code alteration". Doctoral thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/7501.
Pełny tekst źródłaThe genetic code establishes the rules that govern gene translation into proteins. It was established more than 3.5 billion years ago and it is one of the most conserved features of life. Despite this, several alterations to the standard genetic code have been discovered in both prokaryotes and eukaryotes, namely in the fungal CTG clade where a unique seryl transfer RNA (tRNACAG Ser) decodes leucine CUG codons as serine. This tRNACAG Ser appeared 272±25 million years ago through insertion of an adenosine in the middle position of the anticodon of a tRNACGA Ser gene, which changed its anticodon from 5´-CGA-3´ to 5´-CAG-3´. This most dramatic genetic event restructured the proteome of the CTG clade species, but it is not yet clear how and why such deleterious genetic event was selected and became fixed in those fungal genomes. In this study we have attempted to shed new light on the evolution of this fungal genetic code alteration by reconstructing its evolutionary pathway in vivo in the yeast Saccharomyces cerevisiae. For this, we have expressed wild type and mutant versions of the C. albicans tRNACGA Ser gene into S. cerevisiae and evaluated the impact of the mutant tRNACGA Ser on fitness, tRNA stability, translation efficiency and aminoacylation kinetics. Our data demonstrate that these mutants are expressed and misincorporate Ser at CUGs, but their expression is repressed through an unknown molecular mechanism. We further demonstrate, using in vivo forced evolution methodologies, that the tRNACAG Ser can be easily inactivated through natural mutations that prevent its recognition by the seryl-tRNA synthetase. The overall data show that repression of expression of the mistranslating tRNACAG Ser played a critical role on the evolution of CUG reassignment from Leu to Ser. In order to better understand the evolution of natural genetic code alterations, we have also engineered partial reassignment of various codons in yeast. The data confirmed that genetic code ambiguity affects fitness, induces protein aggregation, interferes with the cell cycle and results in nuclear and morphologic alterations, genome instability and gene expression deregulation. Interestingly, it also generates phenotypic variability and phenotypes that confer growth advantages in certain environmental conditions. This study provides strong evidence for direct and critical roles of the environment on the evolution of genetic code alterations.
O código genético regula a correcta descodificação da informação contida nos genes durante a síntese de proteínas. Apresenta um elevado grau de conservação e estima-se que tenha sido originado há mais de 3.5 biliões de anos. Contudo, várias alterações ao código genético foram identificadas em procariotas e eucariotas, nomeadamente nos fungos denominados de “CTG clade”, nos quais um tRNA de serina atípico (tRNACAG Ser) descodifica o codão de leucina CUG como serina. Este tRNACAG Ser foi originado há 272±25 milhões de anos, pela inserção de uma adenosina no centro do anticodão do gene do tRNACGA Ser que alterou a sequência original do anticodão de 5´-CGA-3´ para 5´-CAG-3´. Esta alteração ao código genético promoveu a restruturação do proteoma das espécies denominadas de “CTG clade”. Contudo, permanece por esclarecer o motivo que permitiu que esta alteração atípica fosse preservada no genome destes fungos. Numa tentativa de clarificar os aspectos evolutivos desta alteração ao código genético, procedemos à reconstrução da via evolutiva, proposta para esta alteração, na levedura Saccharomyces cerevisiae. Para tal, induzimos a expressão do gene do tRNACGA Ser de C. albicans, nas versões mutantes e original, em S. cerevisiae e determinámos o impacto das mesmas no crescimento celular, bem como na estabilidade, eficiência na tradução e aminoacilação do tRNA. Os nossos dados, demonstram que as versões mutantes do tRNA, apesar de sua reduzida expressão, induzem a incorporação de serina nos codões CUG de leucina. Observámos ainda, através de uma estratégia de evolução forçada, que o tRNACAG Ser é facilmente inactivado por mutações naturais que impedem o seu reconhecimento pela seryl-tRNA synthetase. O nosso estudo demonstra que a repressão da expressão do tRNACAG Ser, terá desempenhado um papel fundamental na evolução da redefinição do codão CUG de leucina para serina. Com o intuito de compreender a evolução das alterações ao código genético, induzimos redefinições parciais em vários codões de levedura. Os nossos resultados confirmam que a ambiguidade no código genético afecta o crescimento, induz a produção de agregados proteicos, interfere no ciclo celular e promove alterações nucleares, morfológicas, instabilidade genómica e desregulação da expressão genética. Contudo, origina também variedade fenotípica e fenótipos vantajosos em determinadas condições ambientais. Este estudo demonstra o impacto do ambiente na evolução das alterações ao código genético.
Gomes, Ana Catarina Batista. "Molecular evolution of a genetic code alteration". Doctoral thesis, Universidade de Aveiro, 2008. http://hdl.handle.net/10773/939.
Pełny tekst źródłaDurante os últimos anos, foram descritas alterações ao código genético, quer em procariotas, quer em eucariotas, quebrando o dogma de que o código genético é universal e imutável. Estudos recentes sugerem que a evolução de tais alterações requerem modificações ao nível da estrutura da maquinaria da tradução e são promovidas por mecanismos de descodificação ambígua. Em C. albicans, um organismo que é patogénico para o Homem, a alteração ao código genético é mediada por uma alteração na estrutura de um novo tRNACAG de serina que descodifica o codão CUG de leucina como serina. De forma a determinar se este tRNA, que é aminoacilado pelas Seryl- e Leucyl- tRNA sintetases, promove a descodificação ambígua do codão CUG, foi desenvolvido um sistema para a quantificar in vivo, por espectrometria de massa, os níveis de incorporação de serina e de leucina em codões CUG. Os resultados mostraram que em condições normais de crescimento leucina é incorporada a uma taxa de 3% e que serina é incorporada a uma taxa de 97%. No entanto, o nível de ambiguidade na descodificação de codões CUG aumentou para 5% em células crescidas em condições de stress, indicando que a incorporação de leucina em codões CUG é sensível a factores ambientais e é manipulada durante a tradução do mRNA. Tal, levanta a hipótese de que a incorporação de leucina poderá atingir níveis superiores aos determinados neste estudo. Para testar esta hipótese e determinar os níveis máximos de ambiguidade na descodificação do codão CUG tolerados pelas células, aumentou-se artificialmente a ambiguidade do codão CUG em C. albicans. Surpreendentemente, a incorporação de leucina subiu de 5% para 28%, o que representa um aumento na taxa de erro da tradução de 3500 vezes, relativamente ao descrito para o mecanismo de tradução. Dado existirem 13.000 codões CUG no genoma de C. albicans, a sua descodificação ambígua expande de uma forma exponencial o proteoma deste fungo, criando assim um proteoma estatístico, resultante da síntese de um conjunto de moléculas diferentes para cada proteína a partir de um único RNA mensageiro (mRNA) que contenha codões CUG. Os resultados obtidos demonstraram que o proteoma de C. albicans tem uma dimensão muito superior à prevista pelo seu genoma e demonstram um papel central da descodificação ambígua na evolução do código genético.
Alterations to the standard genetic code have been found in both prokaryotes and eukaryotes, demolishing the dogma of an immutable and universal genetic code. Recent studies suggest that evolution of such alterations require structural change of the translation machinery and are driven through mechanisms that require codon decoding ambiguity. In the human pathogen C. albicans, a structural change in a novel sertRNACAG allows for its recognition by both the LeuRS and SerRS in vitro and in vivo, providing such molecular device. In order to determine whether this tRNA charging ambiguity results in ambiguous CUG decoding, we have developed a system for quantification of the level of serine and leucine at the CUG codon by Mass-Spectrometry. The data showed that 3.0% of leucine and 97.0% of serine are incorporated at CUG codons in vivo under standard growth conditions. Moreover, this ambiguity increases up to 5.0% under stress, indicating that it is sensitive to environmental change and raising the hypothesis that leucine incorporation may be higher than determine experimentally. In order to determine the scope of C. albicans tolerance to CUG ambiguity, we have created highly ambiguous C. albicans cell lines through tRNA engineering. These cell lines tolerated up to 28% leucine incorporation at CUGs, which represents an increase of 3500 fold in decoding error rate. Since there are 13,000 CUG codons in C. albicans such ambiguity expands the proteome exponentially and creates a statistical proteome due to synthesis of arrays of protein molecules from mRNAs containing CUG codons. The overall data showed that the dimension of the C. albicans proteome is far higher than that predicted from its genome and provides important new evidence for a pivotal role for codon ambiguity in the evolution of the genetic code.
Silva, Raquel Monteiro Marques da. "Molecular reconstruction of a genetic code alteration". Doctoral thesis, Universidade de Aveiro, 2005. http://hdl.handle.net/10773/948.
Pełny tekst źródłaVárias espécies de Candida traduzem o codão CUG de leucina como serina. Esta alteração ao código genético é mediada por um novo tRNA (sertRNACAG), que pode ser carregado com serina (97 %) e leucina (3 %) in vivo. Por esta razão o codão CUG é ambíguo, pois pode ser descodificado como serina ou leucina. Para elucidar o impacto da ambiguidade do código genético na expressão génica e na fisiologia da célula, o ser-tRNACAG de C. albicans foi expresso em Saccharomyces cerevisiae. Isto induz a descodificação ambígua do codão CUG, devido à competição entre o tRNA endógeno que traduz o codão CUG como leucina e o C. albicans ser-tRNACAG, que o traduz maioritariamente como serina. A caracterização do transcriptoma e do proteoma das linhas celulares manipuladas de S. cerevisiae mostra que a ambiguidade do código genético induz alterações globais na expressão de genes e proteínas, com alterações na resposta ao stress, metabolismo dos hidratos de carbono e dos aminoácidos, estrutura e função da parede celular, síntese e degradação de proteínas. Adicionalmente, os resultados indicam que a tradução errada do codão CUG regula a expressão génica ao nível da tradução. A ambiguidade do codão CUG gera instabilidade do proteoma e genoma, contudo, estas células não perdem viabilidade. Pelo contrário, os dados sugerem que a resposta ao stress despoletada pela ambiguidade do codão CUG aumenta o potencial de adaptação, como é demonstrado pela tolerância que as células ambíguas têm a várias condições de stress. Por estas razões, a reconstrução da alteração na descodificação do codão CUG providenciou dados importantes sobre o impacto que alterações ao código genético têm na adaptação e evolução das células. Este estudo também trouxe novas ideias acerca dos mecanismos que permitem a tolerância das células eucarióticas a elevados níveis de erro na tradução do mRNA.
Several Candida species translate the standard leucine CUG codon as serine. This genetic code alteration is mediated by a novel tRNA (ser-tRNACAG), which can be charged both with serine (97 %) and leucine (3%) in vivo. Therefore, the CUG codon is ambiguous, since it can be decoded either as serine or leucine. To elucidate the impact of genetic code ambiguity on gene expression and cell physiology, the C. albicans ser-tRNACAG was expressed in Saccharomyces cerevisiae. This induces ambiguous decoding of the CUG codon, due to competition between the endogenous tRNA that decodes the CUG codon as leucine and the C. albicans ser-tRNACAG, which decodes it mainly as serine. Transcriptome and proteome characterization of the engineered S. cerevisiae cell lines show that genetic code ambiguity induces global gene and protein expression changes, with alterations in the stress response, carbohydrate and amino acid metabolism, cell wall structure and function, protein synthesis and protein degradation. Additionally, the results indicate that CUG mistranslation regulates gene expression at the translational level. CUG ambiguity generates proteome and genome instability, however, these cells do not lose viability. Instead, the data suggests that the stress response triggered by CUG ambiguity increases adaptation potential, as shown by the tolerance of ambiguous cells to several stress conditions. Therefore, the reconstruction of the CUG reassignment pathway provided important insight on the impact that genetic code alterations have on cell adaptation and evolution. This study also sheds new light on the mechanisms that allow eukaryotic cells to tolerate high levels of mRNA mistranslation.
Bezerra, Ana Rita Macedo. "Molecular genomics of a genetic code alteration". Doctoral thesis, Universidade de Aveiro, 2013. http://hdl.handle.net/10773/12499.
Pełny tekst źródłaThe genetic code is not universal. Alterations to its standard form have been discovered in both prokaryotes and eukaryotes and demolished the dogma of an immutable code. For instance, several Candida species translate the standard leucine CUG codon as serine. In the case of the human pathogen Candida albicans, a serine tRNA (tRNACAGSer) incorporates in vivo 97% of serine and 3% of leucine in proteins at CUG sites. Such ambiguity is flexible and the level of leucine incorporation increases significantly in response to environmental stress. To elucidate the function of such ambiguity and clarify whether the identity of the CUG codon could be reverted from serine back to leucine, we have developed a forced evolution strategy to increase leucine incorporation at CUGs and a fluorescent reporter system to monitor such incorporation in vivo. Leucine misincorporation increased from 3% up to nearly 100%, reverting CUG identity from serine back to leucine. Growth assays showed that increasing leucine incorporation produced impressive arrays of phenotypes of high adaptive potential. In particular, strains with high levels of leucine misincorporation exhibited novel phenotypes and high level of tolerance to antifungals. Whole genome re-sequencing revealed that increasing levels of leucine incorporation were associated with accumulation of single nucleotide polymorphisms (SNPs) and loss of heterozygozity (LOH) in the higher misincorporating strains. SNPs accumulated preferentially in genes involved in cell adhesion, filamentous growth and biofilm formation, indicating that C. albicans uses its natural CUG ambiguity to increase genetic diversity in pathogenesis and drug resistance related processes. The overall data provided evidence for unantecipated flexibility of the C. albicans genetic code and highlighted new roles of codon ambiguity on the evolution of genetic and phenotypic diversity.
O código genético não é universal. Alterações à identidade de vários codões descobertas em procariotas e eucariotas invalidam a hipótese dum código genético universal e imutável. Por exemplo, várias espécies do género Candida traduzem o codão CUG de leucina como serina. Em Candida albicans, um único tRNA de serina (tRNACAGSer) incorpora in vivo 97% de serina e 3% de leucina nas proteínas em resposta a codões CUG presentes nos mRNAs deste fungo patogénico. Esta ambiguidade é flexível e a incorporação de leucina aumenta em condições de stress. De forma a elucidar a função desta ambiguidade e determinar se a identidade dos codões CUG podia ser revertida de serina para leucina, desenvolvemos uma estratégia de evolução forçada e uma proteína recombinante fluorescente cuja actividade depende da incorporação de leucina num codão CUG. Construímos estirpes que incorporam leucina nas proteínas em resposta a codões CUGs em níveis que variam entre 0,64% e 98,46%. Esta reversão de uma alteração ao código genético demostrou de modo inequívoco que o código é flexível e pode evoluir. Testes de crescimento em diferentes meios de cultivo revelaram uma série impressionante de fenótipos com elevado potencial adaptativo nas estirpes mais ambíguas, nomeadamente tolerância a antifúngicos. A sequenciação dos genomas das estirpes que construímos revelou que a ambiguidade do codão CUG resulta na acumulação de polimorfismos de nucleótido únicos (SNP) no genoma. Verificámos também perda de heterozigozidade (LOH) nos cromossomas 5 e R das estirpes que incorporam 80,84% e 98,46% de leucina em locais proteicos codificados por codões CUG. Os SNPs acumularam-se preferencialmente em genes envolvidos na adesão celular, no crescimento filamentoso e na formação de biofilmes, sugerindo que C. albicans utiliza a sua ambiguidade natural para aumentar a diversidade genética dos processos relacionados com a patogénese e resistência a drogas. Estes resultados evidenciam uma notável flexibilidade do código genético de C. albicans e revelam funções inesperadas da ambiguidade do código genético na evolução da diversidade genética e fenotípica.
Lajoie, Marc Joseph. "Genome Engineering Technologies to Change the Genetic Code". Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11265.
Pełny tekst źródłaJääskelä, E. (Esa). "Genetic algorithm in code coverage guided fuzz testing". Master's thesis, University of Oulu, 2016. http://urn.fi/URN:NBN:fi:oulu-201601151058.
Pełny tekst źródłaTietokoneiden tietoturva on kasvava huolenaihe, kun laitteiden määrä lisääntyy. Uusia ja kattavampia testauksia täytyy suorittaa, jotta voidaan estää käyttäjille ja heidän laitteilleen tapahtuvat vahingot. Fuzzausta on pidetty hyvänä testausmetodina, mutta yleensä se ei saavuta hyvää koodikattavuutta tai vaatii joko monimutkaisen asennuksen tai lähdekoodianalyysin. Tämä työ esittelee geneettisen algoritmin, joka automaattisesti tasapainottaa fuzzerin eri mutaatiofunktioiden todennäköisyydet. Tämä tasapainotus pyrkii maksimoimaan saavutetun koodikattavuuden ja parantamaan fuzzaamisen tehokkuutta. Kahden avoimen lähdekoodin kirjaston testaamisen perusteella mutatorit koodikattavuuden perusteella tasapainottava työkalu pärjäsi paremmin kuin perinteinen, lisätietoa hyödyntämätön black-box fuzzaus
Grasso, Katherine Taylor. "Resolving the Limitations of Genetic Code Expansion Platforms:". Thesis, Boston College, 2021. http://hdl.handle.net/2345/bc-ir:109076.
Pełny tekst źródłaThesis advisor: Eranthie Weerapana
Over the past twenty years, the site-specific incorporation of unnatural amino acids (UAAs) into a target protein through genetic code expansion (GCE) has emerged as one of the foremost technologies to selectively modify proteins in their native cellular context. This technology relies on engineered aminoacyl-tRNA synthetase (aaRS)/tRNA pairs that are orthogonal to the host cells’ endogenous aaRS/tRNA pairs. Traditionally, scientists look towards evolutionarily distant domains of life to identify orthogonal aaRS/tRNA pairs that can be further engineered for GCE applications in the host system. For example, bacterial aaRS/tRNA pairs are used for GCE in eukaryotes. The directed evolution of orthogonal aaRS/tRNA pairs for eukaryotic GCE has been less fortuitous due to the cumbersome nature of established yeast-based selection platforms. Recently, our lab circumvented this platform-based limitation by developing “altered translational machinery” (ATM) Escherichia coli strains that enabled the directed evolution of bacterial aaRS/tRNA pairs for eukaryotic GCE applications. In the ATM-tyrosyl (ATMY) E. coli strain, reintroduction of the E. coli tyrosyl-tRNA (tRNAEcTyrCUA) as a nonsense suppressor led to cross-reactivity with the endogenous E. coli glutaminyl-tRNA synthetase (EcGlnRS), restricting the activity range of aaRSs that could be selected, ultimately diminishing the scope of incorporable UAAs. To recover the dynamic range of this platform, cross-reactivity of the tRNAEcTyrCUA was eliminated through directed evolution of the tRNA acceptor stem. This new, orthogonal tRNA revealed weak mutant aaRSs whose suppression efficiencies were boosted through additional rounds of directed evolution. Improved aaRS mutants exhibited higher solubility, thermal stability, and suppression efficiency than their predecessor. While the newly engineered, orthogonal tRNAEcTyrCUA gave access to novel aaRS/tRNA pairs for eukaryotic GCE, some notable UAAs were still missing that could be incorporated with the archaeal Methanococcus jannaschii tyrosyl-tRNA synthetase (MjTyrRS)/tRNA pair in bacteria. Following a systematic investigation into the discrepancy between the E. coli tyrosyl-tRNA synthetase (EcTyrRS)/tRNA and MjTyrRS/tRNA pairs, we found that it can be partially attributed to the low structural robustness of the EcTyrRS. This limitation was overcome by rationally designing chimeric TyrRSs composed of EcTyrRS and a structural homologue from the thermophilic bacterium Geobacillus stearothermophilus. The chimeric scaffolds demonstrated enhanced stability, activity, and resilience to destabilizing active site mutations, offering a potentially more attractive scaffold for GCE
Thesis (PhD) — Boston College, 2021
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
Iqbal, Emil S. "In vitro genetic code expansion and selected applications". VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5580.
Pełny tekst źródłaMa, Natalie Jing. "Altering the Genetic Code to Probe and Control the Flow of Genetic Information". Thesis, Yale University, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10584955.
Pełny tekst źródłaThe genetic code is highly conserved across all domains of life, enabling horizontal gene transfer (HGT) between organisms and across ecosystems via horizontally-transferred genetic elements such as viruses and plasmids. While HGT increases genetic diversity, it poses a risk to engineered biological systems by introducing new genes that destabilize engineered functions or allowing the expression of engineered genes in wild organisms with unknown effects. A model organism engineered with an alternative genetic code may provide new insight into the origins of the genetic code while also providing a stable chassis for engineered biological systems.
The Isaacs Lab recently developed an Escherichia coli strain lacking both UAG stop codons and Release Factor 1, resulting in the first genomically recoded organism (GRO) with an unassigned codon in its genetic code. Here, we demonstrate that this alternative genetic code lacking UAG codon assignment confers resistance to multiple viruses (λ, M13, PI, MS2) at titers up to 1011 PFU/mL and impairs conjugative plasmid function (F and RK2) up to 105-fold. Propagating viruses on a mixed microbial community containing standard and alternative genetic codes also reduced viral population fitness and prompted viral adaptation to the alternative genetic code. In investigating the molecular mechanism underlying the resistance to viruses and conjugative plasmids, we found that UAG-ending genes elicit ribosomal stalling and the tmRNAmediated ribosomal rescue response, resulting in degradation of UAG-ending proteins and suggesting that genomic recoding may be a broadly applicable strategy to impair horizontal gene transfer into other organisms.
To prevent the expression of engineered genes in wild organisms, we reassigned the UAG codon in the GRO to a sense codon incorporating the non-standard amino acid 4-acetylphenylalanine (pAcF) through the introduction of an orthogonal translation system (OTS). We then created a library of UAG-containing variants and assessed escape of UAG-containing genes from the GRO into wild-type organisms for both a non-selective green fluorescent protein (GFP) and selective chloramphenicol acetyltransferase (CAT) gene. While 1 UAG codon impaired the expression of GFP in wild-type organisms, at least 2 UAG codons were required in CAT to consistently prevent escaped expression in wild-type organisms with a standard genetic code. Additionally, sequencing revealed that wild-type organisms enabled expression of CAT by mutating UAG codons to UGG coding for tryptophan or CAG coding for glutamine. By placing UAG at sites in proteins that cannot tolerate a tryptophan or glutamine substitution, we can create UAG-containing genes further isolated from expression in wild organisms.
As biotechnology increasingly targets open-environment applications such as bioremediation or disease treatment in humans, we require methods to stabilize and control the genetic information that we encode in engineered biological systems. Because alternative genetic codes can both confer resistance to horizontal gene transfer into an engineered system and restrict expression of engineered genes in wild-type organisms, genomic recoding of organisms to contain alternative genetic codes is a promising path towards increasing the stability and safety of engineered biological systems. However, open-environment applications will expose engineered biological systems to new stresses not represented in the laboratory environment, and further work is required to validate these methods will be robust in conditions of limiting nutrients or other cellular stresses. Additionally, while we have demonstrated genetic isolation of the GRO with respect to genes both entering and leaving the cell, we cannot currently have both properties simultaneously because UAG is the sole open codon. We envision that current research into further codon reassignments, including the reassignment of sense codons, will pave the way for alternate genetic codes with multiple codon reassignments. By expanding recoding efforts to multiple species, we envision the development of synthetic microbial communities with alternate genetic codes that are genetically isolated and robust to perturbation by HGT.
Ording, Marcus. "Context-Sensitive Code Completion : Improving Predictions with Genetic Algorithms". Thesis, KTH, Skolan för informations- och kommunikationsteknik (ICT), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-205334.
Pełny tekst źródłaInom området kontextkänslig kodkomplettering finns det ett behov av precisa förutsägande modeller för att kunna föreslå användbara kodkompletteringar. Den traditionella metoden för att optimera prestanda hos kodkompletteringssystem är att empiriskt utvärdera effekten av varje systemparameter individuellt och finjustera parametrarna. Det här arbetet presenterar en genetisk algoritm som kan optimera systemparametrarna med en frihetsgrad som är lika stor som antalet parametrar att optimera. Studien utvärderar effekten av de optimerade parametrarna på det studerade kodkompletteringssystemets pre- diktiva kvalitet. Tidigare utvärdering av referenssystemet utökades genom att även inkludera modellstorlek och slutledningstid. Resultaten av studien visar att den genetiska algoritmen kan förbättra den prediktiva kvali- teten för det studerade kodkompletteringssystemet. Jämfört med referenssystemet så lyckas det förbättrade systemet korrekt känna igen 1 av 10 ytterligare kodmönster som tidigare varit osedda. Förbättringen av prediktiv kvalietet har inte en signifikant inverkan på systemet, då slutledningstiden förblir mindre än 1 ms för båda systemen.
Massey, Steven Edward. "Codon reassignment and the evolution of the genetic code". Thesis, University of Kent, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399606.
Pełny tekst źródłaItalia, James Sebastian. "Development and Applications of Universal Genetic Code Expansion Platforms:". Thesis, Boston College, 2019. http://hdl.handle.net/2345/bc-ir:108354.
Pełny tekst źródłaThe emergence of genetic code expansion (GCE) technology, which enables sitespecific incorporation of unnatural amino acids (UAAs) into proteins, has facilitated powerful new ways to probe and engineer protein structure and function. Using engineered orthogonal tRNA/aminoacyl-tRNA synthetase (aaRS) pairs that suppress repurposed nonsense codons, a variety of structurally diverse UAAs have been incorporated into proteins in living cells. This technology offers tremendous potential for deciphering the complex biology of eukaryotes, but its scope in eukaryotic systems remains restricted due to several technical limitations. For example, development of the engineered tRNA/aaRS pairs for eukaryotic GCE traditionally relied on a eukaryotic cell-based directed evolution system, which are significantly less efficient relative to bacteria-based engineering platforms. The work described in this thesis establishes a new paradigm in GCE through the development of a novel class of universal tRNA/aaRS pairs, which can be used for ncAA incorporation in both E. coli and eukaryotes. We achieve this by developing engineered strains of E. coli, where one of its endogenous tRNA/aaRS pair is functionally replaced with an evolutionarily distant counterpart. The liberated pair can then be used for GCE in the resulting altered translational machinery (ATM) strain, as well as any eukaryote. Using this strategy, we have been able to genetically encode new bioconjugation chemistries, post-translational modifications, and facilitate the incorporation of multiple, distinct ncAAs into a single protein. The ATM technology holds enormous promise for significantly expanding the scope of the GCE technology in both bacteria and eukaryotes
Thesis (PhD) — Boston College, 2019
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
Mukre, Prakash. "Hardware accelerator for DNA code word searching". Diss., Online access via UMI:, 2008.
Znajdź pełny tekst źródłaIncludes bibliographical references.
Abedi, Saied. "Genetic multi-user detection for code division multiple access systems". Thesis, University of Surrey, 2000. http://epubs.surrey.ac.uk/843016/.
Pełny tekst źródłaGrewal, Gary William. "Enhanced genetic algorithms and their application in retargetable code generation". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0008/NQ33302.pdf.
Pełny tekst źródłaMiranda, Isabel Alexandra Marcos. "Molecular study of a genetic code alteration in C. albicans". Doctoral thesis, Universidade de Aveiro, 2006. http://hdl.handle.net/10773/8980.
Pełny tekst źródłaA maioria dos organismos utiliza o mesmo código genético, no entanto alterações a este código padrão foram descobertas em procariotas e eucariotas. A maior parte das alterações ao código genético ocorre em mitocôndrias. No citoplasma eucariótico, o único exemplo conhecido de alteração ao código genético envolvendo a substituição de um aminoácido por outro aminoácido, ocorre em várias espécies do género Candida. Em Candida albicans o codão CUG é ambíguo, ou seja, pode ser traduzido como serina ou leucina, com predominância para o primeiro aminoácido. Na origem desta ambiguidade está um tRNACAG Ser de C. albicans que possui elementos de identidade para duas aminoacil-tRNA sintetases, nomeadamente a seril e leucil-tRNA sintetases, podendo, por isso, ser aminoacilado com serina e leucina. Este tRNA surgiu há cerca de 272 milhões de anos no antepassado das leveduras e introduziu dupla identidade (ambiguidade) no codão CUG que começou a ser descodificado como leucina e serina. As consequências biológicas desta ambiguidade e da alteração de identidade do codão CUG de leucina para serina são desconhecidas. O objectivo deste estudo foi elucidar a função biológica da ambiguidade do codão CUG que foi preservada em C. albicans. Pretendeu-se compreender porque é que a ambiguidade do codão CUG foi preservada e conhecer melhor os mecanismos de evolução ao código genético. Para tal, aumentou-se a ambiguidade do codão CUG, usando engenharia de tRNAs e estudaram-se as consequências de tal ambiguidade ao nível fenotípico. Os resultados demonstram de forma inequívoca que a ambiguidade do codão CUG é um gerador de diversidade fenotípica e sugerem que uma das funções da alteração ao código genético é potenciarem a evolução rápida de novos fenótipos. A ambiguidade do codão CUG induz a expressão de vários factores de virulência de C. albicans, nomeadamente variabilidade morfológica, alteração fenotípica, produção de hidrolases extracelulares e adesinas. Assim, a ambiguidade do código genético é fundamental para a biologia de C. albicans.
Most organisms use the same genetic code, however several alterations to the standard code have been found in prokaryotes and eukaryotes. Most alterations occur in mitochondria and the only known case of a cytoplasmatic sense-to-sense codon identity change occurs in several species of the genus Candida. In Candida albicans, standard leucine-CUG codon is decoded mainly as serine but to a lesser extent as leucine. This is due the existence of a novel tRNACAG Ser that has identity elements for both the seryl- and the leucyl-tRNA aminoacyl synthetases and hence can be aminoacylated with serine and leucine. The tRNACAG Ser appeared 272 million years ago in the yeast ancestor, and created a CUG codon with double identity due to its decoding as both serine and leucine. The biological function of such ambiguity, which was preserved to the present day, is still unknown. The objective of this study was to elucidate the role of CUG ambiguity in C. albicans biology. An attempt was made to shed new light i) on the biological role of genetic code ambiguity, ii) on why CUG ambiguity was preserved and iii) on why genetic code alterations evolve. For this, highly ambiguous C. albicans strains were created through tRNA engineering techniques and the effects of such ambiguity were studied at phenotypic level. The data presented herein shows for the first time that genetic code ambiguity is a generator of phenotypic diversity and strongly suggests that genetic code alterations speed up evolution of new phenotypes. Ambiguous decoding of the CUG codon triggers expression of C. albicans virulence factors, namely morphogenesis, phenotypic switching, extracellular hydrolases production and adhesion, indicating that it plays a critical role on C. albicans biology.
Madrzak, Julia. "Site-specific ubiquitination of recombinant proteins via genetic code expansion". Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708739.
Pełny tekst źródłaShi, Aishan. "Decoding the Genetic Code: Unraveling the Language of Scientific Paradigms". Thesis, The University of Arizona, 2013. http://hdl.handle.net/10150/297762.
Pełny tekst źródłaWillis, Julian C. W. "Developing new orthogonal tRNA/synthetase pairs for genetic code expansion". Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/274057.
Pełny tekst źródłaPinto, Desterro Maria Joana. "Role of SUMO-1 modification in transcriptional activation". Thesis, University of St Andrews, 1999. http://hdl.handle.net/10023/2724.
Pełny tekst źródłaTsai, Ya-Lin. "Development of parallel processing algorithms to provide automatic image analysis for medical application". Thesis, University of Sunderland, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336914.
Pełny tekst źródłaHan, Tony. "SWASAD Smith & Waterman-algorithm-specific ASIC design /". St. Lucia, Qld, 2001. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16391.pdf.
Pełny tekst źródłaHenderson, Daryl Stewart. "A genetic analysis of mutagen-sensitive mutations on the second chromosome of Drosophila melanogaster". Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/26418.
Pełny tekst źródłaScience, Faculty of
Zoology, Department of
Graduate
Cai, Zesi. "Genetic Algorithm for Integrated SoftwarePipelining". Thesis, Linköpings universitet, Institutionen för datavetenskap, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-76088.
Pełny tekst źródłaBrodyk, Andr?? Art College of Fine Arts UNSW. "Genetic art and recombinants: introns non-code and the proto-animate condition". Awarded By:University of New South Wales. Art, 2009. http://handle.unsw.edu.au/1959.4/44087.
Pełny tekst źródłaMoghal, Adil Baig. "Context-dependent threats to the fidelity of translation of the genetic code". The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1465925323.
Pełny tekst źródłaCardno, Tony Stuart, i n/a. "Development of a high throughput fluorescent screening assay for genetic recoding". University of Otago. Department of Biochemistry, 2007. http://adt.otago.ac.nz./public/adt-NZDU20071218.145806.
Pełny tekst źródłaButarbutar, Nunut. "Analysis of yeast codon usage patterns using the movable ORF collection /". Online version of thesis, 2007. http://hdl.handle.net/1850/5700.
Pełny tekst źródłaForrest, Megan E. "Regulation of Mammalian Messenger RNA Stability via the Open Reading Frame". Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1579862741902687.
Pełny tekst źródłaWang, Shu-Zhen. "Isolation and characterization of the messenger RNA and the gene coding for a proline-rich zein from corn endosperm". Diss., Virginia Polytechnic Institute and State University, 1985. http://hdl.handle.net/10919/49959.
Pełny tekst źródłaPh. D.
incomplete_metadata
Johansen-Leete, Jason Paul. "Discovery of Bioactive macrocyclic peptides using mRNA display with genetic reprogramming". Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29467.
Pełny tekst źródłaSilva, Ana Rita Guimarães Rodrigues da. "Codon ambiguities as a mechanism to alter the genetic code in Saccharomyces cerevisiae". Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/15394.
Pełny tekst źródłaAlthough the genetic code is generally viewed as immutable, alterations to its standard form occur in the three domains of life. A remarkable alteration to the standard genetic code occurs in many fungi of the Saccharomycotina CTG clade where the Leucine CUG codon has been reassigned to Serine by a novel transfer RNA (Ser-tRNACAG). The host laboratory made a major breakthrough by reversing this atypical genetic code alteration in the human pathogen Candida albicans using a combination of tRNA engineering, gene recombination and forced evolution. These results raised the hypothesis that synthetic codon ambiguities combined with experimental evolution may release codons from their frozen state. In this thesis we tested this hypothesis using S. cerevisiae as a model system. We generated ambiguity at specific codons in a two-step approach, involving deletion of tRNA genes followed by expression of non-cognate tRNAs that are able to compensate the deleted tRNA. Driven by the notion that rare codons are more susceptible to reassignment than those that are frequently used, we used two deletion strains where there is no cognate tRNA to decode the rare CUC-Leu codon and AGG-Arg codon. We exploited the vulnerability of the latter by engineering mutant tRNAs that misincorporate Ser at these sites. These recombinant strains were evolved over time using experimental evolution. Although there was a strong negative impact on the growth rate of strains expressing mutant tRNAs at high level, such expression at low level had little effect on cell fitness. We found that not only codon ambiguity, but also destabilization of the endogenous tRNA pool has a strong negative impact in growth rate. After evolution, strains expressing the mutant tRNA at high level recovered significantly in several growth parameters, showing that these strains adapt and exhibit higher tolerance to codon ambiguity. A fluorescent reporter system allowing the monitoring of Ser misincorporation showed that serine was indeed incorporated and possibly codon reassignment was achieved. Beside the overall negative consequences of codon ambiguity, we demonstrated that codons that tolerate the loss of their cognate tRNA can also tolerate high Ser misincorporation. This raises the hypothesis that these codons can be reassigned to standard and eventually to new amino acids for the production of proteins with novel properties, contributing to the field of synthetic biology and biotechnology.
O código genético é geralmente visto como imutável, no entanto várias alterações à sua forma padrão são conhecidas. Uma das mais notáveis acontece em várias espécies do género Candida, onde o codão Leu-CUG é descodificado como serina por um novo RNA transferência (Ser-tRNACAG). O laboratório de acolhimento fez um grande progresso ao reverter a alteração atípica do código genético do fungo patogénico humano C. albicans, usando uma combinação de tRNAs mutantes, recombinação genética e evolução forçada. Estes resultados levantaram a hipótese que as ambiguidades sintéticas do codão, combinadas com evolução experimental, poderem libertar os codões do seu estado fixo. Nesta tese testamos esta hipótese usando S. cerevisiae como modelo biológico. Geramos ambiguidade em codões específicos, de forma bifásica, envolvendo a deleção de genes de tRNA, seguida pela expressão de tRNAs não-cognatos capazes de compensar o tRNA eliminado. Tendo como base a ideia que os codões raros são mais suscetíveis a alterações que aqueles usados frequentemente, usamos duas estirpes knock-out, nas quais não existem os tRNAs cognatos capazes de descodificar os codões raros CUC-Leu e AGG-Arg. Exploramos então a vulnerabilidade destes codões pela construção de tRNAs mutantes que incorporam erradamente Ser nestes locais. Estas estirpes recombinantes foram evoluídas ao longo do tempo, usando evolução experimental. Apesar de ter havido um forte impacto negativo na taxa de crescimento de estirpes que expressam o tRNA mutante a altos níveis, esta expressão a baixos níveis teve pouco impacto no fitness celular. Descobrimos que não só a ambiguidade do codão, mas também destabilizações da pool de tRNAs endógenos têm um impacto negativo na taxa de crescimento. Após a evolução, as estirpes com elevada expressão do tRNA mutante recuperaram significativamente em vários parâmetros de crescimento, o que mostra que estas adaptam-se e exibem maior tolerância à ambiguidade do codão. Através do sistema repórter fluorescente desenvolvido monitorizamos a incorporação errónea de Ser, o que nos indica que a Ser está de facto a ser incorporada e que, possivelmente, a alteração da identidade do codão foi atingida. Apesar das consequências negativas gerais da ambiguidade do codão, demonstramos que os codões capazes de tolerar a perda do seu tRNA cognato, conseguem também tolerar a incorporação elevada de Ser. Isto levanta a hipótese que estes codões podem ser recodificados para outros aminoácidos naturais e/ou artificiais para a produção de proteínas com novas propriedades, contribuindo assim para o campo da Biologia Sintética e Biotecnologia.
Qi, Xin Dervan Peter B. "Unnatural amino acid incorporation to rewrite the genetic code and RNA-peptide interactions /". Diss., Pasadena, Calif. : California Institute of Technology, 2005. http://resolver.caltech.edu/CaltechETD:etd-05272005-133323.
Pełny tekst źródłaKinney, William D. "Expansion of the Genetic Code to Include Acylated Lysine Derivatives and Photocaged Histidine". VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5903.
Pełny tekst źródłaMathew, Suneeth Fiona, i n/a. "Understanding genetic recoding in HIV-1 : the mechanism of -1 frameshifting". University of Otago. Department of Biochemistry, 2008. http://adt.otago.ac.nz./public/adt-NZDU20081006.115352.
Pełny tekst źródłaHartley, Andrew M. "Using a reprogrammed genetic code to modulate protein activity by novel post-translational control". Thesis, Cardiff University, 2014. http://orca.cf.ac.uk/68901/.
Pełny tekst źródłaKelemen, Rachel Elizabeth. "New tools at the intersection of genetic code expansion, virus engineering, and directed evolution:". Thesis, Boston College, 2019. http://hdl.handle.net/2345/bc-ir:108612.
Pełny tekst źródłaIn the last two decades, unnatural amino acid (UAA) mutagenesis has emerged as a powerful new method to probe and engineer protein structure and function. This technology enables precise incorporation of a rapidly expanding repertoire of UAAs into predefined sites of a target protein expressed in living cells. Owing to the small footprint of these genetically encoded UAAs and the large variety of enabling functionalities they offer, this technology has tremendous potential for deciphering the delicate and complex biology of the mammalian cells. We describe the application of this technology to the modification of adeno-associated virus (AAV) for the first time, enabling the generation of vectors with precisely re-engineered cell-targeting for gene therapy. Our UAA-AAV production platform enables the incorporation of UAAs bearing bio-orthogonal reactive handles into multiple specific sites on the virus capsid and their subsequent functionalization with various labeling molecules. Incorporation of an azido-UAA enabled site-specific attachment of a cyclic-RGD peptide onto the capsid, retargeting the virus to the αv β3 integrin receptors, which are overexpressed in tumor vasculature. This work provides a general chemical approach to introduce various receptor binding agents onto the AAV capsid with site selectivity to generate optimized vectors with engineered infectivity. Next, we used our unique UAA-AAV vector as a tool for the directed evolution of more active UAA incorporation machinery in mammalian cells. It is well known that the efficiency of unnatural amino acid mutagenesis in mammalian cells is limited by the suboptimal activity of the suppressor tRNAs currently in use. The ability to improve their performance through directed evolution can address this limitation, but no suitable selection system was previously available to achieve this. We have developed a novel platform for virus-assisted directed evolution of enhanced suppressor tRNAs (VADER) in live mammalian cells. Our system applies selective pressure for tRNA activity via the nonsense suppression-dependent production of UAA-AAV, and selectivity for the specific incorporation of interest comes from a novel virus purification strategy based on the unique chemistry of the UAA. We demonstrated > 10,000-fold selectivity for active tRNAs out of mock libraries and used this system to evolve libraries generated from the commonly used archaeal pyrrolysyl suppressor tRNA, ultimately identifying a variant which is three times as active as the original tRNA. Finally, we used next-generation sequencing to analyze the fate of every library member over the course of the selection and found that our VADER selection scheme is indeed selective for the enrichment of more active tRNA variants. This work provides a general blueprint for the evolution of better orthogonal suppressor tRNAs in mammalian cells
Thesis (PhD) — Boston College, 2019
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
Schmidt, Moritz Johannes [Verfasser]. "Expanding the Genetic Code to Study the Structure and Interactions of Proteins / Moritz Johannes Schmidt". Konstanz : Bibliothek der Universität Konstanz, 2015. http://d-nb.info/1112604634/34.
Pełny tekst źródłaSimova, Zuzana. "Importance of single molecular determinant in bacterial tryptophanyl-tRNA synthetase fidelity in expanded genetic code". Thesis, Cardiff University, 2011. http://orca.cf.ac.uk/55120/.
Pełny tekst źródłaHart, Jennifer A. "An analysis of the primordial soup hypothesis with respect to DNA structure and the genetic code". Lynchburg, Va. : Liberty University, 1995. http://digitalcommons.liberty.edu.
Pełny tekst źródłaPouyet, Fanny. "Étude bioinformatique de l'évolution de l'usage du code génétique". Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1140/document.
Pełny tekst źródłaIn this manuscript, I introduce my doctoral research in four parts. The first introductive part highlights the properties of the genetic code and its usage bias but also the caracteristics of previous published codons models. The second part presents an evolutionary codons models named SENCA for Sites Evolution at the Nucleotides, Codons and Amino-acids layers that I developped. SENCA takes into account the genetic code structure. I perform simulations and study prokaryotes species to confirm its parametrization. The following part provides two extensions of SENCA to test the hypotheses concerning the evolutive origins of CUB and an application of SENCA to study the genomic consequences of an environmental adaptation. The last part studies the origins of CUB variation within the human genome using a comparative genomic strategy
Oliveira, Lariza Laura de. "Algoritmos evolutivos aplicados na investigação da adaptabilidade do código genético". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/95/95131/tde-24022016-144852/.
Pełny tekst źródłaThe genetic code is highly preserved and it is present in most living organisms. If we consider all codes mapping the 64 codes into 20 amino acids and one stop codon, there are more than 1.51 × 1084 possible genetic codes. The main question related to the organization of the genetic code is why exactly the standard code was selected among this huge number of possible genetic codes.The hypothesis that the genetic code has evolved is supported by its robustness against mutations. Many researchers argue that the organization of the standard code is a product of natural selection and that the codes robustness against mutations would support this hypothesis. Two methodologies have been used to investigate this hypothesis: the first one is the statistical approach which estimates the number of random codes which are better than the standard genetic code. The second is the engineering approach, which compare the standard code with the best hypothetical codes obtained by an optimization algorithm. Both approaches have been used considering only one objective function, which is usually based on the robustness against changes using the polar requirement. In this research, we propose to consider more than one objective simultaneously for the evaluation of genetic codes. For this purpose, three approaches using multi-objective genetic algorithms were employed, are they: lexicographic, weighted, and Pareto-based. The results indicate that considering more than one objective function is promising: the hypothetical codes generated are more similar to the standard genetic code, when compared with the results obtained by the monoobjective approach.
Phung, Viet-Anh. "Input Calibration, Code Validation and Surrogate Model Development for Analysis of Two-phase Circulation Instability and Core Relocation Phenomena". Doctoral thesis, KTH, Kärnkraftssäkerhet, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-202957.
Pełny tekst źródłaValidering av datorkoder och kvantifiering av osäkerhetsfaktorer är viktiga delar vid säkerhetsanalys av kärnkraftsreaktorer. Datorkodanvändaren måste hantera ett stort antal osäkra parametrar vid beskrivningen av fysikaliska fenomen i flera dimensioner från mikro- till makroskala. För att göra analysresultaten mer robusta, är det viktigt att utveckla och tillämpa rutiner för att vägleda användaren vid kvantifiering av osäkerheter.Detta arbete syftar till att vidareutveckla metoder och förfaranden för validering av systemkoder och deras tillämpning på praktiska problem i säkerhetsanalysen. Arbetet delas in i två delar.Första delen presenterar validering av de termohydrauliska systemkoderna (STH) RELAP5 och TRACE vid analys av tvåfasinstabilitet i cirkulationsflödet.Målen för den första delen är att: (a) utveckla och tillämpa effektiva metoder för kalibrering av indatafiler och validering av STH mot flödesexperiment med tvåfas cirkulationsflödeinstabilitet och (b) granska datorkodernas förmåga att förutsäga momentana termohydrauliska parametrar och flödesregimer under transienta förlopp.Två metoder har utvecklats: en icke-automatisk procedur baserad på separat hantering av osäkra indataparametrar (UIPs) och en automatiserad metod som använder genetisk algoritm. Ett flertal uppmätta parametrar och systemresponser (SRQs) används i både kalibrering av osäkra parametrar i indatafilen och validering av RELAP5 och TRACE. Resultatet av modifikationer i hur RELAP5 identifierar olika flödesregimer, och särskilt hur detta påverkar datorkodens prediktioner av termohydrauliska parametrar, har studerats.Resultatet av valideringen visar att RELAP5 och TRACE kan återge det kvalitativa beteende av två-fas flödets instabilitet. Däremot kan ingen av koderna korrekt identifiera den momentana flödesregimen, det var därför ej möjligt att förutsäga experimentella värden på svängningsperiod och maximal inloppsflödeshastighet samtidigt. Resultatet belyser betydelsen av samtidig behandling av flera SRQs liksom olika experimentella flödesregimer för kvantitativ kodvalidering.Den andra delen av detta arbete behandlar härdnedbrytning och omfördelning till reaktortankens nedre plenumdel i en kokarvatten reaktor (BWR). Egenskaper hos härdrester i nedre plenum ger inledande förutsättningar för reaktortanksgenomsmältning, hur smältan rinner ut ur reaktortanken och händelseförloppet i reaktorinneslutningen.Målen i den andra delen är att: (a) erhålla en representativ databas över koden MELCOR:s analysresultat för egenskaperna hos härdrester i nedre plenum under olika händelseförlopp, och (b) utveckla en beräkningseffektiv surrogatsmodell som kan användas i omfattande osäkerhetsanalyser för att förutsäga partikelbäddsegenskaper.MELCOR, kopplad till en genetisk algoritm med slumpmässigt urval användes för att generera en databas av analysresultat med tillämpning på smältans omfördelning i reaktortanken i en Nordisk BWR.Analysen av hur härden omfördelas visar att det finns två huvudgrupper av scenarier: med relativt liten (<20 ton) och stor (> 100 ton) total mängd omfördelade härdrester i nedre plenum. Dessa domäner är åtskilda av övergångsregioner, där små variationer i indata kan resultera i stora ändringar i den slutliga partikelmassan. Flergrupps artificiella neurala nätverk med klassificering av händelseförloppet har använts för utvecklingen av en surrogatmodell för att hantera problemet med kaotiska resultat av den fullständiga modellen, särskilt i övergångsregionen.
QC 20170309
Albuquerque, Julio Cesar Holanda de. "Proposta de constelações de sinais para o codigo genetico". [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/259781.
Pełny tekst źródłaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica e de Computação
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Resumo: A proposta deste trabalho é apresentar uma abordagem aos processos genéticos e moleculares, utilizando a teoria de comunicações e codificação na modelagem do dogma central da biologia molecular. A partir desta modelagem associamos o código genético a um modulador de um sistema de comunicação. Mais especificamente, tal procedimento consiste em construir uma constelação de sinais a partir dos subgrupos de S3 e S4 baseado no código genético. Considerando este método algébrico de construção de sinais, propomos duas possíveis constelações de sinais para o código genético. A representação do código genético em constelações de sinais correlacionadas deu origem à idéia de "constelação de sinais concatenadas", idéia inovadora na teoria de comunicação e codificação. As constelações de sinais concatenadas possui a propriedade de correção de erros, consistindo de novos conceitos úteis para utilização na teoria da comunicação e codificação. Por outro lado, estas representações do código genético não são únicas pois, até o presente momento, desconhecemos uma álgebra que descreva o código genético juntamente com as suas partições geradas pelos aminoácidos.
Abstract: The purpose of this work is to present an approach to the genetic and molecular processes by use of the communication and coding theory in modelling the central dogma of the molecular biology. From this modelling we associate the genetic code to a modulator in the communication system. More specifically, such a procedure consists is in the construction of a signal constellation by use of the S3 and S4 permutation subgroups based on the code genetic. By considering this algebraic method of signal design, we propose two possible signal constellations to the genetic code. The representation of the genetic code as correlated signal constellations provides the idea idea of "concatenated signal constellation", an innovative idea in communication and coding theory. The concatenated signal constellations have the property of error-correction, a new concept being introduced. On the other hand, these representations of the genetic code are not unique for currently, we do not know an algebraic structure capable of describing the genetic code together with the partitioning generated by the amino acids.
Mestrado
Telecomunicações e Telemática
Mestre em Engenharia Elétrica
Gerding, Hanne Rieke [Verfasser]. "Site-specific incorporation of 3-nitrotyrosine in proteins generated via genetic code expansion in E.coli / Hanne Rieke Gerding". Konstanz : Bibliothek der Universität Konstanz, 2018. http://d-nb.info/1179076869/34.
Pełny tekst źródłaDavis, Lloyd Daniel. "The use of the orthogonal pyrrolysyl-tRNA synthetase/tRNACUA pair for further enhancement of genetic code expansion technologies". Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607872.
Pełny tekst źródła