Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2009 [first author]; and, (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2009 [second author]. / Includes bibliographical references (leaves 69-70). / As the public health system in Burundi transitions from a mode of emergency humanitarian response to a sustainable operation, there is a significant opportunity to reduce costs by eliminating the duplication of functions served by multiple parties. Numerous multi-lateral agencies and NGOs play a significant role in the public health supply chain. Additionally, Burundi has several vertical programs focused on specific communicable diseases such as HIV/AIDS, malaria and tuberculosis, which have parallel distribution systems. This thesis assesses the costs of multiplicity in the public health supply chain in Burundi, focusing on identifying the factors contributing to multiplicity and evaluating their cost impacts. We specifically analyze the transportation and inventory costs under four different distribution scenarios in the context of a proposed health sector structural reform while using the current system as a baseline. The analysis also discusses several other relevant factors that affect the costs of multiplicity. The research suggests that the Ministry of Health in Burundi can reduce costs, and improve availability of drugs by shifting from a pickup mode to a delivery mode of distribution, sharing assets between the central procurement agency and vertical programs, and improving the cash flow in the system. / by Jeet N. Shah & Trevor N. Thomas. / M.Eng.in Logistics

Thesis (S.M. in Engineering and Management)--Massachusetts Institute of Technology, Engineering Systems Division, 2012. / Cataloged from PDF version of thesis. Pages 198 and 199 are blank. Vita. / Includes bibliographical references (pages 183-194). / It is possible to categorize four contemporary challenges as the greatest threats to global well-being and the persistence of humankind. These challenges are global climate and ecological change, poor human health management, violence (or the absence of peace), and poverty and hunger. If our children, grandchildren and great-grandchildren are to survive in a peaceful world where fruitful progress can occur, these contemporary global challenges must be addressed thoughtfully and collectively as a human species. It is the contention of this paper that there exists an optimal and necessary set of requirements and conditions (at a global and organizational level) that give us the greatest probability of success in tackling these most urgent human challenges. The goal of this thesis is to prove this hypothesis and that these conditions can be explained by causal models as well as empirically tested through historical application and validation and direct application on a real world situation. A simple model for assessment of potential success for addressing the most challenging human endeavors is delivered. Sub-goals include presenting an analysis of the current global approaches to solving the major human challenges and how they can be improved. / by Anando A. Chowdhury. / S.M.in Engineering and Management

Thesis (S.M. in Toxicology)--Massachusetts Institute of Technology, Biological Engineering Division, 2004. / Includes bibliographical references (leaves 45-47). / Design and fabrication of a microfluidics system capable of generating reproducible and controlled micro-biochemical environments that can be used as a diagnostic assay and microreactor is important. Here, a simple technique was developed to create a robust microfluidics system capable of generating precise gradients of biochemical properties within its channels. Through this approach, it is possible to create a gradient generator with mammalian cells patterned and seeded under its poly(dimethylsiloxane) (PDMS) channels. Cells that were seeded and patterned under the PDMS channels remained viable and capable of performing intracellular reactions. Using the gradient generator within the PDMS microfluidic device, a gradient of specific and controlled biochemicals can be flowed on seeded cells allowing for high-throughput molecular interaction analysis. The microfluidics system provides a way to study and analyze cell response in the presence of a combination of biochemical signals. / by Guan-Jong Chen. / S.M.in Toxicology

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 101-103). / This paper looks at some of these travails as well as the common tools used to approach a volatile priced commodity, diesel fuel. It focuses on the impacts of hedging for companies that are directly impacted through the consumption of diesel fuel in addition to companies that are indirectly impacted because they outsource their transportation. It examines the impact of a fuel surcharge and how it distributes risk throughout the supply chain. To complement the research, analysis was conducted in the form of a survey to benchmark the industry with respect to current practices of hedging and fuel surcharges, a sensitivity test of a fuel surcharge matrix to find its appropriate usage, and a simulation to provide guidance as to the appropriate strategy for hedging. Lessons learned from the survey flowed into the sensitivity testing and simulation. These three segments of analysis highlighted the problem of volatility, increasing cost, and inability to pass on the cost, proving the true pain of fuel in the market. Ultimately, the paper answers: How to utilize hedging and a fuel surcharge program to stabilize the cost of fuel? The survey showed the wide adoption of fuel surcharges, confirming the academic research. The sensitivity test proved the need to keep the escalator variable in line with a carrier's actual fuel efficiency and standardize for all carriers. The simulation recommended longer term derivatives. Putting this together, the fuel surcharge establishes stability for the carrier, at the risk of the shipper. The shipper must maintain that stability through its maintenance of the escalator in the fuel surcharge matrix. Additionally, the shipper should hedge fuel via long term derivatives to establish personal fuel cost stability, creating a competitive advantage and enabling the shipper to compete more effectively. / by Charles A. Shehadi, III and Michael R. Witalec. / M.Eng.in Logistics

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2006. / Includes bibliographical references (p. 139-145). / Developments in light microscopy over the past three centuries have opened new windows into cell structure and function, yet many questions remain unanswered by current imaging approaches. Deep ultraviolet microscopy received attention in the 1950s as a way to generate image contrast from the strong absorbance of proteins and nucleic acids at wavelengths shorter than 300 nm. However, the lethal effects of these wavelengths limited their usefulness in studies of cell function, separating the contributions of protein and nucleic acid proved difficult, and scattering artifacts were a significant concern. We have used short exposures of deep-ultraviolet light synchronized with an ultraviolet-sensitive camera to observe mitosis and motility in living cells without causing necrosis, and quantified absorbance at 280 nm and 260 nm together with tryptophan native fluorescence in order to calculate maps of nucleic acid mass, protein mass, and quantum yield in unlabeled cells. We have also developed a method using images acquired at 320nm and 340nm, and an equation for Mie scattering, to determine a scattering correction factor for each pixel at 260nm and 280nm. These developments overcome the three main obstacles to previous deep UV microscopy efforts, creating a new approach to imaging unlabeled living cells that acquires quantitative information about protein and nucleic acid as a function of position and time. / by Benjamin J. Zeskind. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, 2012. / "September 2012." Cataloged from PDF version of thesis. / Includes bibliographical references (p. 163-167). / The Compatibility Assessment Method (CAM), a new structured process for assessing compatibility between parent systems and child subsystems is proposed and applied to several cases where subsystems are being replaced in legacy systems. CAM is a screening process intended to be used by project managers who need to replace components of complex systems. The functional model-based process uses an extension of the Integrated Definition Modeling Language of IDEFO. The IDEFO method is used for defining compatibility measures based on each of the four constituent arrows that show inputs, controls, outputs, and mechanisms (ICOM). In this extension, the control constituents are replaced with constraints. Each of the ICOM constituents is expanded with parameters which include metrics and values. The ICOMs with their parameters and metrics are then used to characterize two or more subsystems in a matrix format. The differences between these matrices are entered into the sparse "Delta Matrix" which shows analysts the differences between the systems. These differences can be assigned to the appropriate levels of technical expertise to be analyzed and to determine feasibility of the child subsystem in the parent system. The process is compared to current practices in government unmanned aircraft system program offices to determine the usefulness of adopting this compatibility assessment process. This dissertation outlines the need for and development of the method for application by practitioners responsible for replacing subsystems on legacy systems. The development includes evaluations of the method and an experiment with cohorts of student system engineers to compare the output of the Compatibility Assessment Method to less-structured methods. This research contributes additional insight into system architecting theory and proposes a structured method for practitioners to use to improve the processes to perform part replacement in legacy systems. While others have offered methods to measure aspects of system architecture, this proposed method moves beyond the extant literature with tools for practitioners. / by David Scott Andrew Long. / Ph.D.

Thesis: S.M., Massachusetts Institute of Technology, Engineering Systems Division, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 149-152). / The current trend of globalization as well as the growing complexity of multilateral systems engineering endeavors will contribute to the increasingly cross-cultural nature of systems engineering programs and teams in the future. It is thus vital to investigate if cultural differences have an influence on systems engineering endeavors in order to better understand culture's potential contribution, or impediment, to critical systems engineering outcomes. This thesis proposes a definition of culture that will be meaningful to such an investigation, selects Hofstede's cultural dimensions theory as a tool to apply this definition of culture, and analyzes the manned spaceflight programs of the US and China as a case study to determine if culture does indeed have an influence on systems engineering. The results of this analysis reveal that cultural differences do impact systems engineering endeavors from strategic to operational levels. Important differences in the US and China manned spaceflight programs primarily stemming from differences in the cultural norms of the US and China were found in three main areas of analysis. Firstly, in terms of the purpose of the programs, cultural differences led to differences in the kind of motivations each country had for achieving manned spaceflight, the organizations set up to achieve this goal, and the way leadership approval for the programs was attained. Secondly, in terms of the programs themselves, differences in cultural attitudes towards risk and launch failure led to differences in program schedule, program scope, the nature of the flighttesting schedule, and the extent of quality control measures. Thirdly, in terms of the people involved in the programs, differences in cultural norms led to differences in decision-making styles, use of authority, motivations and earnings of the engineers and astronauts, extent of astronaut involvement in the programs, the extent of manual control built into manned spaceflight launches, the degree of formality of the launches, and media coverage of the launches. Furthermore, these two very different programs were eventually judged to be a success in each nation precisely because of these cultural differences, even though each country's program would have been considered a pyrrhic victory in the other. The conclusions of this thesis propose how this demonstrated influence of culture on systems engineering should be used to inform systems engineering endeavors in the future. / by Yeong Li Qian. / S.M.

Thesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, 2005. / Includes bibliographical references (leaves 38-44). / Nitric oxide is postulated to protect cancer cells from the death-inducing effects of tumour necrosis factor alpha by S-nitrosating the active site cysteines, inhibiting cleavage of caspase-9. We aimed to test this hypothesis and to determine its validity across cancer cell types. In addition, we hoped to explain the involvement of certain kinases in nitric oxide-induced apoptosis. The experimental setup involved stimulating human colorectal cancer cells, HT-29 and HCT- 116, and human prostate cancer cells, LNCaP, with cytokines in order to induce cell death. Then, we observed the effects of NO inhibitors, kinase inhibitors, and activation of Akt, a kinase up-stream of the caspase cascade, following transfection of a DNA sequence that was proven to protect cells against apoptosis induction. In our series of experiments, inhibition of the nitric oxide synthases removes nitric oxide protection from apoptosis, but inhibition of only the inducible synthase has opposite effects with prostate and colon cancer cells that are considered insignificant, and its effects on the two types of colon cancer cells are in discord. Transformation and transfection of ARK5 into the colorectal cancer cell line, HT-29 did not prove beneficial. Similarly, glucosamine showed no clear pattern of reducing apoptosis in the cells. Therefore, we propose further exploration of the inhibition of constitutive nitric oxide synthases as a potential therapy. / by S. Julie-Ann Lloyd. / S.M.

Thesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, 2008. / Vita. / Includes bibliographical references (p. 82-89). / TLR-4 is essential in host defense against bacterial infection. By recognition of specific pathogen-associated molecular patterns such as lipopolysaccharide (LPS), TLR-4 can in tandem initiate a pair of downstream signaling pathways to regulate cytokine/chemokine release, endotoxin tolerance and apoptosis, which have been suggested to directly or indirectly participate in the regulation of innate and adaptive immune responses. However, little is known about their detailed signal-response relationships. In this thesis, we sought to identify these potential signal-response relationships in RAW264.7 cells through systematic analysis. We first measured LPS stimulated dynamic signaling profiles over a range of an inhibitor of p38 MAPK, SB202190 concentrations for a distribution of kinases centrally involved in TLR-4 signaling network. We then applied quantitative analytical approaches to determine the most important signals or signal combinations contributing to induction of either IL-6 and TNF-ao secretion or apoptosis and construct their corresponding predictive mathematical models. Particularly, we found that the partial least squares regression (PLSR) models built using the ratio of phosphorylated Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) predicted LPS plus SB202190-induced apoptosis accurately even following perturbation with pharmacological inhibitors of JNK and ERK. Thus, by combining experimental and computational approaches, this thesis has proposed two new potential targets, JNK and ERK, for development of drug therapies against bacterial infection. / by Rongcong Wu. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, 2011. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 163-168). / If we are willing to pay a premium, we may be able to mitigate some of the long-lasting impacts of nuclear waste. Deciding how to navigate this tradeoff, between cost and waste, is a central challenge for stewards of nuclear power. It is made more difficult by uncertainties that characterize the global future of nuclear electricity generation. The recent increase in concern about climate change has prompted U.S. policymakers to back strategies favorable toward nuclear power, so much so that some experts see a "nuclear renaissance" on the horizon. Whether such a renaissance will come to pass, involving the construction of a vast new fleet of nuclear plants, is unclear - especially in light of the March 2011 nuclear accident at the Fukushima Daiichi reactors in Japan. Even more unclear is what should be done with the commercial U.S. nuclear waste, given an array of technical options and a large amount of uncertainty about how much waste will ultimately need to be managed. This study introduces a framework for analysis of strategies to evolve the nuclear fuel cycle which may be helpful in analyzing decision problems for similarly complex, long-lived technical infrastructure systems. The framework consists of a system dynamics simulation coupled with a decision analysis model. The system dynamics code is developed specifically for this study to be simple, fast-running, and also to echo the results of many previous nuclear fuel cycle simulations in demonstrating how various technical options impact important parameters (like uranium consumed, waste generated, etc.). Code results are benchmarked to more complex fuel cycle simulations for the parameters relevant to the decision space. The decision analysis model takes information from the simulation and makes it useful to policymakers, by allowing the explicit analysis of desirable decision pathways under uncertainty, and also considering tradeoffs among system goals. The framework is applied to three nuclear systems, the light-water reactor (LWR) once through fuel cycle, which represents the status quo, an advanced, traditional, plutonium-fed self sustaining fast reactor fuel cycle, and a fast reactor fuel cycle for which initial fast reactor cores are composed of enriched uranium rather than recycled LWR fuel. Fast reactors are highly likely to cost more than LWRs, but they can produce electricity from some of the elements that most plague the long-term management of a nuclear waste repository. A value function compares how these options fare under different scenarios, incorporating system-wide costs and the system waste burden as the two attributes in the function. The primary result is that the best strategy, under a strong preference for eliminating LWR spent nuclear fuel waste, consists of building a few traditional fast reactors now, and then building a full fleet more rapidly later in the century. This allows both for a significant amount of waste mitigation compared to an all-LWR fuel cycle, and for the costs associated with the more expensive fast reactor technology to be incurred primarily later in the century. On the other hand, if cost is the main consideration, the framework advises moving forward with the once-through LWR fuel cycle and avoiding fast reactors altogether, or at least until later in the century. These results are examined from a traditional decision analysis perspective, and then from one that departs somewhat from the assumption of a fully powerful decision maker. In reality, a government decision maker can only offer incentives to industry in order to induce a strategy change. Changing the decision model to reflect this reality causes the framework to more strongly advise moving forward with traditional fast reactors. This occurs because any single attempt at offering incentives to industry might be unsuccessful, and thus prevent a waste concerned government from achieving any significant mitigation. The most important contribution of the methodology is its ability to illuminate which parameters represent strong drivers of system decisions. Preferences across competing attributes are always important: in general, if decision maker preferences for reducing cost vs. waste were to shift significantly, the framework would show a change in the desirable decision strategy. Decision results are not very sensitive, on the other hand, to the rate of nuclear power growth or to the cost of fast reactor technology. A second contribution comes from the initial foray into studying a more complex decision maker perspective, and shows how a different view can complement results using the traditional decision analysis assumption of an "ideal" decision maker. Ultimately, the system dynamics/decision analysis framework presented here helps identify desirable pathways for complex system evolution, identifies factors that bear strongly on decisions and which are deserving of more study, and begins to show how strategy implementation can be considered within the framework in order to further improve decision-making. / by Lara Marie Pierpoint. / Ph.D.