Recursos de colección

CaltechTHESIS (9.725 recursos)

CALIFORNIA INST OF TECH (CIT) Thesis

Status = Unpublished

Mostrando recursos 1 - 20 de 553

  1. Development of Synthetic Strategies for the Total Synthesis of Ent-Kauranoid and Diterpenoid Alkaloid Natural Products

    Mak, Victor Wei-Dek

    As part of an ongoing synthetic effort directed towards biologically active ent-kauranoid natural products, the preparation of two structurally unique natural products, (–)-trichorabdal A and (–)-longikaurin E, is presented. The syntheses intercept an early intermediate from the synthetic route towards the rearranged natural product (–)-maoecrystal Z, and thus, represents a unified synthetic strategy to access structurally unique ent-kauranoids. Specifically, the syntheses are enabled by a palladium-mediated oxidative cyclization of a silyl ketene acetal to install a key quaternary center within the bicyclo[3.2.1]octane unit, as well as a reductive cyclization of an aldehyde-lactone to construct the oxabicyclo[2.2.2]octane motif of (–)-longikaurin E.

    ...

  2. Searching for Black Holes and Other Massive, Compact Bodies Using the Gravitational Waves from Binary Inspirals

    Ryan, Fintan Danh
    We consider several issues involved with searching for and studying different types of compact bodies using the gravitational waves from binary inspirals. In Chapter 2, we use a radiation­ reaction force formalism to compute (to leading post-Newtonian order) the inspiral evolution of a circular, nonequatorial orbit around a spinning black hole. We find that an initially circular orbit remains circular under radiation reaction and is driven towards anti-alignment with the black hole's spin direction. In Chapter 3, we apply this same formalism to orbits which are elliptical as well as nonequatorial. In addition, we prove that circular orbits remain circular...

  3. Microfluidic Analysis in Patient Biopsies: toward Precision Medicine for Glioblastoma Multiforme

    Kim, Jungwoo

    Although every individual has a unique biology, most medicine still relies on the one-size-fits-all approach, which often fails in the treatment of heterogeneous diseases like cancer. An emerging approach to disease treatment is precision medicine, in which a specific treatment is tailored for individual patients using their biological information, including their genome, phenome, and proteome. Two clinical actions are important for implementing precision medicine in cancer therapies: choosing the correct drugs via patient stratification and choosing a suitable drug dosage and duration via drug response monitoring.

    After selecting the potential drug candidate, it is crucial to monitor tumor response to drug...

  4. Engineering Biosynthetic Pathways in Cell-Free Systems for Sustainability and Chemical Innovation

    Wu, Yong Yi

    This work presents the cell-free transcription-translation (TX-TL) system as a research and development platform for renewable synthesis and molecular discovery. TX-TL is easy to use and provides a biomolecular breadboard for the rapid prototyping and engineering of biosynthetic pathways. This work has validated the capabilities of the cell-free TX-TL system for simultaneous protein expression and chemical synthesis. Specifically, this work shows that TX-TL supports the conversion of intermediates from carbohydrate metabolism and amino acids into valuable compounds. Metabolic flux through cofactor dependent pathways confirms that active cofactor metabolism is occurring in TX-TL. This work has also demonstrated the industrial relevance...

  5. Improving the Speed and Performance of Point-of-Care Diagnostics with Microfluidics

    Schlappi, Travis Stratton
    Microfluidic devices play an important role in improving global health because they reduce the study of biological phenomena into physiological scales and lay the foundation for point-of-care (POC) diagnostics. Health is improved and lives are saved because POC diagnostics can enable earlier diagnosis of diseases and therefore more effective treatment. Accurate and available diagnostics also prevent accelerated drug resistance that stems from overtreatment or mistreatment with antibiotics, which is projected to cause up to $100 trillion in lost economic output and 10 million deaths by 2050. This work details new diagnostic assays and theoretical analysis of microfluidic devices that can...

  6. Improvement of Integral Membrane Protein Expression via Optimization of Simulated Integration Efficiency

    Marshall, Stephen Sandell

    Integral membrane protein characterization is limited by the low levels of protein obtainable from heterologous overexpression in hosts such as Escherichia coli. Differences in the efficiencies of subdomains of the co-translational integration processes of membrane proteins into the membrane could explain the observed variation in the experimental expression of closely related homologs in E. coli. We have developed a method to predict and increase the expression of individual membrane proteins by optimizing the efficiency of their translocon-mediated integration into the membrane. The integration efficiency of each component of a membrane protein is calculated using a coarse-grained co-translational simulated integration model....

  7. Computational Studies of Noncovalent Interactions in Ligand-Gated Ion Channels – and - Synthesis and Characterization of Red and Near Infrared Cyanine Dyes

    Davis, Matthew Robert

    This thesis is presented in two parts. The first part, Chapter 2, 3, and 4, offers a series of studies on noncovalent interactions in Ligand Gation Ion Channels (LGICs). The second part describes a series of studies involving the synthesis and characterization of cyanine dyes. The common thread in this work is the use of Density Functional Theory (DFT) to study chemical-scale phenomenon. Chapter 1 offers a brief introduction to DFT and a comparison with other traditional computational chemistry methodology; Hartree-Fock (HF). Summaries of the use of DFT to study both noncovalent interations and electronically excited states are also presented....

  8. On the Effect of Large-Scale Patterned Wettability on Contact Line Hydrodynamics

    Grivel, Morgane Anne Marie

    Numerous studies have investigated how liquid water behaves on solid surfaces with uniformly hydrophilic or uniformly hydrophobic wetting properties. In particular, uniformly hydrophobic surfaces have been widely studied for modifying flow behavior of rivulets and drops at smaller scales, as well as for drag reduction on ships or other free-surface-piercing bodies at larger scales. Despite the extensive body of work on surfaces with uniform wetting properties, minimal work has been done to investigate how combining hydrophilic and hydrophobic regions onto a single surface to create macroscopic non-uniform wetting properties affects flows. Research in this vein has predominantly focused on low...

  9. Proliferation of Twinning in Metals: Application to Magnesium Alloys

    Sun, Dingyi

    In the search for new alloys with a great strength-to-weight ratio, magnesium has emerged at the forefront. With a strength rivaling that of steel and aluminum alloys --- materials which are deployed widely in real world applications today --- but only a fraction of the density, magnesium holds great promise in a variety of next-generation applications. Unfortunately, the widespread adoption of magnesium is hindered by the fact that it fails in a brittle fashion, which is undesirable when it comes to plastic deformation mechanisms. Consequently, one must design magnesium alloys to navigate around this shortcoming and fail in a more...

  10. Visualizing mRNA Translation in situ in Single Cells

    Burke, Kelly

    Translation of mRNA is tightly regulated in cells to ensure that proteins are synthesized at the right time, in the right location, and at appropriate levels. Single-molecule fluorescence in situ hybridization (smFISH) is a simple and widely used method to measure mRNA transcription through determining the abundance and localization of mRNAs in single cells. A comparable single-molecule in situ method to measure mRNA translation would enable a more complete understanding of gene regulation. In this thesis, we describe the development and characterization of a fluorescence assay to detect ribosome interactions with mRNA (FLARIM). The method adapts smFISH to visualize and...

  11. Magnetic Field Effects and Biophysical Studies on DNA Charge Transport and Repair

    Zwang, Theodore Joseph

    DNA-mediated charge transport (DNA CT) is well established in both ground and excited state systems. Although theoretical models are still being developed, it is clear that the integrity of the extended π-stack of the aromatic heterocycles, the nucleic acid bases, plays a critical role. Electron donors and acceptors must be electronically well coupled into the π-stack, typically via intercalation. Perturbations that distort the π-stack, such as single-base mismatches, abasic sites, base lesions, and protein binding that kinks the double helix, attenuate DNA CT dramatically.

    This thesis encompasses work that first aims to understand how DNA duplex structure informs characteristics of DNA...

  12. The Biosynthesis of Ascarosides in Caenorhabditis elegans

    Akagi, Allison Emi

    Ascarosides comprise a family of small signaling molecules that have been shown to regulate important events and behaviors in the life history of the nematode Caenorhabditis elegans. Although the different roles of individual ascarosides appear to be determined by the variances in chemical structure, the mechanisms by which ascarosides are synthesized as well as the locations in which ascarosides are produced within the worm are largely unknown. In this thesis, we examined ascaroside production in the intestine, hypodermis, and body wall muscle of the worm by driving the expression of the protein DAF-22 under different tissue-specific gene promoters. While the...

  13. Studies on the Source of Urea Carbon

    Paigen, Kenneth

    A method has been devised for the testing of any substance as an intermediate in a reaction sequence. Using this technique, thirty-three substances have been tested as precursors of the urea carbon atom. Of the compounds tested, only citrulline and arginine were precursors.

    Garbamyl L-glutamic acid was shown not to be a donor of the urea carbon, although it does have some function in urea synthesis.


  14. Investigations of the Mechanism of Cell Killing Induced by Actinomycin D

    Miller, Mark James

    At high concentration, actinomycin D kills the protozon Chlamydomonas reinhardi with exponential kinetics. The rate of killing is dependent upon the temperature of incubation. This dependence is partially a function of the increased extent of binding of the drug at the higher temperature (33°C), but sensitivity of the cell must also be stimulated by the higher temperature. While actinomycin D probably kills cells in a reaction which requires binding to DNA, there is no correlation between the lethal event and the inhibition of macromolecular synthesis or the breakdown of macromolecules.

    I have developed a simple model to explain the difference in sensitivity of various species of RNA to actinomycin...

  15. Studies in the phototaxis of rhodospirillum rubrum

    Clayton, Roderick Keener

    The bacterium Rhodospirillurn rubrum is capable of a photosynthetic reduction of CO2 similar to plant photo­ synthesis. A decrease in the illumination of R. rubrum induces it to reverse its direction of swimming; an investigation of the probability of this phototactic response as a function of the parameters of the stimulus, such as the intensity of illumination and its time pattern, should enhance our understanding of biological irritability.

    The present investigation is preliminary to such an undertaking. It was attempted to learn more about the responding system through studies of the interaction between the pigments, phototaxis, and metabolism of R. rubrum....

  16. Theoretical Investigations in Nonlinear Quantum Optics, Theory of Measurement, and Pulsations of General Relativistic Models of Neutron Stars

    Schumaker, Bonny Laura

    This thesis is a collection of six papers. The first four constitute the heart of the thesis; they are concerned with quantum mechanical properties of certain harmonic-oscillator states. The first paper is a discourse on single-mode and two-mode Gaussian pure states (GPS), states produced when harmonic oscillators in their ground states are exposed to potentials that are linear or quadratic in oscillator position and moment um variables (creation and annihilation operators). The second and third papers develop a formalism for analyzing two-photon devices (e.g., parametric amplifiers and phase-conjugate mirrors), in which photons in the ouput modes arise from two-photon transitions,...

  17. Black-Hole Electrodynamics

    Macdonald, Douglas Alan
    This dissertation considers several aspects of the structure and dynamics of electromagnetic fields around black holes. The four-dimensional, covariant laws of electrodynamics are reformulated in a 3 + 1 (space+time) language in which the key quantities are three-dimensional vectors lying in hypersurfaces of a constant global time t. This formulation is applied to the Blandford-Znajek model of power generation in quasars, which consists of a supermassive black hole surrounded by an accretion disk that holds a magnetic field on the hole, with the rotational energy and angular momentum of the hole and disk being extracted by electromagnetic torques. The 3...

  18. Dynamical Electromagnetic Fields Near Black Holes and Multipole Moments of Stationary, General Relativistic Systems

    Suen, Wai Mo

    This dissertation contains two works; one of the behavior of dynamical electromagnetic fields in the stationary spacetime generated by a black hole, and the other on the structure of a general stationary vacuum spacetime itself.

    The study of electromagnetic field is carried out in terms of the "membrane formalism" for black holes; and it is part of a series of papers with the aim of developing that formalism into a complete, self-consistent description of electromagnetic and gravitational fields in a black hole background. Various model problems are presented as aids in understanding the interactions of electromagnetic fields with a black hole, and special attention is paid to the concept...

  19. I. The Magnetic Susceptibility of Eu(III) and Eu(II) Ions and the Photochemical Reduction of Water by Eu(II) Ion. II. The Magnetic Susceptibility of Europium and Samarian Amalgams. III. Observations on the Chemistry of Europium. IV. Age Determination by Carbon-14 Content: Ionization Chamber Techniques. V. The Volume Change Due to Hydrogen Bonding of Methanol in Carbontetrachloride Solution

    Douglas, David Lewis

    The discovery of the photchemical reduction of water by europium(II) ion is reported. By use of a chemical actinometer for determining light intensities and a Gouy balance for following the change in magnetic susceptibility overall quantum yields were determined to be about 0.2 for solutions 0.5 m. in HCl and 0.15 m. in EuCl2. A mechanism consistent with the experimental data is

    Eu(II)·H2O + hv = Eu(II)*·H2O

    Eu(II)*·H2O = Eu(III)aq + H + OH-aq

    H + H+aq + Eu(II)aq = Eu(III)aq + H2

    The thermal reaction under these conditions was found to be relatively unimportant.

    The magnetic susceptibility of europium in its liquid amalgam was observed to be 8.09 ±...

  20. I. The magnetic susceptibility of europium(III) and europium(II) ions and the photochemical reduction of water by europium(II) ion. II. The magnetic susceptibility of europium and samarian amalgams. III. Observations on the chemistry of europium. IV. Age determination from carbon-14 content : ionization chamber techniques. V. The volume change due to hydrogen bonding of methanol in carbontetrachloride solution.

    Douglas, David Lewis

    The discovery of the photchemical reduction of water by europium(II) ion is reported. By use of a chemical actinometer for determining light intensities and a Gouy balance for following the change in magnetic susceptibility overall quantum yields were determined to be about 0.2 for solutions 0.5 m. in HCl and 0.15 m. in EuCl2. A mechanism consistent with the experimental data is

    Eu(II)·H2O + hv = Eu(II)*·H2O

    Eu(II)*·H2O = Eu(III)aq + H + OH-aq

    H + H+aq + Eu(II)aq = Eu(III)aq + H2

    The thermal reaction under these conditions was found to be relatively unimportant.

    The magnetic susceptibility of europium in its liquid amalgam was observed to be 8.09 ±...

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