Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007. / Includes bibliographical references (p. 161-172). / Gene therapy has the potential to cure thousands of diseases caused by genetic abnormalities, provide novel combination therapies for cancers and viral infections, and offer a new and effective platform for next generation vaccines. However, after more than three decades of research and development efforts, clinical success has yet to be realized. Successful delivery of DNA is a crucial first step in attaining safe and effective gene therapeutics. While vectors based upon recombinant viruses have shown high delivery and transfection efficiencies, they may also pose certain health risks to patients, can be difficult to target to cell or tissue types of interest, and present difficulties for large-scale manufacturing. Non-viral vectors look to offer a safer alternative and can be engineered to more effectively treat a specific cell type, tissue, or pathology, but these vectors are still plagued with low transfection levels and cannot provide adequate and sustained levels of gene expression. Continued efforts focus on producing next generation non-viral vectors that safely deliver therapeutic transgenes with the efficiency of their viral counterparts. Many barriers exist in the successful trafficking of these non-viral complexes to the nucleus. / (cont.) Current evaluations of non-viral gene delivery treatments in more clinical settings often focus on a single barrier at a time, and as a result, may not lead to an overall improvement in gene delivery. Concurrently, more quantitative or systematic in vitro experiments may not correlate well with in vivo data. Our combined approach of quantitative vector trafficking and expression experiments coupled with computational simulation of vector specific mathematical models that describe every step of the gene delivery process has shown that a systems level approach can glean insight into the most rate-limiting steps for a given vector and generate hypotheses for future vector development and improvement. These studies have been extended to primary liver cultures, coupled with device development to attain a more clinically relevant model system and more spatial resolution to study intracellular vector trafficking and localization. A larger perfused 3-D liver bioreactor has been built that allows for long-term culture of primary hepatocytes that more closely mimic hepatic phenotype than in conventional 2-D cultures and for multiplexed quantitative measurement that is not possible in animal models. / (cont.) A newly constructed density gradient electrophoresis device can separate vesicular organelles and track vector dynamics throughout the cell. These systems have provided more comprehensive data sets which show that vectors behave differently in different culture systems and that different vectors show unique cell trafficking dynamics. These results lend insight for future vector screening methodologies and provide vector specific mathematical models for primary cell transfection that can lead to further optimization of the polymer vectors studied in this work, which can contribute to the development of more efficient next generation in vivo delivery agents. / by Nathan C. Tedford. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, 2008. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 168-177). / This dissertation presents findings on four elements of the relationship between Global Product Development or Globally distributed Product Development (GPD) and product complexity. I examine this relationship in the context of medical, industrial and electronic equipment developed for American companies outside each development program's home-country. In the first study, I use multinomial logistics models and find that product complexity, specificity, strategic importance and designing firm's capability are directly related to the modes of global product development. These modes are namely global partnerships, captive offshoring and global outsourcing. The more complex products are developed through global partnerships or captive offshores, while the less complex products are globally outsourced. However, the difference in complexity among the three modes varies by region when I divide the world into emerging and mature regions. It is largest in emerging regions and statistically non-significant in mature regions. In the second study, I investigate factors that drive product development to different countries around the world. Using negative binomial models, I find that market size, national capability and number of engineering graduates are directly related to the amount of product development in a particular country, while market growth rate and labor cost are not. I also find that as product complexity increases, the importance of the national capability as a location advantage increases, and that national and firm capability are statistically related to each other. / (cont.) In the third study on host national culture, I find that national culture influences the internal team dynamics, but not necessarily where product development is eventually located. Finally, I qualitatively characterize the global product development strategy, organization structure, processes and people, and gather some recommended coordination practices. These include modularizing, not only the product, but the process as well to allow closed-loop monitoring in order to ensure that design expectations were perceived as intended. / by Pedzisayi Onias Makumbe. / Ph.D.

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2004. / Includes bibliographical references (leaves 42-43). / Lessons for how a regional authority should develop its logistics sector are learned through case studies on four areas (section 2). In addition, a "logistics attractiveness" ranking framework is developed and applied (section 3). A learning from the case studies is that a regional authority plays an active role. It leads the development and sustained progress of logistics related activity either directly or through facilitation. Another insight is that training of people and academic research activity in the field of logistics is accompanying the local development of the logistics sector. This is done somewhat independently by the universities but the authorities are playing a supporting role. Countries found to rank high in their overall logistics attractiveness are generally competitive in infrastructure, information & communication technology (ICT) and ease of doing business (EOB. In addition to the case studies and 'logistics attractiveness' ranking framework this thesis provides an overview of other areas around the world where new logistics park type development activity is found to be taking place (section 4). / by Taimur Khan. / M.Eng.in Logistics

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2008. / Includes bibliographical references (leaves 100-102). / As global competition in the manufacturing space grows, so do corporations' needs for sophisticated and optimized management systems to enable continuous flows of information and materials across the many tiers within their supply chains. With the complexities introduced by the variability in the demand for finished goods as well as by the variability in lead-time of transportation, procurement, production and administrative activities, corporations have turned to quantitative modeling of their supply chains to address these issues. Based on the data of a heavy machinery manufacturer headquartered in the US, this research introduces a robust model for the deployment of strategic inventory buffers across a multi-echelon manufacturing system. Specifically, this study establishes a replenishment policy for inventory using a multiple bin, or Kanban, system for each part number in the assembly of products from our sponsors tractor line. We employ a numerical simulation to evaluate and optimize the various inventory deployment scenarios. Utilizing several thousand runs of the simulation, we derive a generalized treatment for each part number based on an econometric function of the parameters associated with lead-time, order frequency, inventory value and order costing. The pilot for the simulation focuses on the parts data for three earthmoving products across eight echelons, but scales to n products across m echelons. Our results show that this approach predicted the optimal quantities of Kanbans for 95% of parts to a level of accuracy +/- 3 bins. / by Philip J. Hodge and Joshua D. Lemaitre. / M.Eng.in Logistics

Thesis (M.Eng.)--Massachusetts Institute of Technology, Engineering Systems Division, 2000. / Includes bibliographical references (leaves 58-64). / Despite a growing body of information about the importance of good logistics and supply chain management, there remains a dearth of research regarding consumer-to-business reverse logistics (the collection of processes required to move individual goods from individual end-consumers to the appropriate retailer, manufacturer, or third party). Indeed, there is not a comprehensive framework to assist enterprises in understanding, evaluating, creating, implementing, or changing a consumer-to-business reverse logistics policy of program. Given the growth of e-commerce and the Internet channel, where goods are often delivered to end-consumers in quantities of one and may likely be returned in quantities of one, this absence of a framework is peculiar. This thesis seeks to fill that gap by utilizing analysis of existing literature, as well as extrapolation of recent trends and developments in reverse logistics service offerings, technology, and last mile solutions. The results are that there is enough available information on the processes and issues surrounding consumer-to-business reverse logistics that a flexible and pragmatic framework can be proposed for use in the United States. This is accomplished by synthesizing results with original analysis, thought, and context. Though the framework cannot be considered comprehensive, it does provide an initial tool for critique and improvement. / by Jonathan M. Fleck. / M.Eng.

Thesis: M. Eng. in Logistics, Massachusetts Institute of Technology, Engineering Systems Division, 2014. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 46-47). / Supply Chain Risk Management ("SCRM") is often discussed in business and academia but is still underdeveloped as a practical tool. Many studies have examined the effects of supply chain disruptions, and many studies have also produced tools for mitigating risk. However, there is still a need for an integrated, practical approach for SCRM that businesses can implement on an enterprise scale. Our thesis attempts to bridge this gap and produce a practical approach for corporations to deploy a SCRM strategy on an enterprise level. Through the use of supply chain visualization and catastrophe modeling software, we have developed a SCRM strategy for a large multi-national chemical company. Our SCRM framework focuses on four key steps: 1) defining the scope of supply chain disruptions; 2) mapping and visualizing the supply chain; 3) evaluating the probability of disruption; and 4) developing a strategy to create an economically resilient supply chain. / by Diwei Xia and Kaiye Lu. / M. Eng. in Logistics

Thesis (S.M. in Technology and Policy)--Massachusetts Institute of Technology, Engineering Systems Division, 2013. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Cataloged from student-submitted PDF version of thesis. / Includes bibliographical references (p. 102-108). / DNA synthesis technologies are advancing at exponential rates, with production of ever longer, more complex, and less expensive sequences of double stranded DNA. This has fostered development of industrial scale design, construction, and sale of synthetic DNA. The tools and methods of synthesis used to create beneficial genetic material can also be used to construct dangerous pathogens. To prevent unknown actors from ordering potentially dangerous genetic material, the largest DNA synthesis firms formed two industry associations that require members to screen the DNA sequences ordered and the customers ordering sequences. The firms also worked with the U.S. Health and Human Services to formulate voluntary screening guidelines for synthetic double stranded DNA. As DNA synthesis technology advances and diffuses, this centralized voluntary approach may become less effective. This thesis identifies strengths and weakness in the current voluntary regime and offers recommendations to improve security in the DNA synthesis industry. It describes the origins and current status of DNA synthesis technologies and the structure of the DNA synthesis industry. Then, it describes the formation of voluntary screening consortia and the U.S. and international guidelines that address security issues in DNA synthesis. Finally, this thesis compares DNA synthesis with other potentially "dual use" technologies, concludes that regulatory approaches may not enhance security in this area, and suggests that governments should focus on education and outreach. / by Ralph Donald Turlington III. / S.M.in Technology and Policy

Thesis (S.M. in Engineering and Management)--Massachusetts Institute of Technology, Engineering Systems Division, 2013. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 123-128). / Innovations are part of everyday reality in the business life of many companies. While for startups, success in business largely depends on success of innovations as they are trying to enter the market, for large monopolistic companies the influx of innovations is a crucial part of strategic decision-making. In a fast clockspeed high technology market, innovations are being introduced every day and have to be evaluated to identify potential threat to existing technology and market share of an incumbent. It is extremely difficult to understand if this new technology is something relevant to the market and will be adopted fast by customers, or it is merely one of many attempts, that will prove unsuccessful. Overarching questions for this work is "Why does the same technology become dominant in some cases while failing in others?" This work focuses on considering several real life examples with different outcomes through the lens of the Incumbent's Dilemma framework. The goal is to identify patterns of dynamics for several typical innovation scenarios and provide explanations that might be useful for product managers as well as top management of any company who want to understand how to use innovations to improve business performance and gain market share. / by Sergey A. Naumov. / S.M.in Engineering and Management

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2004. / "June 2004." / Includes bibliographical references (leaves 104-106). / In this thesis, real options are used to identify the optimal model for the reverse logistics process of a technology company in the circuit board business. Currently, customers return defective boards and the company repairs the boards and sends them back. Now that the new product cost is falling below the level of the repair cost, the company is considering an alternative operational model, which is to scrap the returned boards and swap them with new products. As the product cost declines, it is also widely fluctuating, and it is this fluctuation that makes the switching option between the repair and swap model valuable. The repair and swap models (with and without switching options) will each produce different cost saving amounts with different degrees of risk. As a result of real options analysis, the swap model with the switching option to repair is determined to be optimal and has only modest risk. Specifically, the costs would be reduced by $1.3 million (of which $0.9 million is the option value) and by 18% compared to the costs under the current model, and the volatility will only moderately increase from 8% to 11%. However, it should be noted that the model is sensitive to both volatility and switching cost. Unlike the traditional methodologies, such as optimization or discounted cash flow analysis, real options quantifies the option value as well as the risk and hence shows the maximum investment necessary to obtain the option. That being said, in this thesis, optimization (the news vendor approach), simulation (Monte Carlo simulation), and discounted cash flow analysis take complementary roles to real options analysis. The option value is significant when the key uncertainties (e.g., the product cost, repair cost, and volume) are volatile / (cont.) because the option allows businesses to capture upside opportunities while protecting them from downside risks. / by Akihiro Kaga. / M.Eng.in Logistics

Thesis: Ph. D., Massachusetts Institute of Technology, Engineering Systems Division, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 219-234). / Due to the physics of electricity, and the current high costs of storage technologies, electricity generation and demand need to be instantaneously balanced at all times. The large-scale deployment of intermittent renewables requires increased operational flexibility to accommodate fluctuating and unpredictable power supply while maintaining this balance. This dissertation investigates the value of electricity storage for the economy. Specifically, what is the value of storage under large-scale penetration of renewable energy in the context of climate policy? To answer this question, I develop a new hybrid modeling approach that couples an electricity sector model to the MIT EPPA model, a general equilibrium model for climate change policy analysis. The electricity sector model includes the main constraints for reliable and secure operation; electricity demand; wind, solar and hydro resources on the hourly time-scale; and utility-scale storage technologies. The hybrid modeling approach reconciles the very short-term dynamics required for renewables and storage technologies assessment, and the long-term time-scale required for the analysis of economic and environmental outcomes under climate policy. Using Mexico as a case study, this dissertation analyses policies currently under discussion in the country. The experimental design explores increasing shares of renewables with varying levels of storage capacity. Under scenarios with increasing shares of renewables in the power grid, the value of storage increases sharply. By 2050, with 50% renewables penetration, the present value of storage capacity per MW installed in Mexico is estimated at $1500/MW and $200/MWh. Energy management services resulted in the highest value component (58%), followed by operational reserves provision (22%) and capacity payments (18%). Storage capacity in the system changes both investments and operational decisions, allowing larger penetration of wind technologies and displacing gas technologies. Storage capacity in the system reduces price volatility and the occurrence of negative prices that would otherwise result as renewables scale up. The general equilibrium analysis shows that the availability of competitive storage technologies under an economy-wide climate policy reduces the overall policy costs. Simulating a 50% emissions reduction by 2050, the model demonstrated that storage could decrease total welfare losses by 0.7% when compared to the case without storage. Despite the sharp increase in the value of storage driven by renewables penetration, the findings suggest that the current cost of most storage technologies will still have to drastically be reduced for them to be economical. / by Claudia Alejandra Octaviano Villasana. / Ph. D.