Thesis (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division, 2009. / "June 2009." Cataloged from PDF version of thesis. / Includes bibliographical references (p. 133-139). / This thesis presents an innovative method for evaluating and dynamically planning the development of uncertain technology investments. Its crux centers on a paradigm shift in the way managers assess investments, toward an approach that incorporates uncertainty in the beginning phases of planning instead of first choosing a plan and then considering the effect of risk. By proactively identifying critical uncertainties and "purchasing" flexibility to handle them, management can increase the value of the start-up technology. The method builds on extensive literature in corporate venture capital (CVC), opportunity identification, and opportunity development, to present a new integrated approach that: 1. Explicitly identifies the synergies between an investing company and an opportunity, and articulates the new value network created through a Technology-Implement-Commercialization (TIC) linkage framework. 2. Develops the opportunities articulated in the TIC networks using a tool that identifies current and goal positions for a set of critical issues, and states the critical uncertainties. 3. Combines the outcomes of the TIC and opportunity development steps in a decision analysis of the possible development paths. The result is a recommended dynamic strategy that invests initially in some form of flexibility to enable program directors to avoid paths that eventually appear unproductive, while seizing opportunities that develop along the course of the project. The thesis demonstrates the approach by applying it to a start-up project in solar concentrators, done from the perspective of a corporate sponsor. / (cont.) The purpose of this case study is to provide a comprehensive guide to the process used in the new method. While extensive effort was dedicated to creating a representative and reasonably accurate assessment, the analysis and numbers are neither authoritative nor exhaustive. The goal, indeed a major contribution of the thesis, is to provide a teaching tool to aid future use of the innovative planning and valuation method. / by Samir Omar Mikati. / S.M.

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2011. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 36-37). / Freight vehicle capacity, whether it be road, ocean or air transport, is highly underutilized. This under-utilization presents an opportunity for companies to reduce their vehicular traffic and reduce their carbon footprint through greater supply chain integration. This thesis describes the impact of ordering guidelines on the transport efficiency of a large firm and how those guidelines and associated practices can be changed in order to gain better efficiency. To that end, we present three recommendations on improving the guidelines based on the shipment data analysis. First, we discuss the redundancy of one of the company's fill metrics based on a scatter plot analysis and a chi-square independence test. Second, we explore the impact of using linear programming to allocate SKUs to different shipment, highlighting the reduction in the number of shipments through better truck mixing. Finally, we divide the SKUs into three groups: cube-constrained, neutral, and weight-constrained. Based on this segmentation, we present a basic model that mixes different SKUs and helps a shipment to achieve a much higher utilization rate. The application of the last two findings can be further explored to address under-utilization in freight carriers across different industries. / by Jaya Banik and Kyle Rinehart. / M.Eng.in Logistics

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, February 2008. / MIT Science Library copy: issued as 1 v. / Also issued in 1 v. with pagination as pages. / Includes bibliographical references. / Approximately one in five Americans is affected by arthritis, making it one of the most prevalent diseases and the leading cause of disability in the United States. Post-traumatic arthritis occurs after joint injury (e.g., ACL rupture or intraarticular fracture) and makes up a substantial proportion of the population with arthritis. In previous clinical studies, patients suffering from a traumatic joint injury have shown an increased risk in osteoarthritis (OA), independent of surgical intervention to stabilize the joint. Thus, the early events post-injury have an important effect on tissue within the joint in the long term. To understand the processes involved in the onset of OA and factors leading to OA post-traumatic injury, in vitro models have been developed to isolate components of the complex processes occurring in vivo. While in vitro models do not mimic true physiologic conditions in vivo, by isolating the effects of mechanical compression, cytokine treatment, and cartilage co-cultured with adjacent tissue, in vitro models can give insight into key biological and mechanical pathways occurring in vivo. This study focuses on changes in cartilage gene and protein expression and associated cartilage matrix degradation in response to static or injurious compression of the tissue in the presence or absence of cytokines including TNF-a and IL-6. In addition, normal or injuriously compressed cartilage explants were co-cultured with injured (excised) joint capsule tissue, another in vitro model of post-traumatic cellular behavior. Both young bovine cartilage and human cartilage from a wide range of ages were used. The growth factors insulin-like growth factor-1 (IGF-1) and Osteogenic protein-i (OP-1), as well as the antioxidant, superoxide dismutase mimetic (SODm), were tested to examine if they had the capability to abrogate the negative effects of these injury models. / (cont.) Taking a systems approach, the effects of these stimuli on expression of over 48 genes (in cartilage as well as joint capsule) were quantified, along with measures of chondrocyte viability, biosynthesis, protein expression, and GAG loss. Chondrocyte gene expression was differentially regulated by 50% static compression or IGF- 1 treatment or the combination of compression and IGF- 1. Results showed that IGF- 1 stimulated aggrecan biosynthesis in a transcriptionally regulated manner, whereas compression inhibited aggrecan synthesis in a manner not regulated by transcriptional activity. The injury plus co-culture model was examined in detail, and OP-1 and IGF-1 were unable to rescue changes in transcriptional expressions due to injury. However, these growth factors were able to rescue cells from apoptosis, and slightly increase biosynthesis rates. Human tissue was used to further validate the model of mechanical injury (INJ) combined with co-culture (Co). Immunohistochemical analysis of human cartilage explants after INJ+Co treatment revealed changes in versican and aggrecan protein expression, as well as changes in surface tissue morphology, that mimicked certain changes observed in human osteochondral plugs taken from patients at the time of notchplasty surgery (post ACL reconstruction) at 1, 3, or 57 months post- ACL rupture. The oxidative stress involved in a cytokine plus injury model showed that SODm had no ability to selectively diminish protease transcriptional activity. Cartilage treated with this antioxidant showed significant increases in GAG loss to the medium, but diminished levels of chondrocyte apoptosis. Taken together, this work supports further investigation of the mechanisms of action of OP-1, IGF-1, and SODm in order to elucidate their possible therapeutic value, and demonstrates the usefulness of these complementary in vitro models of cartilage injury. / by Cameron A. Wheeler. / Ph.D.

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. 101-110). / The Renewable Fuels Standard 2 (RFS2) is an important component of alternative transportation fuels policy in the United States (US). By mandating the production of alternative fuels, RFS2 attempts to address a number of imperfections in the transportation fuels market: US economic vulnerability to volatile prices; security and environmental externalities; and a lack of investment in alternatives to petroleum-derived fuels. Although RFS2 aims to reduce the climate impact of transportation fuels, the policy raises a number of additional environmental concerns, including the water and land resource requirements of alternative fuel production. These factors should be considered in order to determine the overall environmental viability of alternatives to petroleum-derived transportation fuels. Middle distillate (MD) fuels, including diesel and jet fuel, are of particular interest because they currently make up almost 30% of liquid fuel consumption in the US, and alternative MD fuels could potentially satisfy 21 of the 36 billion gallons of renewable fuels mandated by RFS2 in 2022. This thesis quantifies the lifecycle blue (surface and ground) water consumption footprint of MD from conventional crude oil; Fischer-Tropsch (FT) MD from natural gas and coal; fermentation and advanced fermentation (AF) MD from biomass; and hydroprocessed esters and fatty acids (HEFA) MD and biodiesel from oilseed crops, in the US. FT and rainfed biomass-derived MD have lifecycle blue water consumption footprints between 1.4 and 18.1 lwater/lMD, comparable to conventional MD, between 4.1 and 7.5 lwater/lMD. Irrigated biomass-derived MD has a lifecycle blue water consumption footprint potentially several orders of magnitude larger, between 2.5 and 5300 lwater/lMD. Results are geospatially disaggregated, and the trade-offs between blue water consumption footprint and areal MD productivity, between 490 and 3710 lMD/ha, are quantified under assumptions of rainfed and irrigated biomass cultivation. / by Mark Douglas Staples. / S.M.in Technology and Policy

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2010. / Cataloged from student submitted PDF version of thesis. / Includes bibliographical references (p. 79-80). / The objective of this thesis was to determine if line-haul rates are impacted by bid type, and if aggregation of bidding lanes can reduce costs for both shippers and carriers. Using regression analysis, we developed a model to isolate and test the cost effects that influence line-haul rate for long-haul shipments. We have determined that aggregation of low-volume lanes from point-to-point lanes to aggregated lanes can provide costs savings when lanes with origins and destinations in close proximity to each other can be bundled. In addition, bidding out region-to-region lanes can supplement point-to-point lanes by reducing the need to turn to the spot market. The model shows that bundling lanes can provide significant cost savings to a shipper because contract lanes of any type are on average less costly than spot moves. This thesis provides guidelines and suggestions for aggregation when creating bids during the first stage of the truckload procurement process. / by Julia M. Collins and R. Ryan Quinlan. / M.Eng.in Logistics

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2008. / Includes bibliographical references. / Parkinson's disease (PD) is a primarily motor disorder which affects at least half a million people in the US alone. Deep brain stimulation (DBS) is a neurosurgical intervention by which neural structures are stimulated electrically by an implanted pacemaker. It has become the treatment of choice for PD, when not adequately controlled by drug therapy. We introduced a novel robotic platform for the study of the effects of DBS on motor control in PD. Subjects performed discrete wrist movements with and without a force field. We found preliminary indication that motor learning may be taking place with stimulation, and demonstrated how robotic testing can augment existing clinical tools in evaluation of the disease. To study the effect of stimulation on movement frequency, we employed a rhythmic task that required movements of the elbow to remain within a closed shape on a phase plane. Three closed shapes required varying frequency/amplitude combinations of elbow movement. The task was performed with and without visual feedback. Analysis of data from the healthy control subjects revealed a non-monotonic relation between accuracy on the phase plane and movement speed. Further kinematic analyses, including movement intermittency and harmonicity, number and type of submovements (movement primitives) fit per movement cycle, and the effects of vision on intermittency were used to support the model we propose, whereby there exist two subtypes of rhythmic movement; small-amplitude, high-frequency movements are nearly maximally harmonic, and harness the elastic properties of the limb to achieve smoothness and accuracy, and large-amplitude, low-frequency movements share characteristics with a string of discrete movements, and make use of visual feedback to achieve smoothness and accuracy. / (cont.) Bradykinesia (slowness of movement) is one of the hallmarks of PD. We examined the effects of visual feedback on bradykinesia. PD patients off dopaminergic medication and healthy age-matched controls performed significantly faster movements when visual feedback was withdrawn. For the bradykinetic subjects, this increase in movement speed meant either a mitigation or an elimination of bradykinesia. Our results support a role of the basal ganglia in sensorimotor integration, and argue for the integration of nonvision exercises into patients' physical therapy regime. / by Shelly Levy-Tzedek. / Ph.D.

Kwan Ho-yuet. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 84-[87]). / Abstracts in English and Chinese. / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- An Overview on Transmitter Optimization --- p.1 / Chapter 1.1.1 --- Transmitter Precoding Methods --- p.2 / Chapter 1.1.2 --- Chip Waveform Optimization --- p.3 / Chapter 1.1.3 --- Signature Sequence Adaptation --- p.3 / Chapter 1.2 --- Receiver Optimization --- p.5 / Chapter 1.3 --- Nonlinear Optimization with Constraints --- p.6 / Chapter 1.3.1 --- Lagrange Multiplier Methods --- p.6 / Chapter 1.3.2 --- Penalty Function Methods --- p.7 / Chapter 1.4 --- Outline of Thesis --- p.8 / Chapter 2 --- Transmitter Adaptation Scheme for AWGN Channels --- p.10 / Chapter 2.1 --- Introduction --- p.10 / Chapter 2.2 --- System Model --- p.12 / Chapter 2.3 --- Adaptation Algorithm --- p.13 / Chapter 2.3.1 --- Receiver optimization --- p.14 / Chapter 2.3.2 --- Single-user transmitter optimization --- p.18 / Chapter 2.3.3 --- Decentralized transmission scheme --- p.20 / Chapter 2.4 --- Modification of the sequence adaptation algorithm --- p.25 / Chapter 2.5 --- Performance Evaluation --- p.28 / Chapter 2.5.1 --- Performance of the decentralized scheme --- p.28 / Chapter 2.5.2 --- System Capacity with Target SNR Constraints --- p.29 / Chapter 2.5.3 --- Performance of modified sequences --- p.31 / Chapter 2.6 --- Summary --- p.33 / Chapter 3 --- Transmitter Adaptation Schemes for Rayleigh Fading Channels --- p.34 / Chapter 3.1 --- Introduction --- p.34 / Chapter 3.2 --- Sequence Adaptation for MC-CDMA Systems --- p.36 / Chapter 3.2.1 --- Multi-sequence MC-CDMA systems --- p.36 / Chapter 3.2.2 --- Single Sequence MC-CDMA systems --- p.41 / Chapter 3.2.3 --- Performance Evaluation --- p.45 / Chapter 3.3 --- Sequence Adaptation for Wideband CDMA System in Fading Channels --- p.50 / Chapter 3.3.1 --- System Model and Algorithm Development --- p.50 / Chapter 3.3.2 --- Performance Evaluation --- p.56 / Chapter 3.4 --- Summary --- p.60 / Chapter 4 --- Practical Issues on Sequence Adaptation --- p.61 / Chapter 4.1 --- Introduction --- p.61 / Chapter 4.2 --- Preliminary --- p.62 / Chapter 4.3 --- Sequence Adaptation Algorithm with Perfect Estimation of SNR --- p.63 / Chapter 4.4 --- Performance Evaluation --- p.68 / Chapter 4.4.1 --- Typical Behaviour Analysis --- p.71 / Chapter 4.4.2 --- Average Performance Analysis --- p.72 / Chapter 4.5 --- Sequence Adaptation Algorithm with imperfect estimation of pre- vious state SNR --- p.75 / Chapter 4.6 --- Performance Evaluation --- p.77 / Chapter 4.7 --- Summary --- p.79 / Chapter 5 --- Conclusions and Future Works --- p.81 / Chapter 5.1 --- Conclusions --- p.81 / Chapter 5.2 --- Future Works --- p.83 / Bibliography --- p.84

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2006. / Includes bibliographical references (p. 153-165). / Cells communicate with other cells, and process cues from their environment, via signaling pathways, in which extracellular cues trigger a cascade of information flow, causing signaling molecules to become chemically, physically or locationally modified, gain new functional capabilities, and affect subsequent molecules in the cascade, culminating in a phenotypic cellular response. Mapping the influence connections among biomolecules in a signaling cascade aids in understanding of the underlying biological process and in development of therapeutics for diseases involving aberrant pathways, such as cancer and autoimmune disease. In this thesis, we present an approach for automatically reverse-engineering the structure of a signaling pathway, from high-throughput data. We apply Bayesian network structure inference to signaling protein measurements performed in thousands of single cells, using a machine called a flow cytorneter. Our de novo reconstruction of a T-cell signaling map was highly accurate, closely reproducing the known pathway structure, and accurately predicted novel pathway connections. The flow cytometry measurements include specific perturbations of signaling molecules, aiding in a causal interpretation of the Bayesian network graph structure. / (cont.) However, this machine can measure only -4-12 molecules per cell, too few for effective coverage of a signaling pathway. To address this problem, we employ a number of biologically motivated assumptions to extend our technique to scale up from the number of molecules measured to larger models, using measurements of overlapping variable subsets. We demonstrate this approach by scaling up to a model of 11 variables, using 15 overlapping 4-variable measurements. / by Karen Sachs. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007. / Includes bibliographical references. / Mechanical forces play an important role in cell morphology, orientation, migration, adhesion and can even induce apoptosis. The eukaryotic cell is equipped with a dynamic frame, known as the cytoskeleton, that provides the cell's structural integrity in order to sustain and react to such forces. Therefore, understanding the mechanical properties of the cytoskeleton is an important step towards building models describing cell behavior. Filamentous actin (F-actin), as one of the major constituents of the cytoskeleton, has been the target of extensive in vitro studies to determine its mechanical properties in bulk. However, there is still a lack in the understanding of how the molecular interactions between F-actin and the proteins that arrange these filaments into networks regulate the dynamic properties of the cytoskeleton Here we present a novel, single molecule assay to test the rupture force of a complex formed by an actin binding protein (ABP) linking two actin filaments. We readily demonstrate the adaptability of this assay by testing it with two different ABPs: filamin, a crosslinker, and a-actinin, a bundler. We measured rupture forces of 28-73 pN and 30-56 pN for filamin/actin and a-actinin/actin respectively, suggesting that the former is a slightly stronger interaction. Moreover, since no ABP unfolding events were observed at our force levels, our results suggest that ABP unbinding is a more relevant mechanism than unfolding for the temporal regulation of the mechanical properties of the actin cytoskeleton. In addition, we explore the micro-scale properties of F-actin networks reconstituted in vitro. / (cont.) Using imaging and microrheology techniques we characterized the effects of filament length and degree of crosslinking on the structural arrangement and mechanical properties of F-actin networks. We found that the mechanical properties of these networks are length-scale dependent. Also, when probed with active methods, the F-actin networks exhibited strain hardening followed by a gradual softening at forces -30 pN, in good agreement with the single molecule rupture force of 28-73 pN. Thus, with the combination of single molecule and network studies, we can expand the knowledge-base on the regulation and control of the cellular machinery starting from the molecular building blocks. / by Jorge M. Ferrer. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Engineering Systems Division, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 477-498). / This inquiry started with the simple question, "Who manages the Internet infrastructure and how?" Since, this question evolved into an evaluation of the routing system and the institutions that manage it. This institutional complex is referred to as the number resource system (NRS). NRS authority is contingent, rooted in consensus based knowledge assessment necessary to adapt apace with Internet growth. The efficiency with which observable negative externalities are remediated is a compelling entry point to this work. The Pakistan-YouTube story is a halcyon parable of "self-repair." Network operators recognized a global negative externality, traced it to the origin, and remediated the complicit networks in approximately three hours. To the casual observer, organic cooperation surfaced to remediate damages, then dissolved into the background noise of "normal operations." Remediation is far from organic; rather, it is a consequence of distinct rights and obligations amongst, and enforced by, NRS participants. Explaining the rationale and mechanics of "ad hoc" crisis management is the first contribution of this work. The early NRS comprised "close-knit yet loosely organized" communities created to 1) share operational knowledge (network operator groups, NOGs); 2) delegate unique network identifiers (Regional Internet Registries, RIRs); 3) create neutral markets for exchanging routes and traffic (Internet eXchanges, IXes); and 4) limit abusive messaging (anti-spam, later anti-abuse). Alongside Internet growth, NRS norms evolved into distinct institutions, replete with function-specific constitutional, collective choice, and operational rules for managing the knowledge commons and facilities supporting routing system function. The NRS institutions form a contingent social order, rooted in shared, authoritative images of system function and externalities management. NRS institutions collectively ensure participants common interests in the jointly provisioned routing system stability. The second contribution of this work explains NRS institutional structures and how the attendant rules keep pace with a high clockspeed Internet infrastructure. NRS institutions are characteristically, and necessarily, adaptive: each comprises a unique consensus process, animated by a diverse set of nominal competitors, that creates and adapts function-specific rules and processes contributing to routing system integrity. Consensus processes evaluate the performance of common resource management rules and, when-not if-necessary, adapt these rules to satisfy changing resource demands and patterns of use in the broader Internet infrastructure industry. Anticipation and evaluation in the consensus process are essential to adaptive capability, framed as a form of joint knowledge assessment. Moreover, diverse representation, comprising experts across industry sub-sectors, animated by constructive conflict amongst these experts, mediated by consensus processes, makes for a durable family of credible knowledge assessment processes that are rare amongst conventional regulatory arrangements. Processes described thus far are largely endogenous to the NRS and its constituencies. Historically these institutions have operated quietly underneath the hood. Adaptation and the resulting policy is scoped to common interests, explicitly avoiding impinging on public policy. In contrast to conventional international regimes, the NRS self-limits to the scope of its authority, namely supporting and enhancing routing system function. Thus far, the NRS's common interests have not run counter to the public interest. Nonetheless, a path-dependent history of harmonious alignment between a common and the public does not carry the assurances of alignment resulting from explicit coordination and cooperation. Some states and state-sanctioned international governance organizations see control of NRS facilities as critical to preserving their own authority. Predatory claims to stewardship of routing system resources further complicates the alignment problem. To better frame and understand this alignment problem, the concluding chapters of the dissertation explore the question: 'Are the incentives and resources of NRS institutions commensurate with the aggregate social loss due to a partial, or worse yet, systemic, failure?" Simply put, absent the progress on the explicit assurances above, the answer is no. Would-be state principals also fall short. State-based authorities are severely deficient in basic operational capacity that form the foundation of knowledge assessment capabilities and subsequent adaptive capabilities in the NRS. States' deficiencies correspond to those capabilities engendered by the NRS. Adding NRS stewardship to a state's portfolio of domestic regulatory interests will expose management processes to powerful short-term interests that will inevitably weaken, if not eliminate, extant credible knowledge assessment and adaptive capabilities. In effect, aggressive predatory rule would likely eliminate precisely the characteristics that make the NRS a valuable steward of a high clockspeed infrastructure. This initial conclusion is not a prediction of adaptive management doomed to failure. Although neither the NRS, nor state authorities, have sufficient capabilities and modes of authority to manage an Internet underpinning an ever-increasing array of public, private, and social goods on their own, a mix of their capabilities is sufficient. Rather, the conclusion frames a discussion of what explicit assurances will look like and the barriers to developing those assurances. The last part of this dissertation lays out the challenges for establishing such a comity, a mutual recognition of the norms and authority between the NRS and state authorities. In the global political arena, the NRS's political capital is credible knowledge assessment and adaptive capacity as the roots of authoritative policy advice. Barriers to explicit assurances draw lessons from the deconstruction and reconstruction of scientific knowledge in political environments, instances of international epistemic consensus, and characteristics of elusive, but effective, adaptation that has survived in conventional regulatory environments. Analytically, the dissertation argues the NRS and state authority need not be competitors-the two can be quite complementary. If these two sets of institutions can avoid the pitfalls of previous efforts, in particular short-term usurpation of the others' authority, the global, nondiscriminatory character of the Internet may be sustainable. / by Jesse Horton Sowell, II. / Ph. D.