Thesis. 1977. M.S.--Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Bibliography : p. 165-168. / M.S.

Thesis. 1979. Sc.D.--Massachusetts Institute of Technology. Dept. of Mechanical Engineering. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Includes bibliographical references. / by Sergio N. Simunović S. / Sc.D.

Yang, Fan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 73-77). / Abstracts in English and Chinese. / Abstract --- p.I / 摘要 --- p.III / Table of Contents --- p.V / List of Figures --- p.i / List of Tables --- p.A / Chapter 1. --- Introduction --- p.1 / Chapter 1.1. --- Literature Review --- p.1 / Chapter 1.2. --- Project Background --- p.10 / Chapter 1.3. --- Objectives --- p.14 / Chapter 2. --- Design of the micro assembly machine --- p.16 / Chapter 2.1. --- Aspects that need to be met --- p.16 / Chapter 2.2. --- Hardware of the micro assembly machine --- p.17 / Chapter 2.2.1. --- The vision system --- p.18 / Chapter 2.2.2. --- The control system --- p.19 / Chapter 2.2.3. --- The Actuating System --- p.21 / Chapter 2.2.3.1. --- The gripper --- p.22 / Chapter 2.2.3.2. --- The three axes --- p.28 / Chapter 2.2.3.3. --- The workbench --- p.31 / Chapter 2.2.4. --- The complete structure of the micro assembly machine --- p.32 / Chapter 2.3. --- The main features of the micro assembly machine --- p.34 / Chapter 3. --- Implementation --- p.35 / Chapter 3.1. --- Vision system --- p.35 / Chapter 3.2. --- Setting up the vision system --- p.36 / Chapter 3.3. --- Efficiency and form of the transferred data --- p.38 / Chapter 3.4. --- Control system --- p.39 / Chapter 3.4.1. --- Structure of the control system --- p.40 / Chapter 3.4.2. --- System control process --- p.44 / Chapter 3.4.3. --- The GUI --- p.45 / Chapter 3.4.4. --- Data processing --- p.48 / Chapter 3.5. --- Cooperation between the vision system and the control system --- p.49 / Chapter 4. --- Experimental results --- p.51 / Chapter 4.1 --- Accuracy in the x and y directions --- p.51 / Chapter 4.2 --- Effect of the vision system on accuracy --- p.57 / Chapter 4.3 --- Depth of the assembled ruby bearings --- p.62 / Chapter 4.4 --- Gradient of the rubies --- p.65 / Chapter 4.5 --- Analysis of the experimental data --- p.68 / Chapter 5 --- Conclusion and Future Work --- p.70 / References --- p.73

This thesis consisted of two computerized simulations of assembling milk from dairy farms and distributing it to milk plants, using TRUCKSTOPS, a commercial truck routing computer program. In the first simulation milk was assembled and delivered to the nearest available plant without regard to protein content, with the high-protein milk delivered to manufacturing plants. Doing so increased the fat and protein in milk delivered to manufacturing plants, and increased cheese production 2.6 percent. It also increased assembly costs and lowered fat and protein in milk delivered to fluid milk plants. The value of the extra cheese was less than the extra assembly costs and the value of the butterfat diverted from fluid milk to manufacturing plants, making the operation economically unfeasible.

Self-assembling peptides have emerged as new nanobiomaterials in the areas of nanoscience and biomedical engineering. In this category are self-assembling, ionic-complementary peptides, which contain a repeating charge distribution and alternating hydrophobic and hydrophilic residues in the amino acid sequence, leading to a unique combination of amphiphilicity and ionic complementarity. These peptides can self-assemble into stable nanostructures or macroscopic membranes that can withstand conditions of high temperature, extreme pH, many digesting enzymes and denaturation agents. Moreover, they exhibit good biocompatibility with various cultured mammalian cells, and do not have detectable immune responses when introduced into animals. These properties make them ideal materials for tissue scaffolding, regenerative medicine and drug delivery. This thesis focuses on the utilization of self-assembling peptides for hydrophobic anticancer drug delivery. The hydrophobic anticancer agent ellipticine was selected as a model drug. The studies include: (i) characterization of the photophysical properties of ellipticine in different environments; (ii) study of the formation of peptide-ellipticine complexes and the release kinetics; (iii) investigation of the cellular toxicity of the complexes and ellipticine uptake; (iv) study of the peptide sequence effect on the complex formation and in vitro delivery. Prior to applying ellipticine to the peptide-based delivery system, the fundamental studies on the effect of solution conditions, especially solvent polarity and hydrogen bonding, on the fluorescence of ellipticine were carried out. Ultraviolet (UV) absorption and fluorescence emission of ellipticine were found to be solvent/environment dependent. The absorption and emission maxima shifted to higher wavelengths (red shift) with increased solvent polarity. Large Stokes’ shifts were due to intramolecular charge transfer (ICT), which was enabled by large solvent polarity and hydrogen bonding of ellipticine with the solvents. The photophysical response of ellipticine to changes in solvent polarity and hydrogen bond formation could be used to infer the location of ellipticine in a heterogeneous medium, such as liposomes and cultured cells. EAK16-II, a model self-assembling peptide, was found to be able to stabilize ellipticine in aqueous solution. The equilibration time required to form peptide-ellipticine complex suspensions was found to be peptide concentration-dependent and related to the peptide critical aggregation concentration (CAC, ~0.1 mg/mL). With different combinations of EAK16-II and ellipticine concentrations, two molecular states (protonated or crystalline) of ellipticine could be obtained in the complexes. The release kinetics of ellipticine from the complex into egg phosphatidylcholine (EPC) vesicles (cell membrane mimics) was also affected by the peptide concentration used in the drug formulation. A higher peptide concentration resulted in a faster transfer rate, in relation to the size of the resulting complexes. Subsequent cellular studies on two cancer cell lines, A549 and MCF-7, showed that the complexes with protonated ellipticine were more effective against both cell lines, but their dilutions were not very stable. In addition, it was found that ellipticine uptake in both cell lines was very fast and through direct membrane permeation. Three peptides, EAK16-II, EAK16-IV and EFK16-II, either having a different charge distribution (EAK16-II vs. EAK16-IV) or hydrophobicity (EAK16-II vs. EFK16-II), were tested for the complexation and in vitro delivery of ellipticine. It was found that EAK16-II and EAK16-IV were able to stabilize protonated or crystalline ellipticine depending on the peptide concentration; EFK16-II, on the other hand, could stabilize neutral ellipticine molecules and ellipticine (micro)crystals. The viability results showed that the charge distribution of the peptides seemed not to affect the complex formation and its therapeutic efficacy in vitro; however, the increase in hydrophobicity of the peptides significantly altered the states of stabilized ellipticine and increased the stability of the complexes. This work provides essential information for peptide sequence design in the development of self-assembling peptide-based delivery of hydrophobic anticancer drugs.

Self-assembling peptides have emerged as new nanobiomaterials in the areas of nanoscience and biomedical engineering. In this category are self-assembling, ionic-complementary peptides, which contain a repeating charge distribution and alternating hydrophobic and hydrophilic residues in the amino acid sequence, leading to a unique combination of amphiphilicity and ionic complementarity. These peptides can self-assemble into stable nanostructures or macroscopic membranes that can withstand conditions of high temperature, extreme pH, many digesting enzymes and denaturation agents. Moreover, they exhibit good biocompatibility with various cultured mammalian cells, and do not have detectable immune responses when introduced into animals. These properties make them ideal materials for tissue scaffolding, regenerative medicine and drug delivery. This thesis focuses on the utilization of self-assembling peptides for hydrophobic anticancer drug delivery. The hydrophobic anticancer agent ellipticine was selected as a model drug. The studies include: (i) characterization of the photophysical properties of ellipticine in different environments; (ii) study of the formation of peptide-ellipticine complexes and the release kinetics; (iii) investigation of the cellular toxicity of the complexes and ellipticine uptake; (iv) study of the peptide sequence effect on the complex formation and in vitro delivery. Prior to applying ellipticine to the peptide-based delivery system, the fundamental studies on the effect of solution conditions, especially solvent polarity and hydrogen bonding, on the fluorescence of ellipticine were carried out. Ultraviolet (UV) absorption and fluorescence emission of ellipticine were found to be solvent/environment dependent. The absorption and emission maxima shifted to higher wavelengths (red shift) with increased solvent polarity. Large Stokes’ shifts were due to intramolecular charge transfer (ICT), which was enabled by large solvent polarity and hydrogen bonding of ellipticine with the solvents. The photophysical response of ellipticine to changes in solvent polarity and hydrogen bond formation could be used to infer the location of ellipticine in a heterogeneous medium, such as liposomes and cultured cells. EAK16-II, a model self-assembling peptide, was found to be able to stabilize ellipticine in aqueous solution. The equilibration time required to form peptide-ellipticine complex suspensions was found to be peptide concentration-dependent and related to the peptide critical aggregation concentration (CAC, ~0.1 mg/mL). With different combinations of EAK16-II and ellipticine concentrations, two molecular states (protonated or crystalline) of ellipticine could be obtained in the complexes. The release kinetics of ellipticine from the complex into egg phosphatidylcholine (EPC) vesicles (cell membrane mimics) was also affected by the peptide concentration used in the drug formulation. A higher peptide concentration resulted in a faster transfer rate, in relation to the size of the resulting complexes. Subsequent cellular studies on two cancer cell lines, A549 and MCF-7, showed that the complexes with protonated ellipticine were more effective against both cell lines, but their dilutions were not very stable. In addition, it was found that ellipticine uptake in both cell lines was very fast and through direct membrane permeation. Three peptides, EAK16-II, EAK16-IV and EFK16-II, either having a different charge distribution (EAK16-II vs. EAK16-IV) or hydrophobicity (EAK16-II vs. EFK16-II), were tested for the complexation and in vitro delivery of ellipticine. It was found that EAK16-II and EAK16-IV were able to stabilize protonated or crystalline ellipticine depending on the peptide concentration; EFK16-II, on the other hand, could stabilize neutral ellipticine molecules and ellipticine (micro)crystals. The viability results showed that the charge distribution of the peptides seemed not to affect the complex formation and its therapeutic efficacy in vitro; however, the increase in hydrophobicity of the peptides significantly altered the states of stabilized ellipticine and increased the stability of the complexes. This work provides essential information for peptide sequence design in the development of self-assembling peptide-based delivery of hydrophobic anticancer drugs.

none

This thesis reported synthesis of TiO2 nanostructures and Fe2O3 nanostructures and studied on self-assembling process. The morphologies, compositions, and physicochemical properties of the prepared samples were characterized by TEM, FESEM, XRD, FTIR, UV, and SQUID etc. Nanoparticles of transition metal oxides own their special function to become an interesting hot research topic in the recent decades. In particular, superparamagnetic iron oxide nanoparticles can be used as drug delivery agent and new hard disc drive materials. They have wide application in environment industry as well. Titanium dioxide nanoparticles can be applied in photocatalysts, UV protectors and dye sensitive solar cell etc. Their wide industrial applications for advanced technology development motivate scientists to develop simple, economical and novel synthetic methods, and explore their applications, so that the commercialization of the production of the nanomaterials becomes feasible. The objective of this project is to develop an effective, simple and economical technical route for synthesis of nanosized iron oxide and titanium oxide particles/rods/films. The approach and the progress are outlined as follows. Based on extensive literature reading on the project related area, a novel self-assembling technical route for iron oxide nanostructure and architecture was proposed which has been confirmed to be effective. Detailed experimental investigation on the synthesis of nanoparticles/rods, and instrumental characterization of the particle size, structure, and crystallites, etc. via TEM, FESEM, XRD, FTIR, UV, SQUID are conducted. Uniform nanorods of hematite iron oxide and titanium oxide nanospheres, and anatase TiO2 thin film with micropores have been successfully achieved. Some preliminary exploration for applications of the synthesized nanomaterials has also been carried out. Firstly, a novel assembled scheme of iron oxide nanostructure and architecture by selfassembling process was investigated. The sol-gel technical route was employed to synthesize nearly uniform nanorods of hematite particles. Morphologies and physicochemical properties of iron oxide nanostructure were characterized by analytical instrument. Secondly, titanium oxide nanospheres were synthesized via a hydrothermal process using titanium isopropoxide as the precursor. Titanium oxide nanospheres with inner nanospace andhighly organized crystallites in the shell structure and surface regions were synthesized. It demonstrated that the technical route developed in this work has a high versatility for structural engineering of various targeted morphological products. Thirdly, a simple process of preparing anatase TiO2 thin film with micropores was pursued. The synthesized nano thin film with micropores was used for the material of dye-sensitive solar cell; and effective electron transfer of titanium oxide electrode was confirmed by electrochemical voltammetry. Preparation of the titanium oxide electrode and its electrochemical analysis was studied. The application of the titanium oxide of microporous thin film material as a promoter for electrochemistry voltammetry measuring system was explored in this thesis. In conclusion, the iron oxide nanorods with superparamagnetic property were successfully synthesized by a simple method with low cost materials. Titanium oxide hollow nanospheres were achieved by the assistance of copolymer template. Titanium oxide thin film with microporous structure with significantly high efficiency in electron transfer was realized. Further researches on the synthesis of hybrid iron oxide and titanium oxide nanoparticles, their crystal growth architecture and mechanism, as well as exploration of their applications are recommended.

Thesis (Ph. D.)--University of Washington, 1997. / Includes bibliographical references (leaves [164]-169).

Thesis (M.Sc.)--Memorial University of Newfoundland, 1999. / Restricted until June 2000. Bibliography: leaves [79]-88.