Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, June 2008. / "May 26, 2008." / Includes bibliographical references (p. 152-156). / All ES evolve as the result of stakeholder decisions and decision processes that affect their design and operation. These decision making problems often involve many stakeholders, each of whom have a say in the outcome. This has been termed a lateral alignment problem, as opposed to a unitary decision making problem. Lateral alignment focuses on group decision making where stakeholders are nominally organizationally independent, interact to maximize their own goals and simultaneously a common goal, and who are able to influence decision outcomes to varying degrees through power and influence. Previous work in the relevant literatures has focused on two variants used to assess and model group decision making. Type 0 Group Decision problems involve anonymous voting, where stakeholders do not interact. Type 1 Group Decision problems involve non-cooperative interaction where stakeholders try to maximize their self-interest through negotiation. We define the lateral alignment problem as a Type 2 Group Decision problem, which involve elements of both non-cooperative and cooperative behavior. Type 2 Group Decisions have not been fully treated in the existing literatures. In this thesis, we evaluate a prototype Type 2 Group Decisions: the Federal Open Market Committee (FOMC) from 1970-1994 as a test case. One major advantage of studying the FOMC is the availability of data and relevant analytical published work. Our original empirical findings include: 1. Information ambiguity is the major factor that impacts coalition dynamics, via the number of starting bids, in FOMC decision making. 2. Deliberation time is directly determined by information ambiguity and the relationship is the same across chairmen eras. 3. Decision efficacy falls off gradually as information ambiguity increases. / (cont.) 4. Members whose past views are best reflected as correct in hindsight appear to build up reputation and have greater influence on decision outcomes. We also develop an agent based model (ABM) to study the FOMC. As we show, the ABM is very effective at predicting observables of the FOMC decision making process. These observables are: 1. Membership in the Winning Coalition. 2. Number of Bargaining Rounds. 3. Decision Outcomes. 4. The Number of Starting Bids. In chapter 6 we discuss issues of generalizing the findings of this to other ES. Our sample includes the Food and Drug Administration (FDA), SEMATECH, and the Next Generation Air Transportation System (NGATS). / by Christopher M. Lawson. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2008. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Includes bibliographical references (p. 165-176). / The aim of my thesis is to help enable the engineering of biological systems that behave in a predictable manner. Well-established techniques exist to engineer systems that behave as expected. Here, I apply such techniques to two aspects of the engineering of biological systems. First, I address the design and construction of standard biological devices in a manner that facilitates reuse in higher-order systems. I describe the design and construction of an exemplar device, an engineered cell-cell communication receiver using standard biological parts (refined genetic objects designed to support physical and functional composition). I adopt a conventional framework for describing the behavior of engineered devices and use the adopted framework to design and interpret experiments that describe the behavior of the receiver. The output of the device is the activity of a promoter reported in units of Polymerases Per Second (PoPS), a common signal carrier. Second, I begin to address the coupling that exists between engineered biological systems and the host cell, or chassis. I propose that the coupling between engineered biological systems and the cellular chassis might be reduced if fewer resources were shared between the system and the chassis. I describe the construction of cellular chassis expressing both T7 RNA polymerases (RNAP) and orthogonal ribosomes that are unused by the chassis but are available for use by an engineered system. I implement a network in which the orthogonal ribosomal RNA and the gene encoding T7 RNAP are transcribed by T7 RNAP. In turn, the orthogonal ribosomes translate the T7 RNAP message. In addition, the T7 RNAP and orthogonal ribosomes express a repressor that inhibits transcription of both the T7 RNAP and orthogonal ribosomes. / (cont.) As a result, the orthogonal RNAP and ribosomes are auto-generating and self-regulating. The provision of resources unused by the cellular chassis and dedicated to an engineered biological system forms the beginnings of a biological virtual machine. / by Bartholomew Canton. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2008. / Includes bibliographical references (leaves 100-112). / Cell survival, growth, differentiation, migration, and communication all depend on the appropriate combination of specific interactions between proteins and biomolecules. Therefore, understanding the molecular mechanisms influencing protein-biomolecule binding interactions is important both for fundamental knowledge and as a foundation for therapeutic applications and biotechnology. This thesis presents two applications of computational modeling to study protein-biomolecule binding in different contexts. First, we sought to characterize effects of applied mechanical force on protein structural and biochemical properties. Despite growing experimental evidence of force-regulated cell behavior, the molecular mechanisms involved in force sensing and transmission are still largely unknown. We adapted a free energy method to directly compute the change in binding affinity upon force application. Our simulations demonstrated that differential responses in the bound and unbound state of a protein-ligand complex can lead to graded force-modulation of binding affinity. Application to a prototypical protein system - the helical bundle complex of a paxillin fragment bound to the FAT domain of focal adhesion kinase (FAK) revealed several structural mechanisms responsible. Second, we used computational methods to design individual mutations computed to improve binding affinity of an antibody-small molecule complex with relevance to cancer treatment. Our calculations suggested several beneficial mutations for experimental characterization. The work illustrates the value of computational modeling for understanding protein-biomolecule interactions with application to therapeutic development and advances in biotechnology. / by Aurore Zyto. / Ph.D.

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2011. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 56). / In the oilfield services industry, healthy margins and the criticality of product availability have often over shadowed the need for operational efficiency. Although those factors have not changed, the emergence of stronger industry competition and challenging economic climates have prompted ABC company to explore efficiency gains via supply chain optimization. This thesis examines and assesses opportunities for ABC Company to employ statistical inventory models, understand a variety of factors that influence inventory levels and costs, and improve its network structure. As many inventory models are not designed to accommodate SKUs that have very low rates of consumption, we also propose a methodology that will provide operational guidance and cost implications to address these types of SKUs. / by Michael Chalapong and Jake Lazarus. / M.Eng.in Logistics

Thesis (S.M. in Technology and Policy)--Massachusetts Institute of Technology, Engineering Systems Division, 2013. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 109-113). / This thesis investigates broader impacts of air transportation on U.S. economic productivity, as well as market access and business location, in order to help identify how aviation supports the national economy. More traditional economic impacts are reviewed before turning to enabling impacts. Mechanisms by which air transportation might enhance economic productivity are proposed and a production model is constructed as a framework for exploring the validity of these mechanisms. Two analyses are conducted which should provide new insights to the FAA on the importance of air transportation to the U.S. economy. Focusing on the demand side of the economy, a detailed analysis of input-output (1-0) data from the Bureau of Economic Analysis (BEA) identifies where air transportation appears to be especially critical to economic production. On the supply side, U.S. Census Bureau data is used to map distributions of population, business establishments, and Fortune 500 headquarters from hub airports. Additional distribution analyses are performed for cargo airports and for select metropolitan areas. Analyses of intermediate use of air transportation provide weaker evidence than initially hypothesized as to aviation's role in supporting productivity growth. Both sets of analyses confirm that the importance of air transportation to industry is not uniform and that the government and services sectors appear to benefit from and take advantage of access to aviation more than other industry sectors. In particular, the analyses of business location relative to airports provide evidence that many service and high-value economic sectors are more concentrated near hub airports than are other industry sectors for which air transportation adds less value. / by Justin Daniel Lawrence Stilwell. / S.M.in Technology and Policy

Thesis (M. Eng.)--Massachusetts Institute of Technology, Biological Engineering Division, 2006. / "September 2006." / Includes bibliographical references (p. 141-147). / Nonviral vector research and development has been stunted by a lack of knowledge and understanding of how vectors are trafficked within the cell. Research currently involves mass screenings of different combinations of vector components without a true understanding of how each component interacts with the target cell. Few tools are currently available for scientists to quantitatively examine these vector-to-cell interactions or determine the rate limiting steps within the gene delivery pathway. Thus, researchers cannot fully optimize the vector design to reach maximal delivery efficiency. This project seeks to address this issue by modifying a density gradient electrophoresis (DGE) device originally developed on Mel Juso cells to segregate primary rat hepatocyte lysate into nuclear, early endosomal, late endosomal/lysosomal, and cytoplasmic fractions. We found that according to the Horseradish Peroxidase assay, late endosomes and lysosomes consistently localize to fractions 11-13 and early endosomes in fractions 18 to 21. There was minimal labeling in fractions 14 through 17 demonstrating that separation of the organelles was achieved. With this higher resolution fractionation, movement through the endosomal pathway can be studied in greater detail. / (cont.) The rates with which each vector moves from outside of the cell into the early endosome, to the late endosome, to the cytoplasm and into the nucleus can be quantified. The steps affected by specific modifications to the vector design and the vector properties most important for delivery efficiency can be identified. As vectors are sorted differently in different cell types, this DGE device will allow researchers to gain insight of the cell-specific sorting mechanisms. Ultimately, DGE can aid design of vectors that reach delivery efficiencies comparable to viruses and tailor the vectors to the tissue of interest. / by Jennifer Fang. / M.Eng.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, 2007. / Includes bibliographical references (p. 111-118). / This thesis considers the problem of achieving better system performance through adaptive experiments. For the case of discrete design space, I propose an adaptive One-Factor-at-A-Time (OFAT) experimental design, study its properties and compare its performance to saturated fractional factorial designs. The rationale for adopting the adaptive OFAT design scheme become clear if it is imbedded in a Bayesian framework: it becomes clear that OFAT is an efficient response to step by step accrual of sample information. The Bayesian predictive distribution for the outcome by implementing OFAT and the corresponding principal moments when a natural conjugate prior is assigned to parameters that are not known with certainty are also derived. For the case of compact design space, I expand the treatment of OFAT by the removal of two restrictions imposed on the discrete design space. The first is that the selection of input level at each iteration depends only on observed best response and does not depend on other prior information. In most real cases, domain experts possess knowledge about the process being modeled that, ideally, should be treated as sample information in its own right-and not simply ignored. / (cont.) Treating the design problem Bayesianly provides a logical scheme for incorporation of expert information. The second removed restriction is that the model is restricted to be linear with pair-wise interactions - implying that the model considers a relatively small design space. I extend the Bayesian analysis to the case of generalized normal linear regression model within the compact design space. With the concepts of c-optimum experimental design and Bayesian estimations, I propose an algorithm for the purpose of achieving optimum through a sequence of experiments. I prove that the proposed algorithm would generate a consistent Bayesian estimator in its limiting behavior. Moreover, I also derive the expected step-wise improvement achieved by this algorithm for the analysis of its intermediate behavior, a critical criterion for determining whether to continue the experiments. / by Hungjen Wang. / Ph.D.

Thesis: M. Eng. in Logistics, Massachusetts Institute of Technology, Engineering Systems Division, 2014. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 86-88). / Less-than-truckload (LTL) is a $32-billion sector of the trucking industry that focuses on moving smaller shipments, typically with weights between 100 and 10,000 pounds, that do not require a full trailer to be moved. Currently, there are no widely accepted methods to estimate carbon emissions from LTL shipments which take into account all the complexities of a typical LTL network. This thesis seeks to address this issue by suggesting a methodology that allows different parties to estimate the emissions of individual LTL shipments with minimal input information. Throughout this research, we worked with C. H. Robinson, a Third-Party Logistics Provider (3PL), and Estes Express Lines, a privately-owned freight transportation company, and analyzed more than 1.5 million shipments. We developed two calculation tools: a detailed model, specifically designed for and based on Estes Express' network and operations, and a lower-precision generic model, adapted from the detailed one so that it could be applied to carriers whose network characteristics are unknown. We also assessed current estimation methods and found that they tend to underestimate the emissions from LTL shipments primarily because (1) they rely on direct over-the-road distances as opposed to actual shipped distances, which must include the intermediate stops, and (2) they fail to factor in the pick-up and delivery (P&D) sections, focusing solely on line haul operations. Therefore, while existing initiatives such as the GHG Protocol and the EPA SmartWay program provide guidance on how to estimate carbon emissions from transportation in general, the LTL industry still needs a specific approach that takes into account all of its unique characteristics. This thesis provides a contribution in that direction by suggesting a methodology to better estimate the carbon emissions of individual LTL shipments. / by Guilherme Veloso de Aguiar and Mark Anderson Woolard. / M. Eng. in Logistics

Thesis (S.M. in Management and Engineering)--Massachusetts Institute of Technology, Engineering Systems Division, System Design and Management Program, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 77-78). / Introduction: What could be easier than taking a pill? The doctor prescribes it, the pharmacist provides it and the patient swallows it with a glass of water twice a day for a cure; a very straightforward system of cause and effect. Unfortunately, statistics show that 66% of all Americans fail to take any of their prescription medicines (American Heart Association, 2009) and as a result many of the medical innovations that have increased life expectancy by 47 years since 1900 (Wan He, 2005) remain left unclaimed. So why than do Seniors, facing the pain of arthritis or the impending certainty of death from congestive heart failure, refuse to take their pills? The first half of this thesis seeks an answer to this question while debunking the view that this is a simple problem of ignorance or laziness on the part of the patient. In place of this oversimplified view, the problem of "medication management" is defined and cast in an in-depth and nuanced way that includes issues involving the patient, their caregiver, the disease state, social circumstances and financial constraints. The second half of this thesis focuses on possible solutions. While rethinking the entire medication system can result in great gains, the innovations discussed (both lead user and off-the-shelf innovations) all work within the current medication system and are addressable by product/service designers. By adhering to these two constraints the resulting solutions remain quickly implementable, cost effective and relevant to industry. In the end we find that end users have created a series of innovations and product modifications that address the physical and cognitive barriers they face, while product manufactures are innovating products and services that address the motivational issues users face. / by Joshua A. Hanson. / S.M.in Management and Engineering

Thesis (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division, 2006. / Includes bibliographical references (leaves 70-77). / The development of complex engineering systems such as aircraft engines involves many cross functional teams that are usually geographically distributed. These teams interact in several ways but one of the most important set of interactions during the product development phase is the flow of technical information which is largely used for coordination and problem solving. For analytical purposes, these technical information flows can be represented as a directed network. This thesis develops a context and a research design that can help one investigate the impact of the resultant network structure on innovation in complex engineering systems. The broad context can be divided into two: theoretical and real world contexts. The theoretical context is developed by reviewing literature at the intersection of networks and innovation, and the real world context is typified by a modular enterprise developing a complex engineering system. Within this broad context, the research area of interest is framed by a set of hypotheses that lead to precise innovation measures and characterizations. The research design is motivated by the context and intended theoretical contributions. It consists of two major sections. / (cont.) The first section discusses and critiques methodologies for constructing networks and proposes a methodology more suited to this engineering systems development context. The second section describes a two-stage model whose variables include network structural properties such as structural holes, nodal degree, tie strength, and innovation output. It also describes a methodology for investigating the relationship between network density and the innovation development subprocess. Finally, the context and research design are tied together to create an instantiation of the measurement and characterization of innovation in complex engineering systems development. The characterization considers product innovation as radical, architectural, modular or incremental, and process innovation as organizational / coordination-based or technical. The measures of innovation include granted patents, implemented employee suggestions, product literature based innovation counts and results from structured interviews with the two leaders from each node in the network. / by Pedzisayi O. Makumbe. / S.M.