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Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Enzymes are proteins which have the ability to catalyze chemical reactions and which do so with a high degree of specificity. Since trypsin has a sharp specificity for two positively charged substrates, arginine and lysine, an attempt was made to assess the role of the positive charge in determining this specificity. Both Pressman and Wilson did similar studies (Pressman on hapten-antibody reactions and Wilson on acetylcholinesterase reactions) in which they compared the hydrolysis of a substrate possessing a charged quaternary ammonium group with that of the same substrate in which the charged group had been replaced by a tertiary butyl group. In both cases, Ko/K+ was approximately eight where Ko is the dissociation constant for the uncharged substrate and K+ is the dissociation constant for the charged species. The free energy change associated with this change in K is about 1.5 kilocalories per mole and was attributed by both authors to the electrostatic contribution to the binding energy. Attempts to relate these changes in free energy to physical force expressions are discussed. Webb attempted to calculate group separation distances from the free energy changes using the expression for the potential energy of two separated charges corrected for ion atmosphere interactions. He tentatively concluded that for both hapten-antibody and cholinesterase-substrate interactions the groups involved are in direct contact without an intervening water molecule. [TRUNCATED] / 2031-01-01

Thesis (M.D.) -- University of Pennsylvania, 1806. / Film 633 reel 62 is part of Research Publications Early American Medical Imprints collection (RP reel 62, no. 1167). DNLM Includes bibliographical references.

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Humans are constantly faced with learning motor tasks throughout their lifespan (e.g., children learning how to throw a ball overhand, elite athletes learning how to become more even more efficient at their sports performance, and an older adult relearning how to walk post-stroke recovery). With such variety in the types of motor tasks that humans try to learn across the lifespan, little is known about the impact of a learner’s previous motor skill experience. Thus, the purpose of this thesis was to investigate when motor learning generalizability or specificity are more likely to occur, respectively. An in-depth background of motor learning generalizability and specificity was provided in chapter one. The scope of the motor learning literature including generalizability and/or specificity was investigated in chapter two. At the end of chapter two, certain limitations of the motor learning literature are addressed and framed into a useable checklist for future motor learning experiments. Chapter three serves as a bridging chapter to connect the scoping review and checklist in chapter two, to the framework implemented in chapter four. In chapter four, the checklist was employed to assess its usefulness in future motor learning experiments. Collectively, this thesis provides organization to the previous motor learning generalizability and specificity literature, as well as recommendations for future motor learning researchers based on a tested framework protocol. / Dissertation / Doctor of Philosophy (PhD) / Our previous movement experiences can impact our capability to learn new motor tasks. These previous movement experiences can be either beneficial or detrimental (or have no effect) on our learning of that task depending on many different things with no real definitive answers to why the outcomes differ and when. The purpose of this thesis is to review how prior motor skill practice may be beneficial to future motor skill learning (generalizability), detrimental to learning, or no effect (specificity) and to organize these findings into a new ‘types of transfer’ taxonomy, create a framework to help guide future motor learning research and conduct an experiment that follows this framework. By considering and organizing this large motor learning literature into a review, creating this taxonomy and outlining an empirical investigative framework, this thesis will help us to better understand motor learning history and provide a pathway forward for future researchers.

Protein-protein interactions are an integral part of virtually all aspects of cellular function. Many of these interactions are mediated by small modular units called protein interaction domains (PIDs). We do not yet understand, however, how much functional information is encoded in these modules. It has previously been shown that Nbp2SH3 and Bem1SH3b domains in S. cerevisiae bind several target peptides with the same consensus sequence, yet display finely tuned affinities for each. In this study, I have shown that there exists an evolutionarily conserved ability of orthologous fungal Nbp2SH3, Bem1SH3b, and Abp1SH3 domains to discriminate between target peptides within the same species. In addition, I have developed a method to quantitatively probe SH3 domain specificity using purified SH3 domains and naturally occurring proline-rich constructs (PRRs) in the context of cell lysate from S. cerevisiae. Expansion of this work may yield valuable insights into intrinsic SH3 domain specificity.

Reaction rates and selectivities were measured for transacylation of fatty acid esters in solvents catalysed by Candida antarctica lipase B and by cutinase from Humicola insolens. With these enzymes classical water-based enzymology can be expanded to many different solvents allowing large variations in interaction energies between the enzymes, the substrates and the surrounding. Further ,hydrolysis reactions catalysed by Bacillus subtilis esterase 2 were investigated. Thermodynamics analyses revealed that the enzyme contribution to reaction rate acceleration compared to acid catalysis was purely entropic. On the other hand, studies of differences in activation entropy and enthalpy between enantiomers and between homologous esters showed that high substrate specificity was favoured by enthalpic stabilisation. Solvent was found to have a profound effect on enzyme catalysis, affecting both reaction rate and selectivity. Differences in substrate solubility will impact enzyme specificity since substrate binding is an equilibrium between enzyme-bound substrate and substrate in free solution. In addition, solven tmolecules were found to act as enzyme inhibitors, showing both competitive and non-competitive behaviour. In several homologous data series enthalpy-entropy compensation relationships were encountered. A possible extrathermodynamic relationship between enthalpy and entropy can easily be lost under co-varying errors propagated from the experiments. From the data in this thesis, one instance was found of a real enthalpy-entropy compensation that could be distinguished from statistical errors, while other examples could not be verified. / QC 20100722

Developer discussions range from in-person hallway chats to comment chains on bug reports. Being able to identify discussions that touch on software design would be helpful in documentation and refactoring software. Design mining is the application of machine learning techniques to correctly label a given discussion artifact, such as a pull request, as pertaining (or not) to design. In this work we demonstrate a simple example of how design mining works. We first replicate an existing state-of-the-art design mining study to show how conclusion stability is poor on different artifact types and different projects. Then we introduce two techniques—augmentation and context specificity—that greatly improve the conclusion stability and cross-project relevance of design mining. Our new approach achieves AUC-ROC of 0.88 on within dataset classification and 0.84 on the cross-dataset classification task. / Graduate

Protein arginine methylation is an important modification of proteins, involved in many cellular processes. Some examples are transcription, RNA editing, cellular communication, DNA repair, viral replication and chromatin remodeling. In recent years, the significance of protein arginine methyltransferases (PRMTs) in human diseases has been increasingly studied, especially in cardiovascular disease and cancer. Although the importance of these enzymes is recognized, the understanding of how exactly PRMTs function is still limited. Very little information is available to explain how or why any of the different PRMTs interact with other proteins or, what determines where in that protein to place their methyl marks. Adding to this complexity, placing one of the three different methylation marks (products) or the other (mono methyl arginine MMA, asymmetric dimethyl ADMA, or symmetric dimethyl SDMA) on a protein can cause a cell to respond differently. Therefore, if we really want to understand how this family of proteins functions and how to control them, it’s essential that we understand how they achieve their product specificity; this means, how they decide which methyl mark to place on an interacting protein. In order to better understand the product specificity of this family of enzymes, I have been using as a model two Protein arginine methyltransferases that are responsible different methylation marks: PRMT1, which can make both ADMA and MMA and TbPRMT7, which can only make MMA. Using the information that crystal structure of these enzymes provide and what we already know about how PRMT activity is regulated, my aim is to better understand the mechanisms by which these enzymes achieve their product specificity.

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