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Rodriguez, Raymond J. "The Pilot Mentor-Protege Program: a viable program for Government procurement?" Thesis, Monterey, California. Naval Postgraduate School, 1993. http://hdl.handle.net/10945/24214.
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Podgornaia, Anna Igorevna. "Pervasive degeneracy and epistasis in a protein-protein interface." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/93041.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2014.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references.<br>Signal transduction pathways rely on transient yet specific protein-protein interactions. How a limited set of amino acids can enforce cognate protein interactions while excluding undesired pairings remains poorly understood, even in cases where the contacting residues have been identified on both protein partners. To tackle this challenge, I performed structure-guided and library-based mutagenesis studies of bacterial two-component signaling pathways. These pathways, typically consisting of a histidine kinase and a response regulator, are an ideal model system for studying protein-protein interactions as they rely almost exclusively on molecular recognition for specificity. The kinase uses a limited set of residues to recognize the regulator in both phosphorylation and dephosphorylation reactions, and to prevent docking with all noncognate regulators. In this thesis I characterized the extent to which interface residues in two-component signaling proteins can be modified without changing the overall behavior of the pathway. In collaboration with another research group I have performed a mutagenesis study of a two-component system from Thermotoga maritima that has proven amenable to structural analysis. By solving the cocrystal structure of a histidine kinase and response regulator containing interface residues from a different interacting pair, we learned the biophysical basis for accommodating these new residues. To understand how many different residue combinations can support a functional interaction, I comprehensively mapped the sequence space of the interface formed by Escherichia coli histidine kinase PhoQ and its partner PhoP. I used a robust high-throughput assay to screen a library of 204 (160,000) PhoQ variants in which I had completely randomized the four key specificity-determining residues. Using deep sequencing, I identified -1,600 (1 %) variants that can phosphorylate and dephosphorylate PhoP as well as the wild-type PhoQ. Strikingly, PhoQ can interact with PhoP via many sets of interfacial residues that are completely different from the wild type. This combinatorial approach to mapping sequence space revealed interdependencies between individual amino acids, illustrating its power relative to screens that only examine substitutions at individual sites. This thesis provides a framework for mapping the sequence space of histidine kinases and has broad implications for understanding protein-protein interaction specificity and the evolution of bacterial signaling pathways.<br>by Anna Igorevna Podgornaia.<br>Ph. D.
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Thomas, Dallas, and University of Lethbridge Faculty of Arts and Science. "Algorithms & experiments for the protein chain lattice fitting problem." Thesis, Lethbridge, Alta. : University of Lethbridge, Faculty of Arts and Science, 2006, 2006. http://hdl.handle.net/10133/535.
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This study seeks to design algorithms that may be used to determine if a given lattice is
a good approximation to a given rigid protein structure. Ideal lattice models discovered
using our techniques may then be used in algorithms for protein folding and inverse protein
folding.
In this study we develop methods based on dynamic programming and branch and bound
in an effort to identify “ideal” lattice models. To further our understanding of the concepts
behind the methods we have utilized a simple cubic lattice for our analysis. The algorithms
may be adapted to work on any lattice. We describe two algorithms. One for aligning the
protein backbone to the lattice as a walk. This algorithm runs in polynomial time. The second
algorithm for aligning a protein backbone as a path to the lattice. Both the algorithms
seek to minimize the CRMS deviation of the alignment. The second problem was recently
shown to be NP-Complete, hence it is highly unlikely that an efficient algorithm exists. The
first algorithm gives a lower bound on the optimal solution to the second problem, and can
be used in a branch and bound procedure. Further, we perform an empirical evaluation of
our algorithm on proteins from the Protein Data Bank (PDB).<br>ix, 47 leaves ; 29 cm.
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Osterloh, Jeannette M. "dSarm/Sarm1 Governs a Conserved Axon Death Program: A Dissertation." eScholarship@UMMS, 2013. https://escholarship.umassmed.edu/gsbs_diss/668.
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Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Using a forward genetic screen in Drosophila, we identified that loss of the Toll receptor adaptor dSarm (sterile a/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct evidence that axons actively promote their own destruction after injury and identify dSarm/Sarm1 as a member of an ancient axon death signaling pathway. This death signaling pathway can be activated without injury by loss of the N-terminal self-inhibitory domain, resulting in spontaneous neurodegeneration. To investigate the role of axon self-destruction in disease, we assessed the effects of Sarm1 loss on neurodegeneration in the SOD1-G93A model of amyotrophic lateral sclerosis (ALS), a lethal condition resulting in progressive motor neuron death and paralysis. Loss of Sarm1 potently protects motor axons and synapses from degeneration, but only extends animal survival by 10%. Thus, there appears to be at least two driving forces in place during ALS disease progression: (1) Sarm1 mediated axon death, and (2) cell body destruction via some unknown mechanism.
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Osterloh, Jeannette M. "dSarm/Sarm1 Governs a Conserved Axon Death Program: A Dissertation." eScholarship@UMMS, 2006. http://escholarship.umassmed.edu/gsbs_diss/668.
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Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Using a forward genetic screen in Drosophila, we identified that loss of the Toll receptor adaptor dSarm (sterile a/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct evidence that axons actively promote their own destruction after injury and identify dSarm/Sarm1 as a member of an ancient axon death signaling pathway. This death signaling pathway can be activated without injury by loss of the N-terminal self-inhibitory domain, resulting in spontaneous neurodegeneration. To investigate the role of axon self-destruction in disease, we assessed the effects of Sarm1 loss on neurodegeneration in the SOD1-G93A model of amyotrophic lateral sclerosis (ALS), a lethal condition resulting in progressive motor neuron death and paralysis. Loss of Sarm1 potently protects motor axons and synapses from degeneration, but only extends animal survival by 10%. Thus, there appears to be at least two driving forces in place during ALS disease progression: (1) Sarm1 mediated axon death, and (2) cell body destruction via some unknown mechanism.
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Gurry, Thomas. "Order, disorder, and protein aggregation." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/97347.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2015.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (pages 114-124).<br>Protein aggregation underlies a number of human diseases. Most notably, it occurs widely in neurodegenerative diseases, including Alzheimer's and Parkinson's. At the molecular level, neurotoxicity is thought to originate from toxic gains of function in multimeric aggregates of proteins that are otherwise predominantly monomeric and disordered, fluctuating between a very large number of structurally dissimilar states on nano- and microsecond timescales. These proteins, termed Intrinsically Disordered Proteins (IDPs), are notoriously difficult to probe using traditional biophysical techniques. In order to obtain structural information pertaining to the aggregation of IDPs, it is often necessary to develop computational and modeling tools, both to leverage the full extent of the experimental data, and to generate testable predictions for future experiments. In this thesis, I present three separate computational studies studying the formation of multimeric aggregates in IDPs, spanning different aspects of the aggregation process, from early nucleation events to fibril elongation. In the first study, I present a conformational ensemble of a-synuclein, the culprit protein of Parkinson's disease, constructed using a Variational Bayesian Weighting algorithm in combination with NMR data collected by our collaborators. We find that the data fit a description in which the protein predominantly exists as a disordered monomer but contains small quantities of multimeric states containing both helical and strand-rich conformations. In the second study, I focus on the process of amyloid fibril elongation in the Amyloid-[beta] (A[beta]) peptide of Alzheimer's disease. I compute the free energy surface associated with the fibril elongation reaction, and find that elongation of both A[beta]40 and A[beta]42 experimental fibril structures occurs on a downhill free energy pathway, proceeding via an obligate, fibril-associated hairpin intermediate. The fibril-associated hairpin is significantly more stable (relative to the fibrillar, elongated state) in A[beta]42 compared with A[beta]40, suggesting a potential clinical target of interest. Finally, I present lengthy, all-atom molecular simulations that suggest that nucleation of the minimum aggregating fragment of c-synuclein proceeds via a helical intermediate, requiring a structural conversion into a strand-rich nucleating species via a stochastic process of individual helices unfolding and self-associating via backbone hydrogen bonds.<br>by Thomas Gurry.<br>Ph. D.
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Robertson, Alexander De Jong. "Understanding regulation of mRNA by RNA binding proteins." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/87474.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2014.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (pages 167-187).<br>Posttranscriptional regulation of mRNA by RNA-binding proteins plays key roles in regulating the transcriptome over the course of development, between tissues and in disease states. The specific interactions between mRNA and protein are controlled by the proteins' inherent affinities for different RNA sequences as well as other features such as translation and RNA structure which affect the accessibility of mRNA. The stabilities of mRNA transcripts are regulated by nonsense-mediated mRNA decay (NMD), a quality control degradation pathway. In this thesis, I present a novel method for high throughput characterization of the binding affinities of proteins for mRNA sequences and an integrative analysis of NMD using deep sequencing data. This thesis describes RNA Bind-n-Seq (RBNS), which comprehensively characterizes the sequence and structural specificity of RNA binding proteins (RBPs), and application to the developmentally-regulated splicing factors RBFOX2, MBNL1 and CELF1/CUGBP1. For each factor, the canonical motifs are recovered as well as additional near-optimal binding motifs. RNA secondary structure inhibits binding of RBFOX2 and CELF1, while MBNL1 favors unpaired Us but tolerates C/G pairing in UGC-containing motifs. In a project investigating how NMD shapes the embryonic transcriptome, this thesis presents integrated genome-wide analyses of UPF1 binding locations, NMD-regulated gene expression, and translation in murine embryonic stem cells (mESCs). Over 200 direct UPF1 binding targets are identified using crosslinking/immunoprecipitation-sequencing (CLIP-seq). Results from ribosome foot printing show that actively translated upstream open reading frames (uORFs) are enriched in transcription factor mRNAs and predict mRNA repression by NMD, while poorly translated mRNAs escape repression.<br>by Alexander De Jong Robertson.<br>Ph. D.
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Bepler, Tristan(Tristan Wendland). "Machine learning for understanding protein sequence and structure." Thesis, Massachusetts Institute of Technology, 2020. https://hdl.handle.net/1721.1/129888.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, February, 2020<br>Cataloged from student-submitted PDF of thesis.<br>Includes bibliographical references (pages 183-200).<br>Proteins are the fundamental building blocks of life, carrying out a vast array of functions at the molecular level. Understanding these molecular machines has been a core problem in biology for decades. Recent advances in cryo-electron microscopy (cryoEM) has enabled high resolution experimental measurement of proteins in their native states. However, this technology remains expensive and low throughput. At the same time, ever growing protein databases offer new opportunities for understanding the diversity of natural proteins and for linking sequence to structure and function. This thesis introduces a variety of machine learning methods for accelerating protein structure determination by cryoEM and for learning from large protein databases. We first consider the problem of protein identification in the large images collected in cryoEM. We propose a positive-unlabeled learning framework that enables high accuracy particle detection with few labeled data points, both improving data quality and analysis speed. Next, we develop a deep denoising model for cryo-electron micrographs. By learning the denoising model from large amounts of real cryoEM data, we are able to capture the noise generation process and accurately denoise micrographs, improving the ability of experamentalists to examine and interpret their data. We then introduce a neural network model for understanding continuous variability in proteins in cryoEM data by explicitly disentangling variation of interest (structure) for nuisance variation due to rotation and translation. Finally, we move beyond cryoEM and propose a method for learning vector embeddings of proteins using information from structure and sequence. Many of the machine learning methods developed here are general purpose and can be applied to other data domains.<br>by Tristan Bepler.<br>Ph. D.<br>Ph.D. Massachusetts Institute of Technology, Computational and Systems Biology Program
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Biddle, Jason Charles. "Methods and applications in computational protein design." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/61792.
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Thesis (S.M.)--Massachusetts Institute of Technology, Computation for Design and Optimization Program, 2010.<br>This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.<br>Cataloged from student-submitted PDF version of thesis.<br>Includes bibliographical references (p. 107-111).<br>In this thesis, we summarize our work on applications and methods for computational protein design. First, we apply computational protein design to address the problem of degradation in stored proteins. Specifically, we target cysteine, asparagine, glutamine, and methionine amino acid residues to reduce or eliminate a protein's susceptibility to degradation via aggregation, deamidation, and oxidation. We demonstrate this technique on a subset of degradation-prone amino acids in phosphotriesterase, an enzyme that hydrolyzes toxic organophosphates including pesticides and chemical warfare agents. Second, we introduce BroMAP/A*, an exhaustive branch-and- bound search technique with enumeration. We compare performance of BroMAP/A* to DEE/A*, the current standard for conformational search with enumeration in the protein design community. When limited computational resources are available, DEE/A* sometimes fails to find the global minimum energy conformation and/or enumerate the lowest-energy conformations for large designs. Given the same computational resources, we show how BroMAP/A* is able to solve large designs by efficiently dividing the search space into small, solvable subproblems.<br>by Jason Charles Biddle.<br>S.M.
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Karydis, Thrasyvoulos. "Learning hierarchical motif embeddings for protein engineering." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/109659.
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Thesis: S.M., Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 2017.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (pages 75-79).<br>This thesis lays the foundation for an integrated machine learning framework for the evolutionary analysis, search and design of proteins, based on a hierarchical decomposition of proteins into a set of functional motif embeddings. We introduce, CoMET - Convolutional Motif Embeddings Tool, a machine learning framework that allows the automated extraction of nonlinear motif representations from large sets of protein sequences. At the core of CoMET, lies a Deep Convolutional Neural Network, trained to learn a basis set of motif embeddings by minimizing any desired objective function. CoMET is successfully trained to extract all known motifs across Transcription Factors and CRISPR Associated proteins, without requiring any prior knowledge about the nature of the motifs or their distribution. We demonstrate that motif embeddings can model efficiently inter- and intra- family relationships. Furthermore, we provide novel protein meta-family clusters, formed by taking into account a hierarchical conserved motif phylogeny for each protein instead of a single ultra-conserved region. Lastly, we investigate the generative ability of CoMET and develop computational methods that allow the directed evolution of proteins towards altered or novel functions. We trained a highly accurate predictive model on the DNA recognition code of the Type II restriction enzymes. Based on the promising prediction results, we used the trained models to generate de novo restriction enzymes and paved the way towards the computational design of a restriction enzyme that will cut a given arbitrary DNA sequence with high precision.<br>by Thrasyvoulos Karydis.<br>S.M.
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Freese, Peter (Peter Dale). "Biochemical and functional characterization of human RNA binding proteins." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/115601.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2018.<br>This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.<br>Cataloged from student-submitted PDF version of thesis.<br>Includes bibliographical references (pages 205-226).<br>RNA not only shuttles information between DNA and proteins but also carries out many other essential cellular functions. Nearly all steps of an RNA's life cycle are controlled by approximately one thousand RNA binding proteins (RBPs) that direct RNA splicing, cleavage and polyadenylation, localization, translation, and degradation. Despite the central role of RBPs in RNA processing and gene expression, they have been less well studied than DNA binding proteins, in part due to the historical dearth of technologies to probe RBP binding and activity in a high-throughput, comprehensive manner. In this thesis, I describe the affinity landscapes of the largest set of human RBPs to date elucidated through a highthroughput version of RNA Bind-N-Seq (RBNS), an unbiased in vitro assay that determines the primary sequence, secondary structure, and contextual preferences of an RBP. The 78 RBPs bound an unexpectedly low diversity of RNA motifs, implying convergence of binding specificity toward a small set of RNA motifs characterized by low compositional complexity. Offsetting the low diversity of sequence motifs, extensive preferences for contextual features beyond short linear motifs were observed, including bipartite motifs, flanking nucleotide content, and preference for or against RNA structure. These features likely refine which motif occurrences are selected in cells, enabling RBPs that bind the same linear motif to act on distinct subsets of transcripts. Additionally, RBNS data is integrated with complementary in vivo binding sites from enhanced crosslinking and immunoprecipitation (eCLIP) and functional (RNAi/RNA-seq) data produced through collaborative efforts with the ENCODE consortium. These data enable creation of "RNA maps" of RBP activity in pre-mRNA splicing and gene expression levels, either with (eCLIP) or without (RBNS) crosslinking-based assays. The mapping and characterization of RNA elements recognized by over 200 human RBPs is also presented in two human cell lines, K562 and HepG2 cells. Together, these novel data augment the catalog of functional elements encoded in the human genome to include those that act at the RNA level and provide a basis for how RBPs select their RNA targets, a fundamental requirement in more fully understanding RNA processing mechanisms and outcomes.<br>by Peter Freese.<br>Ph. D.
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Park, Daniel K. (Daniel Kyu). "Web servers, databases, and algorithms for the analysis of protein interaction networks." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/79146.
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Thesis (S.M.)--Massachusetts Institute of Technology, Computational and Systems Biology Program, 2013.<br>This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.<br>Cataloged from student-submitted PDF version of thesis.<br>Includes bibliographical references (p. 41-44).<br>Understanding the cell as a system has become one of the foremost challenges in the post-genomic era. As a result of advances in high-throughput (HTP) methodologies, we have seen a rapid growth in new types of data at the whole-genome scale. Over the last decade, HTP experimental techniques such as yeast two-hybrid assays and co-affinity purification couple with mass spectrometry have generated large amounts of data on protein-protein interactions (PPI) for many organisms. We focus on the sub-domain of systems biology related to understanding the interactions between proteins that ultimately drive all cellular processes. Representing PPIs as a protein interaction network has proved to be a powerful tool for understanding PPIs at the systems level. In this representation, each node represents a protein and each edge between two nodes represents a physical interaction between the corresponding two proteins. With this abstraction, we present algorithms for the prediction and analysis of such PPI networks as well as web servers and databases for their public availability: 1. In many organisms, the coverage of experimental determined PPI data remains relatively noisy and limited. Given two protein sequences, we describe an algorithm, called Struct2Net, to predict if two proteins physically interact, using insights from structural biology and logistic regression. Furthermore, we create a community-wide web-resource that predicts interactions between any protein sequence pair and provides proteome-wide pre-computed PPI predictions for Homo sapiens, Drosophila melanogaster, and Saccharomyces cerevisiae. 2. Comparative analysis of PPI networks across organisms can provide valuable insights into evolutionary conservation. We describe an algorithm, called IsoRank, for global alignment of multiple PPI networks. The algorithm first constructs an eigenvalue problem that models the network and sequence similarity constraints. The solution of the problem describes a k partite graph that is further processed to find the alignments. Furthermore, we create a communitywide web database, called IsoBase, that provides network alignments and orthology mappings for the most commonly studied eukaryotic model organisms: Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae.<br>by Daniel K. Park.<br>S.M.
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Foster, A. M. "Agronomic aspects of recent developments in a protein quality maize (Zea mays L.) breeding program." Thesis, University of Reading, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379236.
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Round, Elaine Kay. "Identification and analysis of G-protein pathway control in the Caenorhabditis elegans defecation motor program /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/10283.
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Santos, Carlos Neanes. "Avaliação da Reprodutibilidade Interexaminadores, na Polpação Muscular, Após um Programa de Calibração." Universidade de São Paulo, 2000. http://www.teses.usp.br/teses/disponiveis/25/25135/tde-06122004-102800/.
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O objetivo deste estudo foi avaliar a concordância interexaminadores na palpação muscular, após um programa de calibração, assim como, determinar as variações dessa concordância em relação ao tempo, a determinado músculo e ao lado palpado. Para tal, utilizou-se uma amostra de 32 indivíduos, proporcionalmente divididos em relação ao sexo, escolhidos aleatoriamente nas diversas clínicas (dores orofaciais, prótese, periodontia, cirurgia e dentística) da Faculdade de Odontologia de Bauru, da Universidade de São Paulo. Esta amostra foi dividida em dois grupos: sintomático, composto por 16 indivíduos que apresentavam sinais e sintomas de DTM, com queixas compatíveis com patologias de origem muscular e, assintomático, composto por 16 indivíduos, sem queixas de sintomas de DTM. Os exames de palpação foram realizados por quatro examinadores,previamente treinados, utilizando-se um programa de calibração, que consistiu de instruções detalhadas relativas ao exame, demonstração da localização dos músculos e da força exercida durante a palpação. Foram realizados 3 exames: inicial, intermediário (30 dias após) e final (45 dias após o início da pesquisa), utilizando-se músculos de mastigação (Masséter e Temporal) e cervical (Esternocleidomastoideo). A análise de presença ou severidade de resposta do paciente foi feita através de uma escala ordinal de 0 a 3. Apesar da presença de variáveis inerentes à análise da dor, como a oscilação dos sinais e sintomas do paciente, diferenças na reação do indivíduo e na interpretação da dor do paciente pelo examinador, verificou-se, através do teste de concordância de Kendall, que o programa de calibração foi efetivo na obtenção de concordância interexaminadores, obtendo-se valores entre 0.56 (origem do Masséter Superficial) e 0.84 (Esternocleidomastoideo Médio), considerados de aceitáveis a excelentes. O tempo não alterou essa concordância não havendo, também, diferenças na concordância entre os diversos músculos, assim como para o lado palpado. Concluiu-se que programas de calibração podem ser efetivos na padronização da palpação muscular, o que credencia tal procedimento como uma importante etapa no exame das Disfunções Temporomandibulares.<br>This study aimed to evaluate the interexaminer agreement when performing muscle palpation, after a trainning and calibration program. Reliability related to the time of examination and the side palpated were also addressed. Sample was composed of 32 individuals, matched for sex and divided into two groups: symptomatic (16 patients presenting with myogenic TMD) and asymptomatic (16 patients with no TMD symptoms). Palpation procedures were perfomed in three different times by four examiners, in masticatory (masseter and temporalis) and cervical (sternocleidomastoid SCM) muscles. The prescuse and severity of muscle tenderness was judge by an ordinal scale (from 0 to 3). Kendalls concordance test measured agreement between examiners. SCM has shown the highest concordance (0.84) while the worst result was found for the origin of masseter (0.56). Levels of concordance for all muscles were considered fair and excellent, regardless the side or the time of examination. Authors concluded that a calibration program is able to standardize muscle palpation, which makes such procedure an important step in TMD evaluation.
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Gilbert, Richard James. "Novel programs for protein sequence analysis and structure prediction." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305431.
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Ashenberg, Orr. "Predicting and testing determinants of histidine-kinase functions by leveraging protein sequence information." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/79145.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Computational and Systems Biology Program, February 2013.<br>This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.<br>Cataloged from student-submitted PDF version of thesis. "September 2012."<br>Includes bibliographical references.<br>All cells sense and respond to their environments using signal transduction pathways. These pathways control a sweeping variety of cellular processes across the domains of life, but the pathways are often built from a small, shared set of protein domains. At the core of tens of thousands of signal transduction networks in bacteria is a pair of proteins, a histidine kinase and a response regulator. Upon receiving an input signal, a histidine kinase autophosphorylates and then catalyzes transfer of its phosphoryl group to a cognate response regulator, which often activates a transcriptional response. Bacteria typically encode dozens of kinases and regulators, and the kinases function as dimers in all known examples. This dimeric state raises two functional questions. Do histidine kinases specifically form dimers? Once a kinase has dimerized, does a chain in the dimer phosphorylate itself (cis) or its partner chain (trans)? Specific kinase dimerization is likely important to avoid detrimental crosstalk between separate signaling pathways, and how autophosphorylation occurs is central to kinase activity. In my thesis, I have taken biochemical and evolutionary approaches to identify molecular determinants for both dimerization specificity and autophosphorylation. To study dimerization specificity, I developed an in vitro binding assay to measure kinase dimerization, and I then showed that a paralogous pair of kinases from E. coli specifically formed homodimers over heterodimers. Residues important for dimerization specificity were predicted by measuring amino acid coevolution within kinases, which leverages the enormous amount of sequence information available for the kinase family. Experimental verification of these predictions showed that a set of residues at the base of the kinase dimerization domain was sufficient to establish homospecificity. This same region of the kinase, in particular the loops at the base of the kinase dimer, was also important for determining autophosphorylation mechanism. Recent work showed that kinases could autophosphorylate either in cis or in trans, and I found that a trans kinase could be made to autophosphorylate in cis by replacing its loop with the loop from a cis kinase. I also found that two sets of orthologs, despite having significantly diverged loop sequences, had conserved their autophosphorylation mechanisms. This raised the possibility that kinase loops may be under selection to maintain the same autophosphorylation mechanism.<br>by Orr Ashenberg.<br>Ph.D.
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Gura, Sadovsky Rotem. "Measurement of rapid protein diffusion in the cytoplasm by photoconverted intensity profile expansion." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/104576.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2016.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (pages 82-85).<br>Whether at the level of a single protein, or in the cytoplasm as a whole, the diffusive mobility of proteins plays a key role in biological function. To measure protein diffusion in cells, researchers have developed multiple fluorescence microscopy methods, and have tested them rigorously. However, using these methods for precise measurement of diffusion coefficients requires expertise that can be a barrier to broad utilization of these methods. Here, we report on a new method we have developed, which we name Photo-converted Intensity Profile Expansion (PIPE). It is a simple and intuitive technique that works on commercial imaging systems and requires little expertise. PIPE works by pulsing photo-convertible fluorescent proteins, generating a peaked fluorescence signal at the pulsed region, and analyzing the spatial expansion of the signal as diffusion spreads it out. The width of the expanding signal is directly related to the protein ensemble mean-square displacement, from which the diffusion coefficient of the ensemble is calculated. In the main part of the thesis, we demonstrate the success of PIPE in measuring accurate diffusion coefficients in silico, in vitro and in vivo. We then broaden the discussion, and challenge the assumption that the Fickian diffusion equation is the most appropriate model for describing protein motion in the cytoplasm. Since the cytoplasm is crowded with obstacles that trap proteins for a wide range of times, the motion of those proteins may be more accurately described by models of anomalous diffusion. To contribute to the ongoing debate about anomalous diffusion, we show how PIPE can be used to measure the degree of diffusion anomality by examining the temporal scaling of the mean-square displacement. Whether for measuring normal or anomalous diffusion, we suggest that the simplicity and user-friendliness of PIPE could make it a useful tool in molecular and cell biology.<br>by Rotem Gura Sadovsky.<br>Ph. D.
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Xue, Vincent. "Modeling and designing Bc1-2 family protein interactions using high-throughput interaction data." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/120446.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2018.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (pages 153-164).<br>Protein-protein interactions (PPIs) play a major role in cellular function, mediating signal processing and regulating enzymatic activity. Understanding how proteins interact is essential for predicting new binding partners and engineering new functions. Mutational analysis is one way to study the determinants of protein interaction. Traditionally, the biophysical study of protein interactions has been limited by the number of mutants that could be made and analyzed, but advances in high-throughput sequencing have enabled rapid assessment of thousands of variants. The Keating lab has developed an experimental protocol that can rank peptides based on their binding affinity for a designated receptor. This technique, called SORTCERY, takes advantage of cell sorting and deep-sequencing technologies to provide more binding data at a higher resolution than has previously been achievable. New computational methods are needed to process and analyze the high-throughput datasets. In this thesis, I show how experimental data from SORTCERY experiments can be processed, modeled, and used to design novel peptides with select specificity characteristics. I describe the computational pipeline that I developed to curate the data and regression models that I constructed from the data to relate protein sequence to binding. I applied models trained on experimental data sets to study the peptide-binding specificity landscape of the Bc1-xL, Mc1-1, and Bf1-1 anti-apoptotic proteins, and I designed novel peptides that selectively bind tightly to only one of these receptors, or to a pre-specified combination of receptors. My thesis illustrates how data-driven models combined with high-throughput binding assays provide new opportunities for rational design.<br>by Vincent Xue.<br>Ph. D.
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Huff, Andrew Duane. "Implementation of Mentor-Protege Program by a major Department of Defense contractor." Thesis, Monterey, California. Naval Postgraduate School, 1991. http://hdl.handle.net/10945/30952.
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Public Law 101-510 established the pilot Mentor-Protege Program. This is a voluntary program designed incentives for major Department of Defense contractors to furnish disadvantaged small business concerns with assistance designed to enhance their capabilities to perform as subcontractors and suppliers under both Government and commercial contracts. This study was undertaken to assess the environment for program implementation by analyzing the perceptions of one large DoD contractor and the small disadvantaged business community regarding the Mentor-Protege program and DoD's implementing guidance. The results of this study indicate: There is generally a positive impression of this program and the assistance offered by this program would be effective in improving the capabilities of small disadvantaged businesses. There are, however, several barriers present that could prevent program implementation or limit its effectiveness.
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Keramidas, Natacha L. "Personality and Mentoring: An Investigation of the Role of Proteges' personality, Protege-initiation of Mentoring Relationships and Mentoring Received in Doctoral Programs." University of Akron / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=akron1503423084293622.
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Choudhury, Salimur Rashid, and University of Lethbridge Faculty of Arts and Science. "Approximation algorithms for a graph-cut problem with applications to a clustering problem in bioinformatics." Thesis, Lethbridge, Alta. : University of Lethbridge, Deptartment of Mathematics and Computer Science, 2008, 2008. http://hdl.handle.net/10133/774.
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Clusters in protein interaction networks can potentially help identify functional relationships
among proteins. We study the clustering problem by modeling it as graph cut problems.
Given an edge weighted graph, the goal is to partition the graph into a prescribed
number of subsets obeying some capacity constraints, so as to maximize the total weight
of the edges that are within a subset. Identification of a dense subset might shed some light
on the biological function of all the proteins in the subset.
We study integer programming formulations and exhibit large integrality gaps for various
formulations. This is indicative of the difficulty in obtaining constant factor approximation
algorithms using the primal-dual schema. We propose three approximation algorithms for
the problem. We evaluate the algorithms on the database of interacting proteins and on
randomly generated graphs. Our experiments show that the algorithms are fast and have
good performance ratio in practice.<br>xiii, 71 leaves : ill. ; 29 cm.
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Brock, Kelly Paige. "Protein structure and interaction under environmental stress : from quality control recognition to evolution of collective behavior." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/104575.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2016.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references.<br>A protein's function in the cell depends on its structure, which in turn depends on the intracellular environment. Stress like heat shock or nutrient starvation can alter intracellular conditions, leading to protein misfolding - i.e. the inability of a protein to reach or maintain its native conformation. Since many proteins interact with each other, protein misfolding and cellular stress response must be examined both on the scale of individual protein conformational changes and on a more global level, where interaction patterns can reveal larger-scale protein responses to cellular stress. On the individual scale, one example of a protein particularly susceptible to misfolding is the human von Hippel-Lindau (VHL) tumor suppressor. When expressed in the absence of its cofactors, VHL cannot fold correctly and is quickly degraded by the cell's quality control machinery. Here, I present a biophysical characterization of a VHL mutation that confers increased resistance to misfolding. Mathematical modeling provides an explanation for this mutant's increased stability in the cell by predicting how its cofactor and chaperone interaction sites are buried or exposed in the protein's predicted conformation. On a more global level, a budding yeast cell undergoing glucose deprivation both acidifies its cytosol and exhibits widespread protein clustering. By employing a proteome-wide computational assay, I examine how this drop in pH could lead to the formation of higher order protein structures. This modeling framework also provides a rationale for why these two related phenotypes might be beneficial, since protein clustering can help regulate relevant metabolic pathways and provide protection from protein misfolding and/or degradation.<br>by Kelly Paige Brock.<br>Ph. D.
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Miraldi, Emily R. (Emily Rae). "Bridging the gap between protein-tyrosine phosphorylation networks, metabolism and physiology in liver-specific PTP1b deletion mice." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/72824.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Computational and Systems Biology Program, 2012.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references.<br>Metabolic syndrome describes a complex set of obesity-related disorders that enhance diabetes, cardiovascular, and mortality risk. Studies of liver-specific protein-tyrosine phosphatase lb (PTPlb) deletion mice (L-PTPlb-/-) suggests that hepatic PTPlb inhibition would mitigate metabolic syndrome progression through amelioration of hepatic insulin resistance, endoplasmic reticulum stress, and whole-body lipid metabolism. However, the network alterations underlying these phenotypes are poorly understood. Mass spectrometry was used to quantitatively discover protein phosphotyrosine network changes in L-PTP lb-/- mice relative to control mice under both normal and high-fat diet conditions. A phosphosite set enrichment analysis was developed to identify numerous pathways exhibiting PTPlb- and diet-dependent phosphotyrosine regulation. Detection of PTP lb-dependent phosphotyrosine sites on lipid metabolic proteins initiated global lipidomics characterization of corresponding liver samples and revealed altered fatty acid and triglyceride metabolism in L-PTPlb-/- mice. Multivariate modeling techniques were developed to infer molecular dependencies between phosphosites and lipid metabolic changes, resulting in quantitatively predictive phenotypic models.<br>by Emily R. Miraldi.<br>Ph.D.
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Wolf, Maxim Ph D. (Maxim Y. )Massachusetts Institute of Technology. "Evolutionary and structural signatures of protein-coding function : synonymous acceleration, read-through, and structural impact of mutations." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/127716.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2019<br>Cataloged from the PDF of thesis.<br>Includes bibliographical references (pages 87-90).<br>In this thesis I observe evolutionary signatures in coding regions to: (1) understand the sources of highly mutable coding regions in mammals; (2) to elucidate a new candidate function for a stop codon readthrough candidate gene, BRI3BP; and (3) to show how rapid sequence-based structure approximations can help predict the structural impact of amino-acid changes. (1) First, I searched for deviations from the evolutionary signatures of coding regions to recognize synonymous acceleration elements (SAEs) in protein coding genes. I showed that these are driven by an increased mutation rate, which persists in the human lineage, in otherwise evolutionarily-constrained protein-coding regions, providing an important resource to better characterize protein-coding constraint in mammals and within humans. (2) Second, I combined evolutionary signatures at the protein-coding and protein-folding level to characterize the functional implication of stop-codon readthrough in BRI3BP. I showed that this readthrough region has conserved spaced hydrophobic residues that pattern match to the -terminal helix forming a coiled-coil-like domain. This change alters BRI3BP function from pro-growth to pro-apoptotic, similarly to VEGF-A. This suggests that readthrough-triggered apoptosis may represent a general mechanism for limiting growth of cells with aberrant ribosomal termination. (3) Third, I used rapid protein-structure approximation of burial of residues based on protein sequence to predict the structural impact of amino acid alterations. I show that the prediction can be improved over using exclusively the hydrophobicity change of the residue. Overall my work demonstrates how evolutionary and structural signatures can be used to predict highly mutational gene regions, readthrough function and structural impact of mutation.<br>by Maxim Wolf.<br>Ph. D.<br>Ph.D. Massachusetts Institute of Technology, Computational and Systems Biology Program
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Scott, Mark Andrew Ph D. Massachusetts Institute of Technology. "Ultra-rapid 2-D and 3-D laser microprinting of proteins." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/79248.
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Thesis (Ph. D. in Electrical and Medical Engineering)--Harvard-MIT Program in Health Sciences and Technology, 2013.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (p. 124-135).<br>When viewed under the microscope, biological tissues reveal an exquisite microarchitecture. These complex patterns arise during development, as cells interact with a multitude of chemical and mechanical cues in the surrounding extracellular matrix. Tissue engineers have sought for decades to repair or replace damaged tissue, often relying on porous scaffolds as an artificial extracellular matrix to support cell development. However, these grafts are unable to recapitulate the complexity of the in vivo environment, limiting our ability to regenerate functional tissue. Biomedical engineers have developed several methods for printing two- and three-dimensional patterns of proteins for studying and directing cell development. Of these methods, laser microprinting of proteins has shown the most promise for printing sub-cellular resolution gradients of cues, but the photochemistry remains too slow to enable large-scale applications for screening and therapeutics In this work, we demonstrate a novel high-speed photochemistry based on multi-photon photobleaching of fluorescein, and we build the fastest 2-D and 3-D laser microprinter for proteins to date. First, we show that multiphoton photobleaching of a deoxygenated solution of biotin-4-fluorescein onto a PEG monolayer with acrylate end-group can enable print speeds of almost 20 million pixels per second at 600 nanometer resolution. We discovered that the mechanism of fluorescein photobleaching evolves from a 2-photon to 3- and 4-photon regime at higher laser intensities, unlocking faster printing kinetics. Using this 2-D printing system, we develop a novel triangle-ratchet method for directing the polarization of single hippocampal neurons. This ability to determine which neurite becomes an axon, and which neuritis become dendrites is an essential step for developing defined in vitro neural networks. Next, we modify our multiphoton photobleaching system to print in three dimensions. For the first time, we demonstrate 3-D printing of full length proteins in collagen, fibrin and gelatin methacrylate scaffolds, as well as printing in agarose and agarose methacrylate scaffolds. We also present a novel method for 3-D printing collagen scaffolds at unprecedented speeds, up to 14 layers per second, generating complex shapes in seconds with sub-micron resolution. Finally, we demonstrate that 3-D printing of scaffold architecture and protein cues inside the scaffold can be combined, for the first time enabling structures with complex sub-micron architectures and chemical cues for directing development. We believe that the ultra-rapid printing technology presented in this thesis will be a key enabler in the development of complex, artificially engineered tissues and organs.<br>by Mark Andrew Scott.<br>Ph.D.in Electrical and Medical Engineering
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Kirkpatrick, Jesse D. "Protease activity sensors for monivasive diagnosis and monitoring of pulmonary diseases." Thesis, Massachusetts Institute of Technology, 2020. https://hdl.handle.net/1721.1/130206.
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Thesis: Ph. D. in Medical Engineering and Medical Physics, Harvard-MIT Program in Health Sciences and Technology, May, 2020<br>Cataloged from student-submitted PDF version of thesis.<br>Includes bibliographical references (pages 128-139).<br>Effective disease management requires high quality and accurate information about disease state. As science and technology have evolved, the history and physical exam, once the foundations of the diagnostic workflow, have been supplemented with modalities that allow physicians to peer inside the body and acquire otherwise inaccessible information. To gain maximal information about a disease, a promising approach would be to administer a probe that can detect disease activity inside the body and emit a signal to the outside world. To this end, our group has developed "activity-based nanosensors", which detect dysregulated protease activity at the site of disease and release a reporter that can be measured in the urine. Because proteases are implicated in multiple diseases, including cancer, activity-based nanosensors have the potential to enable quantitative, noninvasive, and real-time monitoring of disease activity.<br>Respiratory diseases are leading causes of death and disability, owing in large part to the constant exposure of the lungs to the external environment. Though this accessibility makes the lungs vulnerable to carcinogens and pathogens, it also provides a unique diagnostic opportunity. In this thesis, we aimed to optimize activity-based nanosensors for lung disease sensing in two settings: early detection and treatment response monitoring. Finally, we sought to establish a generalizable pipeline to rationally design such tools for human disease. We first delivered a multiplexed panel of sensors via intrapulmonary administration in two genetically engineered mouse models of lung adenocarcinoma. We found that our sensor panel diagnosed lung cancer in both models, detecting tumors as small as 2.8 mm³ without false positives from benign lung inflammation. We then evaluated this approach in monitoring treatment response in mouse models of malignant and benign pulmonary disease.<br>We observed dramatic treatment-induced shifts in pulmonary protease activity in both models, enabling rapid, noninvasive, and quantitative evaluation of drug response. Finally, we established a suite of ex vivo assays that enabled the bottom-up design of a protease-activated diagnostic probe, opening the door for translation to human disease. Collectively, this thesis provides a framework for the clinical development of activity-based nanosensors for pulmonary disease diagnosis and monitoring.<br>by Jesse D. Kirkpatrick.<br>Ph. D. in Medical Engineering and Medical Physics<br>Ph.D.inMedicalEngineeringandMedicalPhysics Harvard-MIT Program in Health Sciences and Technology
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Myers, Natasha. "Modeling proteins, making scientists : an ethnography of pedagogy and visual cultures in contemporary structural biology." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/40976.
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Thesis (Ph. D. in History, Anthropology, and Science, Technology and Society (HASTS))--Massachusetts Institute of Technology, Program in Science, Technology and Society, 2007.<br>Includes bibliographical references (p. 260-277).<br>This ethnography tracks visualization and pedagogy in the burgeoning field of structural biology. Structural biologists are a multidisciplinary group of researchers who produce models and animations of protein molecules using three-dimensional interactive computer graphics. As they ramp up the pace of structure determination, modeling a vast array of proteins, these researchers are shifting life science research agendas from decoding genetic sequence data to interpreting the multidimensional forms of molecular life. One major hurdle they face is training a new generation of scientists to work with multi-dimensional data forms. In this study I document the formation and propagation of tacit knowledge in structural biology laboratories, in classrooms, and at conferences. This research shows that structural biologists-in-training must cultivate a feel for proteins in order to visualize and interpret their activity in cells. I find that protein modeling relies heavily on a set of practices I call the body-work of modeling. These tacit skills include: a) forms of kinesthetic knowledge that structural biologists gain through building and manipulating molecular models, and by using their own bodies as mimetic models to help them figure out how proteins move and interact; and b) narrative strategies that assume a teleological relationship between form and function, and which figure proteins through analogies with familiar human-scale phenomena, such as the pervasive description of proteins as "machines." What I find is that these researchers are not only transforming the objects of life science research: they are training a new generation of life scientists in forms of knowing attuned to the chemical affinities, physical forces and movements of protein molecules, and keyed to the tangible logic and rhetoric of "molecular machines."<br>(cont.) This research builds on concerns in the feminist science studies literature on modes of embodiment in scientific practice, and contributes to studies of performance in science by examining visual cultures as performance cultures. In addition, I incorporate historical studies of the life sciences to map the making of the protein-this intricately crafted entity whose forms and functions, I argue, are recalibrating scientific expertise, reanimating biological imaginations, and reconfiguring the very contours and temporalities of "life itself."<br>by Natasha Myers.<br>Ph.D.in History, Anthropology, and Science, Technology and Society (HASTS
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Wille, Kirk C. "Examination of the benefits and measures of the Mentor-Protege Program : a case study /." Thesis, Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 1994. http://handle.dtic.mil/100.2/ADA293461.
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Silva, Danielle Izilda Rodrigues da. "Caracterização do proteoma nuclear de folhas de cana-de-açúcar (Saccharum spp) de 1 e 4 meses de idade." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/11/11137/tde-29112012-144814/.
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A cana-de-açúcar é uma cultura economicamente importante, cultivada especialmente pelo seu colmo, que constitui a matéria-prima para produtos como o açúcar e o bioetanol. Ademais, a compreensão do proteoma nuclear é essencial para decifrar os mecanismos que governam a regulação gênica. No presente estudo, é demonstrado o isolamento e a identificação através de 1D SDS-PAGE de proteínas nucleares originadas de folhas jovens de plantas de cana-de-açúcar. Os núcleos foram isolados de folhas F+1 frescas de cana-de-açúcar de 1 e 4 meses, usando o protocolo modificado de Folta e Kaufman (2000). O experimento consistiu em um delineamento inteiramente casualizado, com três repetições de 18 plantas cada. Após a purificação usando o gradiente de percoll, a integridade do núcleo foi avaliada por meio da coloração com orceína acetolática 1% e com DAPI. Os resultados obtidos revelam os núcleos como esferas uniformes com o diâmetro médio de 5 ?m. As proteínas nucleares foram isoladas usando o reagente TRI Reagent (Sigma) e quantificadas por meio do método de Bradford. As análises de Western blot foram usadas para demonstrar o enriquecimento de proteínas nucleares. As membranas foram incubadas com a RUBISCO, PEPCase, OEE1, Histona e PCNA. A presença da PCNA e da Histona foram detectadas apenas no extrato de proteínas nucleares, já a RUBISCO, a PEPCase e a OEE1 foram detectadas de forma abundante no extrato de proteínas total e reduzida na fração nuclear. Para a caracterização do proteoma nuclear, 60 ?g de proteínas foram separadas por SDS-PAGE e cada canaleta dividida em 20 bandas. As proteínas de cada banda foram digeridas e purificadas. A identificação foi realizada por meio de espectrometria de massas (Synapt G2 HDMS) e analisadas usando o ProteinLynx e o banco de dados SUCEST. Programas como BaCelLo, WoLF PSORT, Plant-mPloc, SherLoc e PSORT foram usados para a predição da localização subcelular das proteínas identificadas. A classe de proteínas identificadas mais abundante se relaciona à montagem de nucleossomos, e é representada principalmente pelas histonas, como H2A.2, H2A.8, H3.3, H2B.1, H2B.2, dentre outras. Ademais, ainda foram encontradas classes menos abundantes relacionadas ao metabolismo do DNA, do RNA, regulação da transcrição, dentre outras. Alguns fatores de transcrição e outras proteínas nucleares típicas também foram identificadas, porém, possivelmente em decorrência de sua baixa abundância, não foram observados em todas as repetições. Os resultados encontrados mostram a aplicabilidade da metodologia para criar um perfil preciso do proteoma nuclear de cana-de-açúcar.<br>Sugarcane is a cash crop, cultivated for its stalks which accumulate sucrose, the raw material for products like sugar and bioethanol. Nuclear proteome comprehension is essential for deciphering the mechanisms that governs genome regulation and function. In the present study, we report the isolation and identification by 1D SDS-PAGE of nuclear proteins from young sugarcane leaves. The nuclei were isolated from fresh tissue of one and four-month-old sugarcane F+1 leaves, using the modified protocol of Folta and Kaufman (2000). The experiment consisted on a completely randomized design, three biological repetitions each with 18 plants. After purification using a percoll gradient, nucleus integrity was evaluated by staining with 1% acetolactic orcein and with DAPI. The results obtained reveal nuclei as uniform spheres with an average diameter of 5 ?m. The nuclear proteins were isolated using TRI Reagent (Sigma) and quantified by Bradford. Western blot analysis were used to prove enrichment for nuclear proteins. Membranes were incubated with RUBISCO, PEPCase, OEE1, Histone and PCNA. The presence of PCNA and Histone were detected only in the nuclear fraction. RUBISCO, PEPCase and OEE1 were very abundant in the total protein fraction and reduced in the nuclear fraction. For the characterization of nuclear proteome, 60 ?g of proteins were separated by SDSPAGE and each lane divided into 20 sections, the proteins from each section were digested and purified. Protein identification was carried out by mass spectrometry (Synapt G2 HDMS) and analyzed using ProteinLynx and SUCEST database. Softwares, such as BaCelLo, WoLF PSORT, Plant-mPloc, SherLoc and PSORT were also used to predict the subcelular localization of the identified proteins. The most abundant protein class is related to the nucleosome assembly. It is represented specially by histones like H2A.2, H2A.8, H3.3, H2B.1, H2B.2, among others. Besides, less abundant classes like the ones related to DNA and RNA metabolism, regulation of transcription and others were also found. Some transcription factors and other typical nuclear proteins were identified as well, but, possibly due to their low abundance, they were not observed in all three repetitions. These results show the applicability of this method to create an accurate sugarcane nuclear proteome profile.
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Kotadia, Nayna. "A Study on the Protein Interaction with Different Platinum Compounds." TopSCHOLAR®, 2008. http://digitalcommons.wku.edu/theses/8.
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Since the discovery of anti-tumor activity of cisplatin in 1960, significant progress has been made in treating metastatic or advanced cancer with cisplatin and platinum compounds. Platinum compounds covalently bind to DNA and disrupt DNA function. They are also known to bind with amino acids like methionine, histidine and cysteine to form cisplatin-protein adducts which are responsible for most of its cytotoxicity and side effects. Recent articles on cisplatin-protein have shown that adding bulky adjuncts to cisplatin or using different platinum compounds varies the degree and extent of reaction thus possibly reducing cisplatin resistance and side effects.
One of the proteins to study is cytochrome C, which is an intermediate in apoptosis (a controlled form of cell death used to kill cells in the process of development or in response to infection or DNA damage). Cytochrome C activates caspase 9, a cysteine protease, which in turn goes on to activate caspases 3 and 7, which are responsible for destroying the cell from within.
In this study, we tried to examine how various platinum compounds like cis-Pt(NH3)2Cl2, cis-Pt(NH3)2(NO3)2, Pt(en)(NO3)2, Pt(Me4en)(NO3)2, Pt(NH3)2 (oxalate), Pt(en)(oxalate),Pt(Me4en)(oxalate), which have different ligands/bulk, react with cytochrome C in different physiological conditions.
This research project subsequently focused on three main aspects: 1) to determine whether the concentration of platinum compounds made a difference in the reaction rate, 2) to determine whether the pH of the buffer shows any difference in the reaction rate, 3) to determine how the ligands coordinated to the platinum affected the rate. We used 1) HPLC with vitamin B12 (cyanocobalamin) as an internal standard. 2) Separate samples of platinum compounds with bovine serum albumin were then subjected to dialysis and were then sent to the Materials Characterization Center for analysis by ICP-AES spectroscopy.
In summary, the following conclusions are stated: •The leaving group, pH, bulk and the concentration play a very vital role in determining the reaction rate for platinum-cytochrome C interactions. •Chlorides form excellent leaving groups followed by oxalates then nitrates. •Pt(en) reacts faster than Pt(NH3)2 which reacts faster than Pt(Me4en). •Nitrates, Pt(en) and few oxalate form multiple products showing non-specific binding. Only cis-Pt(NH3)2Cl2 and Pt(Me4en)(oxalate) formed predominately a single product showing target specific binding. •cis-Pt(NH3)2Cl2 showed an increased reaction rate at lower pH while cis-Pt(NH3)2(NO3)2 and Pt(Me4en)(NO3)2 showed higher reactions at higher pH. •Despite platinum compound was present in significant molar excess relative to cytochrome C, at the end of 21 hrs there was a significant amount of unreacted cytochrome C left except in case of cis-Pt(en)Cl2 which reacted with the whole cytochrome C in less than ten minutes. •We saw the rate of reaction in order of cis-Pt(en)Cl2 > Pt(en)(oxalate) > cis-Pt(NH3)2Cl2 > Pt(en)(NO3)2 > cis-Pt(NH3)2(NO3)2 > cis-Pt(NH3)2(oxalate) > Pt(Me4en)(oxalate) > Pt(Me4en)(NO3)2
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Silcox, Christina Elise. "Feasibility of a predictive model of Hsp70b-activated gene therapy protein expression during ultrasound hyperthermia." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/90174.
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Thesis: Ph. D. in Medical Engineering and Medical Physics, Harvard-MIT Program in Health Sciences and Technology, 2014.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (pages 101-113).<br>Gene therapy has been heralded as a possible approach to a variety of diseases and conditions, ranging from cancer and heart disease to blindness and neurodegenerative diseases. However, progress in gene therapy requires a delivery system that can control when and where the therapeutic proteins will be generated. Our study was performed to determine the feasibility of attaching heat-inducible promoters to genes of interest in order to control activation of the gene in vivo via ultrasound-induced hyperthermia monitored by MRI thermometry. We first demonstrated that gene therapy-mediated gene expression could be spatially and temporally controlled with this method. Further studies were subsequently performed to determine if the activation of a particular heat-inducible gene, Hsp70b, could be quantified and predicted a priori during hyperthermia, thus allowing advance knowledge of the protein levels over time. Experiments indicated that as the temperature and duration of a hyperthermic shock increased, peak expression levels of Hsp70b mRNA also increased until a saturation level was reached. In addition, as the duration of a hyperthermic shock increased, the time during which Hsp70b mRNA remained elevated also increased. Most significantly, a correlation was found between total Hsp70b mRNA production generated by thermal shock and thermal dose, a predictor of dose often used in hyperthermia therapies. The relationship found between total Hsp70b mRNA production and thermal dose suggests that a real-time predictive model of therapeutic protein dose kinetics after ultrasound-induced hyperthermia for gene therapy is feasible. However, the creation of such a model would require further precision experimentation for which ultrasonically-induced hyperthermia is not suited. A final study was performed and found that Hsp70b was not activated by the mechanical stress caused by ultrasound. These results confirm that a predictive model applicable to ultrasonically-induced hyperthermia could be developed using waterbath techniques that will allow tighter control of temperature.<br>by Christina Elise Silcox.<br>Ph. D. in Medical Engineering and Medical Physics
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Spriggs, Ruth Verity. "Development of the ASSAM and ASPROTE programs for protein tertiary structure searching." Thesis, University of Sheffield, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269377.
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Lazoroska, Daniela. "The Suburb United Will Never Be Defeated : Youth Organization, Belonging, and Protest in a Million Program Suburb of Stockholm." Thesis, Stockholms universitet, Socialantropologiska institutionen, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-102660.
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This thesis examines the continually reconfiguring response of a youth organization towards a renovation project, Järvalyftet, run by the City of Stockholm in the Million Program suburbs. By analyzing this relationship, I aim to discuss how the youth organization works to mediate inclusion in political and representational spheres. More specifically, I will discuss the intersections between Järvalyftet’s development and the claims of belonging made by the youths upon the particular suburb, Husby, where they resided. My interest lies in understanding the conjuncture and disjuncture of claims that have been made to community, locality, and local knowledge in the interaction between the youth organization and the project Järvalyftet. I argue that the forms of community instigated by the youth organization, which were based on locality and “blackness”, allowed them to position themselves as key proponents of social and political change, as well as mobilize allies in others who identified with those experiences.
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Alnahi, Haitham G. "A machine induction approach to the protein folding problem." Thesis, Brunel University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326864.
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Vaudant, Jérôme. "Evaluation of drying technologies for storage and shipment of recombinant protein drug substance." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/44303.
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Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division; in conjunction with the Leaders for Manufacturing Program at MIT, 2008.<br>Includes bibliographical references (p. 79-80).<br>With growing markets and increasing pipelines, biotechnology companies face a supply chain challenge to manufacture and distribute products using economically feasible methods that protect protein integrity. Adequate storage and shipment of drug substance is an important operation and product quality issues are dependent upon success at this stage of the manufacturing process. While cryopreservation technologies are widely in use today, they may become prohibitively expensive in the future due to increasing product volumes and high operational costs.This thesis presents an evaluation of drying technologies as an alternative to cryopreservation for recombinant protein drug substance storage and shipment. After presenting an assessment of current cryopreservation technologies, the potential of drying technologies to protect protein integrity is examined through process optimization and product characterization at laboratory scale. The economic impact of such technologies and the implications of their implementation in the manufacturing environment are discussed. Recommendations on storage technologies for drug substance are proposed based on results of the analysis. Finally, the thesis builds on this particular study to research the specifics of process development in the biopharmaceutical industry and to discuss implications for future process innovation.<br>by Jérôme Vaudant.<br>S.M.<br>M.B.A.
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Pope, Welkin Hazel. "Genes and structural proteins of the phage SYN5 of the marine cyanobacteria, Synechococcus." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/39190.
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Thesis (Ph. D.)--Joint Program in Biological Oceanography (Massachusetts Institute of Technology, Dept. of Biology; and the Woods Hole Oceanographic Institution), 2005.<br>Includes bibliographical references (p. 157-171).<br>Bacteriophage have been proposed to be the most abundant organisms on the planet, at an estimated 10³¹ particles globally (Hendrix et al., 1999). The majority of bacteriophage isolates (96%) are double-stranded DNA tailed phages (Caudovirales). These phages possess a distinctive icosehedral head, with a protein tail structure protruding from a single vertex. This organelle determines host specificity and provides the mechanism of passage of the phage genome into the host cell. Phages infecting differing microbial hosts may have access to a global pool of genes, albeit at different levels. Marine cyanobacteria of the genera Prochlorococcus and Synechococcus are numerically dominant photosynthetic cells in the large oligotrophic gyres of the open oceans, and contribute an estimated 30% to the oceanic photosynthetic budget. Cyanophages have been isolated which propagate on many strains of Synechococcus and Prochlorococcus. Cyanophages can effect community structure and succession through lytic infection of their hosts, and have implications in lateral gene transfer, mediated through lysogeny, mixed infections, pseudolysogeny, and transduction.<br>(cont.) The broad host ranges (between genera) observed in some phages indicates that lateral gene transfer is not confined to cells of the same strain. These phage/host interactions begin by host recognition by the tail of the infecting phage. Few studies have examined the structural proteins of cyanophage, partially due to the lack of a robust protocol for the growth and purification of phage particles. Cyanophage Syn5 is a short-tailed phage isolated from the Sargasso Sea by Waterbury and Valois (1993) which infects Synechococcus strain WH8109. Methods of growing the host cells and the phage, and concentrating the phage by PEG precipitation were developed. These methods led to highly concentrated purified phage stocks, to titers of 1012 particles/ml. Preliminary characterization of the growth of Syn5 gave a burst size of approximately 30 phage/cell and a lytic period of approximately 10 hours when inoculated into exponentially growing host cells acclimated to a temperature of 26⁰C and a light intensity of 50[mu]E m⁻² s⁻¹. Isolation of the phage nucleic acid yielded dsDNA molecules of approximately 40kb. The Syn5 particles were comprised of twelve structural proteins, as determined by SDS-PAGE.<br>(cont.) The most intense band on the gel was assigned to the capsid protein of Syn5 ([approx.] 35kDa). However, it was not possible to distinguish putative tail proteins via this method. Purified Syn5 particles were sent to the Pittsburgh Bacteriophage Institute for genome sequencing. The completed Syn5 genome was 46,214 bp long with a 237bp terminal repeat. Annotation of the completed Syn5 genome identified 61 putative ORFs, and revealed that Syn5 appeared closely related to the enteric phage T7 and cyanophages P-SSP7 and P60, as determined by gene similarity and synteny, although the genome was [approx.] 10kb longer than T7. Syn5 appeared to possess a more extensive DNA replisome that T7, containing copies of genes that encoded proteins of known T7 host co-factors, such as thioredoxin, utilized by the T7 DNAP. Several large ORFs were identified between the gene encoding the putative tail fiber and the gene encoding the putative terminase. These ORFs encoded proteins similar to some fibrous sequences within the NCBI non- redundant (nr) gene sequence database as of March, 2005; but had unknown functions within the phage. Unlike other recently sequenced cyanophages, SynS did not contain any photosynthetic genes.<br>(cont.) The structural proteins of SynS, as visualized by SDS-PAGE, were characterized by mass-spectroscopy and N-terminal sequencing. This allowed the assignment of sequences to putative ORFs within the Syn5 genome. The Syn5 particle was comprised of eleven discreet protein chains of molecular weight 152kDa, 139kDa, 99kDa, 90kDa, 66kDa, 60kDa, 47kDa, 35kDa, 22kDa, 21kDa, and 16kDa. The identified proteins included the portal, capsid, two tail tube proteins, and three internal virion proteins. Each of the genes encoding these proteins were found in the same gene order in the Syn5 genome as the corresponding genes were ordered in the T7 genome. There were three unidentifiable proteins within the particle (66kDa, 47kDa, and 16kDa). These mapped to the area of the SynS genome between the gene encoding the putative tail fiber and the gene encoding the putative terminase. No minor capsid or decorative capsid proteins were detected. The copy numbers of the corresponding protein chains were similar to those known for T7, with the exception of the tail fiber, which was present at a number of three chains per particle in comparison to T7's eighteen per particle.<br>(cont.) Polyclonal antibodies were raised against Syn5 particles. A Western blot with these antibodies showed that the tail fiber and the two unknown fibrous sequences were highly antigenic. This evidence implies that the unknown structures may act as host recognition proteins in addition to the tail fiber. Characterization of these novel proteins may provide insight to the host recognition abilities of cyanophages. An additional study was also carried out, investigating the high temperature limit of the growth of phage P22. The results revealed that the production of infectious particles was limited by the temperature sensitivity of the folding and assembly of the P22 tailspike protein. This work has been published and is included in the Appendix.<br>by Welkin Hazel Pope.<br>Ph.D.
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Coward-Reid, Mattie Francine. "A case study of the Concerned Black Men of Richmond mentor program for African American males: program structure and practices, perceptions of strengths and weaknesses, mentor-protege relationships." Diss., Virginia Tech, 1994. http://hdl.handle.net/10919/40162.
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Stamm, Marcus [Verfasser], Volker [Gutachter] Dötsch, and Hartmut [Gutachter] Michel. "Comparison of membrane proteins using computational programs / Marcus Stamm ; Gutachter: Volker Dötsch, Hartmut Michel." Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg, 2017. http://d-nb.info/1133168434/34.
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Preuss, Fabian Price Jeffrey L. "An analysis of the role of doubletime's casein kinase activity in regulating the temporal program of period protein and the circadian behavior of drosophila melanogaster." Diss., UMK access, 2006.
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Thesis (Ph. D.)--School of Biological Sciences. University of Missouri--Kansas City, 2006.<br>"A dissertation in molecular biology and biochemistry and cell biology and biophysics." Advisor: Jeffrey L. Price. Typescript. Vita. Title from "catalog record" of the print edition Description based on contents viewed Jan. 29, 2007. Includes bibliographical references (leaves 125-132). Online version of the print edition.
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Voloshynovych, N. S. "Evaluation of specific pregnancy proteins for predicting early reproductive losses in women included in the assisted reproduct program." Thesis, БДМУ, 2021. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/18723.
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Kelm, Sebastian. "Structural modelling of transmembrane domains." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:b4c9fba9-ee25-469b-8baf-b7c1d70c9d05.
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Membrane proteins represent about one third of all known vertebrate proteins and over half of the current drug targets. Knowledge of their three-dimensional (3D) structure is worth millions of pounds to the pharmaceutical industry. Yet experimental structure elucidation of membrane proteins is a slow and expensive process. In the absence of experimental data, computational modelling tools can be used to close the gap between the numbers of known protein sequences and structures. However, currently available structure prediction tools were developed with globular soluble proteins in mind and perform poorly on membrane proteins. This thesis describes the development of a modelling approach able to predict accurately the structure of transmembrane domains of proteins. In this thesis we build a template-based modelling framework especially for membrane proteins, which uses membrane protein-specific information to inform the modelling process.Firstly, we develop a tool to accurately determine a given membrane protein structure's orientation within the membrane. We offer an analysis of the preferred substitution patterns within the membrane, as opposed to non-membrane environments, and how these differences influence the structures observed. This information is then used to build a set of tools that produce better sequence alignments of membrane proteins, compared to previously available methods, as well as more accurate predictions of their 3D structures. Each chapter describes one new piece of software or information and uses the tools and knowledge described in previous chapters to build up to a complete accurate model of a transmembrane domain.
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Schmidt, Manuela. "Characterization of synaptic protein complexes in Drosophila melanogaster." Doctoral thesis, [S.l.] : [s.n.], 2006. http://webdoc.sub.gwdg.de/diss/2006/schmidt.
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Drager, Christopher John. "Effect of DHA supplementation on muscle damage and inflammation during the first two weeks of a novice resistance training program." Thesis, Virginia Tech, 2013. http://hdl.handle.net/10919/19254.
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Aim: The purpose of this study was to investigate docosahexaenoic acid (DHA) ingestion on muscle damage and inflammation during the first two weeks of a novice resistance training (RT) program.
Methods: This study was a placebo-controlled, double-blind design. Forty-one healthy untrained males between the ages of 18 and 28 years consumed 2,000 mg/d of either DHA or corn oil (PCB) for 44 days including a 28 day loading period. Serum fatty acids were analyzed to determine treatment efficacy. During the 17 day training period, an acute eccentric exercise bout was implemented followed by a full-body RT regimen thrice weekly. Six fasted blood draws (days 1, 2, 4, 7, 12, and 17) during this exercise period were analyzed for creatine kinase (CK) and C-reactive protein (CRP). Maximum isometric strength (ISO) of the elbow flexors, delayed onset muscle soreness (DOMS), and range of motion (ROM) were measured on day 1 prior to exercise and also on days 2, 3, 4, 7, 12, and 17.
Results: The CK response and the area under the curve (AUC) analysis for DOMS trended to decrease in the DHA group in comparison to placebo (p=0.0925 and p=0.0536, respectively). Treatment showed no effect on CRP levels. DHA supplementation significantly increased serum DHA by 380% as a proportion of total fatty acids (p<0.0001). Conclusion: This study does not demonstrate convincing benefits of DHA ingestion to recovery from a new resistance exercise program but does suggest a need for further investigation.<br>Master of Science
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Lundberg, Alexander. "Studying the Oligomerization of the Kinase Domain of Ephrin type-B Receptor 2 Using Analytical Ultracentrifugation and Development of a Program for Analysis of Acquired Data." Thesis, Linköpings universitet, Kemi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-110376.
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Ephrin type-B receptor 2 (EphB2) is a receptor tyrosine kinase which phosphorylates proteins and thereby regulates cell migration, vascular development, axon guidance synaptic plasticity, and formation of borders between tissues. It has been seen overexpressed in several cancers, which make it an interesting protein to study. In this thesis EphB2 kinase domain (KD) and juxtamembrane segment with kinase domain (JMS-KD) have been expressed, purified and studied using analytical ultracentrifugation to evaluate the oligomerisation of the KD and how the double mutation S677/680A affects this. A program for data analysis have been written and used for analysis of the acquired data. The values of the dissociation constant were 2.94±1.04 mM for KD wild type and 3.46±2.26 mM for JMS-KD wild type have been calculated. Due to varied problems with the measurements no data was acquired on the double mutant, and not enough data was gained to draw any conclusions. Additional experiments will be needed to understand the oligomerisation of this intriguing protein.
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Hillman, Heather L. (Heather Lorraine) 1970. "Determinants of employer commitment to school-to-work programs : why do Boston's ProTech employers remain involved?" Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/67278.
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Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 1999.<br>Includes bibliographical references (p. 108-109).<br>Work-based School-to-Work programs are being asked to help solve faltering labor market prospects for youth, national educational reform needs and decreasing U.S. economic competitiveness. In 1994, the Congress enacted the School-to-Work Opportunities Act to appropriate more than $2 billion over seven years to lay the grounds for a national School-to-Work framework. While many studies have concerned themselves with the School-to-Work outcomes for youth, fewer have addressed sustainable incentives for employers to remain involved. Such incentives are critical if work-based School-to-Work is to survive at a large scale. This case study highlights which factors have kept the healthcare and financial services employers involved in Boston's ProTech program, and the prospects for expanding a program like ProTech to reach more students. Primary reasons for involvement include: (1) an altruistic commitment to benefit the community and (2) long-term labor force development (including regional labor pool expansion, hiring networks and industry advertisement). Trainee recruitment to the employers' permanent staff is not playing a large role. Important factors in maintaining employer commitment are the high personal rewards to those who work with the youth and the responsiveness of the coordinating entity, the Boston Private Industry Council, to employers' needs. Unfortunately, however, ProTech could not be offered in its current form to all students. Primary constraints to expansion include: (1) the need for supervisors to be interested in and capable of working with youth, (2) employers' need to select students, and (3) employer budgetary limitations. The results of this study highlight the improbability that the ProTech program in its current form could be offered to students on a large scale. However, a simpler, modified version of the program may be able to effectively reach large numbers of students.<br>by Heather L. Hillman.<br>M.C.P.
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Pinney, Benjamin W. "Projects, management, and protean times : engineering enterprise in the United States, 1870-1960." Thesis, Massachusetts Institute of Technology, 2001. http://hdl.handle.net/1721.1/8801.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Program in Science, Technology and Society, 2001.<br>Includes bibliographical references (295-338).<br>In this dissertation, I trace methods for organizing skilled workers engaged in creative, limited-term projects in the United States between the nineteenth century and the 1950s. Examining eras of system building in technical fields-civil engineering in the nineteenth century, laboratory administration in the 1910s and 1920s, aircraft design in the 1930s, and electronics in the 1950s-I show that recent discourse on the management of innovation and change is a manifestation of a cyclically recurring conversation. This story complicates prevalent views of management theory and practice before World War II by recovering a thread obscured by emphasis on the organization of integrated, divisional companies and operative labor within them. Applying ideas from recent work in organization studies to distill common aspects of the management problems and labor processes individuals have confronted and theorized, I find common patterns: managers of construction firms, engineering departments, and research laboratories have again and again theorized the fast-moving, knowledge-intensive, relational organization, doing so long before these terms were available. Such thinking has been driven both by practical needs and because external pressures have forced explanation of seemingly uncontrolled, irrational work. Practically, the transferability of management techniques among settings such as construction and research has reflected kinships between labor and communication processes: each has involved skilled workers producing complex artifacts in uncertain physical, technical, and social environments.<br>(cont.) The need to explain such work, though, has been as much about external representation as internal control. From origins in government oversight of appropriations and military use of esprit de corps to cohere organizations under stress, tools used to manage project-based enterprises have been applied in response to the speed, scale, and complexity of the work itself. At the same time, engineers have explained the management of their work to deflect pressures to apply the logics of factory production and Taylorist scientific management to the organization of skilled labor. As explanations of the differences between building and operating and as delineations of points and terms of physical and cultural contact, representations of engineering work in schedules, budgets, organization charts, and narratives have both controlled and insulated work.<br>by Benjamin W. Pinney.<br>Ph.D.
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Rodriguez, Pedro Xavier Royero. "Regulation of synaptic and plasticity-related proteins by ryanodine receptors during epileptogenesis." reponame:Repositório Institucional da UFABC, 2016.
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Orientador: Prof. Dr. Alexandre Hiroaki Kihara<br>Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Neurociência e Cognição, 2016.<br>Status epilepticus (SE) is a clinical emergency that can lead to the development
of temporal lobe epilepsy (TLE). The term epileptogenesis refers to the transformation
of physiological neuronal networks into a dysfunctional state. In most patients
presenting TLE, the development and maintenance of spontaneous seizures are linked
with calcium (Ca+2)-dependent processes like neuronal loss, reactive gliosis and
pathological neuronal plasticity. It has been shown that SE produces an increase in
ryanodine receptor-dependent intracellular Ca+2 levels in hippocampal neurons, which
remain elevated during the progression of the disease. In this context, the aim of this
work was to investigate the effects of ryanodine receptors (RyRs) inhibition on the
expression of important synaptic and plasticity-related proteins during the latent period
of the pilocarpine model of TLE. First, we performed western blot and immunolabeling
analyses in order to evaluate the pattern of distribution of the activity-regulated
cytoskeleton-associated protein (ARC) in the rat hippocampus during the latent period.
We observed decrease of the total protein levels 48 hours after SE, together with downregulation of its nuclear immunolabeling in granular cells of the dentate gyrus (DG). In
addition, we observed the appearance of intense ARC immunoreactive neurons
(IAINs) colocalizing mainly with excitatory neurons in CA1, CA3 and hilus.
Intrahippocampal injections of the RyRs blocker dantrolene increased the total protein
levels of the presynaptic protein synapsin I (SYN I) 48 hours after SE. We also
observed up-regulation of SYN I and synaptophysin (SYP) in hippocampal regions
known to receive important synaptic inputs. Finally, dantrolene showed
neuroprotective effects by decreasing neuronal loss in CA1 and CA3 of experimental
hippocampi. Our results suggest that ARC might be participating in the overall
hippocampal reorganization and increase of excitability observed during
epileptogenesis. In addition, RyRs may contribute to trigger the hippocampal
neurodegeneration and synaptic alterations that lead to the development of acquired
epilepsy.
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Cobble, Martha M. "A descriptive study of relationships between assigned mentors and proteges in a preservice program for the preparation of school principals." Diss., Virginia Tech, 1993. http://hdl.handle.net/10919/39519.
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Cobble, Martha M. "A descriptive study of relationships between assigned mentors and proteges in a preservice program for the preparation of school principals /." This resource online, 1994. http://scholar.lib.vt.edu/theses/available/etd-10022007-145222/.
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