Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007. / Includes bibliographical references. / The stratum corneum (SC) of the skin functions as a barrier between the body and the environment. Surfactants such as Sodium Dodecyl Sulfate (SDS) are used in skin cleansers and in skin-care formulations because of their ability to stabilize oil-water emulsions and clean the surface of the skin. However, they also have adverse effects on the skin barrier, including enhancing skin barrier perturbation which may lead to a disruption of the protective functions carried out by the skin barrier. On the other hand, humectants, such as Glycerol, which maintain the natural water content of the skin and preserve the skin barrier, have been shown to mitigate surfactant-induced skin barrier perturbation. The primary objective of this thesis was to develop a mechanistic understanding, including visualization and quantification, of: (i) how aqueous surfactant solutions, once in contact with the skin, can induce skin barrier perturbation, and (ii) how surfactant-induced skin barrier perturbation can be effectively mitigated through the addition of humectants to the aqueous surfactant contacting solutions. SDS monomers self-assemble to form micelles at a SDS concentration above the Critical Micelle Concentration (CMC). The SDS skin penetration and associated skin barrier perturbation is dose-dependent, that is, it increases with an increase in the total SDS concentration above the CMC of SDS. / (cont.) However, when Glycerol was added to the aqueous SDS contacting solution, through in vitro quantitative skin radioactivity assays using 14C radiolabeled SDS, I found that the dose-dependence in SDS skin penetration was almost completely eliminated. This is because the addition of Glycerol hinders the ability of the SDS micelles to penetrate into the skin barrier through aqueous pores that exist in the SC. In vitro Mannitol skin permeability and average skin electrical resistivity measurements, in the context of a hindered-transport aqueous porous pathway model of the SC, demonstrated that the addition of 10 wt% Glycerol: (1) reduces the average aqueous pore radius resulting from exposure of the skin to the aqueous SDS contacting solution from 33±5A to 20+5A, such that a SDS micelle of radius 18.5±1 A (as determined using dynamic light scattering (DLS) measurements) experiences significant steric hindrance and cannot penetrate into the SC, and (2) reduces the porosity-to-tortuosity ratio of the aqueous pores in the SC by more than 50%, thereby further reducing the ability of the SDS micelles to penetrate into the SC and perturb the skin barrier. / (cont.) In vitro skin electrical current measurements can be used effectively to rank aqueous contacting solutions containing surfactants and humectants (the enhancer), relative to a PBS aqueous contacting solution (the control), based on their ability to perturb the skin aqueous pores. Specifically, an in vitro ranking metric was introduced using the enhancement in the skin electrical current induced by an enhancer relative to the control. For this study, I considered aqueous contacting solutions of the following chemicals: (1) humectants - Glycerol and Propylene Glycol, (2) surfactants - SDS and C12E6 (Dodecyl Hexa (Ethylene Oxide)), and (3) a control - PBS. Utilizing the in vitro ranking metric, the aqueous solutions above contacting the skin were ranked as follows (from the mildest to the harshest): Glycerol < Propylene Glycol < PBS < C12E6 < SDS. In order to further develop this ranking methodology, which can potentially lead to the reduction of several costly operations associated with identifying surfactant/humectant systems which are mild to the skin, such as, in vivo clinical testing and trial-and-error screening, it was important to correlate the in vitro ranking metric findings with direct in vivo skin barrier measurements. / (cont.) For this purpose, in vivo soap chamber measurements were carried out on human subjects, using the aqueous surfactant/humectant solutions described above. The results of these in vivo measurements of skin barrier perturbation were found to be consistent with the ranking results obtained using the in vitro ranking metric for the aqueous surfactant and humectant contacting solutions considered. In addition, in vivo soap chamber measurements were carried out for aqueous SDS+Glycerol contacting solutions. These in vivo measurements indicated that adding Glycerol to a SDS aqueous contacting solution significantly mitigates SDS-induced in vivo skin barrier perturbation, which is consistent with the results of my in vitro skin electrical current and Mannitol skin permeability measurements. In order to visualize the effects of aqueous surfactant/humectant systems on the skin barrier, an in vitro dual-channel two-photon fluorescence microscopy (TPM) visualization study was carried out. TPM is a non-invasive imaging technique based on two-photon induced nonlinear excitations of fluorophores, with the capability for deep-tissue imaging (up to several hundred micrometers). / (cont.) The following aqueous surfactant and humectant contacting solutions were studied: (i) SDS, (ii) SDS+Glycerol, (iii) SCI (a mild surfactant), (iv) PBS control, and (v) Glycerol. Sulforhodamine B (SRB), which is a hydrophilic fluorescent probe, was used to probe the effect of aqueous contacting solutions (i)-(v) on the skin barrier morphology. The results of this TPM visualization study revealed that SDS induces corneocyte damage by denaturing keratins and creating intra-corneocyte penetration pathways. On the other hand, SDS+Glycerol did not significantly induce corneocyte damage. The dual-channel TPM images corresponding to aqueous contacting solutions (iii)-(v) showed low SRB penetration into the corneocytes, as well as localization of the SRB probe within the lipid bilayers surrounding the corneocytes of the SC. Through a quantification of the amount of SRB that penetrated into the skin as a function of the skin depth, I found that adding Glycerol to SDS could significantly reduce the SDS-induced penetration depth of SRB, which provides evidence of the ability of Glycerol to mitigate SDS-induced skin barrier perturbation. / (cont.) The fundamental understanding of surfactant-induced skin barrier perturbation in the presence of humectants developed in this thesis is of particular relevance to the cosmetic industry in enabling the formulation of mild, non-drying, skin-care products that contain surfactants and humectants. The novel TPM studies that visualize, as well as quantify, skin morphology upon exposure of the skin to surfactant/humectant systems, has the potential to be developed into a high-throughput imaging tool for the screening of new skin-care formulations. Such a strategy can simultaneously screen the skin-mildness potential of many skin-care formulations, thereby significantly speeding up the effort and time required to bring new skin-care formulations to the market. In addition to the practical impact on the formulation of mild skin-care products, this thesis has also advanced fundamental research carried out in the investigative dermatology and related health disciplines. / by Saswata Ghosh. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2008. / Includes bibliographical references (p. 132-136). / The scope of this research work is to characterize the Transformer Coupled Toroidal Plasma (TCTP); to understand gas phase reactions and surface reactions of neutrals in the cleaning chamber by analyzing the concentration of neutrals in downstream cleaning process chamber; and to make a global model that predicts the partial pressure of active species in the cleaning chamber. The final goal is to set-up an optimal cleaning process using the results from the experiment and the global model. The first object is to characterize the TCTP and the power consumed by plasma is measured as one approach to the characterization of plasma. MKS Astex plasma source has a very high power density. Compared to a typical industrial plasma source, the power density of the TCTP source is two orders of magnitude higher. The extremely high power density makes the plasma source very unique and its parameters very different from other plasma sources. It is discussed that there are several factors that affect the plasma power consumption. One factor is the flow rate of inlet gas and the elevated pressure due to the high flow rate of inlet gas increases the power consumption. Experimentally it is observed that the plasma power is linearly dependent upon the plasma source pressure, not upon the process chamber pressure. Another factor of controlling the power consumption is the resistivity of gases. For example, the bonding energy of N-F in NF3 gas is different from the bonding energy of C-F bonding in C2F6. Experimental result shows that C2F6 + 02 gas requires more power than NF3 gas to dissociate in the plasma due to the different resistivity. The second object is to understand gas phase reactions and surface reactions among neutrals in the cleaning chamber. The effect of nitric oxide as a silicon nitride etching enhancement factor is discussed. / (cont.) It is shown that only 4.5% of additives (02, CO and CO2) into NF3 discharge doubles nitride etching rate and the enhancement of etching rate occurs regardless of the additive types. The enhancement results from the production of NO in the discharge of NF3 gas mixture. As the amount of oxygen containing additive increases, the amount of NO increases. However, atomic fluorine decreases as the amount of oxygen containing additive increases because the additive dilutes NF3 plasma. At low process chamber pressure, the effect of NO is offset by the dilution effect of atomic fluorine. At high pressure, addition of oxygen enhances the recombination of atomic fluorine and 25% of 02 in NF3 discharge decreases 54% of atomic fluorine. Therefore, the effect of a decrease in atomic fluorine is remarkably higher than the effect of increase in the concentration of NO by adding 02 at high pressure, which leads to a decrease of nitride etching rate at 5torr. Also, the nitride etching rates of NF3 plasma and NF3/C2F/O2 plasma are compared and it is shown that NF3/C2F/O02 plasma brings better performance than NF3 plasma in increasing the nitride etching rate. The main reason why the nitride etching rate of NF3/C2F6/02 plasma is higher than that of NF3 plasma is because nitric oxide is formed in the gas phase of NF3/C2FdO2 plasma and the nitric oxide reacts with the nitrogen atom on the silicon nitride surface producing N20 or N2, while nitrogen is substituted by oxygen on the surface by the reaction. Removing nitrogen atom from silicon nitride substrate is assumed to be the rate-limiting step in the fluorine base etching of silicon nitride film. In summary, the nitric oxide makes it easier to remove the nitrogen atom from silicon nitride surface in the presence of atomic fluorine, which is the rate-limiting step for nitride etching with F base gas, therefore enhancing silicon nitride etching rate. The last object is to make a global model to predict the partial pressure of neutrals in downstream. / (cont.) It is shown that incorporating kinetics into the global modeling of PECVD chamber cleaning system successfully enables the prediction of the partial pressure of atomic fluorine in NF3/N2 and NF3/02 discharge, which is crucial in estimating cleaning rate of TEOS film. First of all, effect of nitrogen addition in NF3 discharge is experimentally investigated by measuring the etching rates of TEOS film and the partial pressure of neutral species. Both modeling results and experimental results make a good agreement that the addition of nitrogen in NF3 has advantage in increasing TEOS etching rate at high chamber pressure. In other words, at high chamber pressure, TEOS etching rate is increased by adding nitrogen in NF3 plasma. Then, the effect of oxygen in NF3 discharge is studied. TEOS film etching rates and partial pressure of atomic fluorine in the gas phase shows that adding oxygen in NF3 discharge increases F-F recombination, which lowers TEOS etching rate. By incorporating the above kinetics information in the global model, the partial pressure of neutral species in NF3/02 discharge is successfully predicted by the global model. / by Ju Jin An. / Ph.D.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1959. / Vita. / Includes bibliographical references (leaves 171-172). / by Herman Erkku. / Sc.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2006. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Includes bibliographical references (v. 2, leaves [435]-467). / In this thesis, I discuss the application and development of methods for the automated discovery of motifs in sequential data. These data include DNA sequences, protein sequences, and real-valued sequential data such as protein structures and timeseries of arbitrary dimension. As more genomes are sequenced and annotated, the need for automated, computational methods for analyzing biological data is increasing rapidly. In broad terms, the goal of this thesis is to treat sequential data sets as unknown languages and to develop tools for interpreting an understanding these languages. The first chapter of this thesis is an introduction to the fundamentals of motif discovery, which establishes a common mode of thought and vocabulary for the subsequent chapters. One of the central themes of this work is the use of grammatical models, which are more commonly associated with the field of computational linguistics. In the second chapter, I use grammatical models to design novel antimicrobial peptides (AmPs). AmPs are small proteins used by the innate immune system to combat bacterial infection in multicellular eukaryotes. There is mounting evidence that these peptides are less susceptible to bacterial resistance than traditional antibiotics and may form the basis for a novel class of therapeutics. / (cont.) In this thesis, I described the rational design of novel AmPs that show limited homology to naturally-occurring proteins but have strong bacteriostatic activity against several species of bacteria, including Staphylococcus aureus and Bacillus anthracis. These peptides were designed using a linguistic model of natural AmPs by treating the amino acid sequences of natural AmPs as a formal language and building a set of regular grammars to describe this language. is set of grammars was used to create novel, unnatural AmP sequences that conform to the formal syntax of natural antimicrobial peptides but populate a previously unexplored region of protein sequence space. The third chapter describes a novel, GEneric MOtif DIscovery Algorithm (Gemoda) for sequential data. Gemoda can be applied to any dataset with a sequential character, including both categorical and real-valued data. As I show, Gemoda deterministically discovers motifs that are maximal in composition and length. As well, the algorithm allows any choice of similarity metric for finding motifs. These motifs are representation-agnostic: they can be represented using regular expressions, position weight matrices, or any other model for sequential data. / (cont.) I demonstrate a number of applications of the algorithm, including the discovery of motifs in amino acids and DNA sequences, and the discovery of conserved protein sub-structures. The final chapter is devoted to a series of smaller projects, employing tool methods indirectly related to motif discovery in sequential data. I describe the construction of a software tool, Biogrep that is designed to match large pattern sets against large biosequence databases in a parallel fashion. is makes biogrep well-suited to annotating sets of sequences using biologically significant patterns. In addition, I show that the BLOSUM series of amino acid substitution matrices, which are commonly used in motif discovery and sequence alignment problems, have changed drastically over time.The fidelity of amino acid sequence alignment and motif discovery tools depends strongly on the target frequencies implied by these underlying matrices. us, these results suggest that further optimization of these matrices is possible. The final chapter also contains two projects wherein I apply statistical motif discovery tools instead of grammatical tools. / (cont.) In the first of these two, I develop three different physiochemical representations for a set of roughly 700 HIV-I protease substrates and use these representations for sequence classification and annotation. In the second of these two projects, I develop a simple statistical method for parsing out the phenotypic contribution of a single mutation from libraries of functional diversity that contain a multitude of mutations and varied phenotypes. I show that this new method successfully elucidates the effects of single nucleotide polymorphisms on the strength of a promoter placed upstream of a reporter gene. The central theme, present throughout this work, is the development and application of novel approaches to finding motifs in sequential data. The work on the design of AmPs is very applied and relies heavily on existing literature. In contrast, the work on Gemoda is the greatest contribution of this thesis and contains many new ideas. / by Kyle L. Jensen. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1998. / Includes bibliographical references (p. 172-181). / by Lily Chu. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2012. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 104-120). / Microbial production platforms have extraordinary potential to help meet the energy, material and health needs of tomorrow. Through the reactions of cellular metabolism, microbes are an attractive option for the sustainable production of commodity and enantiopure specialty chemicals. One outstanding challenge, however, is the engineering of these systems for economic viability. As a solution to this issue, a metabolite valve is proposed: a biochemical device which may be used to dynamically redirect metabolite flux away from endogenous processes into production pathways. In this work, we develop and characterize a glucose valve. First, a novel E. coli strain was engineered to allow the redirection of glucose flux from central metabolism via glucokinase. Using a promoter library, glucokinase expression was varied with an attendant change in specific growth rate and carbon flux. A model pathway was then constructed to utilize the redirected carbon demonstrating that the efficiency of such pathways may be controlled through glucokinase expression. Next, inducible antisense RNA and inverting genetic circuits were developed to dynamically control glucokinase expression. With dynamic control, carbon was redirected from endogenous processes only once sufficient cellular resources had accumulated, further improving performance. In this manner, yields and titers of the model pathway were increased with a concomitant decrease in acetate waste. Finally, elements of this system were modeled to gain mechanistic insight and to establish a control envelope of viable expression and production regimes. This thesis represents one of the first reports of glucose redirection in E. coli and is an example of the ongoing development of a relatively new paradigm in metabolic engineering: dynamic flux control. With a glucose valve, the needs of cellular health and demands of heterologous production may be balanced, enabling the development of efficient processes with glucose as a sole carbon source for both cell growth and biochemical production. This ability to use a single carbon source simplifies process design, lowering capital and operating costs. Furthermore, a glucose valve has potential applications in the optimization of existing processes where carbon is underutilized and wasted as fermentation products such as acetate. / by Kevin Val-Murvin Solomon. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2008. / Includes bibliographical references (p. 261-270). / Oxygen precipitate caused by oxygen supersaturation is the most common and important defects in Czochralski (CZ) silicon. The presence of oxygen precipitate in silicon wafer has both harmful and beneficial effects on the microelectronic device production. Oxygen precipitates are useful for gathering metallic contaminants away from the device regions and for increasing the mechanical strength of the wafer [Borghesi, 1995], but they also can destroy the electrical and mechanical characteristics of the semiconductor and microelectronic devices [Abe, 1985; Kolbesen, 1985]. The understanding of the mechanism of the formation and growth of the oxygen precipitates in CZ silicon is a key to improve the quality of silicon wafer. The goal of this thesis is to provide a full understanding of the growth of an isolated oxygen precipitate in CZ silicon and its morphological evolution by means of phase-field method, and to gain the insight of the morphological transition of the oxygen precipitate and the distribution of oxygen, vacancy, and self-interstitial around the single oxygen precipitate. The traditional approach to simulate multiphase system is the sharp interface model. Sharp interface model requires tracking the interface between phases, which make the simulation much difficult and complicate. Phase-field model offers an alternative approach for predicting mesoscale morphological and microstructure evolution of inhomogeneous multiphase system. The most significant computational advantage of a phase-field model is that explicit tracking of the interface is unnecessary. In this thesis, the phase-field model is applied to simulate the evolution of oxygen precipitates in CZ silicon. A phase-field model for a two-component inhomogeneous system was first derived to set up the framework of phase-field method and a dynamically adaptive finite element method also was built to specifically solve phase-field equations. This model was used to investigate the effects of interfacial and elastic properties on the growth of a single precipitate, coarsening of two precipitates, and competitive growth of multiple precipitates. For an isolated precipitate growth, both elastic energy and interfacial energy affect the precipitate morphological evolution. / (cont.) Numerical results show the shape of the precipitate is determined by the relative contributions of elastic energy and interfacial energy, the degree of elastic anisotropy, and the degree of interfacial anisotropy. A dimensionless length scale LS3 was defined to represent the relative contributions of the interfacial energy and elastic energy. For large LS3 (LS3 > 5), the anisotropic elasticity plays a dominant role and precipitate evolves to held the elastic anisotropy even if the interfacial anisotropy is very strong. However, if LS3 ~1 or elasticity is isotropic, the strong anisotropy ([epsilon]4 =/> 0.05 ) of the interface will be the dominant factor to determine the precipitate shape. The growth rate of an isolated precipitate follows the diffusion-controlled power law. The elasticity significantly decreases the precipitate growth rate, while the anisotropy of the interface does not. Coarsening of two precipitates was also explored with different interfacial and elastic properties. The results also show that both elasticity and interfacial anisotropy enhance the coarsening rate. For competitive growth of multiple precipitates, a gap was found to be developed between the precipitates because of the precipitate screening, but this gap could be destroyed by increasing the interfacial energy or introducing elastic energy. Based on the framework of the previous phase-field model, another phase-field model coupling CALPHAD thermodynamic assessment was developed to simulate the growth of the oxygen precipitate in CZ isilicon. An asymptotic analysis was performed to understand the phase-field model at the sharp interface limit and all physical principles of the solid precipitate growth problem were recovered. a Cristobalite and amorphous oxygen precipitates were calculated at different orientations and temperatures. Disk-like shape, square, ellipse, a slightly deformed sphere are reproduced for oxygen precipitates, which agrees with the experimental observations very well. In addition, the growth rates of amorphous precipitates and a cristobalite precipitates at different temperatures show that at high temperature 1100 °C, amorphous precipitate has the largest growth rate, while at low temperature 900 °C, a cristobalite precipitate grows faster. / (cont.) This qualitatively explained why different polymorphs and shapes of the oxygen precipitate were observed in experiments at different annealing temperatures. / by Minggang She. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1986. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Bibliography: leaves 319-340. / by Kenneth Donald Allen. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2004. / Includes bibliographical references (leaves 143-152). / The ultimate goal of this research was to develop a greater understanding of the structural components needed to describe transport within the glomerular basement membrane (GBM). Specifically, dimensionless diffusive and convective hindrance factors were investigated by measuring macromolecular permeability through synthetic, two-fiber, agarose-dextran hydrogels at very small or very high Pe, respectively. By comparing diffusion and convection in the synthetic hydrogel with corresponding measurements in isolated rat GBM, further insight regarding the structure responsible for transport through the GBM was gained. In order to compare diffusive hindrances in the synthetic gels with those in isolated GBM, partitioning in agarose-dextran hydrogels was also examined. Additionally, hindered transport theories were tested. In studying diffusion, partitioning, and convection, macromolecules with Stokes-Einstein radii (r) ranging from 2.7 to 5.9 nm were used. Gels with agarose volume fractions of 0.040 and 0.080 were studied with dextran volume fractions (assuming dextran acts as a fiber) ranging from 0 to 0.0076 and 0 to 0.011, respectively. For the diffusion studies, two globular proteins (ovalbumin and bovine serum albumin) and three narrow fractions of Ficoll, a spherical polysaccharide, were used. For the partitioning and convection studies, four narrow fractions of Ficoll were used. Diffusivities of fluorescein-labeled macromolecules were measured in dilute aqueous solution (D[infinity]), agarose gels (D[alpha]), and agarose-dextran composite gels (D) using fluorescence recovery after photobleaching. / (cont.) For both agarose concentrations, the Darcy permeability (K) decreased by an order of magnitude as the dextran concentration in the gel was increased from zero to its maximum value. For a given gel composition, the relative diffusivity (D/D[infinity]) decreased as r increased, a hallmark of hindered diffusion. For a given test molecule, D/D[infinity] was lowest in the most concentrated gels, as expected. As the dextran concentration was increased to its maximum value, 2-3 fold decreases in relative diffusivity resulted for both agarose gel concentrations. The reductions in macromolecular diffusivities caused by incorporating various amounts of dextran into agarose gels could be predicted fairly accurately from the measured decreases in K, using an effective medium model. This suggests that one might be able to predict diffusivity variations in complex, multicomponent hydrogels (e.g. those in body tissue) in the same manner, provided that values of K can be obtained. Equilibrium partition coefficients ([Phi],the concentration in the gel divided by that in free solution) of fluorescein-labeled Ficolls in pure agarose and agarose-dextran composite gels were measured as a function of gel composition and Ficoll size. As expected, [Phi] generally decreased as the Ficoll size increased (for a given gel composition) or as the amount of dextran incorporated into the gel increased (for a given agarose concentration and Ficoll size). The decrease in [Phi] that accompanied dextran addition was predicted well by an excluded volume theory in which agarose and dextran were both treated as rigid, straight, randomly positioned and oriented fibers ... / by Kimberly Bryan Kosto. / Ph.D.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1961. / Includes bibliographical references (p. 167-169). / by Richard G. Miekka. / Sc.D.