This thesis summarizes the application of conventional and modern electron paramagnetic resonance (EPR) techniques to establish proximity relationships between paramagnetic metal centers in metalloproteins and between metal centers and magnetic ligand nuclei in two important and timely membrane proteins: succinate:ubiquinone oxidoreductase (SQR) from Paracoccus denitrificans and particulate methane\r\nmonooxygenase (pMMO) from Methylococcus capsulatus. Such proximity relationships are thought to be critical to the biological function and the associated biochemistry mediated by the metal centers in these proteins. A mechanistic understanding of biological function relies heavily on structure-function relationships and the knowledge of how molecular structure and electronic properties of the metal centers influence the reactivity in metalloenzymes. EPR spectroscopy has proven to be one of the most powerful techniques towards obtaining information about interactions between metal centers as well as defining ligand structures. SQR is an electron transport enzyme wherein the substrates, organic and metallic cofactors are held relatively far apart. Here, the proximity relationships of the metallic cofactors were studied through their weak spin-spin interactions by means of EPR power saturation and electron spin-lattice (T_1)\r\nmeasurements, when the enzyme was poised at designated reduction levels. Analysis of the electron T_1 measurements for the S-3 center when the b-heme is paramagnetic led to\r\na detailed analysis of the dipolar interactions and distance determination between two interacting metal centers. Studies of ligand environment of the metal centers by electron spin echo envelope modulation (ESEEM) spectroscopy resulted in the identication of peptide nitrogens as coupled nuclei in the environment of the S-1 and S-3 centers.
\r\n\r\nFinally, an EPR model was developed to describe the ferromagnetically coupled trinuclear copper clusters in pMMO when the enzyme is oxidized. The Cu(II) ions in these clusters appear to be strongly exchange coupled, and the EPR is consistent with equilateral triangular arrangements of type 2 copper ions. These results offer the first glimpse of the magneto-structural correlations for a trinuclear copper cluster of this type, which, until the work on pMMO, has had no precedent in the metalloprotein literature. Such trinuclear copper clusters are even rare in synthetic models.
\r\n", "doi": "10.7907/ze04-mx93", "publication_date": "2001", "thesis_type": "phd", "thesis_year": "2001" }, { "id": "thesis:3255", "collection": "thesis", "collection_id": "3255", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-08282001-123851", "primary_object_url": { "basename": "JGK_Thesis_for_DBLsided_printing.pdf", "content": "final", "filesize": 3984594, "license": "other", "mime_type": "application/pdf", "url": "/3255/1/JGK_Thesis_for_DBLsided_printing.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Probing Quantum Confinement at the Atomic Scale with Optically Detected Nuclear Magnetic Resonance", "author": [ { "family_name": "Kempf", "given_name": "James G.", "clpid": "Kempf-James-G" } ], "thesis_advisor": [ { "family_name": "Weitekamp", "given_name": "Daniel P.", "orcid": "0000-0003-0079-8000", "clpid": "Weitekamp-D-P" } ], "thesis_committee": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Kuppermann", "given_name": "Aron", "clpid": "Kuppermann-A" }, { "family_name": "Weitekamp", "given_name": "Daniel P.", "orcid": "0000-0003-0079-8000", "clpid": "Weitekamp-D-P" }, { "family_name": "Anson", "given_name": "Fred C.", "clpid": "Anson-F-C" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Near-band-gap circularly polarized excitation in III-V semiconductors provides spin-polarized electrons that transfer spin order to lattice nuclei via fluctuations in the contact hyperfine interaction. This process of optical nuclear polarization and the complementary technique of optical detection of nuclear magnetic resonance (NMR) provide extreme sensitivity enhancement and spatial selectivity in structured samples, enabling collection of NMR spectra from samples such as single quantum wells or dots containing as few as ~10^5 nuclei.
\r\n\r\nCombining these advances with novel techniques for high spectral resolution, we have probed quantum-confined electronic states near the interface of a single epitaxially grown Al(1-x)Ga(x)As/GaAs (x = 0.36) heterojunction. Using a novel strategy that we refer to as POWER (perturbations observed with enhanced resolution) NMR, multiple-pulse time suspension is synchronized with bandgap optical irradiation to reveal spectra of effective spin Hamiltonians that are differences between those of the occupied and unoccupied photoexcited electronic state. The underlying NMR linewidth is reduced by three orders of magnitude in these experiments, enabling resolution of an asymmetric line shape due to light-induced hyperfine interactions. The results are successfully fit with the coherent nuclear spin evolution and relaxation theoretically expected for sites distributed over the volume of an electronic excitation weakly localized at a point defect. This analysis establishes a one-to-one relationship, which can be used to follow nuclear spin diffusion, between optical Knight shift and the radial position of lattice nuclei.
\r\n\r\nWe have also introduced POWER NMR techniques to characterize the change in electric field associated with cycling from light-on to light-off states via a linear quadrupole Stark effect (LQSE) of the nuclear spins. Simulations of these NMR spectra in terms of the radial electric fields of either donor-bound electrons or excitons indicate differences, where the bound-exciton model provides a significantly better fit to the data. The same spin physics enabled our measurement of the heterojunction interfacial field, which we find to be less than 1.3 kV/cm at the sites responsible for optical NMR. Other simulations show the promise of optical NMR as a tool in future studies aimed at atomic-level characterization of quantum-confined systems such as quantum dots and wells.
", "doi": "10.7907/0JZB-N948", "publication_date": "2001", "thesis_type": "phd", "thesis_year": "2001" }, { "id": "thesis:5386", "collection": "thesis", "collection_id": "5386", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11192009-084608026", "primary_object_url": { "basename": "Carlson_mj_2000.pdf", "content": "final", "filesize": 9021815, "license": "other", "mime_type": "application/pdf", "url": "/5386/1/Carlson_mj_2000.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "BUFF: A Biological Universal Forcefield Derived from Quantum Mechanics", "author": [ { "family_name": "Carlson", "given_name": "Matt Jeffrey", "clpid": "Carlson-Matt-Jeffrey" } ], "thesis_advisor": [ { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" } ], "thesis_committee": [ { "family_name": "Rees", "given_name": "Douglas C.", "orcid": "0000-0003-4073-1185", "clpid": "Rees-D-C" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Molecular mechanical simulations of biomolecules require an accurate potential energy function (forcefield) in order to produce meaningful results. Most current forcefields are highly parameterized in order to correctly reproduce high level theory and experiment. Increasingly, new biomolecules are designed and studied that have atypical configurations such as metal centers and nonstandard amino acids. To avoid a lengthy process to develop new parameters for each new system encountered, a generic forcefield is desired. A hierarchical approach is undertaken herein to achieve this flexibility and accuracy.\r\n\r\nBuilding upon the rule based generic forcefields UFF and Dreiding, a new biological universal forcefield, BUFF, is presented for the simulation of proteins and other biological molecules. In addition to its UFF and Dreiding based terms, the BUFF has additional hydrogen bond terms, specialized protein backbone torsions, and a process for deriving charges for amino acids that is independent of other parameterization. These additional parameters have been fit to ab initio quantum mechanical calculations carried out on model systems.\r\n\r\nValidation studies of peptide trimers demonstrate that the BUFF accurately reproduces the quantum mechanical torsional energies. Several other common, highly parameterized forcefields are also applied to the same tripeptide systems, as well as short \u03b1-helical chains and other model systems in order to make a comparison to the BUFF. These studies show that while the BUFF is universal and can be quickly deployed on new systems, such as unnatural amino acids or metal containing systems, it is also at least as accurate as other commonly employed, but highly parameterized, forcefields. The biological universal forcefield described herein is presented as complementary to the MSC forcefield derived for simulations of DNA and other nucleic acids.", "doi": "10.7907/5kyh-4402", "publication_date": "2000", "thesis_type": "phd", "thesis_year": "2000" }, { "id": "thesis:17577", "collection": "thesis", "collection_id": "17577", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07312025-172124033", "primary_object_url": { "basename": "Gordon_DB_2000.pdf", "content": "final", "filesize": 40103293, "license": "other", "mime_type": "application/pdf", "url": "/17577/1/Gordon_DB_2000.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Combinatorial Optimization in Computational Protein Design", "author": [ { "family_name": "Gordon", "given_name": "David Benjamin", "clpid": "Gordon-David-Benjamin" } ], "thesis_advisor": [ { "family_name": "Mayo", "given_name": "Stephen L.", "orcid": "0000-0002-9785-5018", "clpid": "Mayo-S-L" } ], "thesis_committee": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Mayo", "given_name": "Stephen L.", "orcid": "0000-0002-9785-5018", "clpid": "Mayo-S-L" }, { "family_name": "Rees", "given_name": "Douglas C.", "orcid": "0000-0003-4073-1185", "clpid": "Rees-D-C" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The central objective of computational protein design is to develop computational\r\ntechniques for selecting amino acid sequences that fold into proteins with desired\r\nstructures and functions. The work described here is directed toward addressing issues\r\nthat arise in the development of computational methods for the design of solvent-exposed\r\nportions of beta-sheets. However, it is also demonstrated that the results of these\r\ninvestigations extend beyond specific secondary structures and in fact provide a means to\r\naddress a broad spectrum of design problems. Computational issues arise from the fact\r\nthat when constructing a representation of protein sequence space for analysis, significant\r\nconcessions must be made with respect to the physical model and the search criteria in\r\norder to ensure that the calculation remains tractable. One of the limiting factors driving\r\nthese concessions is the sheer number of combinations of amino acid identities and\r\nconfigurations that must be evaluated. We have therefore pursued the development and\r\nrefinement of high-performance combinatorial search algorithms in order to better enable\r\nimprovement of computational methods. The consequent algorithmic work consists of\r\nenhancement strategies based on combining optimization methods and instilling within\r\nthem heuristics that manifest specialized knowledge of protein design problems. The\r\nresults are significant performance enhancements for the well-established Dead-End\r\nElimination algorithm, as well as two new algorithmic approaches, dubbed Branch and\r\nTerminate and Hybrid Rotamer Optimization.", "doi": "10.7907/fzxm-d394", "publication_date": "2000", "thesis_type": "phd", "thesis_year": "2000" }, { "id": "thesis:4974", "collection": "thesis", "collection_id": "4974", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-12122007-134645", "primary_object_url": { "basename": "Cheng_xc_1999.pdf", "content": "final", "filesize": 10238321, "license": "other", "mime_type": "application/pdf", "url": "/4974/1/Cheng_xc_1999.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Investigation of New Devices and Characterization Techniques in the III-V Semiconductor System", "author": [ { "family_name": "Cheng", "given_name": "Xiao-chang", "clpid": "Cheng-Xiao-chang" } ], "thesis_advisor": [ { "family_name": "McGill", "given_name": "Thomas C.", "clpid": "McGill-T-C" } ], "thesis_committee": [ { "family_name": "McGill", "given_name": "Thomas C.", "clpid": "McGill-T-C" }, { "family_name": "Atwater", "given_name": "Harry Albert", "orcid": "0000-0001-9435-0201", "clpid": "Atwater-H-A" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Hunter", "given_name": "A.", "clpid": "Hunter-A" }, { "family_name": "Vahala", "given_name": "Kerry J.", "orcid": "0000-0003-1783-1380", "clpid": "Vahala-K-J" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis concerns the investigation of novel devices and material characterization techniques in the III-V semiconductor system. In the first part of the thesis, we demonstrate that novel devices, such as avalanche photodiodes and tunnel switch diodes, can be fabricated from InAs/GaSb/A1Sb heterostructures by molecular beam epitaxy (MBE). In the second part of the thesis, ballistic electron emission microscopy (BEEM) is employed to examine the local band offset in these heterostructures, which is often found to be crucial in device design.\r\n\r\nIn the avalanche photodiode study, devices with near infrared response out to 1.74 [mu]m were demonstrated. Two types of devices were investigated: those with a bulk Al0.04Ga0.96Sb multiplication region and those with a GaSb/A1Sb superlattice multiplication region. Both types of devices were implemented in a MBE grown p[superscript -]n[superscript +] structure that uses a selectively doped InAs/AlSb superlattice as the n-type layer. This particular structure was optimized through several design, fabrication, characterization cycles. It was found that the photodiode dark current depended critically on the InAs/A1Sb superlattice period and the resulting band offset at the p[superscript -]n[superscript +] heterojunction. The InAs/AlSb superlattice was henceforth optimized by using a three stage design. The ionization rates in bulk multiplication layer devices were measured and found to be consistent with hole impact ionization enhancement in Al0.04Ga0.96Sb. However, direct comparison with superlattice multiplication layer devices revealed the latter to be more promising due to more effective dark current suppression from the larger band gap of the superlattice multiplication layer.\r\n \r\nThe second device studied is the tunnel switch diode. We have fabricated the first such device in the antimonide material system and obtained characteristic \"S\" shaped I-V curves from these devices. The epilayer and barrier dependence of tunnel diode switching were studied and found to deviate significantly from the punch-through model of operation. In addition, the device I-V curve was observed to \"hop\" between two branches when subjected to high levels of stress. We speculate that this was due to instability associated with mobile charges in the A1Sb tunnel barrier. A computer model was used to simulate the device behavior and generated results consistent with the observed dependence of switching on tunnel barrier thickness.\r\n\r\nIn the second part of the thesis, III-V heterostructures were characterized by using ballistic electron emission microscopy (BEEM). BEEM images were shown to reveal sub surface features in AlxGal-xAs. epilayers, whereas BEEM spectroscopy was used to map out the shift in [capital gamma], X, and L band edges with material composition in AlxGal-xAs. BEEM spectroscopy was also applied to device relevant antimonide heterostructures such as A1Sb barriers and InAs/AlSb superlattices. It was found that electron transport in A1Sb was dictated by the conduction band minium near the X point, and there is large local variation in the AlSb Schottky barrier height. These results were in good correlation with the observed barrier characteristics of A1Sb. Due to the small bandgap of InAs/A1Sb superlattice and the associated high level of noise current, only the shortest period superlattice was examined by BEEM. The resulting band offset agreed with the calculated value and demonstrated that BEEM spectroscopy can be applied to structures with a large number of hetero-interfaces.", "doi": "10.7907/4pmy-xb16", "publication_date": "1999", "thesis_type": "phd", "thesis_year": "1999" }, { "id": "thesis:4057", "collection": "thesis", "collection_id": "4057", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-10122007-132811", "primary_object_url": { "basename": "Bridger_pm_1999.pdf", "content": "final", "filesize": 27942077, "license": "other", "mime_type": "application/pdf", "url": "/4057/1/Bridger_pm_1999.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Development of Apertureless Microscopy and Force Microscopy of GaN and CeO\u2082", "author": [ { "family_name": "Bridger", "given_name": "Paul Martin", "clpid": "Bridger-Paul-Martin" } ], "thesis_advisor": [ { "family_name": "McGill", "given_name": "Thomas C.", "clpid": "McGill-T-C" } ], "thesis_committee": [ { "family_name": "McGill", "given_name": "Thomas C.", "clpid": "McGill-T-C" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Quake", "given_name": "Stephen R.", "orcid": "0000-0002-1613-0809", "clpid": "Quake-S-R" }, { "family_name": "Scherer", "given_name": "Axel", "orcid": "0000-0002-2160-9064", "clpid": "Scherer-A" }, { "family_name": "Vahala", "given_name": "Kerry J.", "orcid": "0000-0003-1783-1380", "clpid": "Vahala-K-J" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document.\r\n\r\nThis thesis concentrates on the development of both novel scanning probes as well as \r\nnovel applications of existing ones in three major areas. The first area is our development of apertureless microscopy and progress toward our goal of 1nm optical imaging \r\nand spectroscopy. Fundamental experiments and simulations of the apertureless imaging mechanism were conducted using nanosphere size standards. Fifteen nanometer \r\nresolution as well as optical property discrimination was demonstrated. The apertureless microscope was then used to investigate the near field optical structure of \r\nchromosomes and anti-reflective polymer thin films. The second area is the investigation of the electronic properties of the wide bandgap semiconductor GaN by atomic \r\nforce microscopy. Defects in GaN were correlated to diffusion lengths as measured by \r\nelectron beam induced current. Electric force microscopy (EFM), a varient of atomic \r\nforce microscopy, was subsequently used to investigate sub [...] electric field gradient \r\nand surface potential variation associated with these defects. A novel application of \r\nEFM to measure the surface state density was also demonstrated. The third area \r\nis another novel application of EFM for localized charge storage in double barrier \r\nCe02/Si/Ce02/Si structures which may have relevance for data storage and charge \r\ndirected lithography.", "doi": "10.7907/8ybw-sh03", "publication_date": "1999", "thesis_type": "phd", "thesis_year": "1999" }, { "id": "thesis:1532", "collection": "thesis", "collection_id": "1532", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-04282006-113514", "primary_object_url": { "basename": "Baird_ee_1999.pdf", "content": "final", "filesize": 22043450, "license": "other", "mime_type": "application/pdf", "url": "/1532/1/Baird_ee_1999.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Solid Phase Synthesis of DNA-Binding Small Molecules", "author": [ { "family_name": "Baird", "given_name": "Eldon Eugene", "orcid": "0009-0009-2775-8704", "clpid": "Baird-Eldon-Eugene" } ], "thesis_advisor": [ { "family_name": "Hoffmann", "given_name": "Michael R.", "orcid": "0000-0001-6495-1946", "clpid": "Hoffmann-M-R" } ], "thesis_committee": [ { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Hoffmann", "given_name": "Michael R.", "orcid": "0000-0001-6495-1946", "clpid": "Hoffmann-M-R" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Dervan", "given_name": "Peter B.", "orcid": "0000-0001-8852-7306", "clpid": "Dervan-P-B" }, { "family_name": "Rees", "given_name": "Douglas C.", "orcid": "0000-0003-4073-1185", "clpid": "Rees-D-C" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Small molecules that bind to any predetermined DNA sequence in the human genome are potentially useful tools for molecular biology and human medicine. A twenty year research effort led by Dr. Peter B. Dervan at the California Institute of Technology has led to the development of \"pairing rules\" to control rationally the sequence-specificity of polyamides that bind in the DNA minor groove. During the course of my Ph.D. research, methodology was developed for the machine-assisted solid phase synthesis of these DNA-binding polyamides (Chapter 2). The large number of polyamides made available by the solid phase synthetic methodology has greatly accelerated the development of this class of molecules. Polyamides prepared by solid phase synthetic methodology have been used by a variety of collaborators to: extend the targetable binding-site size (Chapter 3), recognize predetermined DNA sequences with subnanomolar affinity (Chapter 6), regulate gene expression in human cells (Chapter 7), and recognize all four base pairs in the DNA minor groove (Chapter 8).", "doi": "10.7907/zky0-ha94", "publication_date": "1999", "thesis_type": "phd", "thesis_year": "1999" }, { "id": "thesis:1634", "collection": "thesis", "collection_id": "1634", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05052006-141420", "primary_object_url": { "basename": "White_s_1999.pdf", "content": "final", "filesize": 6843436, "license": "other", "mime_type": "application/pdf", "url": "/1634/1/White_s_1999.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Recognition of All Four Watson-Crick Base Pairs in the Minor Groove of DNA by Synthetic Ligands", "author": [ { "family_name": "White", "given_name": "Sarah", "clpid": "White-Sarah" } ], "thesis_advisor": [ { "family_name": "Hoffmann", "given_name": "Michael R.", "orcid": "0000-0001-6495-1946", "clpid": "Hoffmann-M-R" } ], "thesis_committee": [ { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Dervan", "given_name": "Peter B.", "orcid": "0000-0001-8852-7306", "clpid": "Dervan-P-B" }, { "family_name": "Rees", "given_name": "Douglas C.", "orcid": "0000-0003-4073-1185", "clpid": "Rees-D-C" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Hoffmann", "given_name": "Michael R.", "orcid": "0000-0001-6495-1946", "clpid": "Hoffmann-M-R" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The design of synthetic ligands that read the information stored in the DNA double helix has been a long standing goal at the interface of chemistry and biology. Cell-permeable small molecules which target predetermined DNA sequences offer a potential approach for the regulation of gene-expression. Oligodeoxynucleotides that recognize the major groove of double-helical DNA via triple-helix formation bind to a broad range of sequences with high affinity and specificity. Although oligonucleotides and their analogs have been shown to interfere with gene expression, the triple helix approach is limited to purine tracks and suffers from poor cellular uptake. The subsequent development of pairing rules for minor groove binding polyamides containing pyrrole (Py) and imidazole (Im) amino acids offers a second code to control sequence specificity. An Im/Py pair distinguishes G\u2022C from C\u2022G and both of these from A\u2022T/T\u2022A base pairs. A Py/Py pair specifies A,T from G,C but does not distinguish A\u2022T from T\u2022A. In order to break this degeneracy, a new aromatic amino acid, 3-hydroxypyrrole (Hp), has been added to the repertoire to test for pairings which discriminate A\u2022T from T\u2022A. We find that replacement of a single hydrogen atom with a hydroxy group in a Hp/Py pairing regulates affinity and specificity by an order of magnitude. By incorporation of a third amino acid, hydroxypyrrole-imidazole-pyrrole polyamides form four ring-pairings (Im/Py, Py/Im, Hp/Py, and Py/Hp) which distinguish all four Watson-Crick base pairs in the minor groove of DNA.", "doi": "10.7907/wxsr-8x37", "publication_date": "1999", "thesis_type": "phd", "thesis_year": "1999" }, { "id": "thesis:17842", "collection": "thesis", "collection_id": "17842", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01282026-190810142", "type": "thesis", "title": "Advances in High-Resolution Probes for Scanning Probe Microscopy", "author": [ { "family_name": "Unger", "given_name": "Marc Alexander", "clpid": "Unger-Marc-Alexander" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" }, { "family_name": "Quake", "given_name": "Stephen R.", "orcid": "0000-0002-1613-0809", "clpid": "Quake-S-R" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This thesis describes work designed to improve the resolution of Scanned Probe\r\nMicroscopy (SPM). The work falls into three main sections. Sections I and III are both\r\naimed towards making scanned probes with atomic resolution by attaching a single sharp\r\nmolecule to the end of a tip. Section II is aimed towards making a near-field \"optical\"\r\nprobe in the infrared wavelengths.
\r\n\r\nThe first section centers on the Touchdown Scheme, a path towards attachment of a\r\nsingle sharp molecule at the end of a conventional atomic force microscope (AFM) tip.\r\nThe ability to derivatize the tip with a good monolayer was required. Chapters 2 and 3\r\ndescribe the development and optimization of surface chemistry for this purpose.\r\nIncluded in this development were methods for making chemically patterned surfaces\r\nwith simple photolithography techniques. Chapter 1 describes mathematical methods to\r\nextract intermolecular pair potentials from AFM force measurements.
\r\n\r\nThe second section describes a technique for etching infrared-transmitting fibers to very\r\nsharp points. These sharpened fibers serve as probes in a Near-field Scanning Infrared\r\nMicroscope (NSIM). Making tips by chemical etching is far easier than heat-pulling, and\r\nthe etched probes have a power throughput several orders of magnitude higher than\r\npulled probes.
\r\n\r\nThe third section centers on attempts to attach a single molecule to the end of a single\r\ncarbon nanotube for use as an ultrasharp AFM tip. Bulk derivatization and labeling\r\nchemistry of carbon nanotubes was developed and successfully applied to single mounted\r\nnanotubes. Along the way, several new methods for handling nanotubes were developed.\r\nThese include methods for non-oxidative cleaning, making stable suspensions,\r\nfluorescence staining, and removal from solution without coalescence.
", "doi": "10.7907/xqdw-8009", "publication_date": "1999", "thesis_type": "phd", "thesis_year": "1999" }, { "id": "thesis:1866", "collection": "thesis", "collection_id": "1866", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05192003-110022", "primary_object_url": { "basename": "winfree_thesis.pdf", "content": "final", "filesize": 4345371, "license": "other", "mime_type": "application/pdf", "url": "/1866/1/winfree_thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Algorithmic Self-Assembly of DNA", "author": [ { "family_name": "Winfree", "given_name": "Erik", "orcid": "0000-0002-5899-7523", "clpid": "Winfree-Erik" } ], "thesis_advisor": [ { "family_name": "Hopfield", "given_name": "John J.", "clpid": "Hopfield-J-J" } ], "thesis_committee": [ { "family_name": "Abu-Mostafa", "given_name": "Yaser S.", "clpid": "Abu-Mostafa-Y-S" }, { "family_name": "Abelson", "given_name": "John N.", "clpid": "Abelson-J-N" }, { "family_name": "Adleman", "given_name": "Leonard M.", "clpid": "Adleman-Leonard-M" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Barr", "given_name": "Alan H.", "clpid": "Barr-A-H" }, { "family_name": "Hopfield", "given_name": "John J.", "clpid": "Hopfield-J-J" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "How can molecules compute? In his early studies of reversible computation, Bennett imagined an enzymatic Turing Machine which modified a hetero-polymer (such as DNA) to perform computation with asymptotically low energy expenditures. Adleman's recent experimental demonstration of a DNA computation, using an entirely different approach, has led to a wealth of ideas for how to build DNA-based computers in the laboratory, whose energy efficiency, information density, and parallelism may have potential to surpass conventional electronic computers for some purposes. In this thesis, I examine one mechanism used in all designs for DNA-based computer -- the self-assembly of DNA by hybridization and formation of the double helix -- and show that this mechanism alone in theory can perform universal computation. To do so, I borrow an important result in the mathematical theory of tiling: Wang showed how jigsaw-shaped tiles can be designed to simulate the operation of any Turing Machine. I propose constructing molecular Wang tiles using the branched DNA constructions of Seeman, thereby producing self-assembled and algorithmically patterned two-dimensional lattices of DNA. Simulations of plausible self-assembly kinetics suggest that low error rates can be obtained near the melting temperature of the lattice; under these conditions, self-assembly is performing reversible computation with asymptotically low energy expenditures. Thus encouraged, I have begun an experimental investigation of algorithmic self-assembly. A competition experiment suggests that an individual logical step can proceed correctly by self-assembly, while a companion experiment demonstrates that unpatterned two dimensional lattices of DNA will self-assemble and can be visualized. We have reason to hope, therefore, that this experimental system will prove fruitful for investigating issues in the physics of computation by self-assembly. It may also lead to interesting new materials.
\r\n", "doi": "10.7907/HBBV-PF79", "publication_date": "1998", "thesis_type": "phd", "thesis_year": "1998" }, { "id": "thesis:17585", "collection": "thesis", "collection_id": "17585", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08012025-174712767", "primary_object_url": { "basename": "Martin_JI_1998.pdf", "content": "final", "filesize": 35602016, "license": "other", "mime_type": "application/pdf", "url": "/17585/1/Martin_JI_1998.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Statistical Mechanics of End-Attached Polymer Interfaces", "author": [ { "family_name": "Martin", "given_name": "Jeremy Isaac", "orcid": "0000-0001-7233-7217", "clpid": "Martin-Jeremy-Isaac" } ], "thesis_advisor": [ { "family_name": "Wang", "given_name": "Zhen-Gang", "orcid": "0000-0002-3361-6114", "clpid": "Wang-Zhen-Gang" } ], "thesis_committee": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Marcus", "given_name": "Rudolph A.", "orcid": "0000-0001-6547-1469", "clpid": "Marcus-R-A" }, { "family_name": "Wang", "given_name": "Zhen-Gang", "orcid": "0000-0002-3361-6114", "clpid": "Wang-Zhen-Gang" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This dissertation discusses several closely related problems involving end attached polymers\r\nat interfaces. The studies share a numerical self-consistent field approach which is described\r\nin detail in Chapter 1.
\r\n\r\nIn Chapter 2, we consider irreversible polymer brushes (polymers densely end tethered\r\nto a surface). First, we discuss the adequacy of second virial treatments of interchain\r\ninteractions. Next we examine the extent of interbrush penetration between compressed\r\npolymer brushes, and its effect on the interactions between them. Then we identify scaling\r\nvariables which control the behavior of polymer brushes in polymeric solvents. Finally we\r\ninvestigate brush configurations and interactions in mixed solvents, where nonmonotonic\r\ninteraction profiles are predicted with a longer range weak attraction, and strong repulsion\r\nat shorter separations.
\r\n\r\nIn Chapter 3, we discuss the modification of spreading properties of a liquid on a solid\r\nsurface by the addition of end-adsorbing polymers. An end-adsorption polymer additive\r\ncan lead an otherwise non-spreading liquid to spread. A phase diagram for spreading of a\r\nliquid drop of fixed volume as a function of the concentration of end-adsorbing polymers\r\nand the energy of end-adsorption to the surface is obtained. The equilibrium thickness of\r\na spread film is also calculated, and is shown to be closely related to the thickness of a\r\nself-assembled polymer brush in an unbounded fluid and relatively insensitive to the bare\r\nspreading power of the liquid or the Hamaker constant, which determine the equilibrium\r\nthickness of a film of a simple liquid.
\r\n\r\nFinally, in Chapter 4, we study the interaction forces between two plates in a semi-dilute\r\nsolution of polymers each having one weakly adsorbing end-group. This system exhibits\r\nboth repulsive and attractive interactions of comparable magnitude and well-separated\r\nlength scales. The repulsion has a length scale of the end-to-end distance of the endadsorbed\r\npolymer, and a magnitude which is proportional to the end-adsorption energy\r\nand the volume fraction of the polymer, and inversely proportional the chain molecular\r\nweight. At plate separations of order the correlation length of the solution, a depletion\r\nattraction sets in with a magnitude that scales with the bulk osmotic pressure.
", "doi": "10.7907/4pc9-vz14", "publication_date": "1998", "thesis_type": "phd", "thesis_year": "1998" }, { "id": "thesis:17590", "collection": "thesis", "collection_id": "17590", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08042025-205701232", "primary_object_url": { "basename": "Johann_TW_1997.pdf", "content": "final", "filesize": 76248947, "license": "other", "mime_type": "application/pdf", "url": "/17590/1/Johann_TW_1997.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Sequence-Specific Inhibition of DNA Polymerase by Phenanthrene Quinone Diimine Complexes of Rhodium(III)", "author": [ { "family_name": "Johann", "given_name": "Timothy Wilmot", "orcid": "0000-0003-2212-9684", "clpid": "Johann-Timothy-Wilmot" } ], "thesis_advisor": [ { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" } ], "thesis_committee": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" }, { "family_name": "Okumura", "given_name": "Mitchio", "orcid": "0000-0001-6874-1137", "clpid": "Okumura-M" }, { "family_name": "Parker", "given_name": "Carl Stevens", "orcid": "0000-0001-9795-4211", "clpid": "Parker-C-S" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The DNA binding characteristics of several phenanthrenequinone\r\ndiimine (phi) complexes of rhodium (III) as well as their ability to inhibit\r\nfunctionally DNA polymerase have been investigated. Affinity constants\r\nhave been determined to be 5x107 M-1 and 1x108 M-1 for \u0394 and \u039b 1Rh(\r\nMGP)2phi5+ binding to the DNA sequences 5'-CATCTG-3' and 5'-\r\nCATATG-3' respectively. The exchange rate, at 21\u00b0C, has been determined to\r\nbe 16 s-1 for the binding of 1-\u039b-Rh(MGP)2phi5+ to 5'-CATATG-3' through the\r\nuse of variable temperature 1H-NMR. Similar 1H-NMR experiments were\r\ncarried out to determine the kinetics of the interaction of 1-\u0394-Rh(MGP)2phi5+\r\nwith a duplex DNA of the sequence 5'-CGCATCTGAC-3'. 1-\u039b-Rh(\r\nMGP)2phi5+, 1-\u0394-Rh(MGP)2phi5+, and Rh(MT)phi3+, which binds to 5'-\r\nTGCA-3', were found to be potent sequence-specific inhibitors of DNA\r\npolymerase. All of these complexes bind to DNA through intercalation. In\r\nexperiments where two templates competed for extension by DNA\r\npolymerase, these complexes were shown to inhibit the extension of\r\ntemplates containing their binding sequences as compared to control\r\ntemplates. Furthermore, in direct competition experiments containing two\r\ntemplates, where each contained a binding sequence for a different metal\r\ncomplex, the relative activity of DNA polymerase on each template was\r\n\"tuned\" by the addition of metal complex specific for that template. \u0394-Rh(\r\nDPB)2phi3+ was also found to be a potent inhibitor of DNA polymerase,\r\nbut not in a template-specific manner. The relative potency of sequence- specific\r\ninhibition shown by 1-\u039b-Rh(MGP)2phi5+, 1-\u039b-Rh(MGP)2phi5+, and\r\nRh(MT)2phi3+ was compared to the binding kinetics, complex size, complex\r\ncharge, binding affinity and binding induced DNA distortion for these\r\ncomplexes. Greater DNA distortion was found to correlate with greater\r\ninhibition. These studies have shown that these molecules not only bind to\r\nDNA in a sequence-specific manner, but can functionally inhibit enzymatic\r\nreactions in a sequence-specific manner as well.", "doi": "10.7907/fb9e-rw88", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:18550", "collection": "thesis", "collection_id": "18550", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05112026-185336063", "primary_object_url": { "basename": "Rodham_DA_1997.pdf", "content": "final", "filesize": 41838170, "license": "other", "mime_type": "application/pdf", "url": "/18550/1/Rodham_DA_1997.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Spectroscopic Studies of the Gas Phase Complexes Benzene-Ammonia, Sodium-Water, and Sodium-Ammonia", "author": [ { "family_name": "Rodham", "given_name": "David Allen", "clpid": "Rodham-David-Allen" } ], "thesis_advisor": [ { "family_name": "Blake", "given_name": "Geoffrey A.", "orcid": "0000-0003-0787-1610", "clpid": "Blake-G-A" } ], "thesis_committee": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Blake", "given_name": "Geoffrey A.", "orcid": "0000-0003-0787-1610", "clpid": "Blake-G-A" }, { "family_name": "McKoy", "given_name": "Basil Vincent", "clpid": "McKoy-B-V" }, { "family_name": "Myers", "given_name": "Andrew G.", "orcid": "0000-0001-9602-6915", "clpid": "Myers-A-G" }, { "family_name": "Okumura", "given_name": "Mitchio", "orcid": "0000-0001-6874-1137", "clpid": "Okumura-M" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The results of spectroscopic studies of the C6H6(NH3), Na(H2O), and Na(NH3) gas\r\nphase complexes are reported. The goal of these experiments was to obtain information\r\nupon which a more quantitative understanding of the intermolecular interactions\r\nfound within them could be based. These intermolecular interactions, amino-aromatic\r\nhydrogen bonding in the C6H6(NH3) complex and the primarily electrostatic bonding\r\nof Na+ to polar molecules in the Na+(H2O) and Na+(NH3) complexes, form the basis\r\nfor many biologically significant processes.
\r\n\r\nThe C6H6(NH3) dimer was investigated with resonant two-photon ionization (R2PI)\r\nand microwave spectroscopies. Using R2PI via the 610 transition of the benzene in the\r\ncomplex, it was found that the NH3 is located above the benzene plane, on or near\r\nthe benzene C6 axis, and that the monomers undergo free or nearly free internal rotation.\r\nSubsequent high resolution microwave absorption and emission measurements\r\nof the rotational spectrum revealed that the center of mass separation (Rcm-cm) of\r\nthe monomers is 3.59 \u00c5 and that the ammonia C3 axis is tilted 58\u00b0 from the benzene\r\nC6 axis. In this geometry, the ammonia protons interact with the benzene n-cloud in\r\na hydrogen-bonded geometry similar to that observed in high-resolution x-ray crystallography\r\nof protein structures.
\r\n\r\nThe Na(H2O), Na(D2O), Na(NH3), and Na(ND3) complexes were studied with\r\nZEKE-PFI (zero kinetic energy-pulsed field ionization) photoelectron spectroscopy.\r\nSpectra of all four complexes were obtained by single-photon ionization. For the\r\nNa(NH3) and Na(ND3) complexes, two-color (1+1') photoionization was used as well,\r\nwith the \u00c3 2E state serving as the intermediate resonance. Improved values for the\r\nionization energies (IEs) and intermolecular stretching vibrational frequencies of the\r\ncomplexes were determined, while the intermolecular bending vibrational frequencies\r\nof Na(NH3) and Na(ND3) were measured for the first time. From the rotational\r\nstructure observed in the ZEKE-PFI spectra, it was found that the Na-O and Na-N\r\nbond lengths shrink by 5.2 \u00b1 0.5% when the complexes are ionized. The single-photon\r\nZEKE-PFI spectra show transitions only between states of the same vibrational symmetry,\r\nin accord with the selection rule for allowed electronic transitions. Some of\r\nthe two-color ZEKE-PFI spectra, however, show strong transitions between states\r\nof different vibrational symmetry which are attributed to vibronic coupling in the\r\nintermediate state. All of the single-photon spectra as well as the two-color spectra\r\nof Na(NH3) showed unusually strong O-branches, presumably the result of field-induced\r\nrotational autoionization. This effect is commonly observed in ZEKE-PFI\r\nspectroscopy, particularly for species such as Na(H2O) and Na(NH3) which combine\r\nsmall rotational constants with strongly anisotropic ion-electron scattering potentials.
", "doi": "10.7907/mcm8-t491", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:18886", "collection": "thesis", "collection_id": "18886", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08062026-205629732", "primary_object_url": { "basename": "Pack_DW_1997.pdf", "content": "final", "filesize": 82504575, "license": "other", "mime_type": "application/pdf", "url": "/18886/1/Pack_DW_1997.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Protein Targeting to Metal-Chelating Lipid Monolayers: Toward New Materials Inspired by Nature", "author": [ { "family_name": "Pack", "given_name": "Daniel W.", "orcid": "0000-0003-0410-0423", "clpid": "Pack-Daniel-W." } ], "thesis_advisor": [ { "family_name": "Arnold", "given_name": "Frances Hamilton", "orcid": "0000-0002-4027-364X", "clpid": "Arnold-F-H" } ], "thesis_committee": [ { "family_name": "Arnold", "given_name": "Frances Hamilton", "orcid": "0000-0002-4027-364X", "clpid": "Arnold-F-H" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Hubbell", "given_name": "Jeffrey A.", "orcid": "0000-0003-0276-5456", "clpid": "Hubbell-J-A" }, { "family_name": "Kornfield", "given_name": "Julia A.", "orcid": "0000-0001-6746-8634", "clpid": "Kornfield-J-A" }, { "family_name": "Wang", "given_name": "Zhen-Gang", "orcid": "0000-0002-3361-6114", "clpid": "Wang-Zhen-Gang" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Biological membranes are functional structures responsible for controlling\r\nnumerous cellular functions. Many membrane functions (for example, transmembrane\r\nsignaling and endocytosis) are the direct result of the dynamic nature of the membrane.\r\nThe capacity to mimic biomembranes can lead to applications such as the production of\r\nbiosensors and targeted drug delivery systems. In this work, a synthetic membrane-based\r\nrecognition system capable of reproducing important features of biological targeting and\r\nassembly was developed. This system may open new routes to controlling molecular\r\narchitecture in materials and devices, as well as produce new, functional materials.
\r\n\r\nProteins are targeted to membranes through the affinity of surface histidine side\r\nchains for transition metal ions immobilized in the lipid headgroups. A set of metalchelating\r\nlipids for this purpose was previously synthesized in our laboratory. Through\r\nmeasurement of the lipid surface pressure-molecular area (\u03c0-A) isotherms, the capability of\r\nthe iminodiacetate (IDA) headgroups to chelate Cu2+ was demonstrated; the apparent\r\nassociation constant for the IDA lipid-Cu complex is 1.3-1.8 x 108 M-1. In addition, to\r\ntailor the density of metal sites on the membrane, mixing of a pyrene-labeled IDA lipid with\r\ntwo phosphocholine lipids was investigated.
\r\n\r\nThe binding of horse heart myoglobin to IDA-Cu lipid monolayers by naturally\r\noccurring histidines was observed through changes in the lipid \u03c0-A isotherms. In addition,\r\ntargeting of a recombinant rat liver cytochrome b5, engineered to display a hexa-histidine\r\naffinity tag at the C-terminus, to IDA-Cu lipid monolayers was demonstrated. The protein\r\nbinding was measured as a function of the type of IDA-Cu lipid composing the monolayer,\r\nthe concentration of protein in the aqueous subphase, and the fraction of IDA-Cu lipids in\r\nthe monolayer. The hexa-histidine tag was found to provide an apparent affinity for IDA-Cu\r\nlipid binding of at least 2 x 107 M-1. A Frumkin-type adsorption isotherm was\r\ndeveloped to describe the binding of proteins to lipid monolayers.
\r\n\r\nThe inherent two-dimensional order of biological membranes 1s also capable of\r\npromoting ordered growth of organic and inorganic biomaterials. Synthetic lipid\r\nmonolayers can likewise induce growth of 2D protein crystals at the air-water interface.\r\nFor the first time, growth of 2D protein crystals on metal-chelating lipid monolayers via\r\ncoordination of naturally-occurring surface histidines is demonstrated. Two-dimensional\r\ncrystals of the protein streptavidin, grown on IDA-Cu lipid monolayers, were observed\r\nusing Brewster angle and fluorescence microscopies. The IDA-Cu-histidine interaction\r\nmay provide a general route to the growth of 2D protein crystals for structure\r\ndetermination, as well as the production of functional materials based on the properties of\r\nthe proteins, themselves.
\r\n\r\nFinally, many biological membrane functions are produced by ligand-induced\r\nassembly of membrane components (e.g. transmembrane signaling). Mimicking ligand-induced\r\nassembly and subsequent signaling can produce functional materials such as the\r\nIDA lipid-based metal ion sensor (Sasaki, et al. Angew. Chem. Int. Ed. Engl. 34, 905-\r\n907, 1995). In order to probe similar ligand-induced reorganization of a pyrene-labeled\r\nIDA lipid in Langmuir monolayers, a UV-vis fluorescence microphotometer has been\r\nconstructed. As a demonstration of its utility, the instrument was used to quantitate\r\nfluorescence from a pyrene IDA lipid monolayer and estimate a diffusion coefficient for the\r\nlipids. In addition, reorganization of the IDA lipids by binding of a multivalent ligand,\r\npoly(histidine), was observed via the pyrene lipid fluorescence.
", "doi": "10.7907/s3n0-5169", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:17681", "collection": "thesis", "collection_id": "17681", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09152025-212928780", "primary_object_url": { "basename": "Terbrueggen_R_1996.pdf", "content": "final", "filesize": 65415187, "license": "other", "mime_type": "application/pdf", "url": "/17681/1/Terbrueggen_R_1996.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Exploring the Direct and Indirect Readout of DNA with Phenanthrenequinone Diimine Complexes of Rhodium(III)", "author": [ { "family_name": "Terbrueggen", "given_name": "Robert Henry", "clpid": "Terbrueggen-Robert-Henry" } ], "thesis_advisor": [ { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" } ], "thesis_committee": [ { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Lewis", "given_name": "Nathan Saul", "orcid": "0000-0001-5245-0538", "clpid": "Lewis-N-S" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Phenanthrenequinone diimine (phi) complexes of rhodium(III) have been\r\ndesigned and characterized in order to investigate the principles of direct and\r\nindirect readout of double helical DNA The metallointercalator l-Rh(MGP)2phi5+\r\n(MGP = 4-guanidylmethyl-1,10-phenanthroline) binds via intercalation in the\r\nmajor groove of DNA and upon irradiation promotes DNA strand scission. The\r\n\u039b-enantiomer, \u039b-1-Rh(MGP)2phi5+, binds at subnanomolar concentrations to the\r\n6 base pair sequence, 5'-CATATG-3', with enantiospecificity. An essential feature\r\nof this recognition is the sequence-specific unwinding of the DNA helix which\r\npermits direct contacts between guanidinium functionalities on the metal complex\r\nand guanine residues. Deazaguanine substitutions were used to establish direct\r\ncontacts between the N7 nitrogen atoms of guanine and the guanidinium moiety on\r\nthe metal complex. Through an assay developed to test for sequence-specific DNA\r\nunwinding, a 70 \u00b1 10 degrees unwinding of the sequence 5'-CATATG-3' upon\r\nbinding by \u039b-1-Rh(MGP)2phi5+ was established. Thus, the sequence-dependent\r\ntwistability of DNA plays an important role in determining the sequence specificity\r\nof the complex. The \u0394-enantiomer, \u0394-1-Rh(MGP)2phi5+, binds preferentially to\r\nthe 6 base pair sequence, 5'-CATCTG-3'. The hierarchy of recognition sites\r\ndetermined in photocleavage studies on oligonucleotides suggests that DNA\r\nrecognition by this complex also involves sequence specific contacts by the\r\nguanidinium functionalities. Photocleavage studies indicate additional similarities\r\nin the recognition of \u0394 and \u039b-1-Rh(MGP)2phi5+. Both enantiomers of 1-\r\nRh(MGP)2phi5+ display increased binding specificity relative to the parent\r\ncomplex, Rh(phen)2phi3+. The exchange rates of both enantiomers are also\r\ndecreased at least a 1000-fold relative to Rh(phen)2phi3+. Studies in which the\r\nlength of the linker arm between the core of the metal complex and the guanidinium\r\nmoiety was varied demonstrate that proper orientation of the guanidinium moiety is\r\nan essential feature of complex specificity. As the length of the linker arm\r\nincreases, the binding specificity of the complex decreases. DNA recognition\r\nstudies with Rh(APB)2phi5+ (APB= 4-(3-aminopropyl)-4'-2,2'-bipyridine) have\r\ndemonstrated that the amino moiety can also be used to alter the sequence\r\nspecificity of phi complexes of rhodium(III), although the sequence specificity of\r\nthis complex is reduced greatly as compared with \u0394- and \u039b-1-Rh(MGP)2phi5+.\r\nThis work therefore demonstrates that the guanidinium moiety may be used to\r\nenhance both the binding affinity and specificity of phi complexes of rhodium(III).\r\nIn mimicking DNA binding proteins, molecules which recognize their binding sites\r\nthrough direct and indirect readout of the DNA can be designed. Importantly, this\r\nstudy highlights a new structural element of DNA recognition, the sequence-dependent\r\ntwistability of the DNA helix. This sequence-dependent twistability may\r\nbe an essential feature of the recognition of sequences by DNA-binding proteins\r\nand may be powerfully exploited in future design.", "doi": "10.7907/yv86-3710", "publication_date": "1996", "thesis_type": "phd", "thesis_year": "1996" }, { "id": "thesis:333", "collection": "thesis", "collection_id": "333", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-01252005-092413", "primary_object_url": { "basename": "OConnor_sd_1995.pdf", "content": "final", "filesize": 10337823, "license": "other", "mime_type": "application/pdf", "url": "/333/1/OConnor_sd_1995.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Studying Material Properties on the Nanometer Scale: Instrumental Development and Applications", "author": [ { "family_name": "O'Connor", "given_name": "Stephen D.", "clpid": "O'Connor-Stephen-D" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Beauchamp", "given_name": "Jesse L.", "orcid": "0000-0001-8839-4822", "clpid": "Beauchamp-J-L" }, { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" }, { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document.\r\n\r\nThis thesis describes experimental work designed to understand and manipulate material properties on the nanometer scale. Two strategies have been explored: instrument development and experimental applications.\r\n\r\nSection I describes work associated with atomic force microscopy, including application studies of human hair morphology and the surface microstructure of a bulk metallic glass [...]. Also included in this section are two instrumental advances. First, a mathematical algorithm to extract intermolecular potentials from experimental data is described. Second, a simple, robust method for reducing mechanical noise in these experiments is presented.\r\n\r\nSection II outlines early experiments aimed at applying Near-field Scanning Optical microscopy to gas-phase chemical analysis. Standard instruments were constructed and tested. Preliminary work aimed at using the near-field effect to desorb ionized particles from surfaces was also completed.\r\n\r\nSection III describes the construction of temperature and vibration sensors based on material properties in silicon. Unprecedented resolution has been obtained with a simple, inexpensive device. The vibration sensors take advantage of Schottky barrier reshaping while the junction is excited with optically induced charge carriers. In a similar manner, the temperature sensors monitor changes in electron mobility.", "doi": "10.7907/P0AA-7W43", "publication_date": "1995", "thesis_type": "phd", "thesis_year": "1995" }, { "id": "thesis:7703", "collection": "thesis", "collection_id": "7703", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05132013-115254310", "primary_object_url": { "basename": "Oh 1994.pdf", "content": "final", "filesize": 48137719, "license": "other", "mime_type": "application/pdf", "url": "/7703/1/Oh 1994.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Exploration of New Drug Delivery Pathways: I. Mechanism of Folate Uptake in Cultured Human Cells. II. Role of Nuclear Localization Signal Peptides in the Delivery of Oligonucleotide into Reconstituted Nuclei", "author": [ { "family_name": "Oh", "given_name": "Kyoung Joon", "orcid": "0000-0002-4729-9674", "clpid": "Oh-Kyoung-Joon" } ], "thesis_advisor": [ { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" } ], "thesis_committee": [ { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" }, { "family_name": "Dervan", "given_name": "Peter B.", "orcid": "0000-0001-8852-7306", "clpid": "Dervan-P-B" }, { "family_name": "Strauss", "given_name": "James H.", "clpid": "Strauss-J-H" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The roles of the folate receptor and an anion carrier in the uptake of 5-\r\nmethyltetrahydrofolate (5-MeH_4folate) were studied in cultured human (KB)\r\ncells using radioactive 5-MeH_4folate. Binding of the 5-MeH_4folate was inhibited\r\nby folic acid, but not by probenecid, an anion carrier inhibitor. The\r\ninternalization of 5-MeH_4folate was inhibited by low temperature, folic acid,\r\nprobenecid and methotrexate. Prolonged incubation of cells in the presence of\r\nhigh concentrations of probenecid appeared to inhibit endocytosis of folatereceptors\r\nas well as the anion carrier. The V_(max) and K_M values for the carrier\r\nwere 8.65 \u00b1 0.55 pmol/min/mg cell protein and 3.74 \u00b1 0.54\u00b5M, respectively. The\r\ntransport of 5-MeH4folate was competitively inhibited by folic acid, probenecid\r\nand methotrexate. The carrier dissociation constants for folic acid, probenecid\r\nand methotreate were 641 \u00b5M, 2.23 mM and 13.8 \u00b5M, respectively. Kinetic\r\nanalysis suggests that 5-MeH_4folate at physiological concentration is transported\r\nthrough an anion carrier with the characteristics of the reduced-folate carrier\r\nafter 5-MeH_4folate is endocytosed by folate receptors in KB cells. Our data with\r\nKB cells suggest that folate receptors and probenecid-sensitive carriers work in\r\ntandem to transport 5-MeH_4folate to the cytoplasm of cells, based upon the\r\nassumption that 1 mM probenecid does not interfere with the acidification of the\r\nvesicle where the folate receptors are endocytosed.
\r\n\r\nOligodeoxynucleotides designed to hybridize to specific mRNA sequences\r\n(antisense oligonucleotides) or double stranded DNA sequences have been used\r\nto inhibit the synthesis of a number of cellular and viral proteins (Crooke, S. T.\r\n(1993) FASEB J. 7, 533-539; Carter, G. and Lemoine, N. R. (1993) Br. J. Cacer 67,\r\n869-876; Stein, C. A. and cohen, J. S. (1988) Cancer Res. 48, 2659-2668).\r\nHowever, the distribution of the delivered oligonucleotides in the cell, i.e., in the cytoplasm or in the nucleus has not been clearly defined. We studied the kinetics\r\nof oligonucleotide transport into the cell nucleus using reconstituted cell nuclei\r\nas a model system. We present evidences here that oligonucleotides can freely\r\ndiffuse into reconstituted nuclei. Our results are consistent with the reports by\r\nLeonetti et al. (Proc. Natl. Acad. Sci. USA, Vol. 88, pp. 2702-2706, April 1991),\r\nwhich were published while we were carrying this research independently. We\r\nalso investigated whether a synthetic nuclear localization signal (NLS) peptide of\r\nSV40 T antigen could be used for the nuclear targeting of oligonucleotides. We\r\nsynthesized a nuclear localization signal peptide-conjugated oligonucleotide to\r\nsee if a nuclear localization signal peptide can enhance the uptake of\r\noligonucleotides into reconstituted nuclei of Xenopus. Uptake of the NLS\r\npeptide-conjugated oligonucleotide was comparable to the control\r\noligonucleotide at similar concentrations, suggesting that the NLS signal peptide\r\ndoes not significantly enhance the nuclear accumulation of oligonucleotides.\r\nThis result is probably due to the small size of the oligonucleotide.
\r\n", "doi": "10.7907/p6kk-r616", "publication_date": "1994", "thesis_type": "phd", "thesis_year": "1994" }, { "id": "thesis:7722", "collection": "thesis", "collection_id": "7722", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05172013-114618257", "primary_object_url": { "basename": "Ross 1994.pdf", "content": "final", "filesize": 24975103, "license": "other", "mime_type": "application/pdf", "url": "/7722/1/Ross 1994.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Insights into the Mechanism of Human Erythrocyte Hexose Transport: a Transferred NOE Study of Glucose Binding to GLUT1", "author": [ { "family_name": "Ross", "given_name": "Scott Alan", "clpid": "Ross-Scott-Alan" } ], "thesis_advisor": [ { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" } ], "thesis_committee": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" }, { "family_name": "Rees", "given_name": "Douglas C.", "orcid": "0000-0003-4073-1185", "clpid": "Rees-D-C" }, { "family_name": "Weitekamp", "given_name": "Daniel P.", "orcid": "0000-0003-0079-8000", "clpid": "Weitekamp-D-P" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This study examines binding of \u03b1- and \u03b2-D-glucose in their equilibrium mixture to the glucose transporter (GLUT1) in human erythrocyte membrane preparations by an ^1H NMR method, the transferred NOE (TRNOE). This method is shown theoretically and experimentally to be a sensitive probe of weak ligand-macromolecule interactions. The TRNOEs observed are shown to arise solely from glucose binding to GLUT1. Sites at both membrane faces contribute to the TRNOEs. Binding curves obtained are consistent with a homogeneous class of sugar sites, with an apparent KD which varies (from ~30 mM to ~70 mM for both anomers) depending on the membrane preparation examined. Preparations with a higher proportion of the cytoplasmic membrane face exposed to bulk solution yield higher apparent KKDs. The glucose transport inhibitor cytochalasin B essentially eliminates the TRNOE. Nonlinearity was found in the dependence on sugar concentration of the apparent inhibition constant for cytochalasin B reversal of the TRNOE observed in the \u03b1 anomer (and probably the \u03b2 anomer); such nonlinearity implies the existence of ternary complexes of sugar, inhibitor and transporter. The inhibition results furthermore imply the presence of a class of relatively high-affinity (KD < 2mM) sugar sites specific for the \u03b1 anomer which do not contribute to NMR-observable binding. The presence of two classes of sugar-sensitive cytochalasin B sites is also indicated. These results are compared with predictions of the alternating conformer model of glucose transport. Variation of apparent KD in the NMR-observable sites, the formation of ternary complexes and the presence of an anomer-specific site are shown to be inconsistent with this model. An alternate model is developed which reconciles these results with the known transport behavior of GLUT1. In this model, the transporter possesses (at minimum) three classes of sugar sites: (i) transport sites, which are alternately exposed to the cytoplasmic or the extracellular compartment, but never to both simultaneously, (ii) a class of sites (probably relatively low-affinity) which are confined to one compartment, and (iii) the high-affinity \u03b1 anomer-specific sites, which are confined to the cytoplasmic compartment.\r\n", "doi": "10.7907/nb45-1b79", "publication_date": "1994", "thesis_type": "phd", "thesis_year": "1994" }, { "id": "thesis:1057", "collection": "thesis", "collection_id": "1057", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-03222005-105400", "primary_object_url": { "basename": "Baselt_dr_1993.pdf", "content": "final", "filesize": 14972657, "license": "other", "mime_type": "application/pdf", "url": "/1057/1/Baselt_dr_1993.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "The Tip-Sample Interaction in Atomic Force Microscopy and its Implications for Biological Applications", "author": [ { "family_name": "Baselt", "given_name": "David Randall", "clpid": "Baselt-David-Randall" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Okumura", "given_name": "Mitchio", "orcid": "0000-0001-6874-1137", "clpid": "Okumura-M" }, { "family_name": "Revel", "given_name": "Jean-Paul", "clpid": "Revel-J-P" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This thesis describes the construction of an atomic force microscope and its application to the study of tip-sample interactions, primarily through the use of friction and hardness (elasticity) imaging.\r\n\r\nPart one describes the atomic force microscope, which consists of a scanned-cantilever stage (chapter 2); a versatile digital signal processor-based control system with self-optimizing feedback, lock-in amplifier emulation (for hardness imaging), and macro programmability (chapter 3); and image processing software (chapter 4).\r\n\r\nPart two describes a number of results that have helped to characterize the tip-sample interaction and the contact imaging modes used for its study. Meniscus forces act laterally as well as normally, and that they vary with position (chapter 5). Friction measurements couple with scanner position quid feedback, and the meniscus effects friction images (chapter 6). Sliding of the tip over the sample surface introduces slope-dependence into hardness measurements (chapter 7). Dull tips can create prominent topography artifacts even on very flat surfaces (chapter 8).\r\n\r\nIn an investigation of collagen fibrils, AFM has revealed die characteristic 65 nm banding pattern, a second, minor banding pattern, and microfibrils that run along the fibril axis. The distribution of proteoglycans along the fibrils creates a characteristic pattern in friction images. Although imaging in water reduces interaction forces, water can also make biological samples more sensitive to force. However, for robust biological samples imaged in air, tip shape presents a greater obstacle than tip-sample interaction forces to obtaining high-resolution images. Tip contamination increases tip-sample friction and can occasionally improve resolution (chapter 9).\r\n\r\nFor a separate project I have designed a general-purpose nearfield scanning optical microscope (chapter 10).", "doi": "10.7907/5ZMM-7Q64", "publication_date": "1993", "thesis_type": "phd", "thesis_year": "1993" }, { "id": "thesis:7395", "collection": "thesis", "collection_id": "7395", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01112013-110414331", "type": "thesis", "title": "Atomic-Scale Imaging and Spectroscopy Using Scanning Tunneling Microscopy", "author": [ { "family_name": "Youngquist", "given_name": "Michael George", "clpid": "Youngquist-Michael-George" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Beauchamp", "given_name": "Jesse L.", "orcid": "0000-0001-8839-4822", "clpid": "Beauchamp-J-L" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Kaiser", "given_name": "William J.", "clpid": "Kaiser-William-J" }, { "family_name": "Kuppermann", "given_name": "Aron", "clpid": "Kuppermann-A" }, { "family_name": "Rees", "given_name": "Douglas C.", "orcid": "0000-0003-4073-1185", "clpid": "Rees-D-C" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Advances in scanning tunneling microscopy (STM) instrumentation\r\nand applications are presented. An ultrahigh vacuum (UHV) scanning\r\ntunneling microscope incorporating computer-controlled two-dimensional\r\nsample translation and in vacuo tip and sample transfer was developed. Its\r\nperformance is documented through large-area and atomic-resolution\r\nimaging of highly stepped Si(111) 7x7 reconstructed surfaces and physisorbed\r\nclusters on graphite. An STM with automated approach and intra-Dew\u00e4r\r\nspring suspension was developed for operation in cryogenic liquids. A high\r\nperformance digital signal processor (DSP) based control system was\r\nconstructed, and software with advanced spectroscopic imaging and data\r\nprocessing capabilities was developed.
\r\n\r\nThe feasibility of individual-molecule vibrational spectroscopy via\r\nSTM-detected inelastic electron tunneling is assessed. In preliminary\r\nexperiments, a low-temperature STM was used for energy gap and phonon\r\nspectroscopy of superconducting Pb films. The first STM observation of\r\nphonon density of states effects in a superconductor is reported.
\r\n\r\nA systematic UHV STM imaging and spectroscopy study of 2H-MoS_2\r\nwas conducted. Atom-resolved images from three distinct imaging modes\r\nare presented. Occasional appearance of negative differential resistance\r\n(NOR) in I vs. V measurements is traced to changing tip electronic structure\r\nrather than localized surface states. Other potential NOR mechanisms are\r\ndiscussed including electron trap charging and resonant tunneling through a\r\ndouble-barrier quantum well structure arising from layer separation in the\r\nMoS_2 crystal.
\r\n\r\nDNA was imaged at atomic resolution with a UHV STM. Images show\r\ndouble-helical structure, base pairs, and atomic-scale substructure.\r\nExperimental STM profiles have atom-for-atom correlation with the A-DNA\r\nvan der Waals surface. This work demonstrates the potential of the STM for\r\ncharacterization of large biomolecular structures.
\r\n\r\nImpurity-pinned steps on silicon and gold surfaces were imaged by\r\nSTM. Pinned gold steps have short linear coherence lengths and form step\r\nloops at impurities by an Orowan-type bypassing mechanism. Step loops\r\nwere not observed at Si(111) pinning sites; step contours seem to be correlated\r\nwith the degree of order in the Si surface reconstruction.
", "doi": "10.7907/0d6k-be86", "publication_date": "1993", "thesis_type": "phd", "thesis_year": "1993" }, { "id": "thesis:7310", "collection": "thesis", "collection_id": "7310", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12062012-140020355", "primary_object_url": { "basename": "Barrans_re_1993.pdf", "content": "final", "filesize": 69752237, "license": "other", "mime_type": "application/pdf", "url": "/7310/1/Barrans_re_1993.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Investigations in molecular recognition: statistical tools and experimental studies", "author": [ { "family_name": "Barrans", "given_name": "Richard E., Jr.", "clpid": "Barrans-R-E-Jr." } ], "thesis_advisor": [ { "family_name": "Dougherty", "given_name": "Dennis A.", "clpid": "Dougherty-D-A" } ], "thesis_committee": [ { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" }, { "family_name": "Dougherty", "given_name": "Dennis A.", "clpid": "Dougherty-D-A" }, { "family_name": "Imperiali", "given_name": "Barbara", "clpid": "Imperiali-B" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The free energies of formation of intermolecular complexes in solution are often\r\nestimated by fitting a nonlinear model to an NMR titration experiment. A regression\r\nprocedure that assigns weights to each observation on the basis of expected measurement\r\nerrors has been developed, and yields better parameter estimates than\r\nother methods in common use. Procedures for critically evaluating the fit of the\r\nmodel to the experimental data and for assigning confidence limits to the fitted parameters\r\nhave also been developed. These employ Monte Carlo simulations of the\r\nNMR titration experiment to obtain probability distributions that are not available\r\nby theoretical means.
\r\n\r\nAspects of the complexation behavior of a family of water-soluble macrocyclic\r\ncyclophanes are also described. Significant heat capacity effects, which are interpreted\r\nin terms of hydrophobic hydration, are seen in variable-temperature studies.\r\nThe alkylation reactions of pyridine-based compounds are accelerated by complexation\r\nwith these cyclophanes; an interpretation based on the dynamic properties of\r\nthe alkylation reaction, the solvent, and the cyclophane is offered. In addition, accounts\r\nof efforts to make axially-substituted cyclophanes, to synthesize cyclophanes\r\nincorporating a diphosphine ligand, to append additional water-solubilizing groups\r\nto the cyclophanes, and to employ small cyclophanes as complexants for alkali metal\r\ncations are given.
", "doi": "10.7907/42WC-0V58", "publication_date": "1993", "thesis_type": "phd", "thesis_year": "1993" }, { "id": "thesis:7294", "collection": "thesis", "collection_id": "7294", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11292012-090633873", "primary_object_url": { "basename": "Driscoll_rj_1993.pdf", "content": "final", "filesize": 36345789, "license": "other", "mime_type": "application/pdf", "url": "/7294/1/Driscoll_rj_1993.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Scanning Tunneling Microscopy and Spectroscopy: I. Semimetals and Semiconductors. II. Atom-Resolved Imaging of DNA", "author": [ { "family_name": "Driscoll", "given_name": "Robert James", "clpid": "Driscoll-Robert-James" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Beauchamp", "given_name": "Jesse L.", "orcid": "0000-0001-8839-4822", "clpid": "Beauchamp-J-L" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Okumura", "given_name": "Mitchio", "orcid": "0000-0001-6874-1137", "clpid": "Okumura-M" }, { "family_name": "Revel", "given_name": "Jean-Paul", "clpid": "Revel-J-P" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The topographic and electronic structure of semiconductor and semimetal surfaces were investigated using scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS), respectively. The longrange morphology and atomic-scale characteristics of cleaved materials such as highly oriented pyrolitic graphite (HOPG), boronated pyrolitic graphite (BPG), titanium disulfide, and gallium arsenide (GaAs) were revealed by STM performed under ultrahigh vacuum (UHV) conditions.
\r\n\r\nAtomic resolution constant-current and current-imaging data, as well as barrier height information obtained from tunneling gap modulation, are presented. Both point and line defects were observed on these surfaces; the origin and role of native and adsorbed surface defects are discussed. Visual evidence of coulombic screening caused by adsorption of charged species on n-type GaAs(110) is provided. The atomic corrugation of the GaAs surface was measured to be as little as 0.03 \u00c5 peak-to-valley, attesting to the stability of the microscope design. The BPG sample used in these studies consisted of up to 0.5% boron; boron is the only known substitutional impurity of graphite. Boron substituent atoms appeared as small protrusions approximately 3 \u00c5 in diameter, with an atom density consistent with the assumed concentration.The BPG surface exhibited frequent line defects, including large-angle grain\r\nboundaries, and monolayer-depth etch pits. Images of BPG in air using graphite tips showed similar results; the validity of the popular \"sliding-planes\" mechanism for graphite imaging is evaluated.
\r\n\r\nThe effects of anisotropic stress on the morphology and reconstruction of a thermally annealed Si(111) wafer were explored. The height and orientation of step bunches, as well as terrace widths, on the (7x7) surface were determined. Electromigration effects were also observed; although the overall surface slope was conserved, the step bunches were \"smeared out\" by reversal of the current direction during heating. Line fault defects at step\r\nkinks were observed; a theory for the origin and structure of these features based on stress relief is proposed. Current imaging tunneling spectroscopy (CITS) and localized STS revealed differences between the adatom sites of the\r\n(7x7) surface. Atom-resolved barrier height images were also obtained;comparison to constant-current images may in fact provide a means of differentiating between defects and adsorbed species on the surface. The local effective barrier height was seen to depend strongly on the \"cleanliness\" of the STM tip. The barrier height increased dramatically following voltage pulsing on the order of ten volts. The large height of the step bunches also provided a good test to evaluate the sharpness of the STM tip; examples of \"tip changes\" affecting image resolution and \"multiple-tipping\" are provided. Silicon samples annealed at temperatures below 1000\u00b0C revealed substantial\r\nsilicon carbide (SiC) contamination which effected step pinning. No SiC islands were observed on samples annealed above 1250\u00b0C.
\r\n\r\nIn addition, atom-resolved STM images of duplex DNA supported on a HOPG surface were obtained in UHV. These images revealed double-helical structure, major and minor groove alternation, base pairs, and atomic-scale substructure. Comparison of the DNA dimensions derived from the STM data were in agreement with those from x-ray crystallography for \"random-sequence\" A-form DNA. Cross sectional profiles of the experimental STM data showed excellent correlation with the atomic contours of the van der Waals surface of A-DNA. Barrier height cross-sections showed general correlation with the atomic-scale topography over the phosphate-sugar backbone but distinct anticorrelation (complementarity) over the base pair region. The problems of aggregation and deposition coverage are discussed in the context of possible future applications of STM to DNA sequencing. The use of alternate techniques of DNA deposition, including electrospray\r\nionization, for increased experimental reproducibility are described. The limitations of HOPG as a substrate for biomolecular adsorbates in STM experiments are evaluated.
\r\n", "doi": "10.7907/fp55-ng98", "publication_date": "1993", "thesis_type": "phd", "thesis_year": "1993" }, { "id": "thesis:7284", "collection": "thesis", "collection_id": "7284", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11262012-114541543", "primary_object_url": { "basename": "Fujiwara_m_1993.pdf", "content": "final", "filesize": 14388032, "license": "other", "mime_type": "application/pdf", "url": "/7284/1/Fujiwara_m_1993.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Characterization of pH-Dependent Poly(Acrylic Acid)-Vesicle Interaction and its Application in Cellular Drug Delivery", "author": [ { "family_name": "Fujiwara", "given_name": "Mitsuko", "clpid": "Fujiwara-Mitsuko" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Revel", "given_name": "Jean-Paul", "clpid": "Revel-J-P" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Polymers can be used to control drug targeting and drug release from phospholipid vesicles through changes in pH. Understanding the effect of polymers on vesicle properties is important in obtaining a better control over drug delivery using phospholipid vesicles. The pH-dependent interaction of poly(acrylic acid) (PAA) with phosphatidylcholine (PC) vesicles (bilayers) and monolayers was investigated to elucidate the mechanism of P AA-induced vesicle destabilization. PAA induced aggregation of vesicles below pH 4.6 and lipid intermixing of vesicles below pH 4.1. Mixing of aqueous contents was not observed, indicating that the process is not a true membrane fusion. An increase in the membrane permeability accompanied lipid intermixing of vesicles. Both the hydrocarbon chain and phospholipid headgroup packing was more disordered from\r\npolymer association as evidenced by the increase in the CH_2 asymmetric stretching peakwidth and peak position and by the increase in the binding of potential-sensitive dye to\r\nthe vesicle surface, respectively. Polymer binding to vesicles at pH 3.8 showed a negative cooperativity with a K_b of 1.5 x 10^6 M^(-1).The driving force for PAA adsorption on vesicles is the formation of hydrogen-bonds between the protonated carboxyl groups of the polymer and the phospholipid molecule. The polymer mobility was restricted upon complexation with vesicles as evidenced by the anisotropy measurements of polymerassociated fluorophore. The polymer-associated vesicles exhibited fused vesicles and tubular structures in freeze-fracture images. Formation of nonbihyer phases or phase separation was not detected in freeze-fracture images or ^(31)P-NMR powder spectra of PC vesicles. PAA induced expansion of PC monolayers at low pH, and the extent of expansion was dependent on the monolayer surface pressure and on the pH of the subphase. Polymer-induced expansion became more difficult at increasing monolayer packing density and increasing pH. Therefore PAA-induced destabilization of vesicles is believed to be initiated by partial penetration of PAA on vesicle surface. The stress on the membrane created by PAA association presumably resulted in the rupture of bilayer and lipid intermixing of vesicles.
\r\n", "doi": "10.7907/ky3h-q886", "publication_date": "1993", "thesis_type": "phd", "thesis_year": "1993" }, { "id": "thesis:7275", "collection": "thesis", "collection_id": "7275", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11192012-103302776", "primary_object_url": { "basename": "Clark_sm_1993.pdf", "content": "final", "filesize": 37671547, "license": "other", "mime_type": "application/pdf", "url": "/7275/1/Clark_sm_1993.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Advances in scanning force microscopy of biological structures", "author": [ { "family_name": "Clark", "given_name": "Steven Manning", "clpid": "Clark-Steven-Manning" } ], "thesis_advisor": [ { "family_name": "Revel", "given_name": "Jean-Paul", "clpid": "Revel-J-P" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Revel", "given_name": "Jean-Paul", "clpid": "Revel-J-P" }, { "family_name": "Bjorkman", "given_name": "Pamela J.", "orcid": "0000-0002-2277-3990", "clpid": "Bjorkman-P-J" }, { "family_name": "Fraser", "given_name": "Scott E.", "orcid": "0000-0002-5377-0223", "clpid": "Fraser-S-E" }, { "family_name": "Rees", "given_name": "Douglas C.", "orcid": "0000-0003-4073-1185", "clpid": "Rees-D-C" }, { "family_name": "Wold", "given_name": "Barbara J.", "orcid": "0000-0003-3235-8130", "clpid": "Wold-B-J" }, { "family_name": "Hood", "given_name": "Leroy E.", "orcid": "0000-0001-7158-3678", "clpid": "Hood-L-E" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "A multifacted approach to the imaging of biological structures by scanning force microscopy is described. The major problems addressed are the distortion of biological samples by excessive forces applied by the cantilever stylus and sample motion relative to the imaging substrate.
\r\n\r\nThe first two chapters discuss the design of digital signal processor based scanning force microscope control electronics and a novel microscope head that eliminates the application of excessive forces to the sample caused\r\nby electronic or vibrational noise.
\r\n\r\nThe third chapter presents a novel use of chemical vapor deposition for application of heterofunctional alkoxysilanes to scanning force microscopy imaging subsrates. This technique provides imaging substrates which have chemical groups that can be used for sample immobilization without compromising substrate smoothness. The use of the chemically derivatized substrates for scanning force microscopy is also explored.
\r\n\r\nThe final chapter presents high resolution images of bovine liver catalase micro-crystals. The images of the protein micro-crystals show resolution on the order of 2 to 3 nanometers allowing the visualization of individual catalase tetramers. To our knowledge this is the first report of images of protein micro-crystals taken by scanning force microscopy which have resolution comparable to that of electron microscopy.
\r\n", "doi": "10.7907/0vhp-pk35", "publication_date": "1993", "thesis_type": "phd", "thesis_year": "1993" }, { "id": "thesis:6671", "collection": "thesis", "collection_id": "6671", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09152011-080428062", "primary_object_url": { "basename": "Wang_w_1992.pdf", "content": "final", "filesize": 56468825, "license": "other", "mime_type": "application/pdf", "url": "/6671/1/Wang_w_1992.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Expression, structural and functional studies of fasciclin I", "author": [ { "family_name": "Wang", "given_name": "Wen-Ching", "clpid": "Wang-Wen-Ching" } ], "thesis_advisor": [ { "family_name": "Bjorkman", "given_name": "Pamela J.", "orcid": "0000-0002-2277-3990", "clpid": "Bjorkman-P-J" } ], "thesis_committee": [ { "family_name": "Rees", "given_name": "Douglas C.", "orcid": "0000-0003-4073-1185", "clpid": "Rees-D-C" }, { "family_name": "Bjorkman", "given_name": "Pamela J.", "orcid": "0000-0002-2277-3990", "clpid": "Bjorkman-P-J" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Zinn", "given_name": "Kai George", "orcid": "0000-0002-6706-5605", "clpid": "Zinn-K-G" }, { "family_name": "Davidson", "given_name": "Norman R.", "clpid": "Davidson-N-R" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Fasciclin I is a cell surface glycoprotein thought to be involved in growth cone guidance in the embryonic insect nervous system. It is expressed on the cell surfaces of all\r\nperipheral nervous system (PNS) axons, a subset of central nervous system (CNS) axons and on some nonneuronal cells. Fly embryos bearing mutations eliminating expression of\r\nboth fasciclin I and the Abelson tyrosine kinase exhibit a severe phenotype in which many axon pathways fail to form. Fasciclin I mediates homophilic adhesion in transfected tissue culture cells, suggesting that it may affect growth cone guidance through homophilic interactions. To facilitate structure-function studies of fasciclin I, we have generated mammalian (CHO) cell lines expressing fasciclin I at a high level. The expressed fasciclin I\r\nprotein was released from the cell surface in a soluble form by phospholipase C treatment. Milligram quantities of soluble expressed fasciclin I were purified on an immunoaffinity column. Large single crystals were obtained that diffracted to ~5 \u00c5 resolution which is\r\ninsufficient for a structure determination to atomic resolution by x-ray crystallography. In an effort to produce a form of fasciclin I more amenable to crystallization, we also generated CHO and Drosophila cell (S2) lines that produce a truncated form of fasciclin I.\r\nThe soluble fasciclin I expressed in S2 cells contains significantly less carbohydrate (~15 kDa) as compared to the molecules expressed in CHO cells. Therefore, S2-derived\r\nfasciclin I may be more suitable for crystallization. Biochemical characterization of the expressed fasciclin I indicates that fasciclin I exists as a monomer in solution, an observation consistent with homophilic interaction properties only if the interaction is of low affinity. Electron micrographs of fasciclin I suggest that it has a compact rectangular shape with no obvious flexible linker regions, in contrast to what has been seen in electron\r\nmicroscopic studies of other adhesion molecules. Circular dichroism analysis suggests that fasciclin I contains significant amounts of \u03b1-helical structure, which together with the electron microscopic results, suggests that its structure is substantially different from the \u03b2-sheet structures predicted for adhesion molecules that are members of the immunoglobulin superfamily and/or contain fibronectin III repeats. Future structural and functional studies of fasciclin I will ultimately increase our understanding of neuronal cell surface recognition\r\nand axon guidance.\r\n", "doi": "10.7907/ykbt-jt41", "publication_date": "1992", "thesis_type": "phd", "thesis_year": "1992" }, { "id": "thesis:6644", "collection": "thesis", "collection_id": "6644", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09012011-151648229", "primary_object_url": { "basename": "Baker_sm_1992.pdf", "content": "final", "filesize": 52406562, "license": "other", "mime_type": "application/pdf", "url": "/6644/1/Baker_sm_1992.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Scanning Tunneling Microscopy and Spectroscopy of Silicon and Carbon Surfaces", "author": [ { "family_name": "Baker", "given_name": "Shenda Mary", "orcid": "0000-0002-9985-473X", "clpid": "Baker-Shenda-Mary" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Rossman", "given_name": "George Robert", "orcid": "0000-0002-4571-6884", "clpid": "Rossman-G-R" }, { "family_name": "Beauchamp", "given_name": "Jesse L.", "orcid": "0000-0001-8839-4822", "clpid": "Beauchamp-J-L" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Scanning Tunneling Microscopy (STM) investigations and additional surface analyses were performed on carbon and silicon surfaces. A number of anomalies have been observed on highly oriented pyrolytic graphite (HOPG), including large corrugations, distorted images, large range of tip motion and the absence of defects. A mechanism involving direct contact between tip and sample or contact through a contamination layer to provide an additional conduction pathway is proposed. This model of point-contact imaging provides an explanation for added stability of the STM system, a mechanism for producing multiple tips or sliding graphite planes and an explanation for the observed anomalies. These observations indicate that the use of HOPG for testing and calibration of STM instrumentation may be misleading. Designs for the atmospheric STM used in this study are also presented.
\r\n\r\nThe conditions necessary for preparing a dean silicon(111) (7x7) surface are discussed. The design and analysis of heaters necessary to prepare the silicon reconstructed surface at ultrahigh vacuum (UHV) are described. Results from both radiatively and resistively heated samples are shown in addition to a comparision of topographic and barrier height images of the boron (\u221a3 x\u221a3) reconstructed surfaces. A spectroscopic distinction between sites of boron, silicon or contaminants is demonstrated.
\r\n\r\nA synthetic boron-doped diamond was examined by a number of analytical techniques in order to determine its composition and surface morphology. Current-voltage spectroscopy taken with the STM indicates that the diamond Fermi level can be pinned in atmospheric conditions. In ultrahigh vacuum, band bending is observed, but the strength of the electric field experienced by the diamond semiconductor is less than expected; introduction of surface charges is shown to account for the field screening.
\r\n\r\nPresentation of an STM study of a protein-antibody complex on a gold surface illustrates the requirements for and difficulties of imaging large biomolecules. A flat, conducting substrate and sample stability on the surface\r\nare shown and discussed. Molecular manipulation by the STM tip is also presented. Although routine imaging of large adsorbates on surfaces is not yet possible, this study presents the obstacles and the potential afforded by the STM in attaining this goal.
\r\n", "doi": "10.7907/5JGQ-4X60", "publication_date": "1992", "thesis_type": "phd", "thesis_year": "1992" }, { "id": "thesis:6665", "collection": "thesis", "collection_id": "6665", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09132011-085913260", "primary_object_url": { "basename": "Di_simone_c_1992.pdf", "content": "final", "filesize": 33456897, "license": "other", "mime_type": "application/pdf", "url": "/6665/1/Di_simone_c_1992.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "The Membrane Fusion Activities of Native and Reconstituted Mumps and Sendai Viruses", "author": [ { "family_name": "Di Simone", "given_name": "Christopher", "clpid": "Di-Simone-Christopher" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Richards", "given_name": "John H.", "clpid": "Richards-J-H" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Dervan", "given_name": "Peter B.", "orcid": "0000-0001-8852-7306", "clpid": "Dervan-P-B" }, { "family_name": "Strauss", "given_name": "James H.", "clpid": "Strauss-J-H" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The structure and activities of whole and reconstituted Sendai and mumps viruses were examined using a number of physical and biological techniques: electron microscopy, photon correlation spectroscopy, perturbed angular\r\ncorrelation spectroscopy, gel electrophoresis, hemagglutination assays, plaque assays, fluorescence microscopy and fluorescent assays of membrane fusion. The fluorescent probe octadecyl rhodamine (RIB) was found to have a proximal transfer behavior which reduced usage of the probe as a membrane fusion indicator to short time periods. Simple bireactant and mass action kinetic models were sufficent to fit the data provided by the fluorescent assays on viral fusion with cell membranes. The\r\nreconstitution of mumps virus was optimized by using the detergent Triton X-IOO. Reconstituted virus envelopes which were the same size as whole virus and which were active in binding and fusing to cells were produced. The reconstituted Sendai and mumps virus accumulated in the reticuloendothelial system when injected into mice and hamsters, respectively. The kinetics of the membrane fusion activity of mumps with ghost erythrocytes and CV-I cells was measured and analysed. A general rate of reaction of 3 (\u00b11) x 10^9 M^-l sec^-1 was found. The membrane fusion activity of reconstituted Sendai with HL60, U937, Cos, H9\r\nand PBL cell lines was also measured and analyzed. The fusion activity was utilized to deliver plasmids for transfection to the interiors of the HL60 and Cos cells. Luciferase expression was found in the Cos cells but not in the HL60 cells. Loading of plasm ids into the vesicle interiors was enhanced by a factor of ten by complexing the DNA with the positive proteins polylysine, lysozyme and protamine.\r\n", "doi": "10.7907/rr73-5d56", "publication_date": "1992", "thesis_type": "phd", "thesis_year": "1992" }, { "id": "thesis:2576", "collection": "thesis", "collection_id": "2576", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06132007-103520", "primary_object_url": { "basename": "Kramar_ja_1990.pdf", "content": "final", "filesize": 12143834, "license": "other", "mime_type": "application/pdf", "url": "/2576/1/Kramar_ja_1990.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Scanning Tunneling Microscopy and Spectroscopy of Molybdenum Disulfide", "author": [ { "family_name": "Kramar", "given_name": "John Adam", "orcid": "0000-0001-6038-637X", "clpid": "Kramar-John-Adam" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Beauchamp", "given_name": "Jesse L.", "orcid": "0000-0001-8839-4822", "clpid": "Beauchamp-J-L" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Marcus", "given_name": "Rudolph A.", "orcid": "0000-0001-6547-1469", "clpid": "Marcus-R-A" }, { "family_name": "Okumura", "given_name": "Mitchio", "orcid": "0000-0001-6874-1137", "clpid": "Okumura-M" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Scanning tunneling microscopy (STM) is a recently developed surface analysis technique that is capable of atomic resolution imaging in real space. In STM, a sharp electrically conducting tip is brought near the sample and a tunneling current is established between the two. For topographical imaging, the tip is then raster-scanned over the surface while a feedback control system maintains constant current by adjusting the position of the tip in the surface normal. The trajectory that the tip follows is displayed as the surface topography. The unique geometry of the STM has also allowed the electronic nature of surfaces to be probed with unprecedented spatial resolution. This can be implemented, for example, by posing the probe tip over a specific surface location and examining the current-versus-voltage characteristics.\r\n\r\nCareful consideration must be given in the design of an STM system. The crucial elements of vibration isolation and microscope rigidity must be optimized within the constraints of allowing coarse positioning of the tip and sample and permitting high-resolution scanning. A stable feedback control system must also be designed with flexibility to allow for different operating conditions.\r\n\r\nWe have built an ultrahigh vacuum (UHV) STM that is similar to the familiar pocket STM design. The UHV system includes a separate sample preparation chamber and vacuum-transfer load lock to facilitate in studies of clean, carefully prepared surfaces. The instrument is interfaced with a microprocessor for control of scanning, data acquisition, and coarse tip-sample approach and positioning. A high-resolution graphics monitor is also included for displaying the topographic images and the current-voltage spectra during acquisition and for reviewing previously stored images.\r\n\r\nStudies of the basal cleavage plane of MoS2 have been performed with this instrument. Large area images up to 360 x 360 nm reveal a high degree of variability in surface morphology, ranging from atomically smooth planes, to islands or mounds ranging from 1 to 10 nm in diameter, to areas of complete surface roughness. Many unusual imaging phenomena were also observed in these scans, including bias-dependent images and surface modifications that were due to tip-sample interactions.\r\n\r\nAtomic-resolution images revealing the trigonal symmetry of the surface plane were obtained in both the constant-current and current-imaging modes on the smooth areas of the surface. Two distinct sites can be seen, corresponding to the known molybdenum and sulfur atomic positions.\r\n\r\nA simple description of the distance dependence of tunneling between the STM tip and an ideal semiconductor surface (no surface Fermi level pinning) is presented, based on conventional metal-insulator-semiconductor (MIS) theories. The current conduction mechanism involves thermionic emission over the semiconductor diffusion-potential barrier, which is a decreasing function of the tip-sample separation, followed by tunneling through the vacuum gap. The competition between the decreased vacuum-tunneling probability and the increased carrier population at the semiconductor surface for increasing separation gives rise to a predicted peak in the I-s curves at small separations, and a lowering of the apparent tunneling barrier height out to separations of more than 1 nm. The normally rectified current-voltage characteristics are also found to be a function of the tip-sample spacing, showing a weakening and then a reversal of rectification as the separation is increased. These predicted effects are substantiated by means of a detailed numerical calculation for the passivated n-type Si(111) surface.\r\n\r\nThe current-voltage spectroscopy of MoS2, which is expected to behave as an ideal semiconductor, was examined. The surface-averaged spectra show a high degree of variability, with different data sets showing rectification in opposite polarities for the same physical tip and sample. The results are shown to be qualitatively different from known mechanisms for rectification in STM, including tip-curvature-induced field gradient effects and effects that are due to the separation dependence of rectification in ideal MIS structures. The results are best explained as doping inhomogeneities in our mineralogical samples.\r\n", "doi": "10.7907/Q36A-AW73", "publication_date": "1990", "thesis_type": "phd", "thesis_year": "1990" }, { "id": "thesis:2519", "collection": "thesis", "collection_id": "2519", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06082007-084319", "primary_object_url": { "basename": "Hardy_wr_1990.pdf", "content": "final", "filesize": 13015288, "license": "other", "mime_type": "application/pdf", "url": "/2519/1/Hardy_wr_1990.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "The characterization and processing of the nonstructural proteins of Sindbis virus", "author": [ { "family_name": "Hardy", "given_name": "Winters Reef", "clpid": "Hardy-W-R" } ], "thesis_advisor": [ { "family_name": "Richards", "given_name": "John H.", "clpid": "Richards-J-H" } ], "thesis_committee": [ { "family_name": "Campbell", "given_name": "Judith L.", "clpid": "Campbell-J-L" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Emr", "given_name": "Scott D.", "clpid": "Emr-S-D" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document.\n\nSHORT ABSTRACT:\n\nThe nonstructural proteins of Sindbis virus, the type alphavirus of the family Togaviridae, are produced by proteolytic cleavage of two polyprotein precursors. One precursor (P123) is 1,896 amino acids in length and contains the sequences of nsP1, nsP2, and nsP3, while the second (P1234) of 2,513 amino acids is produced by readthrough of an opal termination codon and contains a fourth nonstructural protein, nsP4.\n\nIn order to study the kinetics of processing of these polyproteins, monospecific antisera were produced in rabbits to fusion protein antigens containing the N-terminal two-thirds of the trpE protein of E. coli fused to a large part of the sequence within each of the nonstructural proteins of Sindbis virus. Using these antisera the following details of processing were elucidated: i) most nonstructural proteins arise from the processing of the completed precursor P123 and its cleavage product, P12; ii) in the P123 precursor, the primary cleavage occurs in trans, between nsP2 and nsP3 to generate P12 and nsP3 with a half-life of [...]19 min. in vivo, followed by processing of P12 to produce nsP1 and nsP2, either intramolecularly or in trans, at a rate which exceeds that of the first cleavage; iii) processing of the 3-4 site is complex; and iv) nsP3 was found to be phosphorylated during posttranslational modification.\n\nIn vitro, processing could be inhibited with antibodies to nsP2, but not with antisera to the other three nonstructural proteins, suggesting that the nonstructural proteinase is in nsP2. Deletion-mapping studies were performed which further localized the proteinase to a region of approximately 334 amino acids at the C terminus of nsP2. From a comparison of the deduced sequences of several alphaviruses in this part of nsP2 with the sequences of cellular proteinases, a hypothesis was presented that the proteinase is a thiol protease related to papain. Finally, the examination of several temperature-sensitive mutants of Sindbis virus has confirmed the importance of this region as only mutants that possessed a mutation in the C-terminal domain of nsP2 produced aberrant processing patterns at the nonpermissive temperature.\n", "doi": "10.7907/gk9d-5371", "publication_date": "1990", "thesis_type": "phd", "thesis_year": "1990" }, { "id": "thesis:8602", "collection": "thesis", "collection_id": "8602", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07242014-161229419", "primary_object_url": { "basename": "Kibbe_WA_1990.pdf", "content": "final", "filesize": 13189151, "license": "other", "mime_type": "application/pdf", "url": "/8602/1/Kibbe_WA_1990.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "A Detailed Analysis of Transcriptional Regulators Affecting the Saccharomyces cerevisiae Heat-shock Gene SSA1", "author": [ { "family_name": "Kibbe", "given_name": "Warren Alden", "clpid": "Kibbe-W-A" } ], "thesis_advisor": [ { "family_name": "Parker", "given_name": "Carl Stevens", "clpid": "Parker-C-S" } ], "thesis_committee": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Campbell", "given_name": "Judith L.", "clpid": "Campbell-J-L" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" }, { "family_name": "Richards", "given_name": "John H.", "clpid": "Richards-J-H" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The yeast Saccharomyces cerevisiae contains a family of hsp70 related genes. One member of this family, SSA1, encodes a 70kD heat-shock protein which in addition to its heat inducible expression has a significant basal level of expression. The first 500 bp upstream of the SSA1 start point of transcription was examined by DNAse I protection analysis. The results reveal the presence of at least 14 factor binding sites throughout the upstream promoter region. The function of these binding sites has been examined using a series of 5' promoter deletions fused to the recorder gene lacZ in a centromere-containing yeast shuttle vector. The following sites have been identified in the promoter and their activity in yeast determined individually with a centromere-based recorder plasmid containing a truncated CYC1 /lacZ fusion: a heat-shock element or HSE which is sufficient to convey heat-shock response on the recorder plasmid; a homology to the SV40 'core' sequence which can repress the GCN4 recognition element (GCRE) and the yAP1 recognition element (ARE), and has been designated a upstream repression element or URE; a 'G'-rich region named G-box which can also convey heatshock response on the recorder plasmid; and a purine-pyrimidine alternating sequence name GT-box which is an activator of transcription. A series of fusion constructs were made to identify a putative silencer-like element upstream of SSA1. This element is position dependent and has been localized to a region containing both an ABF1 binding site and a RAP1 binding site. Five site-specific DNA-binding factors are identified and their purification is presented: the heat-shock transcription factor or HSTF, which recognizes the HSE; the G-box binding factor or GBF; the URE recognition factor or URF; the GT-box binding factor; and the GC-box binding factor or yeast Sp1.
", "doi": "10.7907/fraq-3065", "publication_date": "1990", "thesis_type": "phd", "thesis_year": "1990" }, { "id": "thesis:8609", "collection": "thesis", "collection_id": "8609", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07252014-124055207", "primary_object_url": { "basename": "Novick-sl-1990.pdf", "content": "final", "filesize": 25152660, "license": "other", "mime_type": "application/pdf", "url": "/8609/1/Novick-sl-1990.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Chemical Studies of Viral Entry Mechanisms: I. Hydrophobic Protein-Lipid Interactions During Sendai Virus Membrane Fusion. II. Kinetics of Bacteriophage \u03bb DNA Injection", "author": [ { "family_name": "Novick", "given_name": "Steven Louis", "clpid": "Novick-Steven-Louis" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Richards", "given_name": "John H.", "clpid": "Richards-J-H" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" }, { "family_name": "Strauss", "given_name": "James H.", "clpid": "Strauss-J-H" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Viruses possess very specific methods of targeting and entering cells. These methods would be extremely useful if they could also be applied to drug delivery, but little is known about the molecular mechanisms of the viral entry process. In order to gain further insight into mechanisms of viral entry, chemical and spectroscopic studies in two systems were conducted, examining hydrophobic protein-lipid interactions during Sendai virus membrane fusion, and the kinetics of bacteriophage \u03bb DNA injection.
\r\n\r\nSendai virus glycoprotein interactions with target membranes during the early stages of fusion were examined using time-resolved hydrophobic photoaffinity labeling with the lipid-soluble carbene generator3-(trifluoromethyl)-3-(m-^(125\r\n)I] iodophenyl)diazirine (TID). The probe was incorporated in target membranes prior to virus addition and photolysis. During Sendai virus fusion with liposomes composed of cardiolipin (CL) or phosphatidylserine (PS), the viral fusion (F) protein is preferentially labeled at early time points, supporting the hypothesis that hydrophobic interaction of the fusion peptide at the N-terminus of the F_1 subunit with the target membrane is an initiating event in fusion. Correlation of the hydrophobic interactions with independently monitored fusion kinetics further supports this conclusion. Separation of proteins after labeling shows that the F_1 subunit, containing the putative hydrophobic fusion sequence, is exclusively labeled, and that the F_2 subunit does not participate in fusion. Labeling shows temperature and pH dependence consistent with a need for protein conformational mobility and fusion at neutral pH. Higher amounts of labeling during fusion with CL vesicles than during virus-PS vesicle fusion reflects membrane packing regulation of peptide insertion into target membranes. Labeling of the viral hemagglutinin/neuraminidase (HN) at low pH indicates that HN-mediated fusion is triggered by hydrophobic interactions, after titration of acidic amino acids. HN labeling under nonfusogenic conditions reveals that viral binding may involve hydrophobic as well as electrostatic interactions. Controls for diffusional labeling exclude a major contribution from this source. Labeling during reconstituted Sendai virus envelope-liposome fusion shows that functional reconstitution involves protein retention of the ability to undergo hydrophobic interactions.
\r\n\r\nExamination of Sendai virus fusion with erythrocyte membranes indicates that hydrophobic interactions also trigger fusion between biological membranes, and that HN binding may involve hydrophobic interactions as well. Labeling of the erythrocyte membranes revealed close membrane association of spectrin, which may play a role in regulating membrane fusion. The data show that hydrophobic fusion protein interaction with both artificial and biological membranes is a triggering event in fusion. Correlation of these results with earlier studies of membrane hydration and fusion kinetics provides a more detailed view of the mechanism of fusion.
\r\n\r\nThe kinetics of DNA injection by bacteriophage \u03bb. into liposomes bearing reconstituted receptors were measured using fluorescence spectroscopy. LamB, the bacteriophage receptor, was extracted from bacteria and reconstituted into liposomes by detergent removal dialysis. The DNA binding fluorophore ethidium bromide was encapsulated in the liposomes during dialysis. Enhanced fluorescence of ethidium bromide upon binding to injected DNA was monitored, and showed that injection is a rapid, one-step process. The bimolecular rate law, determined by the method of initial rates, revealed that injection occurs several times faster than indicated by earlier studies employing indirect assays.
\r\n\r\nIt is hoped that these studies will increase the understanding of the mechanisms of virus entry into cells, and to facilitate the development of virus-mimetic drug delivery strategies.
\r\n", "doi": "10.7907/k40w-2z72", "publication_date": "1990", "thesis_type": "phd", "thesis_year": "1990" }, { "id": "thesis:2503", "collection": "thesis", "collection_id": "2503", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06072007-091301", "type": "thesis", "title": "Modification of Membrane Surfaces with Carbohydrates: An Approach for Stabilization During Freezing and Drying", "author": [ { "family_name": "Goodrich", "given_name": "Raymond Paul, Jr.", "orcid": "0000-0002-5945-4571", "clpid": "Goodrich-Raymond-Paul-Jr" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Revel", "given_name": "Jean-Paul", "clpid": "Revel-J-P" }, { "family_name": "Imperiali", "given_name": "Barbara", "orcid": "0000-0002-5749-7869", "clpid": "Imperiali-B" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "A new class of molecules possessing amphipathic character was prepared. These compounds possessed a hydrophobic region capable of intercalation into a lipid bilayer, a hydrophilic linker group capable of extending beyond the surface of a membrane, and a carbohydrate attached at the end of this linker group. These features of this class of compounds permitted their direct incorporation into vesicle formulations and hence the direct examination of interactions occuring in the dry state between carbohydrates and lipid groups in such vesicle membrane systems.
\r\n\r\nSamples of treated vesicle preparations were subjected to freezing and thawing as well as to direct dehydration via lyophilization. Under these conditions, the stability and integrity of the membrane was examined via several spectroscopic techniques.
\r\n\r\nThrough these studies of systems in which a carbohydrate is directly bound to a membrane surface, it was possible to determine a defined ratio, independent of solution and concentration effects, at which carbohydrates can afford protection to dehydrated membranes. In addition, the interactions responsible for conferring the protection were determined. It was found that direct intercalation of the carbohydrates into a membrane interface preserves the membrane structure and organization that is normally observed in the presence of water. This behavior prevents the phase transitions, lipid phase separations, and fusion phenomena that normally compromise dehydrated membrane systems. This phenomena is directly related to the amount of carbohydrate that is present and the structure of the carbohydrate that is used. These results indicate that the partitioning behavior of the carbohydrates at the interface is of prime importance in determining the effectiveness in this regard.
", "doi": "10.7907/ff9e-th51", "publication_date": "1990", "thesis_type": "phd", "thesis_year": "1990" }, { "id": "thesis:2518", "collection": "thesis", "collection_id": "2518", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06082007-081855", "type": "thesis", "title": "Disulphide Polymerizeable Phosphatidylcholines: Characterization of Membrane Physical Properties and Investigations of in vivo Behavior", "author": [ { "family_name": "Handel", "given_name": "Tracy Marie", "orcid": "0000-0002-2558-6138", "clpid": "Handel-Tracy-Marie" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Dervan", "given_name": "Peter B.", "orcid": "0000-0001-8852-7306", "clpid": "Dervan-P-B" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "In the past ten years, polymerizeable amphiphiles have been recognized as an important class of synthetic phospholipids due to their ability to modify the mechanical and chemical stability of membranes. The motivation behind studies of polymerizeable phospholipids is based on the potential importance of stable membranes in a wide variety of applications including reactivity control, encapsulation technologies and drug delivery. However, compared to nonpolymerizeable lipids, there is a relative paucity of information correlating membrane physical properties with the structure of the polymeric lipid. The present investigation involves the synthesis of a series of disulfide polymerizeable phosphatidylcholines, the characterization of the physical properties of membranes formed from these lipids, and an investigation of the biodistributions, vascular clearance rates and degradation rates of these liposomes in vivo.
\r\n\r\nThe structures of the lipids under investigation are analogous to saturated phosphayitdylcholines but with a thiol either alpha to the carbonyl of the acyl chain (\u03b1-THIOL) or at the chain terminus (\u03c9-THIOL). It is found that the presence and position of the polymerizeable moiety drastically alters the physical characteristics of the membranes. A variety of physical techniques have been utilized to understand both the bulk properties of the lipids such as morphology and permeability, as well as the molecular details of the lipid conformation and dynamics. On the basis of such studies including Raman, FT-IR and DSC, it appears that the presence of the polymerizeable group at the interfacial region (\u03b1-THIOLS) causes a reduction in the lipid packing and an increase in chain disorder compared to nonpolymerizeable analogs. For the monomeric form of the \u03b1-THIOLS, the decreased interlipid interaction may be ascribed to the presence of an additional hydrophilic pendant group at the interface that interferes with tight crystalline packing, most likely by a combination of steric and hydration effects. In contrast to the general expectations for polymerized versus nonpolymerized phospholipids, upon polymerization, the membrane disorder is augmented even further. We believe this to be a consequence of the conformational restrictions of polymerization which inhibit the ability of the polymeric lipids to adopt a highly ordered and uniform packing state. Instead it is suspected that the reduced conformational freedom of polymerized lipids promotes the formation of surface defects between unlinked polymer chains. As a morphological consequence, the polymeric \u03b1-THIOLS tend to form smaller and largely unilamellar vesicles on dispersion in water. Furthermore because of the disorder in the hydrocarbon chain region, they are quite permeable to entrapped solutes and when administered in vivo, are cleared rapidly from the circulatory system. The latter effect is likely the result of facilitated absorption of opsonizing proteins into the disordered membrane surface which subsequently accelerates vascular clearance and uptake by the cells of the reticuloendothelial system (RES).
\r\n\r\nOn the basis \u00b3\u00b9P NMR relaxation measurements, it was observed that the motion of the headgroups in polymeric \u03b1-THIOLS was reduced relative to nonpolymerizeable analogs. Furthermore a reduced chemical shift anisotropy of polymeric \u03b1-THIOLS in the liquid-crystalline state relative to nonpolymerizeable lipids was observed and suggests an alteration in the average orientation of the headgroup for the polymer. Because the headgroup of phosphatidylcholines is zwitterionic, changes in the average orientation can have marked effects on the electrostatic properties of the membrane surface, which in turn can affect membrane morphology and interactions with cell-surfaces and proteins.
\r\n\r\nFor \u03c9-THIOLS, a distinctly different behavior was observed compared to the \u03b1-THIOLS. For the monomers and especially the polymers, results from vibrational spectroscopy and DSC suggest that the membrane conformational order and rigidity is increased relative to nonpolymerizeable phosphatidylcholine analogues. However, in contrast to the \u03b1-THIOLS that form normal self-sealed liposomal structures in both the monomeric and polymeric state, polymerization induces the transformation of \u03c9-THIOLS into bilayer fragments lacking an internal aqueous compartment. The most likely explanation for this was derived from \u00b9\u00b3C NMR relaxation experiments, which indicated that the mobility at the bilayer midplane of polymeric \u03c9-THIOLS is as restricted as the interfacial region. This contrasts to nonpolymerizeable phospholipids and \u03b1-THIOLS, which have the bilayer interior as the most fluid portion of the membrane. The rigidity at the midplane may prohibit the ability of the polymeric \u03c9-THIOLS to form curved or continuous multilamellar sheets or to respond to transient defects in the membrane without fragmentation.
\r\n\r\nAn interesting and unexpected result concerning the \u03c9-THIOLS was retention of a phase transition after polymerization. For most polymeric lipids that have the polymerizeable moiety at the chain terminus, polymerization has resulted in the disappearance of the transition due to crosslinking of the hydrocarbon chains. The presence of the transition in polymerized \u03c9-THIOLS may be evidence for the fact that polymerization results in a predominance of intra- rather than inter-leaflet coupled chains.
", "doi": "10.7907/x0z5-ef38", "publication_date": "1989", "thesis_type": "phd", "thesis_year": "1989" }, { "id": "thesis:5377", "collection": "thesis", "collection_id": "5377", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11132009-134341582", "type": "thesis", "title": "Insights on Enzymes and Polymers from Molecular Dynamics Simulations: Applications to Dihydrofolate Reductase Complexes and Starburst Dendrimers", "author": [ { "family_name": "Naylor", "given_name": "Adel Marie", "clpid": "Naylor-Adel-Marie" } ], "thesis_advisor": [ { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" } ], "thesis_committee": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Richards", "given_name": "John H.", "clpid": "Richards-J-H" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Examples are given for the role of simulation and theory in designing artificial biomimetic and biocatalytic systems. Simulations on the \u03b2-alanine starburst dendrimer polymers indicate that, for the higher generation systems: (1) ~50% of the surface area is internal, and (ii) ~50% of the spheroidal volume is solvent- filled. These studies suggest a design for encapsulating and delivering dopamine to the kidney for cardiovascular therapies. Investigations of the penta-erythritol based polyether starburst dendrimers show that: (i) the later generations lack any internal surface area or volume and (ii) the dense-packed limit for these polymers to be the third generation, consistent with experiment. For Dihydrofolate Reductase (DHFR), the modeling and simulations: (i) explain the high degree of kinetic similarity between two dissimilar forms of DHFR; (ii) indicate why site specific mutation (Phe-31\u2192Tyr-31, Leu-54\u2192Ile-54, or Leu-54\u2192Gly-54) causes a significant change in the catalytic rate; and (iii) suggest modifications to engineer E. coli Chicken hybrid proteins capable of reducing folate.
", "doi": "10.7907/0789-jw44", "publication_date": "1989", "thesis_type": "phd", "thesis_year": "1989" }, { "id": "thesis:7948", "collection": "thesis", "collection_id": "7948", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08272013-134530519", "primary_object_url": { "basename": "Vogelaar 1989.pdf", "content": "final", "filesize": 28258634, "license": "other", "mime_type": "application/pdf", "url": "/7948/1/Vogelaar 1989.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Structural and Mechanistic Motifs in Membrane Proteins: The Three-Dimensional Modelling of Rhodopsin, Band 3, and the Nicotinic Acetylcholine Receptor", "author": [ { "family_name": "Vogelaar", "given_name": "Nancy Swick", "clpid": "Vogelaar-Nancy-Swick" } ], "thesis_advisor": [ { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Chan", "given_name": "Sunney I.", "clpid": "Chan-S-I" } ], "thesis_committee": [ { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" }, { "family_name": "Marsh", "given_name": "Richard Edward", "clpid": "Marsh-R-E" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Because so little is known about the structure of membrane proteins, an attempt has been made in this work to develop techniques by which to model them in three dimensions. The procedures devised rely heavily upon the availability of several sequences of a given protein. The modelling procedure is composed of two parts. The first identifies transmembrane regions within the protein sequence on the basis of hydrophobicity, \u03b2-turn potential, and the presence of certain amino acid types, specifically, proline and basic residues. The second part of the procedure arranges these transmembrane helices within the bilayer based upon the evolutionary conservation of their residues. Conserved residues are oriented toward other helices and variable residues are positioned to face the surrounding lipids. Available structural information concerning the protein's helical arrangement, including the lengths of interhelical loops, is also taken into account. Rhodopsin, band 3, and the nicotinic acetylcholine receptor have all been modelled using this methodology, and mechanisms of action could be proposed based upon the resulting structures.
\r\n\r\nSpecific residues in the rhodopsin and iodopsin sequences were identified, which may regulate the proteins' wavelength selectivities. A hinge-like motion of helices M3, M4, and M5 with respect to the rest of the protein was proposed to result in the activation of transducin, the G-protein associated with rhodopsin. A similar mechanism is also proposed for signal transduction by the muscarinic acetylcholine and \u03b2-adrenergic receptors.
\r\n\r\nThe nicotinic acetylcholine receptor was modelled with four trans-membrane helices per subunit and with the five homologous M2 helices forming the cation channel. Putative channel-lining residues were identified and a mechanism of channel-opening based upon the concerted, tangential rotation of the M2 helices was proposed.
\r\n\r\nBand 3, the anion exchange protein found in the erythrocyte membrane, was modelled with 14 transmembrane helices. In general the pathway of anion transport can be viewed as a channel composed of six helices that contains a single hydrophobic restriction. This hydrophobic region will not allow the passage of charged species, unless they are part of an ion-pair. An arginine residue located near this restriction is proposed to be responsible for anion transport. When ion-paired with a transportable anion it rotates across the barrier and releases the anion on the other side of the membrane. A similar process returns it to its original position. This proposed mechanism, based on the three-dimensional model, can account for the passive, electroneutral, anion exchange observed for band 3. Dianions can be transported through a similar mechanism with the additional participation of a histidine residue. Both residues are located on M10.
", "doi": "10.7907/mgah-n841", "publication_date": "1989", "thesis_type": "phd", "thesis_year": "1989" }, { "id": "thesis:7946", "collection": "thesis", "collection_id": "7946", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08262013-151906759", "type": "thesis", "title": "Preparation and Characterization of and Intramolecular Electron Transfer in a Pentaammineruthenium Derivative of Candida krisei Cytochrome c", "author": [ { "family_name": "Selman", "given_name": "Mary", "clpid": "Selman-Mary" } ], "thesis_advisor": [ { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" } ], "thesis_committee": [ { "family_name": "Campbell", "given_name": "Judith L.", "clpid": "Campbell-J-L" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Hopfield", "given_name": "John J.", "clpid": "Hopfield-J-J" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "A semisynthetic binuclear metalloprotein has been prepared by appending the pentaammineruthenium moiety to histidine 39 of the cytochrome c from the yeast Candida krusei. The site of ruthenium binding was identified by peptide mapping. Spectroscopic and electrochemical properties of the derivative indicate the protein conformation is unperturbed by the modification. A preliminary (minimum) rate constant of 170s-1 has been determined for the intramolecular electron transfer from ruthenium(II) to iron(III), which occurs over a distance of at least 13\u00c5 (barring major conformational changes). Electrochemical studies indicate that this reaction should proceed with a driving force of ~170mV. The rate constant is an order of magnitude faster than that observed in horse heart cytochrome c for intramolecular electron transfer from pentaammineruthenium(II)(histidine 33) to iron(III) (over a similar distance, and with a similar driving force), suggesting a medium or orientation effect makes the Candida intramolecular electron transfer more favorable.
", "doi": "10.7907/hpxj-n706", "publication_date": "1989", "thesis_type": "phd", "thesis_year": "1989" }, { "id": "thesis:7504", "collection": "thesis", "collection_id": "7504", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03072013-150951099", "primary_object_url": { "basename": "Shepodd-tj-1988.pdf", "content": "final", "filesize": 23057021, "license": "other", "mime_type": "application/pdf", "url": "/7504/1/Shepodd-tj-1988.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Studies in Molecular Recognition: Hydrophobic Binding of Water-Soluble Guests by High Symmetry, Chiral Hosts", "author": [ { "family_name": "Shepodd", "given_name": "Timothy Jon", "clpid": "Shepodd-Timothy-Jon" } ], "thesis_advisor": [ { "family_name": "Dougherty", "given_name": "Dennis A.", "clpid": "Dougherty-D-A" } ], "thesis_committee": [ { "family_name": "Dervan", "given_name": "Peter B.", "clpid": "Dervan-P-B" }, { "family_name": "Dougherty", "given_name": "Dennis A.", "clpid": "Dougherty-D-A" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "A new class of high-symmetry, water-soluble receptors has been synthesized. The enantiomerically pure hosts are D\u2082-symmetric and are synthesized in 8 steps with an overall yield of 5-10%. An asymmetric Diels-Alder reaction between di-(+)-menthyl fumarate and 2,6-di-t-butyldimethylsiloxyanthracene leads to two diastereomeric Diels-Alder adducts that are elaborated to the key intermediates: (+)- and (-)-2,6-dihydroxy-11,12-dicarbomethoxy-9,10-ethenoanthracene. A number of hosts are synthesized from these intermediates when they are connected by variable linker units. These hosts possess chiral cavities (receptor sites) surrounded by an array of substituted aromatic rings.
\r\n\r\nThe ability of these hosts to complex water-soluble guests with different sizes, shapes, and degrees of preorganization has been quantified by NMR. The electron-rich hosts have a general affinity for electron-deficient guests. Hosts P and M show a moderate hydrophobic-type attraction towards a variety of aromatic and aliphatic guests (3-4 kcal/mol). Host P shows an added attraction towards trimethylammonium (TMA) substituted guests. In almost all cases studied, NMR-shift patterns indicate that when the hostguest complex forms, the polar TMA group lies deepest within the electron-rich, yet hydrophobic, receptor.
\r\n\r\nHosts P and M have a strong attraction towards adamantyltrimethylammonium iodide (ATMA). PR and PS have binding viaffinities of 6.6 \u00b1 0.2 kcal/mol with ATMA and bind the guest, encapsulated within the receptor site, in one guest orientation. MR and MS have binding affinities of 5.5 \u00b1 0.2 kcal/mol with ATMA and bind the guest in a non-specific fashion, yet they demonstrate a preferred attraction towards the TMA group of the guest.
\r\n\r\nAromatic-linked hosts PR, PS, MR and MS show an enhanced ion-dipole attraction towards charged quinolinium-type, flat aromatic guests as compared to neutral ones (P \u2248 1 kcal/mol and M \u2248 2 kcal/mol). Host C, with aliphatic linkers, does not experience an enhanced attraction to the charged flat guests.
\r\n\r\nHosts PR and PS demonstrate enantioselective binding with certain guests. For one case, a simple model for the cause of the enantioselectivity is presented.
", "doi": "10.7907/cgn8-6h63", "publication_date": "1988", "thesis_type": "phd", "thesis_year": "1988" }, { "id": "thesis:885", "collection": "thesis", "collection_id": "885", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-03052008-111804", "primary_object_url": { "basename": "Grader_gs_1987.pdf", "content": "final", "filesize": 7213605, "license": "other", "mime_type": "application/pdf", "url": "/885/1/Grader_gs_1987.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Fourier Transform Infrared Spectroscopy of a Single Aerosol Particle", "author": [ { "family_name": "Sageev Grader", "given_name": "Gideon", "clpid": "Sageev-Grader-Gideon" } ], "thesis_advisor": [ { "family_name": "Seinfeld", "given_name": "John H.", "clpid": "Seinfeld-J-H" } ], "thesis_committee": [ { "family_name": "Seinfeld", "given_name": "John H.", "clpid": "Seinfeld-J-H" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Gavalas", "given_name": "George R.", "clpid": "Gavalas-G-R" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Throughout this thesis, the phenomenon of radiation-induced particle size change is studied both on a theoretical as well as experimental level. The thrust of this study is aimed at using the size changes due to heat absorption to develop a technique for obtaining the particle chemical composition.
\r\n\r\nThe experiments here involve charged particles, generated with an impulse jet, and trapped by the electric field of an electrodynamic balance. The particles under study are all aqueous solutions of non-volatile salts, where upon heating a partial evaporation of water occurs. The evaporation and subsequent condensation processes are modeled in both the continuum and the transition regimes. The models developed are tested and the agreement between theory and experimental results is demonstrated. The models are also used to extract the values of the water, thermal, and mass accommodation coefficients from the data. The results for the thermal accommodation show that its value is near unity, however the corresponding results for the mass accommodation are not conclusive.
\r\n\r\nA method is developed for obtaining the molecular composition of a single suspended microparticle by Fourier transform infrared spectroscopy. The particle is irradiated simultaneously by the infrared output from a Michelson interferometer and the visible light from a dye laser. The laser is tuned to an edge of an optical resonance of the particle while the IR beam is chopped. Through evaporation and condensation the chopped IR beam causes a size modulation of the droplet, which in turn induces a fluctuation in the laser light scattered from the particle. The scattered light is detected at 90\u00b0 with a photomultiplier, and the amplitude of the light fluctuation is measured with a lock-in amplifier. The lock-in signal is then inverted by a discrete fast Fourier transform routine (FFT), to yield the particle absorption spectrum. Spectra of (NH4)2SO4 droplets at different solute concentrations are presented.
\r\n", "doi": "10.7907/de8x-sp79", "publication_date": "1987", "thesis_type": "phd", "thesis_year": "1987" }, { "id": "thesis:5305", "collection": "thesis", "collection_id": "5305", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10192009-083321412", "primary_object_url": { "basename": "Allison_jn_1985.pdf", "content": "final", "filesize": 3603329, "license": "other", "mime_type": "application/pdf", "url": "/5305/1/Allison_jn_1985.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Theoretical Studies of Heterogeneous Catalysis of Molybdates", "author": [ { "family_name": "Allison", "given_name": "Janet Noel", "clpid": "Allison-Janet-Noel" } ], "thesis_advisor": [ { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" } ], "thesis_committee": [ { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Beauchamp", "given_name": "Jesse L.", "orcid": "0000-0001-8839-4822", "clpid": "Beauchamp-J-L" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Sparks", "given_name": "Randal K.", "clpid": "Sparks-Randal-K" }, { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Chapter 1: We use thermochemical results from ab initio quantum chemical calculations (generalized valence bond) to examine the reaction mechanism for
\r\n\r\nH3COH + \u00bd O2 \u2192 H2CO + H2O
\r\n\r\nas catalyzed by MoO3. We find that surface dioxo sites
\r\n\r\n[Chemical structure; see abstract in scanned thesis for details.]
\r\n\r\nare critical to activating the methanol, but we find that the Trifiro proposal of a single site-single step process
\r\n\r\n[Chemical structure; see abstract in scanned thesis for details.]
\r\n\r\nis not favorable (\u2206H \u2243 +31.5 kcal). Our conclusion is that the catalytic site involves two adjacent surface dioxo units (the dual dioxo site), with each dioxo site extracting one H in a sequence of steps. The required dual dioxo site exists on the (010) surface of MoO3 but does not exist on the other low index surfaces. This mechanism is supported by atmospheric pressure experimental studies which indicate that MoO3 (010) is selective for CH2O products. A detailed sequence of reaction steps and the associated thermochemistry is proposed.
\r\n\r\nChapter 2: Molybdates involving various metal additives play a dominant role in such industrially important catalytic processes as selective oxidation (propene to acrolein) and ammoxidation (propene to acrylonitrile); however, the details of the reaction mechanism and of the surface sites responsible are yet quite uncertain. In order to establish the thermo-chemistry and detailed mechanistic steps involved with such reactions, we have performed ab intitio quantum chemical calculations [generalized valence bond (GVB) and configuration interaction (CI)]. These studies indicate a special importance of multiple surface dioxo Mo sites (possessing two Mo-O double bonds and hence spectator oxo groups) arranged together so as to provide the means for promoting the sequence of transformations.
\r\n\r\nChapter 3: Extensive ab initio calculations have been carried out on molybdenum (VI, V and IV) complexes containing oxygen and nitrogen. A detailed description of the bonding of oxo, nitrido and imido terminally attached ligands to molybdenum is presented. These results are used to explain the preferred geometries of complexes as well as the periodic trends as ligands to molybdenum are varied from O, N, NH.
\r\n\r\nChapter 4: We find that the ground state of MoN (4\u2211-) has a covalent triple bond where the \u03c3 bond is dz2-like on the Mo, leading to a quartet state with unpaired electrons in the Mo 5s, Mo 4d\u03b4xy and Mo 4d\u03b4x2-y2 orbitals. The first excited state (4\u03a0) corresponds to the 5p\u03c0 \u2190 5s excitation. The calculated properties of Re = 1.60 \u00c5, \u03c9e = 1100 cm-1, De = 4.07 eV, and \u2206E (4\u03a0-4\u2211- = 2.128 eV are in good agreement with recent experimental results (Re = 1.63 \u00c5 and \u2206E = 2.011 eV). Particularly interesting is a dramatic nonmonotonic change of dipole moment with distance (\u00b5 = -3.123 D at Re = 1.60 \u00c5, -5.982 D at R = 2.60 \u00c5 and \u00b5 = -0.176 D at R = 5.0 \u00c5. This effect is explained.
\r\n", "doi": "10.7907/wpmx-ff05", "publication_date": "1985", "thesis_type": "phd", "thesis_year": "1985" }, { "id": "thesis:8597", "collection": "thesis", "collection_id": "8597", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07232014-143633362", "primary_object_url": { "basename": "BOLAND_JJ_1985.pdf", "content": "final", "filesize": 5267851, "license": "other", "mime_type": "application/pdf", "url": "/8597/1/BOLAND_JJ_1985.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Experimental and Theoretical Developments in Extended X-Ray Absorption Fine Structure (EXAFS) Spectroscopy", "author": [ { "family_name": "Boland", "given_name": "John James", "clpid": "Boland-John-James" } ], "thesis_advisor": [ { "family_name": "Kuppermann", "given_name": "Aron", "clpid": "Kuppermann-A" } ], "thesis_committee": [ { "family_name": "Kuppermann", "given_name": "Aron", "clpid": "Kuppermann-A" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Dervan", "given_name": "Peter B.", "orcid": "0000-0001-8852-7306", "clpid": "Dervan-P-B" }, { "family_name": "Weinberg", "given_name": "William Henry", "clpid": "Weinberg-W-H" }, { "family_name": "McGill", "given_name": "Thomas C.", "clpid": "McGill-T-C" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "To obtain accurate information from a structural tool it is necessary to have an understanding of the physical principles which govern the interaction between the probe and the sample under investigation. In this thesis a detailed study of the physical basis for Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy is presented. A single scattering formalism of EXAFS is introduced which allows a rigorous treatment of the central atom potential. A final state interaction formalism of EXAFS is also discussed. Multiple scattering processes are shown to be significant for systems of certain geometries. The standard single scattering EXAFS analysis produces erroneous results if the data contain a large multiple scattering contribution. The effect of thermal vibrations on such multiple scattering paths is also discussed. From symmetry considerations it is shown that only certain normal modes contribute to the Debye-Waller factor for a particular scattering path. Furthermore, changes in the scattering angles induced by thermal vibrations produces additional EXAFS components called modification factors. These factors are shown to be small for most systems.
\r\n\r\nA study of the physical basis for the determination of structural information from EXAFS data is also presented. An objective method of determining the background absorption and the threshold energy is discussed and involves Gaussian functions. In addition, a scheme to determine the nature of the scattering atom in EXAFS experiments is introduced. This scheme is based on the fact that the phase intercept is a measure of the type of scattering atom. A method to determine bond distances is also discussed and does not require the use of model compounds or calculated phase shifts. The physical basis for this method is the absence of a linear term in the scattering phases. Therefore, it is possible to separate these phases from the linear term containing the distance information in the total phase.
\r\n", "doi": "10.7907/YGM3-F114", "publication_date": "1985", "thesis_type": "phd", "thesis_year": "1985" }, { "id": "thesis:11317", "collection": "thesis", "collection_id": "11317", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12142018-113612227", "primary_object_url": { "basename": "Pearson_LT_1984.pdf", "content": "final", "filesize": 38709673, "license": "other", "mime_type": "application/pdf", "url": "/11317/1/Pearson_LT_1984.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "A Model for the Lateral Organization of Protein Molecules in Lipid Bilayers", "author": [ { "family_name": "Pearson", "given_name": "Laurence Timothy", "clpid": "Pearson-Laurence-Timothy" } ], "thesis_advisor": [ { "family_name": "Hopfield", "given_name": "John J.", "clpid": "Hopfield-J-J" } ], "thesis_committee": [ { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Davidson", "given_name": "Norman R.", "clpid": "Davidson-N-R" }, { "family_name": "Hopfield", "given_name": "John J.", "clpid": "Hopfield-J-J" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Interactions between membrane bound proteins are examined using freeze-fracture etch electron microscopy. The pair distribution functions (PDF's) of protein particles in natural and synthetic membrane systems are examined, and compared with PDF's that are calculated from potential energy functions. In particular, PDF's calculated from the hard-disc only interaction between particles serve as a useful reference for determining whether particle interactions are attractive or repulsive. Of particular interest is the possibility that the lipid bilayer membrane mediates protein interactions. A model is presented for a lipid-mediated interaction that predicts that if protein molecules perturb the bilayer membrane away from its equilibrium (protein free) configuration and that if the perturbation is propagated laterally through the membrane over a sufficient distance, then an attractive interaction is the result.
\r\n\r\nThe model is tested on recombinants of cytochrome c oxidase with dimyristoyl phosphatidyl choline and glycerol and with cardiolipin. Each recombinant is frozen from above the phase transition temperature of the lipid, so the membranes are expected to be fluid. Aggregation of protein into patches is seen, but all PDF's are indicative of a long-ranged repulsion. The model must be modified to account for the repulsion, a modification that would explain the observations in the inclusion of a vector membrane order parameter, namely lipid tilt, into the model. Tilt perturbation can be described by using the formalism already developed for describing nematic and smectic liquid crystals. A repulsive interaction between protein particles that is analogous to that seen between Schlieren textures in liquid crystals can be shown to occur if protein molecules induce tilt deformations in the bilayer around their boundaries.
", "doi": "10.7907/k7m9-xb92", "publication_date": "1984", "thesis_type": "phd", "thesis_year": "1984" }, { "id": "thesis:4440", "collection": "thesis", "collection_id": "4440", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-11072005-153348", "primary_object_url": { "basename": "Baxter_dv_1984.pdf", "content": "final", "filesize": 4083120, "license": "other", "mime_type": "application/pdf", "url": "/4440/1/Baxter_dv_1984.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "EXAFS Studies of La-Ga Metallic Glasses", "author": [ { "family_name": "Baxter", "given_name": "David Verge", "orcid": "0000-0003-2812-0904", "clpid": "Baxter-David-Verge" } ], "thesis_advisor": [ { "family_name": "Johnson", "given_name": "William Lewis", "clpid": "Johnson-W-L" } ], "thesis_committee": [ { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "McGill", "given_name": "Thomas C.", "clpid": "McGill-T-C" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Tombrello", "given_name": "Thomas A.", "clpid": "Tombrello-T-A" }, { "family_name": "Johnson", "given_name": "William Lewis", "clpid": "Johnson-W-L" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Extended X-ray Absorption Fine Structure ( EXAFS ) measurements have been performed on the Ga edge of several La-Ga metallic glasses, using an in-lab spectrometer. The results obtained are compared with earlier experiments on the same materials where X-ray diffraction and isomorphous substitution were used to determine partial pair correlation functions. This is, therefore, a rigorous test of the EXAFS technique when applied to strongly disordered systems, such as metallic glasses. It is found that the glass La80Ga20 has a comparatively simple local Ga environment and that the EXAFS for this glass can be described very well with a single asymmetric shell of La atoms surrounding the Ga. As the Ga concentration is increased, however, it is found that the local Ga environment becomes more complicated. Traditional methods of EXAFS analysis, based on nonlinear least squares curve fitting, are then unable to distinguish between several different possible local Ga environments. Finally a new, essentially non-parametric, method of analyzing EXAFS data is discussed and tests are conducted to demonstrate the circumstances under which this new method could prove advantageous over the more traditional methods.
\r\n", "doi": "10.7907/NHED-5T47", "publication_date": "1984", "thesis_type": "phd", "thesis_year": "1984" }, { "id": "thesis:3840", "collection": "thesis", "collection_id": "3840", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09302005-132833", "type": "thesis", "title": "Studies of Chemical Adsorption Using Low-Energy Electron Diffraction", "author": [ { "family_name": "Williams", "given_name": "Ellen D.", "clpid": "Williams-Ellen-D" } ], "thesis_advisor": [ { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" } ], "thesis_committee": [ { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Weinberg", "given_name": "William Henry", "clpid": "Weinberg-W-H" }, { "family_name": "Kuppermann", "given_name": "Aron", "clpid": "Kuppermann-A" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "local_group": [ { "literal": "Caltech Distinguished Alumni Award" }, { "literal": "div_chem" } ], "abstract": "Both experimental and computational studies based on low-energy electron diffraction (LEED) have been performed to determine the nature of order in chemically adsorbed overlayers. These studies have been directed towards obtaining a better understanding of adatom-adatom interactions by measurement of their most obvious manifestations; change in overlayer order during adsorption and co-adsorption, island formation, and order-disorder phenomena.
\r\n\r\nThe effect of the co-adsorption of hydrogen on the ordering of CO on Rh(111) has been studied using LEED and thermal desorption mass spectrometry. The results indicate that the adsorption of CO proceeds via a physically adsorbed intermediate. In addition, there is a strong repulsive interaction between CO molecules and hydrogen atoms co-adsorbed on Rh(111). This interaction is apparent at distances up to 2.7-3.1 \u00c5 indicating that it is a through-metal effect.
\r\n\r\nA series of LEED patterns has been observed during the adsorption of sulfur on the reconstructed IR(110)-(1x2) surface. The structure observed at lowest coverages has a p2mg symmetry. This allows a determination of the absolute coverage, and indicates a probable binding site for the sulfur atoms.
\r\n\r\nA Monte Carlo simulation of the order-disorder behavior of oxygen on W(110) has been performed. General expressions relating the values of the interaction energies to the transition temperatures for a lattice gas with first, second and third neighbor interactions have been determined. Symmetry considerations in selecting a model for the interaction energies are discussed.
\r\n\r\nThe effect of the ordering of adsorbed molecules into small islands on the LEED beam profile has been determined. In the limit of a random distribution of island positions the overall intensity is shown to be the weighted sum of the intensities from the individual islands. Computer simulations of island-containing overlayers have been used to determine the effect on the beam profiles of deviations from a random distribution of islands.
\r\n\r\nExperimental studies of island formation for CO on Ru(001) have been performed. The finite size of the ordered islands has a strong effect on the order-disorder behavior. Quantitative measurements of this effect have allowed a determination of the island size distribution and thus, the mean island size as a function of coverage.
\r\n", "doi": "10.7907/DYY3-MQ42", "publication_date": "1982", "thesis_type": "phd", "thesis_year": "1982" }, { "id": "thesis:10780", "collection": "thesis", "collection_id": "10780", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03222018-144512817", "type": "thesis", "title": "Part A. Theoretical Studies of the X-Ray Absorption Edge in Copper Complexes. Part B. Electron Correlation Consistent Calculation of Bond Dissociation Energies", "author": [ { "family_name": "Bair", "given_name": "Raymond Alan", "clpid": "Bair-Raymond-Alan" } ], "thesis_advisor": [ { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" } ], "thesis_committee": [ { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" }, { "family_name": "Beauchamp", "given_name": "Jesse L.", "orcid": "0000-0001-8839-4822", "clpid": "Beauchamp-J-L" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Part A: In order to elucidate the nature of the transitions involved in the x-ray absorption edge of molecular systems, we have used ab initio methods to examine the discrete transitions corresponding to the atomic 1s \u2192 3d, 4s, 4p, 5s, and 5p transitions and the corresponding shakeup processes for Cu atom and for a Cu(II) model system, CuCl2. The three common features of the K edge are described by the calculations. For CuCl2, the lowest strong transitions have the character 1s \u2192 4p (f = 0.00133). About 7.5 eV lower is a group of transitions involving 1s \u2192 4p simultaneous with ligand-to-metal shakedown. About 18.7 eV below the main peak is a weak (65 times weaker) quadrupole-allowed transition corresponding to 1s \u2192 3d (i.e., 1s23d9 \u2192 1s13d10. In each case the spectral feature has been assigned to an allowed transition. Previously, the middle transition was assigned as 1s \u2192 4s, whereas in this study the 1s \u2192 4s transition was calculated to be too weak to be observed. We propose that the observed peak is due to the allowed transition involving 1s \u2192 4p plus shakedown.
\r\n\r\nPart B: Ab initio generalized valence bond (GVB) and configuration interaction (CI) methods have been used to develop a generally applicable method for directly calculating bond energies. Particular effort has been put into obtaining a scheme in which all correlation terms that change upon dissociation of a particular bond are included consistently. The method uses in an essential way the localized orbitals from a GVB calculations, and is readily applicable to large systems [e.g., (CH3)3C-C(CH3)3]. To test our method, we selected two benchmark series of compounds, where the experimental bond energies are well known. Calculated bond energies are reported for the R-H bonds of CH4, NH3, H2O, and HF, which are low by 3.5, 2.5, 3.0, and 2.7 .kcal/mol, respectively. We also report calculations of the R-R bond energies of C2H6, N2H4, H2O2, and F2, which are low by 0.1, -3.2, -1.8, and 0.8 kcal/mol, respectively. In the application of our method, we have calculated all of the O-O, O-C, and O-H bond energies of HOOH, CH3OOH, CH3OOCH3, CH3OH, C2H5OH (O-H only), and CH3O-. Finally, we obtain the electron affinities of F, OH, and CH3O with the same techniques.
", "doi": "10.7907/ez8r-aj04", "publication_date": "1982", "thesis_type": "phd", "thesis_year": "1982" }, { "id": "thesis:10756", "collection": "thesis", "collection_id": "10756", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03062018-123026017", "primary_object_url": { "basename": "Reimer_JA_1981.pdf", "content": "final", "filesize": 67599808, "license": "other", "mime_type": "application/pdf", "url": "/10756/1/Reimer_JA_1981.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "The Development of Novel Nuclear Magnetic Resonance Techniques for the Study of Solids, Thin Films and Surfaces with Particular Application to Amorphous Semiconducting Silicon-Hydrogen Films", "author": [ { "family_name": "Reimer", "given_name": "Jeffrey Allen", "clpid": "Reimer-Jeffrey-Allen" } ], "thesis_advisor": [ { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "thesis_committee": [ { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" }, { "family_name": "Zewail", "given_name": "Ahmed H.", "clpid": "Zewail-A-H" }, { "family_name": "Cole", "given_name": "Terry", "clpid": "Cole-Terry" }, { "family_name": "McGill", "given_name": "Thomas C.", "clpid": "McGill-T-C" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Part 1
\r\n\r\nProton magnetic resonance data are presented for twenty different plasma-deposited amorphous silicon-hydrogen films. The two phase compositional inhomogeneity observed in these films is found to be independent of film thickness down to less than 1\u03bc. Models for various structural configurations show that these films contain heavily monohydride clustered regions such as divacancies and voids, as well as (SiH2)n and SiH3 local bonding configurations. The presence of the divacancies in films showing predominantly monohydride vibrational modes provides some insight into the controversy over the assignment of the 2090 cm-1 vibrational mode. The films also contain regions in which monohydride groups are distributed at random. Based on changes in a film whose proton NMR lineshapes are metastable as deposited, a model based on strain relief is proposed for film development which explains the ubiquitous presence of the two phase inhomogeneity. Examination of the changes in proton NMR data as a function of deposition conditions furnishes new insight on the role SiH2 and SiH+x groups have in models for the gas phase reactions involved in the developing films. Finally, p- or n-type doping is found to increase the the hydrogen content of the films, and, under heavy p-type doping with diborane, boron clustering may occur within the films. Proton NMR lineshapes are also presented as a function of annealing temperature up to 650\u00b0C. The data indicate that hydrogen diffuses internally before major evolution occurs, that transfer of hydrogen occurs from a heavily clustered phase to a dilute phase coincident with evolution and that evolution occurs initially from the heavily clustered phase. Internal hydrogen diffusion is found to be concomitant with the reduction in paramagnetic center density.
\r\n\r\nSilicon-29 and hydrogen magic angle sample spinning experiments on amorphous silicon-hydrogen films (involving cross-polarization and homonuclear multiple pulse techniques respectively) fail to yield quantitative determinations of local silicon-hydrogen bonding environments. However, the 29Si data are qualitatively consistent with infra-red assignments of (SiH2)n groups. Furthermore, the lack of significant line narrowing for the 29Si spectra upon magic angle sample spinning shows that there are large chemical shift dispersions, indicative of the disorder in the amorphous lattice.
\r\n\r\nProton spin-lattice relaxation data are presented for several plasma deposited amorphous silicon-hydrogen films when (i), homonuclear dipolar interactions are suppressed, (ii), deuterium is isotopically substituted for hydrogen, and (iii), films are annealed. These data are consistent with a model in which proton nuclei are relaxed by hydrogen-containing disorder modes. Analysis of these data shows that the density of disorder modes is ~30% higher in the low hydrogen density domain and that more than one hydrogen nucleus is associated with each disorder mode. The behavior of T1 upon annealing indicates that a small fraction of unpaired spins or \"dangling bonds\" may be associated with the disorder modes. These results suggest that the role of hydrogen in amorphous silicon is more complex than passivation of \"dangling bond\" intrinsic defects.
\r\n\r\nFinally, proton magnetic resonance data are presented for the hydrogen alloys of plasma-deposited amorphous boron, carbon, silicon carbide and silicon nitride. Linewidth and lineshape analysis leads to the conclusion that hydrogen nuclei are clustered in a-Si/C:H, a-C:H, and a-Si/N:H. Both a-Si/C:H and a-C:H data show hydrogen exists in two phases. Modeling of linewidths in a-Si/C:H indicates that the two phases are heavily hydrogenated carbon clusters imbedded in a weakly hydrogenated a-Si lattice. In addition, evidence is presented for the presence of motionally narrowed hydrogen spectra in a-Si/N:H, a-B:H, and a-C:H. It is suggested that the hydrogen nuclei giving rise to these spectra are associated with disorder modes.
\r\n\r\nPart 2
\r\n\r\nThe production of heteronuclear dipolar modulated chemical shift spectra of specific protons within polycrystalline solids is described by consideration of explicit double resonance pulse schemes which remove both heteronuclear and homonuclear dipolar interactions. These spectra furnish an accurate method of determining bond distances in local environments of complicated chemical systems. When used in conjunction with selectively observed chemical shift spectra, these schemes present a means for characterization of both geometrical and electronic properties in the solid state. To demonstrate the utility of these experiments, selective proton observed NMR results are presented for the carbonyl protons of adsorbed formic acid on ammonium-Y zeolite and the hydrogen bonded proton in polycrystalline acetanilide. Chemical shift information for the adsorbed formic acid shows a chemisorbed species consistent with formate ions. The data for the amide bond in polycrystalline acetanilide show a hydrogen bond with a chemical shift anisotropy of 17.7 ppm and a N-H distance of 1.05 \u00b1 0.01 \u00c5.
", "doi": "10.7907/c2h9-0m19", "publication_date": "1981", "thesis_type": "phd", "thesis_year": "1981" }, { "id": "thesis:4011", "collection": "thesis", "collection_id": "4011", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-10102006-095702", "type": "thesis", "title": "Solid State NMR at High Magnetic Fields Using Multiple Pulse Techniques", "author": [ { "family_name": "Carson", "given_name": "Douglas Glenn", "clpid": "Carson-Douglas-Glenn" } ], "thesis_advisor": [ { "family_name": "Vaughan", "given_name": "Robert W.", "clpid": "Vaughan-R-W" }, { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" } ], "thesis_committee": [ { "family_name": "Chan", "given_name": "Sunney I.", "orcid": "0000-0002-5348-2723", "clpid": "Chan-S-I" }, { "family_name": "Weinberg", "given_name": "William Henry", "clpid": "Weinberg-W-H" }, { "family_name": "Rhim", "given_name": "Won-Kyu", "clpid": "Rhim-Won-Kyu" }, { "family_name": "Rossman", "given_name": "George Robert", "orcid": "0000-0002-4571-6884", "clpid": "Rossman-G-R" }, { "family_name": "Baldeschwieler", "given_name": "John D.", "clpid": "Baldeschwieler-J-D" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Part I of this thesis is concerned with measuring the proton chemical shift in solids using a homebuilt high field (6.3 tesla) multiple pulse spectrometer. The distinctive features of the spectrometer are described. The chemical shift tensors for the carboxylic protons in potassium hydrogen malonate, potassium hydrogen oxydiacetate, and potassium hydrogen dicrotonate are reported as determined by multiple pulse experiments. The isotropic part of the chemical shifts relative to a spherical sample of TMS and the anisotropies for the three compounds are -20.5(5), -19.6(7), -18.2(7), and 27.6(6), 28.3(9), 28.9(9) ppm respectively.
\r\n\r\nPart II of this thesis presents a two pulse double quantum nuclear magnetic resonance (NMR) experiment which is designed to measure the Pake doublet splitting in systems of isolated proton pairs which are inhomogeneously broadened. This experiment is applied to the water molecules in the channels of a single crystal of cordierite as a function of orientation and temperature to obtain structural information about the water molecules. Based on the NMR data, the water molecules are found to exhibit substantial anisotropic motion at room temperature and combined with previously reported infrared absorption data, a two site hopping model is proposed where the water spends 85% of its time with its proton-proton vector parallel to the channels and 15% of its time perpendicular. The difference in free energy between these two sites is 0.8 kcal/mole.
\r\n\r\nAverage hamiltonian theory is extended to cover the case of strongly coupled proton-pair systems by transforming the hamiltonian to the dipolar pair-toggling reference frame. It is found that the residual dipolar hamiltonian for the Burum-Rhim 24-pulse cycle is governed by a four-body interaction and any other multiple pulse cycle based on phase alternated WAHUHA 4-pulse cycles will do no better than the 24-pulse cycle at reducing the residual dipolar hamiltonian.
", "doi": "10.7907/172t-m550", "publication_date": "1981", "thesis_type": "phd", "thesis_year": "1981" } ]