Thèses : « Sequence-function »

1

McDougall, Rachel Clare. « Schizosaccharomyces pombe : from sequence to function ». Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627369.

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Spencer, Sarah Jean. « Linking sequence to function in microbial genomics ». Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/113437.

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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2017.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 129-140).
Microbial genomes show high plasticity due to horizontal transfer, large community sizes, and rapid growth paired with adaptive mutations. Despite this mutability of gene content, most studies of microbial communities still rely on bulk, single-gene amplicon sequencing. In this thesis, I present methods that interrogate the gene content of single cells derived from complex natural communities. In the first project, I present a novel molecular biology method to link a bacterial functional gene to its host species with single-cell resolution. This high-throughput protocol is applied to assess the distribution of anaerobic respiration genes in a lake ecosystem. In the second project, I demonstrate extensions of this methodology to link genes between spatially proximal microbial cells, and apply this approach to probe the spatial organization of human dental plaque using DNA sequencing. In the final project, I completed whole-genome sequencing of environmental isolates derived from single, cultivable cells and employ mutational and horizontal transfer analysis to demonstrate adaptation to harsh environmental conditions in contaminated groundwater. These projects demonstrate the rich information stored within each microbial genome and the impact of spatial distribution in the environment. Each effort also contributes or highlights new molecular biology techniques to generate genomic data from individual microbial cells.
by Sarah Jean Spencer.
Ph. D.

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3

Warnecke, Tobias. « Determinants of coding sequence evolution- beyong protein function ». Thesis, University of Bath, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531341.

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4

Otto, Gary Edward. « Sequence comparison and the prediction of protein function ». Thesis, Massachusetts Institute of Technology, 1986. http://hdl.handle.net/1721.1/14888.

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5

Hamilton, Russell S. « DAROGAN : enzyme function prediction from multiple sequence alignments ». Thesis, University of Edinburgh, 2006. http://hdl.handle.net/1842/14972.

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The function of an enzyme is often dependent on a few key functional residues and the principal objective of this project was to develop a novel function prediction system which takes advantage of this by comparing the conserved amino acids in known enzyme families to those in a putative enzyme. Multiple sequence alignments of well characterised enzyme families (with an E.C. number assigned) are used to create unordered sets of conserved functional residues, termed Treads. Comparison of a query proteins Tread to the reference Treads is undertaken by projecting them in multidimensional space and measuring distance between them. A major advantage of this prediction strategy implemented in DAROGAN is that it should be able to recognise similarities in the functions of enzymes that are not similar in structure or sequence. The method has been tested with regard to its ability to predict cofactor-dependencies toward pyridoxal-5’-phosphate, thiamine, glutathione and folic acid utilising enzymes. An area of application for DAROGAN is the prediction of previously described enzyme functions in organisms with completed genomes to which no gene and protein sequence could be assigned though the standard annotation processes. Investigations were made into the potential of utilising the DAROGAN method to propose candidates for the missing pyridoxal-5’-phosphate utilising enzymes in the E. coli genome according to EcoCyc. Candidates are proposed by assessing the 511 sequences from the GeneQuiz project, to which there are homologues in other species, but with uncertain functions. The assessment takes the form of using the DAROGAN method to determine the similarities of each of the sequences to the reference Treads.

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Colafranceschi, Mauro. « Distribution of Hydrophobicity patterns in proteins primary structures : a statistical study ». Doctoral thesis, La Sapienza, 2005. http://hdl.handle.net/11573/916823.

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Rünger, Dennis. « On the generation and function of conscious sequence knowledge ». Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät II, 2008. http://dx.doi.org/10.18452/15845.

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Es besteht weitgehend Einigkeit darüber, dass inzidentelles Lernen bewusstes Wissen über eine sequenziell strukturierte Regelhaftigkeit erzeugen kann, auch wenn die zu Grunde liegenden Lernprozesse nur ungenügend verstanden sind. Ob jedoch Sequenzlernen auch „implizit“ oder unbewusst erfolgen kann, ist umstritten. Fortschritte in diese Frage sind von Untersuchungen zu bewusstem und unbewusstem Lernen zu erwarten, die vor dem Hintergrund übergreifender Bewusstseinstheorien erfolgen. Rünger und Frensch (2008a) zeigen, wie „bewusstes Sequenzwissen“ in Rückgriff auf die „global workspace“-Theorie des Bewusstseins definiert und operationalisiert werden kann. Im Rahmen dieser Theorie wird „inferenzielle Promiskuität“ als zentrales funktionales Merkmal bewusster mentaler Repräsentationen betrachtet. Rünger und Frensch (2008b) überprüfen eine zentrale Vorhersage der „unexpected event“-Hypothese, einer Theorie zur Entstehung bewussten Wissens in inzidentellen Lernsituationen. In einer Serie von Experimenten wurden unerwartete Ereignisse durch Unterbrechungen des inzidentellen Lernprozesses experimentell induziert. In Übereinstimmung mit der „unexpected event“-Hypothese fanden die Autoren, dass sich die Verfügbarkeit bewussten Sequenzwissens erhöhte. Rünger, Nagy und Frensch (in Druck) untersuchen schließlich die Funktion bewussten Sequenzwissens im Kontext eines Rekognitionstests. Die empirischen Befunde deuten darauf hin, dass bewusstes Sequenzwissen die epistemische Grundlage für rationale Urteile im Gegensatz zu intuitiven oder heuristischen Urteilen darstellt.
There is a general consensus that incidental learning can produce conscious knowledge about a hidden sequential regularity, even though the underlying learning mechanisms are still poorly understood. By contrast, whether sequence learning can also be “implicit” or nonconscious is a matter of intense debate. Progress can be achieved by grounding research on conscious and nonconscious learning in larger theoretical frameworks of consciousness. Rünger and Frensch (2008a) show how “conscious sequence knowledge” can be defined and operationalized in reference to global workspace theory of consciousness that depicts “inferential promiscuity” as the functional hallmark of conscious mental representations. Rünger and Frensch (2008b) test a central prediction of the unexpected-event hypothesis — a theoretical account of the generation of conscious knowledge in incidental learning situations. In a series of experiments, unexpected events were induced experimentally by disrupting the incidental learning process. In line with the unexpected-event hypothesis, the authors observed an increased availability of conscious sequence knowledge. Finally, Rünger, Nagy, and Frensch (in press) explore the function of conscious sequence knowledge in the context of a sequence recognition test. The empirical results suggest that conscious sequence knowledge provides the epistemic basis for reasoned — as opposed to intuitive or heuristic — judgments.

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Kandaswamy, Krishna Kumar [Verfasser]. « Sequence function classification by machine learning methods / Krishna Kumar Kandaswamy ». Lübeck : Zentrale Hochschulbibliothek Lübeck, 2012. http://d-nb.info/1023624257/34.

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9

Pryde, Fiona E. « Function of subtelomeric repeat sequence in the yeast Saccharomyces cerevisiae ». Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302603.

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10

Wang, Pam Shou-Ping. « Exploring the sequence-structure-function relationship in beta-peptide foldamers ». Thesis, Yale University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3580893.

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The interplay between sequence, structure and function is an underlying theme in biological systems. Proteins, in particular, have evolved the ability to access a virtually infinite set of three-dimensional architectures from a small collection of building blocks; it is precisely this complexity of form that finely tunes their functional specificity. β-Peptides are a class of unnatural polyamides known to adopt structural motifs that are in many ways reminiscent of protein folds in nature. This dissertation first investigates the relationship between sequence and structure in self-assembling β-peptides, then demonstrates how the latter translates into function.

Chapter 1 provides an overview of the fundamental principles guiding β-peptide helix formation and self-assembly, and describes their applications both within and outside of the biological context. The ability of β-peptides to mimic natural α-helices while maintaining proteolytic resistance allows them to serve as therapeutic agents by targeting, for example, protein-protein interactions. Their unique stability in both aqueous and organic environments further enables the development of β-peptide-based nanomaterials and organocatalysts.

Chapter 2 elucidates the relationship between β-peptide primary sequence and quaternary structure based on the biophysical characterization of the Acid-3Y bundle. Acid-3Y was designed by substituting isoleucine for leucine side-chains in the sequence of the previously characterized octamer, Acid-1Y. The finding that Acid-3Y assembles into a tetrameric bundle suggests that branching at the γ-carbon of hydrophobic residues plays a critical role in determining β-peptide bundle stoichiometry.

Chapter 3 explores the potential of β-peptide bundles to mimic enzyme structure and function. The demonstration of β-peptide mutarotase activity in benzene highlights the importance of macromolecular preorganization in catalysis, while the ability of rationally designed β-peptide bundles to catalyze ester hydrolysis in water represents a crucial step towards the functionalization of these unnatural macromolecules. The dependence of catalytic activity on both active site geometry and bundle assembly, together with their substrate selectivity, underscores the unique biomimetic capacity of β-peptides.

Chapter 4 describes the rational design of a β-peptide ligand for the parathyroid hormone 1 receptor (PTH1R). Using previous strategies that led to the identification of p53 and GLP-1 mimics, a 12-member β-peptide library was constructed and tested in vitro for binding to the receptor protein. Although no hits were found from this initial screen, subsequently designed α/β-peptide chimeras showed promise as synthetic antagonists of PTH1R with improved pharmacokinetic properties.

Chapter 5 summarizes the key results of this dissertation and offers a perspective on possible future research directions. A breakthrough in the field of β-peptides would rely on the development of a method to synthesize genuine "β-proteins" with more sophisticated structure and function.

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11

Crowley, Louis J. « Structure-function studies of conserved sequence motifs of cytochrome b5 reductase ». [Tampa, Fla] : University of South Florida, 2007. http://purl.fcla.edu/usf/dc/et/SFE0001913.

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Hvidsten, Torgeir R. « Predicting Function of Genes and Proteins from Sequence, Structure and Expression Data ». Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4490.

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13

Berti, Paul J. (Paul Joseph). « Cysteine proteases : interaction with cystatin C and sequence to structure-function relationships ». Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41350.

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An alignment/phylogeny of the papain superfamily of cysteine proteases was created from which the existence of at least 11 families of mammalian cysteine proteases was inferred, including two as yet uncharacterized ones. Character weighting increased the average speed of maximum parsimony phylogenetic searches two- to three-fold. To study a sequence motif in pro-cysteine proteases and mammalian cystatins, cystatin C, a cysteine protease inhibitor, was expressed and purified using a new affinity method giving $>$99% purity. Methionine oxidation to the sulfoxide occurring during protein production was eliminated. Reduced stability caused by Met14 oxidation was demonstrated. No function for the sequence motif was found, however cystatin C underwent a conformational change at acidic pH that rendered the His86-Asp87 peptide bond labile to proteolysis. This could constitute a mechanism for clearing inappropriately localized cystatins from the acid environment of lysosomes and explain differences between the X-ray and NMR structures of the homologous chicken cystatin.

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Mukendi, Mujinga Grace. « Sequence and function-based screening of goat rumen metagenome for novel lipases ». Thesis, Vaal University of Technology, 2019. http://hdl.handle.net/10352/463.

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M. Tech. (Department of Biotechnology, Faculty of Applied and Computer Sciences), Vaal University of Technology
Lipases have been one of the important biocatalysts that catalyse the transformation of lipids to yield very important products that can be of beneficial in food, agriculture, pharmaceutical medicine and for the biodiesel production. In the search for novel biocatalysts, notably lipases, the conventional culture-based techniques were used but it can only address sourcing the biomolecule from 1-10% of the microbial population leaving the wealth of the biomolecules packed in 90-99% of the microbial community unaccounted for. Metagenomic technique, which is culture-independent, was developed as a comprehensive approach to address literally 100% of the microbial population thereby maximizing the chances of obtaining novel biocatalysts with superior physico-chemical and catalytic traits. In principle, any biomolecule including lipase could be sourced from any biologically-active environment, of which animal rumen is one. However, among the rumenant animals goat has diverse feeding habit, thereby laying ground for increased microbial diversity in its gastro-intestinal tract. It was thus, postulated that goat rumen could be potential source of novel lipase isoforms. Therefore, the aim of the study was to extract metagenomic DNA from goat rumen and construct a metagenomic fosmid library and screen the library for lipase isoforms. The fosmid clones were functionally screened using 1% tributyrin as a substrate and five positive clones were selected. From the five clones, two fosmids were selected for further study. Following nucleotide sequencing and in-silico analysis of the insert of the two selected clones, one lipase encoding open reading frame (Lip-VUT3 and Lip-VUT5) from each fosmid clones of approximately 212 and 248 amino acids, respectively, was identified. The amino acid sequences of the Lip-VUT3 ORF contained a classical conserved lipase GSDL sequence motif while the amino acid sequences of the Lip-VUT5 ORF contained a classical G-L-S-L-G conserved lipase/esterase motif sequence. The two genes (Lip-VUT3 and Lip-VUT5) were successfully expressed in Escherichia coli BL21 (DE3) and the purified enzymes exhibited respective temperature optima of 60 °C and 70 °C, and respective pH optima of 6.0 and 10.0. Further biochemical characterisation indicated that Lip-VUT3 and Lip-VUT5 lipases showed tolerance towards a wide concentration (50%-100%) of methanol. Lip-VUT3 had a Km value of 0.287 mM while Lip-VUT5 had a Km value of 0.556 Mm. This shows that Lip-VUT3 lipase has a higher affinity for olive oil than Lip-VUT5. Lip-VUT3 and Lip-VUT5 were characterised to be true lipases that have been recovered from the rumen environment through metagenomic approach. Therefore, the study proved that metagenomic approach helps in recovering novel lipase isoforms with potential down stream industrial and therapeautic applications from goat rumen metagenome, a rich but untapped source.

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Wass, Mark Nicholas. « Development of a sequence based method for the prediction of protein function ». Thesis, Imperial College London, 2008. http://hdl.handle.net/10044/1/11542.

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Di, Domenico Tomás. « Computational Analysis and Annotation of Proteome Data : Sequence, Structure, Function and Interactions ». Doctoral thesis, Università degli studi di Padova, 2014. http://hdl.handle.net/11577/3423805.

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With the advent of modern sequencing technologies, the amount of biological data available has begun to challenge our ability to process it. The development of new tools and methods has become essential for the production of results based on such a vast amount of information. This thesis focuses on the development of such computational tools and method for the study of protein data. I first present the work done towards the understanding of intrinsic protein disorder. Through the development of novel disorder predictors, we were able to expand the available data sources to cover any protein of known sequence. By storing these predicted annotations, together with data from other sources, we created MobiDB, a resource that provides a comprehensive view of available disorder annotations for a protein of interest, covering all sequences in the UniProt database. Based on observations obtained from this resource, we proceeded to create a data analysis workflow with the goal of furthering our understanding of intrinsic protein disorder. The second part focuses on tandem repeat proteins. The RAPHAEL method was developed to assist in the identification of tandem repeat protein structures from PDB files. Identified repeat structures were then manually classified into a formal classification schema, and published as part of the RepeatsDB database. Finally, I describe the development of network-based tools for the analysis of protein data. RING allows the user to visualise and study the structure of a protein as a network of nodes, linked by physico-chemical properties. The second method, PANADA, enables the user to create protein similarity networks and to assess the transferability of functional annotations between clusters of proteins.
Con l'avvento delle tecnologie di sequenziamento moderne, la quantità di dati biologici disponibili ha cominciato a sfidare la nostra capacità di elaborarli. È diventato quindi essenziale sviluppare nuovi strumenti e tecniche capaci di produrre dei risultati basati su grandi moli di informazioni. Questa tesi si concentra sullo sviluppo di tali strumenti computazionali e dei metodi per lo studio dei dati proteici. Viene dapprima presento il lavoro svolto per la comprensione delle proteine intrinsecamente disordinate. Attraverso lo sviluppo di nuovi predittori di disordine, siamo stati in grado di sfruttare le fonti di dati attualmente disponibili per annotare qualsiasi proteina avente sequenza nota. Memorizzando queste predizioni, insieme ai dati provenienti da altre fonti, è stato creato MobiDB. Questa risorsa fornisce una visione completa sulle annotazioni di disordine disponibili per una qualsiasi proteina di interesse presente nel database UniProt. Sulla base delle osservazioni ottenute da questo strumento, è stato quindi creato un workflow di analisi dei dati con l'obiettivo di approfondire la nostra comprensione delle proteine intrinsecamente disordinate. La seconda parte della tesi si concentra sulle proteine ripetute. Il metodo RAPHAEL è stato sviluppato per contribuire nell'identificazione di strutture proteiche ripetute all'interno dei file PDB. Le strutture selezionate da questo strumento sono state poi catalogate manualmente utilizzando uno schema formale di classificazione, e pubblicate quindi come parte del database RepeatsDB. Infine, viene descritto lo sviluppo di strumenti basati su grafi per l'analisi di dati proteici. RING consente all'utente di visualizzare e studiare la struttura di una proteina come una rete di nodi collegati da tra loro da proprietà fisico-chimiche. Il secondo metodo, PANADA, consente all'utente di creare reti di similarità di proteine e di valutare la trasferibilità delle annotazioni funzionali tra cluster diversi.

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Milburn, Duncan. « Computational analysis of the functional sites in proteins ». Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325850.

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18

Al-Shahib, Ali Walid. « Addressing the core challenges in predicting protein function from sequence using machine learning ». Thesis, University of Glasgow, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425167.

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19

Yekta, Soraya. « An evolutionary perspective on the sequence, mechanism, and regulatory function of animal microRNAs ». Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/43791.

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"December 2007." After leaf 110, three appendices appear as journal articles with separate numberings (p. 991-1008, 1309-1332, 671-674); printed as pages but counted as leaves. Numbering sequence of thesis: leaves [1]-110; p. 991-1008; leaf 120; p. 1309-1322; leaf 128; p. 671-674.
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, June 2008.
Includes bibliographical references.
(cont.) The vertebrate-specific miR-196 family is encoded at three paralogous loci in the mammalian Hox clusters, and has complementarity to messages of several Hox genes, including Hox8 paralogues. RNA fragments diagnostic of miR-196-directed cleavage of Hoxb8 were detected in mouse embryos. Cell culture experiments demonstrated down-regulation of Hoxb8, Hoxc8, Hoxd8, and Hoxa7 and supported a cleavage mechanism for miR-196-directed repression of Hoxb8. These results point to a miRNA-mediated mechanism for the posttranscriptional restriction of Hox gene expression during vertebrate development and demonstrate that metazoan miRNAs can repress expression of their natural targets through mRNA cleavage in addition to inhibiting a translational step. Inhibition of the two Hox miRNAs in chick embryos, resulted in axial skeletal patterning defects in domains that overlap considerably with Hox target and miRNA expression, supporting a specialization of miRNAs in Hox gene regulation, and consistent with action by miR-196 and miR-10 to refine posterior boundaries at relative levels of expression for multiple Hox genes. The genomic distribution of target sites and Hox patterns of expression suggest that the miRNAs further act in concert with more posteriorly expressed Hox genes to impose a functional hierarchy over more anterior ones, a molecular mechanism consistent with 'posterior prevalence'. The posttranscriptional downregulation of more 3' and anteriorly expressed Hox genes by miR-196 constitutes an evolutionarily recent regulatory layer of the highly constrained Hox network, one which recapitulates modes of interactions existing at multiple levels of gene expression.
Noncoding RNAs are encoded by diverse genomes and play many functional roles. MicroRNAs (miRNAs) are endogenous -22-nucleotide noncoding RNAs, derived from larger hairpin precursors, which act by base-pairing to mRNAs to target these transcripts for destruction or translational repression. miRNA genes have been discovered in viral and multicellular genomes. The computational procedure MiRscan was developed to identify miRNA genes conserved in more than one genome and applied to the identification of vertebrate miRNAs. Starting with conserved mouse and human sequences with potential for hairpin formation, and subsequent comparison to fish, 15,000 human genomic loci were identified within aligned regions outside protein coding genes, and ranked according to criteria based on shared features of a training set of the first 50 experimentally verified C. elegans miRNAs. 188 high-scoring candidates, including 74% of human miRNAs known in 2002, were further examined. Fourteen candidate miRNAs were close paralogues of known miRNAs, and 38 candidates were experimentally validated using cDNA libraries of small RNAs made from zebrafish. Of the 38 verified miRNAs, 21 were sequences identified by random cloning and sequencing of cDNA libraries, while 17 were found by applying a directed PCR approach to the same libraries. The miR-196 and miR-10 families are transcribed from genomic loci within clusters of Hox transcription factor genes, and in turn mediate the posttranscriptional repression of neighbouring Hox transcripts, with conserved and extensive targeting of Hox genes located in paralogous groups that are 3' but not 5' of each miRNA locus, relative to the direction of transcription within a given cluster.
by Soraya Yekta.
Ph.D.

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Lai, Meng-Jiun. « From sequence to structure and function : an analysis of the A20-like family ». Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613812.

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Staniforth, Gemma Louise. « Characterisation of the function, sequence polymorphism and toxicity of the yeast Rnq1p prion protein ». Thesis, University of Kent, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.590014.

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The Saccharomyces cerevisiae Rnq 1 p prion protein plays an integral role in the dynamics of other aggregation-prone proteins, be they other prion proteins or glutamine-rich proteins. The conformational conversion of a prion protein to its prion state is often associated with changes to cellular physiology and two interesting questions arise from this. One, what impact do these physiological changes have on our ability to interpret experimental findings in this model organism? Two, are these changes non-random, representing a novel means of altering cellular physiology? An understanding of the cellular function of Rnq 1 P is important in addressing these questions. Further, the role of Rnq 1 P in its [PIN+] prion state as a universal catalyst for amyloid-formation provides a useful model for dissecting mechanisms of amyloid toxicity, and once again, cellular function is one parameter of multiple that determine the [mal toxicity profile of a protein. To identify a cellular function for Rnqlp both phenotypic assays and a mass spectrometry-based label-free quantitative proteomics analysis were performed. A role for Rnq 1 P as a negative regulator of translation termination was characterised and eo-localisation of Rnq 1 p with P-bodies, tightly packed clusters of untranslating rnRNA, was observed indicating that Rnqlp is intimately associated with mRNA dynamics within the cell. Additionally, evidence for a role in the maintenance of mitochondrial respiratory capacity pertaining to ATP-generation is presented, along with indications that this latter role may be through transcriptional regulation. To further understand the mechanisms of toxic protein aggregation, two analyses were performed. One, a study on the impact of natural Rnqlp polymorphisms identified fifty-three novel RNQI alleles and sequence features affecting Rnq 1 P toxicity. Two, a screen for genetic modifiers of both Rnqlp and mutant huntingtin demonstrated the role of P-bodies and mRNA degradation pathways in modulating amyloid or glutamine-based toxicity, along with a possible role for energy. homeostasis. The results presented in this thesis provided new insight into the functional roles of Rnq 1 P within the cell, and consequently the possible impact on cellular physiology associated with Rnqlp's [pin-] to [PIN+] conversion, and also identified novel modulators of toxic aggregation events in the cell.

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Steffen-Munsberg, Fabian [Verfasser]. « Structure– and sequence–function relationships in (S)-amine transaminases and related enzymes / Fabian Steffen-Munsberg ». Greifswald : Universitätsbibliothek Greifswald, 2015. http://d-nb.info/1074259610/34.

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Koester, Dirk [Verfasser]. « Hierarchy, sequence, function : a contribution to the architecture of the human neurocognitive system / Dirk Koester ». Bielefeld : Universitätsbibliothek Bielefeld, 2016. http://d-nb.info/1122285779/34.

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Hetherington, Simon Lee. « Sequence variation within the platelet adenosine diphosphate receptor genes, platelet function and premature myocardial infarction ». Thesis, University of Leicester, 2006. http://hdl.handle.net/2381/27869.

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Damry, Adam. « From Protein Sequence to Motion to Function : Towards the Rational Design of Functional Protein Dynamics ». Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39211.

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Protein dynamics are critical to the structure and function of proteins. However, due to the complexity they inherently bring to the protein design problem, dynamics historically have not been considered in computational protein design (CPD). Herein, we present meta-MSD, a new CPD methodology for the design of protein dynamics. We applied our methodology to the design of a novel mode of conformational exchange in Streptococcal protein G domain B1, producing dynamic variants we termed DANCERs. Predictions were validated by NMR characterization of selected DANCERs, confirming that our meta-MSD framework is suitable for the computational design of protein dynamics. We then performed a thorough NMR characterization of the sequence determinants of dynamics in one DANCER, isolating two mutations responsible for the novel dynamics this protein exhibits. The first, A34F, is responsible for destabilizing the highly stable native Gβ1 conformation, allowing the protein to sample other conformational states. The second, V39L mediates subtle interactions that stabilize the designed conformational trajectory in the context of the A34F mutation. Together, these results highlight the role of protein plasticity in the development of dynamics and the need for highly accurate computational tools to approach similar design problems. Finally, we present an NMR-based characterization of structural dynamics in a family of related red fluorescent proteins (RFPs) and pinpoint regions of the RFP structure where dynamics correlate to RFP brightness. This overview of the RFP dynamics-function relationship will be used in future projects to perform a computation design of functional dynamics in RFPs.

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Choi, Hyunjin. « An Interdisciplinary Approach : Computational Sequence Motif Search and Prediction of Protein Function with Experimental Validation ». Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/51762.

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Pathogens colonize their hosts by releasing molecules that can enter host cells. A biotrophic oomycete plant pathogen, Phytophthora sojae harbors a superfamily of effector genes whose protein products enter the cells of the host, soybean. Many of the effectors contain an RXLR-dEER motif in their N-terminus. More than 400 members belonging to this family have been previously identified using a Hidden Markov Model. Amino acids flanking the RXLR motif have been utilized to identify effector proteins from the P. sojae secretome, despite the high level of sequence divergence among the members of this protein family. I present here machine learning methods to identify protein candidates that belong to a particular class, such as the effector superfamily. Converting the flanking amino acid sequences of RXLR motifs (or other candidate motifs) into numeric values that reflect their physical properties enabled the protein sequences to be analyzed through these methods. The methods evaluated include Support Vector Machines and a related spherical classification method that I have developed. I also approached the effector prediction problem by building functional linkage networks and have produced lists of predicted P. sojae effector proteins. I tested the best candidate through gene gun bombardment assays using the beta-glucuronidase reporter system, which revealed that there is a high likelihood that the candidate can enter the soybean cells.
Ph. D.

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Yedida, Venkata Rama Kumar Swamy. « Protein Function Prediction Using Decision Tree Technique ». University of Akron / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=akron1216313412.

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Crowley, Louis J. « Structure-Function Studies of Conserved Sequence Motifs of Cytochrome b₅ Reductase : ». Scholar Commons, 2007. https://scholarcommons.usf.edu/etd/682.

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NADH:Cytochrome b5 Reductase (cb5r) catalyzes the two electron reduction of the iron center of the heme cofactor found within cytochrome b5 (cb5) utilizing reducing equivalents of the nicotinamide adenine dinucleotide (NADH) coenzyme. Cb5r is characterized by two domains necessary for proper enzyme function: a flavin-binding domain and a pyridine nucleotide-binding domain. Within these domains are highly conserved "motifs" necessary for the proper binding and orientation of both the NADH coenzyme and the FAD cofactor. To address the importance of these conserved motifs site-directed mutagenesis was utilized to generate a series of variants upon residues found within the motifs to allow for the full characterizations. Second, naturally occurring recessive congenital methemoglobinemia (RCM) mutants that are found within or in close proximity to these highly conserved motifs were analyzed utilizing site-directed mutagenesis. The flavin-binding motif "91RxYSTxxSN97" was characterized by the generation of variants T94H, T94G, T94P, P95I, V96S, and S97N. In addition to this, the naturally occurring double mutant P92H/E255- was fully characterized to establish a role of the P92 residue giving rise to RCM. The role of the "124GRxxST127" was determined by the introduction of a positive charge, charge reversal, and conserved amino acid mutations through site-directed mutagenesis of the G124, K125, and M126 residues. Based on the data presented here, each of the residues of the GRxxST motif are directly involved in maintaining the proper binding and orientation of the cb5r flavin prosthetic group. Analysis of the NADH-binding motif "273CGxxx-M278" was accomplished through the characterization of the type II RCM variant M272- and the type I RCM variant P275L. This demonstrates that the deletion of the M272 residue causes a frame shift leading to the inability of the NADH substrate to bind. The introduction of the P275L variant showed that substrate affinity was diminished, yet turnover was comparable to wild-type cytochrome b5 reductase, indicating that although P275 is required for proper substrate binding it is not essential for overall catalytic function. Finally, analysis of the naturally occurring double mutant G75S/V252M provided the first insight into a methemoglobinemia variant that possessed mutations in both the FAD-binding and NADH-binding domains.

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Ghebru, Alexander. « Metodik för testning av styrsystem ». Thesis, KTH, Mikro- och nanosystemteknik, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-109524.

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I detta examensarbete har en generell metodik skapats för testning av styrsystem för pumpar. Testmetodiken beskrivs med modeller som på ett strukturerat sätt går igenom testningens förberedelse och utförande. Metodiken tillämpas sedan genom en stegvis mall för hur testningen går till praktiskt. En metod för att optimera antalet tester presenteras. Denna metod minskar antalet tester genom att använda de mest prioriterade signalerna som skickas mellan styrsystem och pump. Denna prioritering sker genom en viktning av hur viktig signalen är för systemet. Ett beräkningsschema har skapats i Excel som tar fram den prioriterade testordningen för testaren att följa.
In this thesis, a general test methodology is created for the testing of control system for pumps. The test methodology is described with models that in a structured way help planning the testing preparation and execution. The methodology is then applied through a stepwise template for how to do the testing in practice. A method for optimizing the numbers of tests is presented. This method will reduce the number of test using the signals with the highest priority that are sent between the controller and pump. A calculation scheme in Excel has been created that brings out the prioritized test procedure for the tester to follow.

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Alderson, Rosanna Grace. « Tracking the evolution of function in diverse enzyme superfamilies ». Thesis, University of St Andrews, 2016. http://hdl.handle.net/10023/10496.

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Tracking the evolution of function in enzyme superfamilies is key in understanding how important biological functions and mechanisms have evolved. New genes are being sequenced at a rate that far surpasses the ability of characterization by wet-lab techniques. Moreover, bioinformatics allows for the use of methods not amenable to wet lab experimentation. We now face a situation in which we are aware of the existence of many gene families but are ignorant of what they do and how they function. Even for families with many structurally and functionally characterized members, the prediction of function of ancestral sequences can be used to elucidate past patterns of evolution and highlight likely future trajectories. In this thesis, we apply in silico structure and function methods to predict the functions of protein sequences from two diverse superfamily case studies. In the first, the metallo-β-lactamase superfamily, many members have been structurally and functionally characterised. In this work, we asked how many times the same function has independently evolved in the same superfamily using ancestral sequence reconstruction, homology modelling and alignment to catalytic templates. We found that in only 5% of evolutionary scenarios assessed, was there evidence of a lactam hydrolysing ancestor. This could be taken as strong evidence that metallo-β-lactamase function has evolved independently on multiple occasions. This finding has important implications for predicting the evolution of antibiotic resistance in this protein fold. However, as discussed, the interpretation of this statistic is not clear-cut. In the second case study, we analysed protein sequences of the DUF-62 superfamily. In contrast to the metallo-β-lactmase superfamily, very few members of this superfamily have been structurally and functionally characterised. We used the analysis of alignment, gene context, species tree reconciliation and comparison of the rates of evolution to ask if other functions or cellular roles might exist in this family other than the ones already established. We find that multiple lines of evidence present a compelling case for the evolution of different functions within the Archaea, and propose possible cellular interactions and roles for members of this enzyme family.

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Chan, Yvonne H. « The Complex Role of Sequence and Structure in the Stability and Function of the TIM Barrel Proteins ». eScholarship@UMMS, 2011. http://escholarship.umassmed.edu/gsbs_diss/934.

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Sequence divergence of orthologous proteins enables adaptation to a plethora of environmental stresses and promotes evolution of novel functions. As one of the most common motifs in biology capable of diverse enzymatic functions, the TIM barrel represents an ideal model system for mapping the phenotypic manifestations of protein sequence. Limits on evolution imposed by constraints on sequence and structure were investigated using a model TIM barrel protein, indole-3-glycerol phosphate synthase (IGPS). Exploration of fitness landscapes of phylogenetically distant orthologs provides a strategy for elucidating the complex interrelationship in the context of a protein fold. Fitness effects of point mutations in three phylogenetically divergent IGPS proteins during adaptation to temperature stress were probed by auxotrophic complementation of yeast with prokaryotic, thermophilic IGPS. Significant correlations between the fitness landscapes of distant orthologues implicate both sequence and structure as primary forces in defining the TIM barrel fitness landscape. These results suggest that fitness landscapes of point mutants can be successfully translocated in sequence space, where knowledge of one landscape may be predictive for the landscape of another ortholog. Analysis of a surprising class of beneficial mutations in all three IGPS orthologs pointed to a long-range allosteric pathway towards the active site of the protein. Biophysical and biochemical analyses provided insights into the molecular mechanism of these beneficial fitness effects. Epistatic interactions suggest that the helical shell may be involved in the observed allostery. Taken together, knowledge of the fundamental properties of the TIM protein architecture will provide new strategies for de novo protein design of a highly targeted protein fold.

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Chan, Yvonne H. « The Complex Role of Sequence and Structure in the Stability and Function of the TIM Barrel Proteins ». eScholarship@UMMS, 2017. https://escholarship.umassmed.edu/gsbs_diss/934.

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Sequence divergence of orthologous proteins enables adaptation to a plethora of environmental stresses and promotes evolution of novel functions. As one of the most common motifs in biology capable of diverse enzymatic functions, the TIM barrel represents an ideal model system for mapping the phenotypic manifestations of protein sequence. Limits on evolution imposed by constraints on sequence and structure were investigated using a model TIM barrel protein, indole-3-glycerol phosphate synthase (IGPS). Exploration of fitness landscapes of phylogenetically distant orthologs provides a strategy for elucidating the complex interrelationship in the context of a protein fold. Fitness effects of point mutations in three phylogenetically divergent IGPS proteins during adaptation to temperature stress were probed by auxotrophic complementation of yeast with prokaryotic, thermophilic IGPS. Significant correlations between the fitness landscapes of distant orthologues implicate both sequence and structure as primary forces in defining the TIM barrel fitness landscape. These results suggest that fitness landscapes of point mutants can be successfully translocated in sequence space, where knowledge of one landscape may be predictive for the landscape of another ortholog. Analysis of a surprising class of beneficial mutations in all three IGPS orthologs pointed to a long-range allosteric pathway towards the active site of the protein. Biophysical and biochemical analyses provided insights into the molecular mechanism of these beneficial fitness effects. Epistatic interactions suggest that the helical shell may be involved in the observed allostery. Taken together, knowledge of the fundamental properties of the TIM protein architecture will provide new strategies for de novo protein design of a highly targeted protein fold.

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Liu, Kwong Ip. « Digital net experimental designs, function interpolations using low discrepancy sequence and goodness of fit tests by discrepancy ». HKBU Institutional Repository, 2007. http://repository.hkbu.edu.hk/etd_ra/807.

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Chia, Nicholas Lee-Ping. « Sequence alignment ». Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1154616122.

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Canty, James Ignatius. « Investigating the properties of brown dwarfs using intermediate-resolution spectroscopy ». Thesis, University of Hertfordshire, 2015. http://hdl.handle.net/2299/15194.

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This thesis is an investigation into some properties of brown dwarfs using medium-resolution spectroscopy. In the first part of the thesis, I address the issue of parameter degeneracy in brown dwarfs. In the course of my analysis, I derive a gravity-sensitive spectral index which can be used, statistically at least, to differentiate populations of young objects from field dwarfs. The index is also capable of finding the difference between a population of ~1 Myr objects and a population of ~10 Myr objects and may be used to separate low-mass members from foreground and background objects in young clusters and associations. The second part of my thesis is an investigation into the major opacity sources in the atmospheres of late T dwarfs. I look particularly at CH4 and NH3 absorption features in the near-infrared spectra of these objects. In my analysis, I identify new absorption features produced by these molecules. I also correct features which had previously been wrongly identified. This has been made possible by the use of high quality data, together with a new CH4 synthetic line list, which is more complete at these temperatures than any previously available list.

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Vogel, Constantin [Verfasser], et Jürgen [Akademischer Betreuer] Pleiss. « Systematic analysis of the sequence-structure-function relationships of thiamine diphosphate-dependent enzymes / Constantin Vogel. Betreuer : Jürgen Pleiss ». Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2015. http://d-nb.info/1069815462/34.

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Blasingame, Tiffany. « Characterization of a novel aggregate-gland-derived spider silk protein in Latrodectus Hesperus : from sequence to propsoed function ». Scholarly Commons, 2009. https://scholarlycommons.pacific.edu/uop_etds/741.

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Spider silk from the female black widow spider, Latrodectus hesperus, is made of extraordinary biomolecules of nature. Efforts of the scientific community to commercially synthesize silks have become a collaborating, yet competitive race, to characterize the proteins that contribute to its intriguing biomechanics. Little has been reported on aqueous silk molecules in black widow spider silk, which are quite different from the large water insoluble core fibroins. In this study, a novel, aqueous aggregate gland derived silk factor (AgSF 1) was investigated using proteomics and immunological approaches. Western blot analyses of whole tissue lysates and solublized silk fibers revealed high levels of AgSFl in the aggregate gland, in the web scaffolding junctions, and in wrapping silk. MS/MS analyses of tryptic digest products from solubilized wrapping silk and aggregate gland whole cell lysate also confirmed the presence of AgSFl in these samples. Possible post-translational modifications were also analyzed by two-dimensional gel electrophoresis (2DE) and MS/MS analysis. AgSFl was localized in the web scaffolding junctions and our data supports a role as an adhesive silk protein that serves as a center for connecting scaffolding fibers that functions to reduce the tensile strength of scaffolding fibers, which facilitates capture of aerial insects.

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Zhang, Zhiling. « The structure and function of troponin T upon metal ion binding and the detection of nucleic acid sequence variations ». Thesis, University of North Texas, 2005. https://digital.library.unt.edu/ark:/67531/metadc5565/.

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Numerous troponin T (TnT) isoforms are generated by alternative RNA splicing primarily in its NH2-terminal hypervariable region, but the functions of these isoforms are not completely understood. In this dissertation work, calcium and terbium binding behavior of several forms of TnT were investigated by spectroscopic and radioactive techniques. Chicken breast muscle TnT binds calcium and terbium through its NH2-terminal Tx motif (HEEAH)n with high affinity (10-6 mM) and fast on-rate (106 - 107 M-1 s-1). Chicken leg muscle TnT and a human cardiac TnT NH2-terminal fragment, which both lack the Tx motif on their NH2-terminal regions, do not have affinities for calcium in the physiological range. Computational predictions on TnT N47 suggest that the TnT NH2-terminal region might fold into an elongated structure with at least one high affinity metal ion binding pocket comprised primarily of the Tx motif sequence and several lower affinity binding sites. In addition, calcium binding to TnT N47 might alter its conformation and flexibility. Luminescence resonance energy transfer measurements and other experimental observations are consistent with the computational predictions suggesting the computational simulated atomic model is reasonable. TnT mutations are responsible for 15% of familiar hypertrophic cardiomyopathy (FHC) cases with a phenotype of relatively mild hypertrophy, but a high incidence of sudden death. Detection of those genetic mutations would facilitate the clinical diagnosis and initiation of treatment at an early stage. This dissertation also investigated a novel hybridization proximity assay (HYPA) combining molecular beacon and luminescence resonance energy transfer (LRET) technologies. Experimental results suggest that a shared stem probe design produces a more consistent response upon hybridization, whereas the internally labeled probe was less consistent, but can yield the highest responses. Using the optimally designed molecular probes, the HYPA provides a detection of alterations in nucleic acid structure of as little as a single nucleotide. This novel HYPA is expected to expand its applications in the analysis and screening of genetic diseases.

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Jung, Guhung. « Structure-function analysis of PRD1 DNA polymerase ; nucleotide sequence, overexpression and in vitro mutagenesis of the PRD1 DNA polymerase gene ». Diss., The University of Arizona, 1989. http://hdl.handle.net/10150/184654.

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A small lipid-containing bacteriophage PRD1 specifies its own DNA polymerase which utilizes terminal protein as a primer for DNA synthesis. The PRD1 DNA polymerase gene has been sequenced and its amino acid sequence deduced. This protein-primed DNA polymerase consists of 553 amino acid residues with a calculated molecular weight of 63,300. Thus, it is the smallest DNA polymerase ever isolated from prokaryotic cells. Comparison of the PRD1 DNA polymerase with other DNA polymerases whose sequences have been published, yielded segmental but significant homologies. These results strongly suggest that many prokaryotic and eukaryotic DNA polymerase genes regardless of size have evolved from a common ancestral gene. The results further indicate that those DNA polymerases which use either an RNA or protein primer are related. We propose to classify DNA polymerases on the basis of their evolutionary relatedness. In order to overexpress PRD1 DNA polymerase in E. coli cells, the 2kb Hae II fragment was isolated from phage genomic DNA. This fragment was then cloned into pEMBLex3 expression vector. Phagemid pEMBLex3 contains lambda pR promoter and cI857 gene as a repressor. A specific 57 bp deletion was performed by using uracil containing ss DNA and oligonucleotide spanning each region to remove an unwanted non-coding region. After this deletion, the PRD1 DNA polymerase gene is totally under the control of the vector promoter and SD sequence. Upon heat induction, a protein with an apparent size of 68 kdal was overexpressed as an active PRD1 DNA polymerase. The expression of DNA polymerase was about 1% of total E. coli protein. The PRD1 DNA polymerase is a small multifunctional DNA polymerase and has three major conserved amino acid sequences which are shared among many DNA polymerases including human DNA polymerase alpha. Therefore, the PRD1 DNA polymerase provides an useful model system to study structure-function analysis of DNA polymerases. Four specific amino acid changes generated in conserved regions by the site-directed mutagenesis, in order to investigate their functional roles. Based on complementation test, three conserved regions are functional domains of PRD1 DNA polymerase.

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Hsieh, Jui-Cheng. « Structure-function analysis of the bacteriophage PRD1 DNA terminal protein : Nucleotide sequence, overexpression, and site-directed mutagenesis of the terminal protein gene ». Diss., The University of Arizona, 1990. http://hdl.handle.net/10150/184974.

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The nucleotide sequence of the PRD1 terminal protein gene has been determined. The coding region for PRD1 terminal protein is 777 base pairs long and encodes 259 amino acid residues (29,326 daltons). The deduced amino acid sequence of PRD1 terminal protein reveals no overall homology with other known terminal proteins or related proteins. A closer examination revealed a highly conserved amino acid sequence, YSRLRT, exist among all identified DNA terminal proteins including PRD1, PZA, Nf, φ29 and adenovirus. This is the first conserved amino acid sequence that has been found in all identified DNA terminal proteins. Not only is the YSRLRT sequence conserved, but its spatial location is similar as well. Therefore, the significance of the YSRLRT conserved sequence is suggested by both its conservative spatial location and high degree of homology across species. To study the structure-function relationship of the YSRLRT sequence of PRD1 terminal protein, in vitro site-directed mutagenesis was performed to determine the role of each amino acid in this conserved region. The PRD1 terminal protein and DNA polymerase genes were cloned into phagemid pEMBLex3, and the recombinant plasmid used for constructing mutants. Eleven PRD1 terminal protein mutant clones were examined for their priming complex formation activities. Our results have strongly demonstrated that the positive charge residue of arginine-174 plays an important role for PRD1 terminal protein function. There are 13 tyrosine residues in the predicted PRD1 terminal protein. It was of interest to known which tyrosine is actually linked to terminal nucleotide of the PRD1 DNA. We used a new approach involving replacing the tyrosine residues with phenylalanine residues in the carboxyl terminal portion of the protein. From analyses, the tyrosine-190 has been determined to be the most likely linkage site between terminal protein and PRD1 DNA.

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Buchholz, Patrick Christopher Frank [Verfasser], et Jürgen [Akademischer Betreuer] Pleiss. « Data integration and data mining for the exploration of enzymatic sequence-structure-function relationships / Patrick Christopher Frank Buchholz ; Betreuer : Jürgen Pleiss ». Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2018. http://d-nb.info/1173163808/34.

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Buchholz, Patrick C. F. [Verfasser], et Jürgen [Akademischer Betreuer] Pleiss. « Data integration and data mining for the exploration of enzymatic sequence-structure-function relationships / Patrick Christopher Frank Buchholz ; Betreuer : Jürgen Pleiss ». Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2018. http://d-nb.info/1173163808/34.

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Langan, Paul. « X-ray and neutron diffraction studies on the variation of the B conformation of deoxyribonucleic acid as a function of base sequence ». Thesis, Keele University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304459.

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Malomo, Sunday. « Structure-function properties of hemp seed proteins and protein-derived acetylcholinesterase-inhibitory peptides ». Elsevier, 2014. http://hdl.handle.net/1993/30736.

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Hemp seed proteins (HSP) were investigated for physicochemical and functional properties in model food systems. In addition, the HSP were enzymatically digested and the released peptides investigated as potential therapeutic agents. Membrane isolated HSP (mHPC) were the most soluble with >60% solubility at pH 3-9 when compared to a maximum of 27% for isoelectric pH-precipitated proteins (iHPI). However, iHPI formed emulsions with smaller oil droplet sizes (<1 µm) while mHPI formed bigger oil droplets. The iHPI was subjected to enzymatic hydrolysis using different concentrations (1-4%) of six proteases (pepsin, pancreatin, flavourzyme, thermoase, papain and alcalase) to produce various HSP hydrolysates (HPHs). HPHs had strong in vitro inhibitions of angiotensin converting enzyme (ACE) and renin activities, the two main enzyme systems involved in hypertension. Oral administration of the HPHs to spontaneously hypertensive rats led to fast and persistent reductions in systolic blood pressure. The HPHs also inhibited in vitro activities of acetylcholinesterase (AChE), a serine hydrolase whose excessive activities lead to inadequate level of the cholinergic neurotransmitter, acetylcholine (ACh). Inadequate ACh level in the brain has been linked to neurodegenerative diseases such as dementia and Alzheimer’s disease (AD); therefore, AChE inhibition is a therapeutic target. The 1% pepsin HPH was the most active with up to 54% AChE inhibition at 10 µg/mL peptide concentration. The 1% pepsin HPH (dominated by <1 kDa) was subjected to reverse-phase HPLC peptide purification coupled with tandem mass spectrometry, which led to identification of several peptide sequences. Some of the peptides inhibited activities of both animal and human AChE forms with LYV being the most potent against human AChE (IC50 = 7 µg/ml). Thus the LYV peptide may serve as a useful template for the development of future potent AChE-inhibitory peptidomimetics. In conclusion, several novel AChE-inhibitory peptides were discovered and their amino acid sequences elucidated for the first time. Results from this work identified HSP products that could serve as functional ingredients in the food industry. The work also produced and confirmed the in vitro AChE-inhibitory activities of several new peptide sequences that may serve as therapeutic agents for AD management.
October 2015

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Roma, Glenn W. « Systematic Analysis of Structure-Function Relationships of Conserved Sequence Motifs in the NADH-Binding Lobe of Cytochrome b₅ Reductase ». [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002558.

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Souza, Antonio Marcos de. « A sequencia Fedathi para uma aprendizagem significativa da funÃÃo afim : uma proposta didÃtica com o uso do software geogebra ». Universidade Federal do CearÃ, 2015. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=14602.

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No cenÃrio da escola pÃblica brasileira, a cada nova geraÃÃo de educandos que surge o ensino da MatemÃtica torna-se cada vez mais desafiador. Como consequÃncia, os indicadores das avaliaÃÃes em larga escala revelam resultados insatisfatÃrios com relaÃÃo Ã aprendizagem. Diante disso, o presente trabalho apresenta uma proposta de ensino da FunÃÃo Afim, estruturada a partir dos pressupostos da teoria da Aprendizagem Significativa e da proposta metodolÃgica de ensino SequÃncia Fedathi, utilizando como recurso tecnolÃgico auxiliar o software Geogebra. A pesquisa foi direcionada aos alunos do 1Â ano do Ensino MÃdio de uma escola pÃblica do Estado do CearÃ. O objetivo foi oferecer condiÃÃes para que os alunos, a partir de atividades prÃ-elaboradas construÃssem o conceito de FunÃÃo Afim, partindo de um problema e, em seguida diferenciassem este conceito fazendo simulaÃÃes no ambiente do Geogebra, assumindo uma postura protagonista neste processo. Como procedimento metodolÃgico de investigaÃÃo foram utilizadas sessÃes didÃticas, que sÃo aulas estruturadas a partir de uma anÃlise ambiental e teÃrica, seguindo as etapas da SequÃncia Fedathi (tomada de posiÃÃo, maturaÃÃo, soluÃÃo e prova), em que tambÃm foram considerados os princÃpios programÃticos do conteÃdo (DiferenciaÃÃo Progressiva, ReconciliaÃÃo Integrativa, OrganizaÃÃo Sequencial e ConsolidaÃÃo) e os Mapas Conceituais. Durante o processo de construÃÃo e diferenciaÃÃo de conceitos pelos alunos, o professor pesquisador assumiu a chamada âpostura mÃo no bolsoâ, evitando dÃ respostas prontas Ãs perguntas dos alunos. Os resultados da anÃlise qualitativa das sessÃes didÃticas e quantitativa do prÃ-teste, pÃs-teste e questionÃrios evidenciaram que: os alunos vivenciarem o processo de construÃÃo do conceito assumindo uma postura autÃnoma em relaÃÃo ao seu processo de aprendizagem; o conteÃdo aprendido foi representado de forma substantiva; o Geogebra e os Mapas Conceituais facilitaram a DiferenciaÃÃo Progressiva do conceito de funÃÃo afim, bem como a ReconciliaÃÃo Integrativa das especificaÃÃes deste conceito; os alunos nÃo conheciam o Geogebra, nem qualquer outro software para o estudo das funÃÃes antes da proposta; a grande maioria dos discentes assimilaram satisfatoriamente os conceitos explorados. Conclui-se, entÃo, que os novos desafios da aprendizagem impÃem aos educadores do sÃculo XXI um constante enriquecimento de sua prÃtica pedagÃgica a partir de teorias, metodologias e uso pedagÃgico de recursos tecnolÃgicos de forma integrada ao currÃculo.
In the scenario of the Brazilian Public School, every generation of education workers that join in the teaching of Mathematics becomes even more challenging. Consequently, large-scale assessment indicators unveil undesired results relating to learning processes. Considering that, the present work shows a proposal of teaching Affine Function, structured from the assumption of Meaningful Learning Theory and from the methodological proposal of teaching Fedathi Sequence, using as an auxiliary technological resource the software Geogebra. The research was directed to students of the first grade of high school of a State Public School in CearÃ, Brazil. The goal was offer conditions for students, beginning with pre-arranged activities, to build the concept of Affine Function, starting from a problem and, after that, have a clue of this concept by doing simulations in the Geogebra environment, taking the first role in this process. As a methodological procedure of investigation, didactic sessions were achieved, which are classes structured from an environmental and theoretical analysis, following the step of Fedathi Sequence (positioning, maturation, solution and test) that also were considered the programmatic principles of the content (Progressive Differentiation, Integrative Reconciliation, Organizational Sequence and Consolidation) and the Conceptual Maps. During the process of construction and differentiation of concepts by students, the researcher teacher took the so called âhands-in-the-pocket attitudeâ, avoiding give prepared answers to studentsâ questions. The results of qualitative analyses of the didactic sessions and quantitative of pre-test, after-test and questionnaires reveal that: students experienced the process of construction of the concept, taking independent attitude in relation to his/her learning process.; The learned content was represented in a substantive way; The software Geogebra and the conceptual maps facilitated the Progressive Differentiation of the concept of Affine Function, as well as the Integrative Reconciliation of specifications of this concept. Students did not know the software Geogebra, and do not even know another software to study functions before this proposal; the majority of the students successfully learned the exploited concepts. Concluding, the new challenges of learning moves the 21st century teachers to a continuous enrichment of the pedagogic practices from the theories, methodologies and the pedagogic usage of technological resources integrates to the scholar curriculum.

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MendonÃa, Adriana Ferreira. « SequÃncia Fedathi na formaÃÃo docente : o conceito de funÃÃo ». Universidade Federal do CearÃ, 2017. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=19279.

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FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico
O objetivo deste trabalho foi verificar se a proposta SequÃncia Fedathi contribui para o ensino do conceito matemÃtico de funÃÃo. Os participantes desta pesquisa foram professores de uma escola da rede pÃblica que fizeram uma formaÃÃo para apreenderem os fundamentos da proposta. Especificamente identificou-se as concepÃÃes docentes acerca deste conceito, contribuindo com sua (re)construÃÃo, discutiu-se elementos histÃricos e epistemolÃgicos e, ainda, analisou-se as mudanÃas na prÃtica docente apÃs a formaÃÃo continuada. A escolha da SequÃncia Fedathi foi associada Ã sua finalidade de orientar as aÃÃes docentes no processo de elaboraÃÃo e planejamento de aulas e, ainda, porque tem uma conexÃo muito forte com o ensino de conceitos ao valorizar a resoluÃÃo de problemas, a investigaÃÃo, generalizaÃÃo e formalizaÃÃo. As produÃÃes Andrade (2011), Fontenele (2013), Sousa (2015), Pinheiro (2016), Borges Neto (2013, 2017) fazem parte de nosso referencial acerca da proposta Fedathi, enquanto Descartes (1989), Kleiner (1989), Davis e Hersh (1986), Fischbein (2002) Ãvila (2010) compÃem a referencial sobre a intuiÃÃo e a formalizaÃÃo de conceitos. Metodologicamente, esta pesquisa empregou os princÃpios da etnometodologia com suporte na pesquisa participante que permitiu a interaÃÃo do pesquisador com os participantes da pesquisa, flexibilidade para mudanÃas de percurso devido Ãs visÃes dos sujeitos e Ãnfase no processo. Os resultados apontam para mudanÃas significativas nas atitudes dos professores que consideraram que a proposta Fedathi contribui no ensino do conceito de funÃÃo e que pode ser utilizada em contextos diversos propiciando uma aula mais dinÃmica, com a participaÃÃo ativa dos alunos.

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Prokop, Jeremy W. « The SRY Gene and Reductionism in Molecular Biology : How to Move from the Benchtop to a Systems Approach ». University of Akron / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1373365929.

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Van, Niekerk Christopher. « Investigating self-fabrication in the context of artiﬁcial chemistries ». Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/96051.

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Thesis (MSc)--Stellenbosch University, 2014.
ENGLISH ABSTRACT: This thesis gives a broad overview of what artificial chemistries (ACs) are, a brief review of several ACs and their applications, and an in depth analysis of one speci c AC: the four-bit binary string system. The model designed by Banzhaf [1] for in silico examination was recreated using the Python programming language. The initial motivation was to identify an existing AC that could be used to elucidate the sequence-function relationship, which led to the simultaneous investigation of self-organization in AC systems [7]. The interest in sequence-function relationships stems from their importance for self-production of objects [35]. For self-replication to be possible in larger organizations, the components of the organization must be able to continuously produce themselves [3, 7]. We chose the four-bit binary string system for investigation because of its simple design and implementation, its ability to yield complex results from interactions between a small population of objects, and its analogy to the DNA{RNA{protein organisation. When a population of objects are allowed to continuously interact, self-production and self-organization occur, even in simple arti cial systems [7, 8]. The stability of the emergent organizations depends on the interactions of its components, which must be capable of self-production if they are to maintain the organization [27]. Self-production of objects depends on their sequence-function relationship, which determines their rate of replication when interacting with other objects.
AFRIKAANSE OPSOMMING: Hierdie tesis verskaf `n bree oorsig van die algemene aard van artifisiele chemies (ACs), `n kort opsomming van `n paar ACs en hul toepassings, en `n diepgaande analise van een spesifieke AC: die 4-bis binere stringstelsel. Die model wat Banzhaf [1] ontwerp het vir in silico eksperimentering is hier herskep in die Python programmeringstaal. Die aanvanklike motivering was om `n bestaande AC te identifiseer wat gebruik kon word om die sekwens-funksie verwantskap te ontrafel, en dit het gelei tot die gelyktydige ondersoek van self-organisasie in AC stelsels [7]. Ons belangstelling in sekwens-funksie verwantskappe spruit uit hul belang vir die selfproduksie van objekte [35]. Om selfreplisering in meer omvangryke organisasies moontlik te maak moet die komponente in staat wees om hulself eenstryk te produseer [3, 7]. Ons het `n 4-bis stelsel vir hierdie studie gekies omdat die ontwerp en implementering eenvoudig is, omdat interaksies binne `n klein populasie van objekte komplekse resultate gee, en omdat die stelsel se organisasie analoog aan die DNA-RNA-proteien organisasie is. Wanneer `n populasie van objekte toegelaat word om eenstryk op mekaar te reageer vind self-produksie en self-organisasie vanself plaas, selfs in eenvoudige artifsiele stelsels [7, 8]. Die stabiliteit van die emergente organisasies hang af van die interaksies tussen die komponente, wat self die vermoe tot selfproduksie moet he indien hulle die organisasie in stand wil hou [27]. Selfproduksie van objekte hang af van hul sekwens-funsieverwantskap, wat op hul beurt bepaal hoe vinnig hulle repliseer wanneer in interaksie met ander objekte.

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Sangar, Vineet Lesk Arthur M. « Protein function inferences from sequence and structure / ». 2008. http://etda.libraries.psu.edu/theses/approved/WorldWideIndex/ETD-2453/index.html.

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Thèses sur le sujet « Sequence-function »

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