Advanced Analytical Microscopy at the Nanoscale: Applications in Wide Bandgap and Solid Oxide Fuel Cell Materials

The atomic-level structure and chemistry of materials ultimately dictate their observed macroscopic properties and behavior. As such, an intimate understanding of these characteristics allows for better materials engineering and improvements in the resulting devices. In our work, two material systems were investigated using advanced electron and ion microscopy techniques, relating the measured nanoscale traits to overall device performance. First, transmission electron microscopy and electron energy loss spectroscopy (TEM-EELS) were used to analyze interfacial states at the semiconductor/oxide interface in wide bandgap SiC microelectronics. This interface contains defects that significantly diminish SiC device performance, and their fundamental nature remains generally unresolved. The impacts of various microfabrication techniques were explored, examining both current commercial and next-generation processing strategies. In further investigations, machine learning techniques were applied to the EELS data, revealing previously hidden Si, C, and O bonding states at the interface, which help explain the origins of mobility enhancement in SiC devices. Finally, the impacts of SiC bias temperature stressing on the interfacial region were explored. In the second system, focused ion beam/scanning electron microscopy (FIB/SEM) was used to reconstruct 3D models of solid oxide fuel cell (SOFC) cathodes. Since the specific degradation mechanisms of SOFC cathodes are poorly understood, FIB/SEM and TEM were used to analyze and quantify changes in the microstructure during performance degradation. Novel strategies for microstructure calculation from FIB-nanotomography data were developed and applied to LSM-YSZ and LSCF-GDC composite cathodes, aged with environmental contaminants to promote degradation. In LSM-YSZ, migration of both La and Mn cations to the grain boundaries of YSZ was observed using TEM-EELS. Few substantial changes however, were observed in the overall microstructure of the cells, correlating with a lack of performance degradation induced by the H2O. Using similar strategies, a series of LSCF-GDC cathodes were analyzed, aged in H2O, CO2, and Cr-vapor environments. FIB/SEM observation revealed considerable formation of secondary phases within these cathodes, and quantifiable modifications of the microstructure. In particular, Cr-poisoning was observed to cause substantial byproduct formation, which was correlated with drastic reductions in cell performance.

Microfluidics-based single-cell functional proteomics microchip for portraying protein signal transduction networks within the framework of physicochemical principles, with applications in fundamental and translational cancer research

Single-cell functional proteomics assays can connect genomic information to biological function through quantitative and multiplex protein measurements. Tools for single-cell proteomics have developed rapidly over the past 5 years and are providing unique opportunities. This thesis describes an emerging microfluidics-based toolkit for single cell functional proteomics, focusing on the development of the single cell barcode chips (SCBCs) with applications in fundamental and translational cancer research.

The microchip designed to simultaneously quantify a panel of secreted, cytoplasmic and membrane proteins from single cells will be discussed at the beginning, which is the prototype for subsequent proteomic microchips with more sophisticated design in preclinical cancer research or clinical applications. The SCBCs are a highly versatile and information rich tool for single-cell functional proteomics. They are based upon isolating individual cells, or defined number of cells, within microchambers, each of which is equipped with a large antibody microarray (the barcode), with between a few hundred to ten thousand microchambers included within a single microchip. Functional proteomics assays at single-cell resolution yield unique pieces of information that significantly shape the way of thinking on cancer research. An in-depth discussion about analysis and interpretation of the unique information such as functional protein fluctuations and protein-protein correlative interactions will follow.

The SCBC is a powerful tool to resolve the functional heterogeneity of cancer cells. It has the capacity to extract a comprehensive picture of the signal transduction network from single tumor cells and thus provides insight into the effect of targeted therapies on protein signaling networks. We will demonstrate this point through applying the SCBCs to investigate three isogenic cell lines of glioblastoma multiforme (GBM).

The cancer cell population is highly heterogeneous with high-amplitude fluctuation at the single cell level, which in turn grants the robustness of the entire population. The concept that a stable population existing in the presence of random fluctuations is reminiscent of many physical systems that are successfully understood using statistical physics. Thus, tools derived from that field can probably be applied to using fluctuations to determine the nature of signaling networks. In the second part of the thesis, we will focus on such a case to use thermodynamics-motivated principles to understand cancer cell hypoxia, where single cell proteomics assays coupled with a quantitative version of Le Chatelier's principle derived from statistical mechanics yield detailed and surprising predictions, which were found to be correct in both cell line and primary tumor model.

The third part of the thesis demonstrates the application of this technology in the preclinical cancer research to study the GBM cancer cell resistance to molecular targeted therapy. Physical approaches to anticipate therapy resistance and to identify effective therapy combinations will be discussed in detail. Our approach is based upon elucidating the signaling coordination within the phosphoprotein signaling pathways that are hyperactivated in human GBMs, and interrogating how that coordination responds to the perturbation of targeted inhibitor. Strongly coupled protein-protein interactions constitute most signaling cascades. A physical analogy of such a system is the strongly coupled atom-atom interactions in a crystal lattice. Similar to decomposing the atomic interactions into a series of independent normal vibrational modes, a simplified picture of signaling network coordination can also be achieved by diagonalizing protein-protein correlation or covariance matrices to decompose the pairwise correlative interactions into a set of distinct linear combinations of signaling proteins (i.e. independent signaling modes). By doing so, two independent signaling modes – one associated with mTOR signaling and a second associated with ERK/Src signaling have been resolved, which in turn allow us to anticipate resistance, and to design combination therapies that are effective, as well as identify those therapies and therapy combinations that will be ineffective. We validated our predictions in mouse tumor models and all predictions were borne out.

In the last part, some preliminary results about the clinical translation of single-cell proteomics chips will be presented. The successful demonstration of our work on human-derived xenografts provides the rationale to extend our current work into the clinic. It will enable us to interrogate GBM tumor samples in a way that could potentially yield a straightforward, rapid interpretation so that we can give therapeutic guidance to the attending physicians within a clinical relevant time scale. The technical challenges of the clinical translation will be presented and our solutions to address the challenges will be discussed as well. A clinical case study will then follow, where some preliminary data collected from a pediatric GBM patient bearing an EGFR amplified tumor will be presented to demonstrate the general protocol and the workflow of the proposed clinical studies.

Nested Sampling and its Applications in Stable Compressive Covariance Estimation and Phase Retrieval with Near-Minimal Measurements

Compressed covariance sensing using quadratic samplers is gaining increasing interest in recent literature. Covariance matrix often plays the role of a sufficient statistic in many signal and information processing tasks. However, owing to the large dimension of the data, it may become necessary to obtain a compressed sketch of the high dimensional covariance matrix to reduce the associated storage and communication costs. Nested sampling has been proposed in the past as an efficient sub-Nyquist sampling strategy that enables perfect reconstruction of the autocorrelation sequence of Wide-Sense Stationary (WSS) signals, as though it was sampled at the Nyquist rate. The key idea behind nested sampling is to exploit properties of the difference set that naturally arises in quadratic measurement model associated with covariance compression. In this thesis, we will focus on developing novel versions of nested sampling for low rank Toeplitz covariance estimation, and phase retrieval, where the latter problem finds many applications in high resolution optical imaging, X-ray crystallography and molecular imaging. The problem of low rank compressive Toeplitz covariance estimation is first shown to be fundamentally related to that of line spectrum recovery. In absence if noise, this connection can be exploited to develop a particular kind of sampler called the Generalized Nested Sampler (GNS), that can achieve optimal compression rates. In presence of bounded noise, we develop a regularization-free algorithm that provably leads to stable recovery of the high dimensional Toeplitz matrix from its order-wise minimal sketch acquired using a GNS. Contrary to existing TV-norm and nuclear norm based reconstruction algorithms, our technique does not use any tuning parameters, which can be of great practical value. The idea of nested sampling idea also finds a surprising use in the problem of phase retrieval, which has been of great interest in recent times for its convex formulation via PhaseLift, By using another modified version of nested sampling, namely the Partial Nested Fourier Sampler (PNFS), we show that with probability one, it is possible to achieve a certain conjectured lower bound on the necessary measurement size. Moreover, for sparse data, an l1 minimization based algorithm is proposed that can lead to stable phase retrieval using order-wise minimal number of measurements.

MINING AND VERIFICATION OF TEMPORAL EVENTS WITH APPLICATIONS IN COMPUTER MICRO-ARCHITECTURE RESEARCH

Computer simulation programs are essential tools for scientists and engineers to understand a particular system of interest. As expected, the complexity of the software increases with the depth of the model used. In addition to the exigent demands of software engineering, verification of simulation programs is especially challenging because the models represented are complex and ridden with unknowns that will be discovered by developers in an iterative process. To manage such complexity, advanced verification techniques for continually matching the intended model to the implemented model are necessary. Therefore, the main goal of this research work is to design a useful verification and validation framework that is able to identify model representation errors and is applicable to generic simulators. The framework that was developed and implemented consists of two parts. The first part is First-Order Logic Constraint Specification Language (FOLCSL) that enables users to specify the invariants of a model under consideration. From the first-order logic specification, the FOLCSL translator automatically synthesizes a verification program that reads the event trace generated by a simulator and signals whether all invariants are respected. The second part consists of mining the temporal flow of events using a newly developed representation called State Flow Temporal Analysis Graph (SFTAG). While the first part seeks an assurance of implementation correctness by checking that the model invariants hold, the second part derives an extended model of the implementation and hence enables a deeper understanding of what was implemented. The main application studied in this work is the validation of the timing behavior of micro-architecture simulators. The study includes SFTAGs generated for a wide set of benchmark programs and their analysis using several artificial intelligence algorithms. This work improves the computer architecture research and verification processes as shown by the case studies and experiments that have been conducted.

SECURITY, PRIVACY AND APPLICATIONS IN VEHICULAR AD HOC NETWORKS

With wireless vehicular communications, Vehicular Ad Hoc Networks (VANETs) enable numerous applications to enhance traffic safety, traffic efficiency, and driving experience. However, VANETs also impose severe security and privacy challenges which need to be thoroughly investigated. In this dissertation, we enhance the security, privacy, and applications of VANETs, by 1) designing application-driven security and privacy solutions for VANETs, and 2) designing appealing VANET applications with proper security and privacy assurance. First, the security and privacy challenges of VANETs with most application significance are identified and thoroughly investigated. With both theoretical novelty and realistic considerations, these security and privacy schemes are especially appealing to VANETs. Specifically, multi-hop communications in VANETs suffer from packet dropping, packet tampering, and communication failures which have not been satisfyingly tackled in literature. Thus, a lightweight reliable and faithful data packet relaying framework (LEAPER) is proposed to ensure reliable and trustworthy multi-hop communications by enhancing the cooperation of neighboring nodes. Message verification, including both content and signature verification, generally is computation-extensive and incurs severe scalability issues to each node. The resource-aware message verification (RAMV) scheme is proposed to ensure resource-aware, secure, and application-friendly message verification in VANETs. On the other hand, to make VANETs acceptable to the privacy-sensitive users, the identity and location privacy of each node should be properly protected. To this end, a joint privacy and reputation assurance (JPRA) scheme is proposed to synergistically support privacy protection and reputation management by reconciling their inherent conflicting requirements. Besides, the privacy implications of short-time certificates are thoroughly investigated in a short-time certificates-based privacy protection (STCP2) scheme, to make privacy protection in VANETs feasible with short-time certificates. Secondly, three novel solutions, namely VANET-based ambient ad dissemination (VAAD), general-purpose automatic survey (GPAS), and VehicleView, are proposed to support the appealing value-added applications based on VANETs. These solutions all follow practical application models, and an incentive-centered architecture is proposed for each solution to balance the conflicting requirements of the involved entities. Besides, the critical security and privacy challenges of these applications are investigated and addressed with novel solutions. Thus, with proper security and privacy assurance, these solutions show great application significance and economic potentials to VANETs. Thus, by enhancing the security, privacy, and applications of VANETs, this dissertation fills the gap between the existing theoretic research and the realistic implementation of VANETs, facilitating the realistic deployment of VANETs.

Acoustic manipulation and alignment of particles for applications in separation, micro-templating and device fabrication

This dissertation studies the manipulation of particles using acoustic stimulation for applications in microfluidics and templating of devices. The term particle is used here to denote any solid, liquid or gaseous material that has properties, which are distinct from the fluid in which it is suspended. Manipulation means to take over the movements of the particles and to position them in specified locations. ^ Using devices, microfabricated out of silicon, the behavior of particles under the acoustic stimulation was studied with the main purpose of aligning the particles at either low-pressure zones, known as the nodes or high-pressure zones, known as anti-nodes. By aligning particles at the nodes in a flow system, these particles can be focused at the center or walls of a microchannel in order to ultimately separate them. These separations are of high scientific importance, especially in the biomedical domain, since acoustopheresis provides a unique approach to separate based on density and compressibility, unparalleled by other techniques. The study of controlling and aligning the particles in various geometries and configurations was successfully achieved by controlling the acoustic waves. ^ Apart from their use in flow systems, a stationary suspended-particle device was developed to provide controllable light transmittance based on acoustic stimuli. Using a glass compartment and a carbon-particle suspension in an organic solvent, the device responded to acoustic stimulation by aligning the particles. The alignment of light-absorbing carbon particles afforded an increase in visible light transmittance as high as 84.5%, and it was controlled by adjusting the frequency and amplitude of the acoustic wave. The device also demonstrated alignment memory rendering it energy-efficient. A similar device for suspended-particles in a monomer enabled the development of electrically conductive films. These films were based on networks of conductive particles. Elastomers doped with conductive metal particles were rendered surface conductive at particle loadings as low as 1% by weight using acoustic focusing. The resulting films were flexible and had transparencies exceeding 80% in the visible spectrum (400-800 nm) These films had electrical bulk conductivities exceeding 50 S/cm. ^

Development of Safety Performance Functions for SafetyAnalyst Applications in Florida

In 2010, the American Association of State Highway and Transportation Officials (AASHTO) released a safety analysis software system known as SafetyAnalyst. SafetyAnalyst implements the empirical Bayes (EB) method, which requires the use of Safety Performance Functions (SPFs). The system is equipped with a set of national default SPFs, and the software calibrates the default SPFs to represent the agency’s safety performance. However, it is recommended that agencies generate agency-specific SPFs whenever possible. Many investigators support the view that the agency-specific SPFs represent the agency data better than the national default SPFs calibrated to agency data. Furthermore, it is believed that the crash trends in Florida are different from the states whose data were used to develop the national default SPFs. In this dissertation, Florida-specific SPFs were developed using the 2008 Roadway Characteristics Inventory (RCI) data and crash and traffic data from 2007-2010 for both total and fatal and injury (FI) crashes. The data were randomly divided into two sets, one for calibration (70% of the data) and another for validation (30% of the data). The negative binomial (NB) model was used to develop the Florida-specific SPFs for each of the subtypes of roadway segments, intersections and ramps, using the calibration data. Statistical goodness-of-fit tests were performed on the calibrated models, which were then validated using the validation data set. The results were compared in order to assess the transferability of the Florida-specific SPF models. The default SafetyAnalyst SPFs were calibrated to Florida data by adjusting the national default SPFs with local calibration factors. The performance of the Florida-specific SPFs and SafetyAnalyst default SPFs calibrated to Florida data were then compared using a number of methods, including visual plots and statistical goodness-of-fit tests. The plots of SPFs against the observed crash data were used to compare the prediction performance of the two models. Three goodness-of-fit tests, represented by the mean absolute deviance (MAD), the mean square prediction error (MSPE), and Freeman-Tukey R2 (R2FT), were also used for comparison in order to identify the better-fitting model. The results showed that Florida-specific SPFs yielded better prediction performance than the national default SPFs calibrated to Florida data. The performance of Florida-specific SPFs was further compared with that of the full SPFs, which include both traffic and geometric variables, in two major applications of SPFs, i.e., crash prediction and identification of high crash locations. The results showed that both SPF models yielded very similar performance in both applications. These empirical results support the use of the flow-only SPF models adopted in SafetyAnalyst, which require much less effort to develop compared to full SPFs.

The actinin family of actin crosslinking proteins: natural functions and potential applications in synthetic biology

Actinin and spectrin proteins are members of the Spectrin Family of Actin Crosslinking Proteins. The importance of these proteins in the cytoskeleton is demonstrated by the fact that they are common targets for disease causing mutations. In their most prominent roles, actinin and spectrin are responsible for stabilising and maintaining the muscle architecture during contraction, and providing shape and elasticity to the red blood cell in circulation, respectively. To carry out such roles, actinin and spectrin must possess important mechanical and physical properties. These attributes are desirable when choosing a building block for protein-based nanoconstruction. In this study, I assess the contribution of several disease-associated mutations in the actinin-1 actin binding domain that have recently been linked to a rare platelet disorder, congenital macrothrombocytopenia. I investigate the suitability of both actinin and spectrin proteins as potential building blocks for nanoscale structures, and I evaluate a fusion-based assembly strategy to bring about self-assembly of protein nanostructures. I report that the actinin-1 mutant proteins display increased actin binding compared to WT actinin-1 proteins. I find that both actinin and spectrin proteins exhibit enormous potential as nano-building blocks in terms of their stability and ability to self-assemble, and I successfully design and create homodimeric and heterodimeric bivalent building blocks using the fusion-based assembly strategy. Overall, this study has gathered helpful information that will contribute to furthering the advancement of actinin and spectrin knowledge in terms of their natural functions, and potential unnatural functions in protein nanotechnology.

UT Austin | Portugal Workshop on Nonlinear Mechanics and Applications in Life Sciences

This is a CoLab Workshop organized as an initiative of the UT Austin | Portugal Program to reinforce the Portuguese competences in Nonlinear Mechanics and in complex problems arising from applications to the mathematical modeling and simulations in the Life Sciences. The Workshop provides a place to exchange recent developments, discoveries and progresses in this challenging research field. The main goal is to bring together doctoral candidates, postdoctoral scientists and graduates interested in the field, giving them the opportunity to make scientific interactions and new connections with established experts in the interdisciplinary topics covered by the event. Another important goal of the Workshop is to promote collaboration between members of the different areas of the UT Austin | Portugal community.

Poultry litter and pig slurry applications in an integrated crop-livestock system.

2016

Approches générales de résolution pour les problèmes multi-attributs de tournées de véhicules et confection d'horaires

Thèse réalisée en cotutelle entre l'Université de Montréal et l'Université de Technologie de Troyes

The effect of demand distributions on the performance of inventory policies

Inventory policies provide instructions on how to calculate stock levels and order quantities. This paper examines the effect of the demand distribution on the performance of several well-known policies. Their performance is compared in terms of achieved service levels. As a conclusion from these comparisons, a nonparametric demand model is proposed to be used in inventory policies.

Technology adoption in small and medium-sized logistics providers

Purpose - The main aim of the research is to shed light on the role of information and communication technology (ICT) in the logistics innovation process of small and medium-sized third party logistics providers (3PLs). Design/methodology/approach - A triangulated research strategy was designed using a combination of quantitative and qualitative methods. The former involved the use of a questionnaire survey of small and medium-sized Italian 3PLs with 153 usable responses received. The latter comprised a series of focus groups and the use of seven case studies. Findings - There is a relatively low level of ICT expenditure with few companies adopting formal technology investment strategies. The findings highlight the strategic importance of supply chain integration for 3PLs with companies that have embarked on an expansion of their service portfolios showing a higher level of both ICT usage and information integration. Lack of technology skills in the workforce is a major constraint on ICT adoption. Given the proliferation of logistics-related ICT tools and applications in recent years it has been difficult for small and medium-sized 3PLs to select appropriate applications. Research limitations/implications - The paper provides practical guidelines to researchers in the effective use of mixed-methods research based on the concept of methodological triangulation. In particular, it shows how questionnaire surveys, focus groups and case study analysis can be used in combination to provide insights into multi-faceted supply chain phenomena. It also identifies several potentially fruitful avenues for future research in this specific field. Practical implications - The paper's findings provide useful guidance for practitioners on the effective adoption of ICT as part of the logistics innovation process. The findings also provide support for ICT vendors in the design of ICT solutions that are aligned to the needs of small 3PLs. Originality/value - There is currently a paucity of research into the drivers and inhibitors of ICT in the innovation processes of small and medium-sized 3PLs. This paper fills this gap by exploring the issue using a range of complementary research approaches. Copyright © 2013 Emerald Group Publishing Limited. All rights reserved.