Operationally friendly protocols to produce libraries of novel small molecules with high molecular complexity are in huge demand for the interrogation of biological systems. As such, development of new MCRs and post-condensation modification of the MCR products have proven fruitful in the quest for new molecular probes and their expedited progression along the drug discovery value chain. The products thereof have found their way into numerous corporate compound collections. Crixivan (Indinavir), an antiretroviral, and Xylocaine (Lidocaine), a local anesthetic, are two examples of drugs derived from an MCR that have been marketed. The research topic of this dissertation encompasses the design and development of fifteen novel drug-like chemotypes in an operationally friendly, green, and expedited (≤ 3 synthetic operations) manner involving the Ugi MCR coupled with MAOS and high-throughput purification platforms. Over 500 drug-like small molecules (purity > 90% based on UV 214 nm and ELSD) have been synthesized, purified, and submitted to the NIH MLSMR for further biological evaluation against protein targets of interest. Furthermore, non-electrochemical carbamate oxidations enabling formation of N-acyliminium ion precursors, which are reactive intermediates that form the basis of a multitude of synthetic routes to natural products, have also been developed.

This thesis is directed towards expanding and refining a free radical multi-component polymerization model. The model considers up to six monomers (unique in the literature), both in bulk and solution polymerization, for either batch or semi-batch reactor modes. As the simulator database contains 13 monomers, 5 initiators, 4 solvents, 3 chain transfer agents and 2 inhibitors, all tested over a wide range of polymerization conditions, from data in both academic and industrial laboratories, several hundred combinations of ingredients can be modeled. The many outputs generated by the model include conversion, molecular weight, polymer composition, branching indicators, sequence length, as well as many others polymerization characteristics related to both production rate and polymer quality. Although the only literature data found to-date contains a maximum of four monomers, model predictions for homo-, co-, ter- and tetra-polymerizations show reasonable agreement against the data at both regular and elevated temperatures. Recently, with the basic polymerization kinetics modeled sufficiently, several expansions to the simulation software have been added. Specifically, depropagation, multiple initiators, back-biting, and composition control have been incorporated and/or improved, each adding to the advancement of the polymerization simulation tool. Depropagation is a vital mechanism that should be accounted for at elevated temperatures. Currently the software has the functionality to implement depropagation but requires further literature resources for improving the kinetic predictions for conversion and polymer composition. Consequently, depropagation research is ongoing. Back-biting and beta-scission of butyl acrylate (BA) is a recent development in free radical polymerization. The completed extension can model BA under the same diverse conditions as the base model, in homo-, co- and ter-polymerizations with depropagation, if applicable. The ability to generate a polymer with a constant (or controlled) composition throughout the reaction has several practical uses. Originally, three composition control scenarios were considered. At present, several methods as well as combinations of methods have been integrated into the model. With these new expansions and the ability to simulate several initiators at the same time, this model is directed towards becoming a complete free radical polymerization tool for training and educational uses both in industry and academia.

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第17065号 / 工博第3614号 / 新制||工||1548(附属図書館) / 29785 / 京都大学大学院工学研究科分子工学専攻 / (主査)教授 佐藤 啓文, 教授 白川 昌宏, 教授 山本 量一 / 学位規則第4条第1項該当

<div>This research aims at investigating the direct in-situ synthesis of high-performance multi-component alloys such as high entropy alloys, bulk metallic glasses, and metal matrix composites using the directed energy deposition (DED) process, and modeling the entire solidification and microstructure evolution of these alloys via a novel three-dimensional cellular automata-phase field (3D CA-PF) model. These alloys are currently the focus of significant attention in the materials and engineering communities due to their superior material properties. In the 3D CA-PF model, the growth kinetics including the growth velocity and solute partition at the local solid/liquid interface is calculated by the multi-phase and multi-component PF component, and the 3D CA component uses the growth kinetics as inputs to calculate the dendrite morphology variation and composition redistribution for the entire domain, which could save the computational cost more than five orders of magnitude compared to the PF modeling that can only be applied to small domains due to its heavy computational requirements. Coupled with the temporal and spatial temperature history predicted by the experimentally validated DED model, this computation-efficient 3D CA-PF model can predict the microstructure evolution within the entire macro-scale depositions, which is known to be nonuniform due to the particular nature of additive manufacturing (AM) processes. </div><div>To achieve the final goal of direct in-situ synthesis of five-component CoCrFeCuNi high entropy alloys (HEA), and modeling of the solidification and microstructure evolution during the DED process, the proposed research is carried out in progressive stages with the increasing complexity of alloy systems. First, a simple binary material system of Ti-TiC composite was studied. The thermodynamically-consistent binary PF model is used to simulate the formation mechanism of detrimental resolidified dendritic TiCx. To capture the polycrystalline solidification, a grain index is introduced to link different crystallographic orientations for each grain. This PF model simulates the microstructure evolution of TiCx in different zones in the molten pool by combining the temperature history predicted by the DED model. The simulated results provide the solution of limiting the free carbon content in the melt, according to which, the formation of TiCx dendrites is successfully avoided by experimentally controlling the melting degree of premixed TiC particulates.</div><div>Second, the solidification, grain structure evolution, and phase transformation in the DED-built ternary Ti6Al4V alloy under the influences of thermal history are systematically simulated using the established simulation framework and a phase prediction model. The thermal history in a three-track deposition is simulated by the DED model. With such thermal information, the 3D CA model simulates the grain structure evolution on the macro-scale. The thermodynamically-consistent PF model predicts the local grain structure and concentration distributions of solutes Al and V on the micro-scale. The meso-scale CA-PF model captures the sub-grain microstructure evolution and concentration distributions of solutes within the entire molten pool. The dendritic morphology is captured within the large β grains. When the temperature drops below the β-transus temperature, the solid-state phase transformation of β→α/ is studied by the phase prediction model. Based on the predicted volume fractions of and α, the microhardness is also successfully assessed using rules of mixtures. </div><div>Third, the material system is expanded to a four-component ZrAlNiCu bulk metallic glass composite, whose raw composition is prepared by premixing the four pure elemental metals. The DED model is employed to obtain the temperature field and heating/cooling rates in single-track ZrAlNiCu bulk metallic glass composite, which provides insights for microstructure evolution. By delicate control of the material composition and utilization of the thermal history of the DED process, an amorphous-crystalline periodic structure is produced with in-situ formed crystalline particulates embedded in the amorphous matrix. This crack-free microstructure is successfully maintained within bulk parts, where a high fraction of the amorphous phase and crystalline phases are produced in the fusion zone and heat-affected zone, respectively. The large volume percentage of the amorphous phase contributed to the hardness, strength, and elastic modulus of the composite while the various soft crystalline phases improve the ductility by more than three times compared to monolithic metallic glasses. Nanoindentation tests are also performed to study the deformation behavior on the micron/sub-micron length scale. </div><div>Fourth, the material system is expanded to a five-component CoCrFeNiTi HEA alloy. Three CoCrFeNiTi HEA alloys with different compositions are designed and synthesized from premixed elemental powders via the DED process. Through a delicate design of composition and powder preparation, different microstructures are formed. H3-Co24.4Cr17.4Fe17.5Ni24.2Ti16.5 is mainly composed of a soft face-centered cubic (FCC)-γ phase while σ-FeCr, δ-NiTi2, and a small amount of Ni3Ti2 are precipitated and uniformed distributed in the FCC matrix for H1-Co22.2Cr16.1Fe19Ni21.8Ti20.9 and H2-Co25.9Cr15Fe17Ni20.8Ti21.3. With a large percent of the secondary phases, H1 exhibits a hardness value of about 853 HV0.5. These HEA alloys display a high oxidation resistance comparable to Inconel 625 superalloy. A detailed evaluation of the hardness, oxidation resistance, and wear resistance of these HEAs are conducted as compared with those of a reference HEA and two popular anti-wear steels.</div><div>Finally, a novel 3D Cellular Automata-Phase Field (CA-PF) model that can accurately predict the dendrite formation in a large domain, which combines a 3D CA model with a 1D PF component, is developed. In this integrated model, the PF component reformulated in a spherical coordinate is employed to accurately calculate the local growth kinetics including the growth velocity and solute partition at the solidification front while the 3D CA component uses the growth kinetics as inputs to update the dendritic morphology variation and composition redistribution throughout the entire domain. Taking advantage of the high efficiency of the CA model and the high fidelity of the PF model, the 3D CA-PF model saves the computational cost more than five orders of magnitude compared to the 3D PF models without losing much accuracy. By coupling the thermodynamic and kinetic calculations into the PF component, the CA-PF model is capable of handling the microstructure evolution of any complex multi-component alloys. Al-Cu binary alloys with 2 wt.% and 4 wt.% Cu are first used to validate the 3D CA-PF model against the Lipton-Glicksman-Kurz analytical model and a 3D PF model. Then, the 3D CA-PF model is applied to predicting the dendrite growth during large-scale solidification processes of directional solidification of Al-30wt.%Cu and laser welding of Al-Cu-Mg and Al-Si-Mg alloys. </div>

No description available.

Many new instrumentation and different instrumental techniques have been developed to deal with increasing complexity of samples encountered. Many researchers also have coupled these instrumental techniques with chemometric algorithms to assist in the quantitative analysis of multi-component samples in the hope of alleviating the need of tedious separation and cleanup procedures. These newer chemometric procedures tend to be complex and difficult to understand and implement and are successful under different circumstances and conditions. In this study, we start from the very simple beginning and examine the factors that can present difficulties with obtaining the correct results and observe how the system behaves so as to find a better and simpler chemometric procedure to perform mixture quantitative analysis. We have used simulated and actual experimental data obtained from a UV-VIS spectrophotometric measurement of metal complexes to conduct the study. Well understood and defined systems tend to give good results. The main obstacle has been, and still is, interferences in spectral information one gets from the measurement.

U-Mo metallic fuels with Al alloys as the matrix/cladding are being developed as low enriched uranium fuels under the Reduced Enrichment for Research and Test Reactor (RERTR) program. Significant interactions have been observed to occur between the U-Mo fuel and the Al alloy during fuel processing and irradiation. U-Zr metallic fuels with stainless steel claddings have been developed for the generation IV sodium fast reactor (SFR). The fuel cladding chemical interaction (FCCI) induced by the interdiffusion of components was also observed. These interactions induce deleterious effects on the fuel system, such as thinning of the cladding layer, formation of phases with undesirable properties, and thermal cracking due to thermal expansion mismatches and changes in molar volume. The interaction between the fuel and the cladding involves multi-component interdiffusion. To determine the ternary interdiffusion coefficients using a single diffusion couple, a new method based on regression via the matrix transformation approach is proposed in this study. This new method is clear in physical meaning and simple in mathematical calculation. The reliability and accuracy of this method have been evaluated through application to three case studies: a basic asymptotic concentration profile, a concentration profile with extrema and a smoothed concentration profile with noise. Generally, this new method works well in all three cases. In order to investigate the interdiffusion behavior in U-Mo alloys, U vs. Mo diffusion couples were assembled and annealed in the temperature range of 650 to 1000°C. The interdiffusion microstructures and concentration profiles were examined via scanning electron iv microscopy (SEM) and electron probe microanalysis (EPMA), respectively. Interdiffusion coefficients and activation energies were calculated as functions of temperature and Mo composition. The intrinsic diffusion coefficients of U and Mo at the marker composition were also determined. The activity of U and the thermodynamic factor of the U-Mo alloy have been calculated using the ideal solution, the regular solution, and the subregular solution models based on the molar excess Gibbs free energy of the U-Mo alloy. The calculated intrinsic diffusivities of U and Mo along with the thermodynamic factor of the U-Mo alloy were employed to estimate the atomic mobilities and the vacancy wind effects of U and Mo according to Manning’s description. To explore potential diffusion barrier materials for reducing the fuel cladding chemical interaction between the U-Mo fuel and the Al alloy matrix/cladding, the interdiffusion behavior between U-Mo alloys and Mo, Zr, Nb and Mg were systematically studied. U-10wt.%Mo vs. Mo, Zr and Nb diffusion couples were annealed in the temperature range from 600 to 1000°C. A diffusion couple between U-7wt.%Mo and Mg was annealed at 550°C for 96 hours. SEM and transmission electron microscopy (TEM) were applied to characterize the microstructure of the interdiffusion zone. X-ray energy dispersive spectroscopy (XEDS) and EPMA were utilized to examine the concentration redistribution and the phase constituents. For the U-Mo vs. Mo diffusion couples, the interdiffusion coefficients at high Mo concentrations ranging from 22 to 32 at.%Mo were determined for the first time. In the U-Mo vs. Zr diffusion couples, the Mo2Zr phase was found at the interface. The diffusion paths were estimated and investigated according to the Mo-U-Zr ternary phase diagram. Thermal cracks and pure U precipitates were found within the diffusion zone in the U-Mo vs. Nb system. The growth rate of the interdiffusion zone v was found to be lower by about 103 times for Zr, 105 times for Mo and 106 times for Nb compared to those observed in the U-10wt.%Mo vs. Al or Al-Si systems. For the diffusion couple of U-Mo vs. Mg, the U-Mo was bonded very well to the Mg and there was negligible diffusion observed even after 96 hours annealing at 550°C. For a more fundamental understanding of the complex diffusion behavior between U-Zr fuels and their stainless steel claddings, U vs. Fe, Fe-15wt.%Cr and Fe-15wt.%Cr-15wt.%Ni diffusion couples were examined to investigate the interdiffusion behaviors between U and Fe and the effects of the alloying elements Cr and Ni. The diffusion couples were annealed in the temperature range from 580 to 700°C for various times. Two intermetallic phases, U6Fe and UFe2, developed in all of the diffusion couples with the U6Fe layer growing faster than the UFe2 layer. For the diffusion couples of U vs. Fe, extrinsic growth constants, intrinsic growth constants, integrated interdiffusion coefficients and activation energies in each phase were calculated. The results suggest that U6Fe impeded the growth of UFe2, and the boundary condition change caused by the allotropic transformation of U played a role in the growth of the U6Fe and UFe2 layers. The reasons why U6Fe grew much faster than UFe2 are also discussed. The additions of Cr and Ni into Fe affected the growth rates of U6Fe and UFe2. The solubility of Cr and Ni in U6Fe and UFe2 were determined, and it was found that Cr diffused into U more slowly than Fe or Ni.

Yes / Chemical manufacturing typically requires more than one step, involving multiple batch processes, which makes synthesis at scale laborious and wasteful. Herein, we demonstrate that several reactions can be telescoped into a single continuous process and/or be carried out as a continuous multi-component reaction (MCR), by twin screw extrusion (TSE), in the complete absence of solvent. / EPSRC (EP/L019655/1).

No / This paper studies the selective maintenance problem for multi-state systems with structural dependence. Each component can be in one of multiple working levels and several maintenance actions are possible to a component in a maintenance break. The components structurally form multiple hierarchical levels and dependence groups. A directed graph is used to represent the precedence relations of components in the system. A selective maintenance optimization model is developed to maximize the system reliability in the next mission under time and cost constraints. A backward search algorithm is used to determine the assembly sequence for a selective maintenance scenario. The maintenance model helps maintenance managers in determining the best combination of maintenance activities to maximize the probability of successfully completing the next mission. Examples showing the use of the proposed method are presented.

La thèse concerne trois problématiques indépendantes : le transport dissipatif dans des milieux hétérogènes; échange de masse entre un réservoir de gaz et aquifère ; ségrégation compositionnelle. Le point commun entre les problèmes traités sont les processus irréversibles de redistribution de la composition chimique. Le premier chapitre est consacré à la déduction, en accord avec les principes de la thermodynamique, d’un modèle généralisé de transport simultané de matière et de chaleur. Le chapitre 2 est consacré à l’étude de diffusion multi-compositionnelle dans un milieu hétérogène. Cette étude vise une application aux phénomènes de transport dans les réservoirs des hydrocarbures qui, d’une part, sont le siège de divers des processus de transport (plusieurs composants + chaleur) en interaction (processus croisés au sens d’Onsager) et, d’autre part, sont anisotropes pour les processus de transport étudiés. Le chapitre 3 est consacré à l’étude du processus de balayage d’un réservoir par une nappe aquifère. Le chapitre 4 est consacré au développement d’un code « éléments finis » conçu pour résoudre le même problème que dans le chapitre 3, mais dans une approche moins idéalisée. Le chapitre 5 est consacré à l’étude de la convection forcée dans un réservoir avec des champs de gravité et de température non colinéaires. Cette convection est une des composantes du processus de séparation thermo-gravitationnelle des espèces chimiques qui peut avoir lieu dans les réservoirs souterrains / The thesis concerns three independent subject areas: the dissipative transport in heterogeneous geological media; a transport problem in an underground gas reservoir; compositional segregation in reservoirs. The common point of all examined problems is the irreversible redistribution of chemical composition of a fluid in the reservoirs. The first chapter is devoted to development of a microscopic model of simultaneous mass and heat transfer in agreement with thermodynamic principles. The second chapter is dedicated to study of multi-component diffusion in a heterogeneous medium. This study aims an application to transport phenomena in hydrocarbon reservoirs characterized firstly by diversity of transported substances (several components + heat) and their interaction (in Onsager’s meaning) and secondly by anisotropy of medium where they take place. The third chapter is dedicated to analytical study of underground gas storage sweeping due to gas dissolution in aquifer. In the fourth chapter the same problem (gas sweeping) was studied numerically in a less idealized approach using finite element method. The fifth chapter is dedicated to study of forced convection taking place in the reservoirs where the temperature gradient and gravity force are not collinear. This convection represents an element of the thermo-gravitational component segregation employed in industry (thermo-gravitational columns) and can take place in underground reservoirs