Thesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004. / Includes bibliographical references (p. 63-65). / In the wake of the development of technology to sequence the complete genome of an organism, it has become expedient to generate methodologies to elucidate and characterize the function of all genes constituting the complete genetic makeup of an organism, whereby the knowledge of the genetic code may be for scientific and intellectual profit. This work consists of an investigation into two possible methods for determining the role of genes involved in the DNA and cellular damage response, though the methods are generally applicable to investigating a wide variety of biological pathways and responses. A library of approximately 4,800 yeast (Saccharomyces cerevisiae) deletion strains produced by the Saccharomyces Genome Deletion Project and consisting essentially of all possible mutants having one non-essential gene deleted (and replaced with unique identification tags called "bar codes") from the genome are employed in this endeavor. The methods focus on gathering phenotype data in a high-throughput manner and in response to the alkylating agent methyl methanesulfonate (MMS). The first method makes use of a new technology called the Living ChipTM, which can hold libraries of compounds or cell cultures in an array of 50-nl channels and which could ideally accommodate all deletion strains on a single array. The second method involves pooling all strains together in a single culture and allowing them to grow competitively to determine their relative fitness based on a specific treatment. / by Daniel S. Ericksen. / S.M.

Thesis (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division, 2013. / "February 2013." Cataloged from PDF version of thesis. / Includes bibliographical references (p. 108-112). / Historically, 70% of change initiatives in organizations and businesses fail. Change involves people. Throughout decades, as the generations change, we've seen a major change in the leader's approach and the medium they have used to connect with people. It is predicted that enterprise social media will become the main communications channel for 20% of business users by 2014. Investigation in this thesis shows the extent to which corporate leaders have used enterprise social media to bring a change in an organization. This research is an examination of how enterprise social media can deliver value in bringing an enterprise transformation. Fundamentals that have been laid out by Dr. Kotter to implement change in the organizations by the corporate leaders still hold. This thesis includes a practical examination of the effectiveness of using enterprise social media for each of the Dr. Kotter's 8-stages for leading change. To investigate the impact of enterprise social media in enterprise transformation, several full scale and brief interviews were conducted with key stakeholders in small, medium, and large scaled organizations. In addition to the standard Lean Advancement Initiative (LAI) suite of tools, the effectiveness of social media was evaluated in various stages using Kaplan's Balanced Scorecard, Force Field Analysis, Matrix Scorecard, System Dynamics Model, and a Weighted Scoring Card. Analysis suggests that based on the existing set of enterprise social tools, enterprise social media can play a key role in 3 of the 8 steps of leading change described by Dr. Kotter. Currently, enterprise social media can provide limited advantages in 5 of the 8 steps of leading change. Going forward, with the emerging set of enterprise social tools that are more integrated into business processes, the role of enterprise social media in bringing an enterprise transformation is expected to increase significantly. / by Raj (Pratik) Rajani. / S.M.

Thesis (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division, 2013. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 107-110). / Companies are always looking for ways to reduce their costs, cost reductions which allow companies to increase their overall profits. There are various cost reductions strategies, such as: change materials and/or design of the products, change suppliers, and offshore engineering. This last strategy, offshore engineering, is a common practice in today's global industries. This thesis applies the cost-reduction strategy of offshore engineering to the automotive industry. Specifically, this thesis presents an analysis of the Seat Subsystem, which assists the corporation in selecting which components of the subsystem are optimal to be offshored. Based on product architecture design structure matrices, this analysis identifies clusters of components within the Seat Subsystem which are highly interrelated. After adding three variables: experience needed to develop each of the components, current experience of the offshore office, and supplier location of these components, a proposal of which components should be offshored is presented. Further, in this thesis a Process/Organization DSM is used to identify when in the seat development process the Seat Engineers have closer relations with other departments within the organization. The results of this Process/Organization DSM will assist the company in creating travel plans for the engineers. After establishing which components of the seat should be offshored, an additional analysis is presented which assists the organization in determining where to offshore these components. This analysis is based on three frameworks: CAGE, ADDING, and Porter's and virtual diamond. A summary of the results of this analysis presents a quantitative evaluation of three offshoring options: China, India, and Mexico. In addition, in this thesis an analysis is presented to determine how the Seat Organization Architecture needs to be adapted in order to support the Offshore Strategy. This organization transformation is based on three methodologies: Enterprise Architecture Sequence Model, 4P's of Strategy, and Seven Strategy Questions. At the end of this thesis, a six-step process is presented to assist other organizations when an offshore strategy is needed to breakdown the development of a product or system and determine where to offshore each of the components. / by Carlos Xavier Zamora Torres. / S.M.

Thesis (S.M. in Engineering and Management)--Massachusetts Institute of Technology, Engineering Systems Division, 2013. / Cataloged from PDF version of thesis. / Includes bibliographical references (page 61). / This thesis used Dr. Leveson's STAMP (Systems-Theoretic Accident Model and Process) model of accident causation to analyze a friendly fire accident that occurred on 22 March 03 between a British Tornado aircraft and a US Patriot Missile battery. This causation model analyzes system constraints, control loops, and process models to identify inadequate control structures leading to hazards and preventative measures that may be taken to reduce the effect of these hazards. By using a system-based causation model like STAMP, rather than a traditional chain of events model, this thesis aimed to identify systemic factors and component interactions that may have contributed to the accident, rather than simply analyzing component failures. Additionally, care was taken to understand the rationale for decisions that were made, rather than assigning blame. The analysis identified a number of areas in which control flaws or inadequacies led to the friendly fire incident. A set of recommendations was developed that may help to prevent similar accidents from occurring in the future. / by Scott McCarthy. / S.M.in Engineering and Management

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2003. / Includes bibliographical references (leaves 48-53). / A business-to-business (B2B) e-marketplace brings together buyers and sellers using the Internet to conduct or facilitate business transactions. They came onto the scene in the late 1990's. There are independent exchanges, those formed by industry consortia, and private exchanges which are formed for the exclusive use of the single owner and its suppliers and customers. E-marketplaces support nearly all major types of B2B transactions, such as sales via catalogs, contracts, auctions, procurement via reverse auctions and RFQ's (request for quotes), and trading via exchanges. At the height of the dot-com boom, there were approximately 2,500 B2B exchanges worldwide. There was tremendous hype and expectations surrounding them. They were to revolutionize the way companies do business and fundamentally transform industries and the global economy. But the B2B e-marketplace has experienced a shakeout, and most have merged, closed down, or been converted to software vendors. Only about 1,000 are still operating, and this number will likely decline further. Even so, there are still great benefits to be had in the B2B exchange arena. B2B digital marketplaces reduce transaction costs by automating purchasing and sales processes. They reduce information inefficiencies by making prices more transparent and aggregating relevant real-time industry news into one easily accessible place, and they diminish geographic limitations. This research examines the different types and strategies of B2B marketplaces, the rise and fall of exchanges, examples of successful marketplaces, and future trends in the area. / by Denise Nicole Minier. / M.Eng.in Logistics

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007. / Includes bibliographical references. / Cholesterol gallstones are exceptionally common and cost nearly 10 billion U.S. dollars annually. Despite a half-century of basic and clinical research questions still remain about cholesterol gallstone pathogenesis. The purpose of the study presented herein is to analyze the roles of infection, and immunity in cholelithogenesis. The first two aims of this work were to analyze the role of enterohepatic Helicobacter spp. and the human gastric pathogen H. pylori in cholesterol gallstone formation. To test this, we prospectively infected C57UJ mice with a variety of Helicobacter spp. and fed infected and uninfected mice a lithogenic diet for eight weeks and analyzed biliary phenotype. Mice infected with H. bilis or coinfected with H. hepaticus and H. rodentium and fed a lithogenic diet developed cholesterol gallstones at 80% prevalence compared with approximately 10% in uninfected controls (P<0.05). Monoinfections with H. hepaticus, H. cinaedi, H. rodentium, and H. pylori gave a cholesterol gallstone prevalence of 40% (P<0.05), 30%, 20% and 20%, respectively; with the exception of H. hepaticus, cholesterol gallstone formation in these groups did not differ significantly from uninfected animals. / (cont.) These findings suggest that some Helicobacter spp. play a role in the cholesterol gallstone formation in mice and perhaps humans. We further hypothesized that inflammation and immunity were important in cholesterol gallstone formation and that cholelithogenic bacteria were promoting gallstones through immune stimulation. To test this we utilized BALB/c and isogenic Rag2-/- mice. When fed a lithogenic diet for eight-weeks, wild-type mice developed cholesterol gallstones (27-80% prevalence) significantly more than Rag2-/- mice (~5%, P<0.05). Transfer of functional splenocytes, or T-lymphocytes to Rag2-/- mice markedly increased cholesterol gallstone formation (26% and 40% respectively, P<0.05) whereas transfer of B-cells did not (13%). The presence of T-cells and solid cholesterol monohydrate crystals induced proinflammatory cytokine expression in the gallbladder. These studies indicate that T-cells are critical in murine cholelithogenesis and function by promoting gallbladder inflammation. In summary, these results illustrate that microbial pathogens can influence cholesterol gallstone formation; this most likely occurs by modulating the immune response with T-cells being a critical component in this immunomodulation. / by Kirk J. Maurer. / Ph.D.

Thesis (M. Eng.)--Massachusetts Institute of Technology, Biological Engineering Division, 2008. / Includes bibliographical references (p. 43-46). / One erythropoietin molecule binds asymmetrically to two identical receptor monomers via erythropoietin site 1 and site 2, although it is unclear how asymmetry affects receptor activation and signaling. Here we report the computational design and experimental validation of two mutant erythropoietin receptors: one that binds only to erythropoietin site 1 but not site 2, and one that binds only to site 2 but not site 1. Expression of either mutant receptor alone in Ba/F3 cells cannot elicit a signal in response to erythropoietin, but when co-expressed, there is a proliferative response and activation of the JAK2 Stat5 signaling pathway. A truncated erythropoietin receptor with only one cytosolic tyrosine (Y343), on only one receptor monomer is sufficient for signaling in response to erythropoietin, regardless of the monomer on which it is located. The same results apply to having only one conserved juxtamembrane hydrophobic L253 or W258 residue, essential for JAK2 activation, in the full-length receptor dimer. We conclude that despite asymmetry in the ligand-receptor dimer interaction, both sides are competent for signaling, and we suggest that the receptors signal equally. / by Yingxin Zhang. / M.Eng.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 117-121). / Vehicle weight reduction is a known strategy to address growing concerns about greenhouse gas emissions and fuel use by passenger vehicles. We find that every 10% reduction in vehicle weight can cut fuel consumption by about 7%. In the U.S., vehicle weight reduction is essential for meeting future, more stringent fuel economy standards. New vehicles are required on average to achieve at least 34.1 miles per gallon (MPG) by year 2016, up from 28.8 MPG today. Scenarios of future vehicle characteristics and sales mix indicate that the target is aggressive. New vehicles must not only become lighter, but also forgo horsepower improvements, and progressively use advanced, more fuel-efficient powertrains, such as hybrid-electric drives. We can reduce weight by substituting some of the iron and steel used in vehicles with lighter-weight high-strength steel or aluminum, redesigning the vehicle, and/or downsizing the vehicle. Using these approaches, it is possible to achieve up to 40% (690 kg) vehicle weight reduction. However, the cost associated with manufacturing lighter-weight vehicles is a nontrivial $3 to $4 per kilogram of total weight saved. In addition, the life-cycle energy impacts of using alternative lightweight materials, which tend to be more energy-intensive to process, must also be considered. In this dissertation, the energy implications of pursuing this lightweighting strategy are explored on a vehicle life-cycle- and vehicle fleet system-level basis. A model of the energy and material flows through the evolving vehicle fleet system over time has been developed, which accounts for potential changes in future vehicle weight and material composition. The resultant changes in material production energy and fleet fuel savings, which are the main energy burdens for the entire product system - the vehicle fleet - are estimated. The new 2016 fuel economy standards and more stringent standards beyond can realize significant fuel savings of 1,550 billion liters through year 2030. However, the advanced powertrains that are expected to enter the marketplace are heavier and require more energy to produce. Their production impact may be offset by efforts to use less energy-intensive high-strength steel to lightweight new vehicles, as well as efficiency gains in material processing. / by Lynette W. Cheah. / 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. 103-113). / As the global marketplace becomes increasingly interconnected and multidisciplinary, graduates of undergraduate engineering programs face new challenges in communication, creative thinking, and teamwork as they enter the international workforce. To address this shift, over the last two decades American universities have adjusted educational objectives of undergraduate engineering programs to include new themes in international awareness, communication, teamwork, and other professional skills. Motivated by student leadership development programs at the new Singapore University of Technology and Design (SUTD), this thesis examines how student engagement in co-curricular and extracurricular activities promotes professional skill development in engineering education at the undergraduate level. Using a two-stage analysis of MIT student organizations and current literature in student involvement, this work presents a two-dimensional framework of the leadership and professional skills developed through participation in 22 categories of co-curricular and extracurricular involvement. The relevance of these skills to engineering education and practice is validated through interviews with managers and supervisors of entry-level engineers. In addition, these skills are compared with key educational outcomes specified by ABET, Inc. (previously known as the Accreditation Board for Engineering and Technology), further validating the relevance of the two-dimensional framework of skill development to engineering practice. Lastly, this thesis provides an analysis of strategies to promote student involvement and leadership development in engineering undergraduates. / by Dara R. Fisher. / S.M.in Technology and Policy

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004. / Includes bibliographical references. / Deoxyribose oxidation in DNA forms strongly electrophilic terminal blocking groups and abasic sites capable of stopping polymerases, forming DNA-protein crosslinks and nucleobase adducts. These threats to the genetic integrity of cells are caused by exogenous and endogenous oxidizing agents and may contribute to diseases such as cancer. To better understand the role of oxidative DNA damage in these diseases, it is necessary to quantify deoxyribose oxidation both in vitro and in vivo. Current methods lack the sensitivity required to measure low concentrations of deoxyribose oxidation products. The goals of the research findings reported here is to develop a sensitive method that can accurately and reproducibly quantify 3'-phosphoglycolaldehyde (PGA), one example of a deoxyribose oxidation product, and to apply the method to quantify PGA in vitro and in cells. Given the presence of reactive carbonyl groups in many deoxyribose oxidation products, the method should be widely applicable to other studies of oxidative ])NA damage. The analytical method exploits the reactive carbonyl moiety in PGA by derivatization as a stable oxime with pentafluorobenzylhydroxylamine, followed by solvent extraction and gas chromatography/negative chemical ionization/mass spectrometry. A stable isotopically-labeled [13C2]-PGA is synthesized and used as an internal standard. The method is linear in response over the range of 30 fmol to 300 pmol and precision is verified by analysis of a synthetic, PGA-containing oligodeoxynucleotide. The limit of detection in the presence of DNA is 30 fmol of PGA. The analytical method was then applied to the quantification of PGA in purified DNA and cultured cells treated with several oxidants. / (cont.) y-Radiation forms PGA in a linear dose response both in vitro and in cells with a 1000-fold quenching effect in vivo. The total quantity of deoxyribose oxidation, determined by plasmid topoisomer analysis, allows the calculation of PGA formation per deoxyribose oxidation event. PGA is formed in 1% of deoxyribose oxidation events induced by y-radiation versus 7% for a-particles. PGA formation induced by Fe(II), Fe(II)/EDTA/H202, and peroxynitrite follows a nonlinear dose response best fitted to a second-order polynomial, in contrast to a linear response induced by Fe(II)/EDTA, with PGA formation representing 5% of deoxyribose oxidation events. Peroxynitrite-induced DNA damage is studied under conditions of both hydroxyl radical and carbonate radical formation. With increasing carbonate radical formation, PGA induction is suppressed which indicates that the carbonate radical is not capable of inducing PGA. / by Christine Collins. / Ph.D.