Doctor of Philosophy / Department of Mechanical and Nuclear Engineering / Amy R. Betz / Boiling is a very effective way of heat transfer due to the latent heat of vaporization. Large amount of heat can be removed as bubbles form and leave the heated surface. Boiling heat transfer has lots of applications both in our daily lives and in the industry. The performance of boiling can be described with two important parameters, i.e. the heat transfer coefficient (HTC) and the critical heat flux (CHF). Enhancing the performance of boiling will greatly increase the efficiency of thermal systems, decrease the size of heat exchangers, and improve the safety of thermal facilities. Boiling heat transfer is an extremely complex process. After over a century of research, the mechanism for the HTC and CHF enhancement is still elusive. Previous research has demonstrated that fluid properties, system pressures, surface properties, and heater properties etc. have huge impact on the performance of boiling. Numerous methods, both active and passive, have been developed to enhance boiling heat transfer. In this work, the effect of pressure was investigated on a plain copper substrate from atmospheric pressure to 45 psig. Boiling heat transfer performance enhancement was then investigated on Teflon© coated copper surfaces, and graphene oxide coated copper surfaces under various system pressures. It was found that both HTC and CHF increases with the system pressure on all three types of surfaces. Enhancement of HTC on the Teflon© coated copper surface is contributed by the decrease in wettability. It is also hypothesized that the enhancement in both HTC and CHF on the graphene oxide coated surface is due to pinning from micro and nanostructures in the graphene oxide coating or non-homogeneous wettability. Condensation and freezing experiments were conducted on engineered surfaces in order to further characterize the pinning effect of non-homogeneous wettability and micro/nano structure of the surface.

京都大学 / 0048 / 新制・論文博士 / 博士(地球環境学) / 乙第12836号 / 論地環博第9号 / 新制||地環||25(附属図書館) / 31374 / (主査)教授 ショウ ラジブ, 教授 岡﨑 健二, 准教授 古川 愛子 / 学位規則第4条第2項該当 / Doctor of Global Environmental Studies / Kyoto University / DFAM

Multiple myeloma is a plasma cell cancer that progressively evolves to an aggressive, multi-drug resistant disease, which presents an unmet clinical need. In clinical trials, myeloma shows susceptibility to novel immunotherapeutic agents, particularly those targeting B-cell maturation antigen (BCMA). Among different classes of immunotherapies, T cell-based approaches have progressed the most due to their ability to induce durable responses in patients with advanced drug-resistant blood cancers. Most T cell engineering strategies rely on the use of chimeric antigen receptors (CARs), which although effective, can cause serious life-threatening toxicities. We created a new synthetic receptor, T cell antigen coupler (TAC), which recruits the endogenous T cell receptor and allows T cells to autoregulate their activity. Our experience in solid tumor models has shown that TAC-T cells are similarly efficacious and significantly less toxic than CAR-T cells. This thesis describes our optimization of BCMA-specific TAC-T cells and analysis of different anti-BCMA antigen-binding domains. TAC receptor functions by engaging endogenous TCR-CD3 complex and redirecting it to the target of interest. In Chapter 3, we characterize optimization and humanization of the CD3-recruitment domain in the TAC scaffold and provide evidence that TAC-T cells are effective against multiple myeloma, irrespective of receptor surface levels. In Chapter 4, we describe selection of the human BCMA-binding domain and the creation of a fully humanized TAC receptor against BCMA. Chapters 5 and 6 describe how a BCMA-targeting antigen-binding domain that cross-reacts with an unknown antigen in mice augments in vivo efficacy of TAC- and CAR-T cells, respectively. The work described in Chapters 3 and 4 presents an optimized, fully human BCMA-TAC that is being moved into clinical testing. The work in Chapters 5 and 6 improves our understanding of how antigen-targeting domains in synthetic receptors influence the functionality of engineered T cells. / Thesis / Doctor of Science (PhD) / Multiple myeloma is an incurable blood cancer that has a remarkable ability to develop resistance to different types of chemotherapy. In recent years, treatments redirecting immune cells against tumors have shown impressive clinical responses against different types of chemotherapy-resistant blood cancers, including multiple myeloma. Our lab has developed a new technology for redirecting T cells against tumors, called T cell antigen coupler (TAC) receptor. This thesis describes optimization of a fully human TAC receptor specific for a target on the surface of myeloma cells, known as BCMA. Durable remissions induced by TAC-engineered T cells in a preclinical mouse model of myeloma in the absence of toxicity warrant further testing of this therapeutic in a clinical trial.

The objectives of this research were to investigate the heat resistant performance of a structural adhesive and to analyze the contribution of the adhesive to the chemical emissions from the glued wood products affected by the elevated temperatures. Phenol-resorcinolormaldehyde (PRF) and two wood species, southern pine (Pinus palustris) and Douglasir (Pseudotsuga menziesii), were investigated. The dynamic mechanical analysis (DMA) test results showed that the heat durability performance of cured PRF resin was better than that of the two wood species used in this study. The results indicated that the fire safety of PRF bonded wood products should be comparable to solid wood products. The pyroysis products obtained from pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) system showed that most of the pyrolysis products of glued wood samples were same as those of wood and adhesive samples at the same temperature level except a few compounds, such as carbon disulfide, Cyclopropyl carbinol, acetaldehyde, furfural and others.

The use of engineered wood products (EWP) in residential construction has increased in recent years. Most specifications for the installation of these components are found in proprietary manufacturer literature rather than in the building code. Although some home inspections include EWP prescriptive compliance, very little applied and academic literature addresses this practice. This lack of practical information and the lack of standardized inspection methods can result in undetected non-compliant EWP installations that fail to meet the minimum safety provisions of the building code. The goal of this project was to develop a visual inspection methodology, associated knowledge base, and software application for the inspection of EWPs and connector hardware (CH) in new residential construction at the pre-drywall stage. The methodology was based upon subject matter expert (SME) inputs and validation was derived from the use of a modified Delphi method that was able to the gather, collate, refine, and validate the research process and outputs based on the expertise of the subject matter experts. The concept of high face validity was used to establish project validity. Installation problems with EWPs and CH were noted by the SMEs partly because the use and installation instructions for proprietary products are not found in building codes. Building code officials (BCO) and home inspector (HI) SME responses indicated a need for a methodology and software to aid in the inspection process. Although authoritative reference materials for prescriptive installation are available, the scope of material is not consistent between manufacturers, and is presented in different formats for different brands. The developed software application provides ready access to reference materials needed for EWP and CH installations. No widely accepted inspection methodology is available, although the HI SMEs used systematic inspection methods. Inspection methods such as the top-down method and sighting along the patterns of repetitious framing elements can improve the detection of non-compliant installations. BCO and HI SMEs identified both component-specific and zone-specific techniques as a part of the systematic inspection methodology. Definable high risk areas for each EWP and CH were identified and the associated inspection methods may help the inspector reduce the incidence of undetected problem areas. Knowledge of the high-risk areas may also enhance the inspection. The developed software application was found to be a useful inspection tool. BCO and HI SMEs determined that functions of the computer software necessary for use included ease of use, onboard reference materials, specific inspection techniques, prepared comments, and technical illustrations. / Ph. D.

Thesis (M.S.)--Oregon State University, 2009. / Printout. Includes bibliographical references (leaves 62-64). Also available on the World Wide Web.

No description available.

Multiple sclerosis is a neurodegenerative disorder affecting the central nervous system (CNS). Currently, the disease is incurable and immunomodulating drugs are the only option to control the disease. CD49d is an adhesion receptor expressed on most immune cells. Antibodies that bind to CD49d and block immune cells from trafficking toward the CNS are being pursued as one class of therapeutics. In this work, by combining recombinant antibody and phage display technologies we isolated 10 anti-CD49d single domain antibodies from a synthetic antibody light chain variable domain (VL) phage display library. Isolated VLs (~ 12 kDa) were expressed in Escherichia coli, purified and analysed for biophysical characteristics. The majority were expressed in good yields and were non-aggregating. All 10 VLs bound recombinant CD49d by ELISA, and 7 bound to CD49d-expressing cells in flow cytometry experiments. To empower the VLs for better therapeutic efficacy (thru increasing avidity and half-life), three of the lead VLs were re-engineered as fusions to fragment crystallisable (Fc) of human immunoglobulin gamma (IgG). The engineered hFc-VL fragments (~ 70 – 90 kDa) retained their specificity for CD49d by flow cytometry. With (i) being less immunogenic due to their human nature, (ii) their efficient access to cryptic epitopes (iii) having half-lives comparable to IgGs’ and (iv) being more cost effective compared to IgGs, these novel antibody fragments (monovalent VLs and bivalent hFc-VLs) provide a promising therapeutic platform against multiple sclerosis.

Ingeniero Civil Industrial / La mejora de procesos es una de las estrategias más utilizadas por las empresas para mejorar su posición competitiva. De sus disciplinas, el rediseño de procesos (BPR, por Business Process Redesign) es una de las más usadas y ha permitido a muchas empresas mejorar la eficiencia y eficacia de sus procesos de forma considerable, dejando de lado las pretensiones de cambios radicales que la literatura de BPR proponía inicialmente. Enercom S.A. es una empresa chilena especializada en el diseño y fabricación de equipos industriales en procesos térmicos, de secado y combustión. Estos son altamente complejos y diseñados a medida según las especificaciones del cliente, clasificando a la empresa como de diseño a la medida (ETO, por Engineered to Order). La gerencia de la empresa desea realizar una revisión de sus procesos, en particular del proceso de ingeniería de detalle que detectan como fuente de numerosos errores. El objetivo del proyecto se centrará en la reducción del número de Productos No Conformes (PNC) originados en el proceso de ingeniería de detalle, basándose en la metodología de Cameron y Braiden [2004]. Una evaluación de la organización permite comprender el funcionamiento y las características particulares del proceso de venta, diseño y fabricación de equipos, que concentra el 90% de sus ingresos anuales. Se detecta en esta etapa que el proceso de ingeniería de detalle concentra el 38,7% de los Productos No Conformes detectados, validando la decisión de rediseñar este proceso particular. El consecuente levantamiento del proceso de ingeniería de detalle, junto con un análisis de causa-efecto y de causa raíz de los PNC detectados, deja en evidencia que la falta de especificación de requerimientos y criterios de diseño y el alto nivel de incertidumbre del proceso son responsables de casi el 80% de las no conformidades detectadas. Durante el rediseño del proceso se pone especial énfasis en mitigar las principales causas de no conformidad detectadas, seleccionando de la literatura las mejores prácticas que reduzcan los costos y mejoren la calidad del proceso. También se rediseñan los sistemas que soportan el proceso: la estructura organizacional y los sistemas de información de la empresa. Finalmente, se incluye una propuesta de plan de implementación como un primer acercamiento hacia la implementación de este rediseño en la empresa. Este trabajo muestra que el proyecto tiene beneficios económicos importantes y que el costo de implementación es relativamente bajo, por lo que se recomienda continuar con las siguientes etapas del proyecto propuestas en la metodología. Se determina que BPR es aplicable a empresas del sector ETO y que permite obtener beneficios importantes, siempre que se limite a procesos unitarios y dentro una misma unidad de negocios.

The gold standard treatment for patients with AVD is surgical replacement of the aortic valve with either mechanical or fixed tissue prostheses. These implants have a limited lifespan and are associated with serious adverse events. Patient autologous tissue engineered heart valves (TEHVs) offer a solution. Vital to the development of a TEHV is determining a source of donor tissue(s) that most closely mimics the native valve tissue. In pursuit of determining an alternative cell source for patient autologous TEHVs we compared a number of phenotypic and genotypic characteristics of atrial fibroblasts, dermal fibroblasts and differentiated bone marrow-derived progenitor cells (BMCs) and made a comparison to valvular interstitial cells (VICS). We demonstrate that while VICs share some phenotypic similarities with fibroblasts and BMCs, they also possess unique characteristics and demonstrate differential mRNA expression of key regulatory pathways that may influence their phenotype. / October 2016