Thesis (S.M. in Engineering Systems)--Massachusetts Institute of Technology, Engineering Systems Division, 2013. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 103-104). / As ocean shipments have increased alongside globalization, transit time uncertainty has increased as well. This problem was observed to have variable levels of impacts on logistics cost and safety stock levels. This thesis examines the effects of bimodality in transit time distributions -in particular, the cost of ignoring bimodality. One method common in practice is to completely ignore variability. On the other hand, a popular theoretical method to account for transit time variability is to assume that demand over transit time is normally distributed. Which is, in many cases, false. To display the incorrectness of such assumptions, the paper will compare the two approaches to empirical analysis on bimodal transit time distributions. / by Lita Das. / S.M.in Engineering Systems

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2004. / Includes bibliographical references (leaves 49-52). / When trying to envision what the future might look like, different methods of forecasting are often used. However, there is a growing consensus that discontinuity and abrupt change are inherent to the very nature of the future and should be incorporated into futurist studies. One such study is the MIT Center for Transportation and Logistics' Future of Supply Chain 2020 (SC2020). This paper reviews the future-studies method of Scenario Planning and evaluates its applicability to the SC2020 project. / by Yishai Boasson. / M.Eng.in Logistics

Thesis (Ph. D. in Genetic Toxicology)--Massachusetts Institute of Technology, Biological Engineering Division, 2004. / 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. 139-161). / It is a widely-held hypothesis that environmental mutagens play an essential role in human somatic and germinal cell mutagenesis. In particular, the finding of small amounts of chemical mutagens in cigarette smoke has led to the general hypothesis that mutagens in cigarette smoke induce oncomutations and thus account for the carcinogenic effect of cigarette smoking in human lungs. However, this hypothesis has not been tested by an assay of nuclear point mutations in lungs of smokers and nonsmokers. Mismatch amplification mutation assay (MAMA), an effective form of allele-specific PCR, was applied for detection of point mutations in TP53 bp742, bp746 and bp747, K-ras bp35 and HPRT bp508 from a total of 291 tracheal-bronchial epithelial sectors from six smokers and nine non-smokers, yielding 949 individual mutational assays. The conditions of MAMA for each target point mutations were optimized such that the sensitivity of each was equal to or below 10⁻⁵. Lung epithelial sectors of 2.3x10⁶ cells in average contained 0-200 mutant cells in general, equivalent to mutant fractions (MFs) of 0-10⁻⁴ with an exception of rare sectors with MF larger than 4x 10⁻⁴ (4.6%). Noticeably, the distributions of the MFs among sectors did not vary appreciably with the donor's smoking status. The mean MFs per lung were very similar between smokers and non-smokers for all five target mutations assayed (p >> 0.05). The mean MFs were slightly higher in females than males (p = 0.015). The mean MFs increased with age of the subjects although the correlation did not reach statistical significance due to large variances within the same age group. The distributions of MF among sectors of smokers and non-smokers did not differ significantly by Kolmogorov-Smirnov test / (cont.) for all target mutations but HPRT. By using hypothetical turnover unit sizes and Poisson distribution, the turnover unit size of human tracheal bronchial epithelium was estimated as 64 cells (p = 0.05). These observations do not support the widely-held hypothesis that cigarette smoking causes lung cancer through its induction of point mutations in nuclear genes. The current findings demonstrate the necessity of investigation on alternative mechanisms for tobacco smoke in lung carcinogenesis. / by Hiroko Sudo. / Ph.D.in Genetic Toxicology

Thesis (S.M. in Engineering and Management)--Massachusetts Institute of Technology, Engineering Systems Division, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 81). / A strong and growing desire exists, throughout society, to consume electricity from clean and renewable energy sources, such as solar, wind, biomass, geothermal, and others. Due to the intermittent and variable nature of electricity from these sources, our current electricity grid is incapable of collecting, transmitting, and distributing this energy effectively. The "Smart Grid" is a term which has come to represent this 'next generation' grid, capable of delivering, not only environmental benefits, but also key economic, reliability and energy security benefits as well. Due to the high complexity of the electricity grid, a principle based System Architecture framework is presented as a tool for analyzing, defining, and outlining potential pathways for infrastructure transformation. Through applying this framework to the Smart Grid, beneficiaries and stakeholders are identified, upstream and downstream influences on design are analyzed, and a succinct outline of benefits and functions is produced. The first phase of grid transformation is establishing a robust communications and measurement network. This network will enable customer participation and increase energy efficiency through smart metering, real time pricing, and demand response programs. As penetration of renewables increases, the high variability and uncontrollability of additional energy sources will cause significant operation and control challenges. To mitigate this variability reserve margins will be adjusted and grid scale energy storage (such as compressed air, flow batteries, and plugin hybrid electric vehicles or PHEV's) will begin to be introduced. Achieving over 15% renewable energy penetration marks the second phase of transformation. The third phase is enabling mass adoption, whereby over 40% of our energy will come from renewable sources. This level of penetration will only be achieved through fast supply and demand balancing controls and large scale storage. Robust modeling must be developed to test various portfolio configurations. / by Gregory Sachs. / S.M.in Engineering and Management

Thesis (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division, 2012. / 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. 88-90). / In todays' global economy, having a lean operation is no longer considered a competitive edge; rather has become the new necessity and norm [15]. The new source of this competitive edge is innovation [15]. What sets an organization apart from its competitors is the ability to develop products that constantly meet customers' demands. An organization must have a New Product Development Process (NPDP) that enhances, expedites and fosters development of innovative products on consistent basis in order to tie innovation to market success. Many organizations have a difficult time determining whether or not the NPDP they are using is adequate because there are no standard methods or processes that organization can use to assess their NPDP [16]. In order to assist a specific medical device organization to assess its NPDP, a partnership with Performance Measure Group (PMG) was established. PMG is a leader in benchmarking and performance measurement. This thesis gives insight into the various new product development and benchmarking processes that are in practice today. It also explores the challenges and benefits associated with conducting benchmarking. Finally, this thesis reveals some of the challenges that this particular medical device company confronts with their NPDP. / by Sassan Zelkha. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2002. / Includes bibliographical references (leaves 193-218). / Specific interactions between heparan sulfate glycosaminoglycans (HSGAGs) and proteins are central to a wide range of biological processes such as anticoagulation, angiogenesis and growth factor activation. The specificity involved in the HSGAG-protein interactions stems from the structural heterogeneity of HSGAGs, which are highly acidic biopolymers associated on the cell surface and in the extracellular matrix. It is believed that structural specificity in the HSGAG-protein interactions determines the biological functions mediated by HSGAG-binding proteins such as basic fibroblast growth factor (FGF2). A number of models have been proposed to account for the mode of FGF-FGFR interactions and the role of HSGAGs in modulating FGF2 signaling. It was hypothesized that one role played by HSGAGs was to stabilize FGF2 oligomers in a "side-by-side" or cis fashion for presentation to fibroblast growth factor receptor (FGFR). In this thesis research, we systematically examined different proposed modes of FGF2 dimerization and showed that extensive oligomerization of a FGF2 mutant protein could be achieved by oxidatively crosslinking. Heparin, a highly sulfated form of HSGAGs, was demonstrated to increase the extent of oligomerization. Therefore, the results reported here were consistent with the hypothesis that HSGAGs promoted FGF2 oligomerization in a "side-by-side" mode. The functional significance of a FGF2 dimer was tested using a genetically engineered dimeric FGF2 (dFGF2). Biochemical and biophysical properties of dFGF2, such as protein folding, heparin affinity and receptor / (cont.) binding, were assayed. dFGF2 was found to exhibit higher activities in stimulating cell proliferation and cell survival in vitro compared with the monomeric wildtype. An in vivo rat cornea pocket model further corroborated the in vitro findings. The functional role of HSGAGs derived from the cell surface was studied here. It was found that distinct HSGAG fragments released by heparinase treatment were capable of modulating FGF2-stimulated cell proliferation depending on the expression of FGFR isoforms. This founding is consistent with the proposal that structural specificity of distinct HSGAG fragments dictated the interaction of HSGAGs with FGF and FGFR. The role of heparinase-generated HSGAG fragments in inhibiting cell proliferation was investigated. B16 melanoma cells treated with heparinase III were found to exhibit biochemical and morphological hallmarks of apoptosis. Conditioned medium derived from heparinase-treated cells was shown to be effective in suppressing cell growth. Gene array experiments and caspase activity assays further suggested that apoptotic cell death was mediated through a caspase 8-, death receptor-dependent pathway. Thus, the present study lends further credence to the proposal that cell surface HSGAGs plays a critical role in orchestrating cell phenotype. This thesis work provides the framework for understanding the molecular mechanism of growth factor activation and the structure-function relationship of HSGAG-mediated cell signaling. Results from this study may potentially be useful for therapeutic protein engineering and carbohydrate-based drug discovery. / by Chi-Pong Kwan. / Ph.D.

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2010. / Page 98 blank. Cataloged from PDF version of thesis. / Includes bibliographical references (p. 91-92). / Do demographic factors play a role in the choice of supply chain risk management practices by supply chain professionals? Are there stronger relationships between certain demographic factors and supply chain risk management practices? Most supply chains today cuts across multiple countries, cultures, languages, income levels, and industries just to name a few. This means there are differences in supply chain risk management behaviors or attitudes. Is there a way to understand some of these differences better and will the management of global supply chains benefit from this knowledge? / by Kenneth Kanyagui. / M.Eng.in Logistics

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2013. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 55-57). / Third party spend accounts for a significant amount of a business' costs. When procuring unique, highly-engineered components, this cost is often negotiated with suppliers during the procurement process. Due to the limited understanding of the suppliers' true production cost, various techniques and models for determining how much a procured product should cost have been tried. One such approach is known as "should-cost modeling," where estimates for the cost of a product or service are made based on product architecture and/or firm financials. Both these approaches to should-cost modeling require extensive data collection and are time consuming. In this thesis, we expand an approach that uses aggregate industry-specific financial data to develop a simple, scalable tool to estimate a product's should-cost. One major challenge in building this tool is unifying the simple aggregate data available into an estimated price for a complex product. This is a major challenge of developing a should-cost estimate using existing methods. We develop an approach to simplifying a complex product, construct our model, and create a ready-to-use tool. We demonstrate the working of the model and the tool using the case of a semi-complex product (the fluid end of a pump) representative of a company's procured products. We then compare the price estimated by our model with that currently negotiated with our sponsor company's supplier and solicit qualitative feedback from procurement professionals regarding the should-cost tool's accuracy. The price estimated by our tool is within 9% of the actual negotiated price and required significantly less time to compute compared to the current approach based on product architecture. The company's sourcing and procurement executive strongly endorses the benefits of our approach. This tool can remove the reliance on supplier-supplied quotes and strengthen the purchasing company's negotiating position. The tool developed in this thesis is shown to provide a more accurate estimate of product cost, with significantly less estimation effort. / by Clayton M. Mealer and Sung Hwan Park. / 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. / Includes bibliographical references (pages 98-102). / Improvement of business performance is an enduring subject of research across a diverse set of disciplines such as accounting, operations management, marketing, finance, economics and even psychology and sociology. In any discipline the ability to create self-awareness, a capacity to evaluate and compare their own behavior to internal standards and values, is a pre-requisite of improvement. In an organization, self-awareness is created with assessments. The results of assessments can help the organization to adapt to changing market conditions by defining more valuable objectives to direct its new businesses as well as to restructure its operations for eliminating deficiencies that limit its abilities to achieve its business goals at lower costs. For an organization with core businesses in product development (PD), assessment of PD is an essential element of all business improvement initiatives. However, in order to perform a focused PD assessment, the analysis needs to be structured with a systematic top-down approach which relates the findings of evaluations starting from high-level business goals down to the metrics for the most detailed operational activities. In this thesis, an existing Product Development Self-Assessment tool is integrated into this context, and implementation of a top-down assessment is presented using a three-step process. Other supplemental tools and methods are also incorporated into the discussion of the implementation framework such as; Goal-Question-Metric (GQM) and IDEFO function modeling methodologies. With the use of illustrative examples, the application steps of the framework and the use of supplemental methods are presented. / by Ziya Deniz Eralp. / S.M.in Engineering and Management

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2004. / Includes bibliographical references (leaf 62 ). / To be competitive and quick-to-market in today's global marketplace, Electronic Manufacturing Service (EMS) providers should focus on their core competencies, partnership relationships and continuous improvements. As Original Equipment Manufacturers (OEMs) Customers shift their focus on marketing and product development, EMS providers have been assuming the leading role to develop creative manufacturing solutions based on the core competencies in their supply chains. A tightly-coupled and synergistic relationship with OEM customers and key components suppliers is critical to EMS providers' success. This thesis focuses on applying system dynamics approach to supplier partnership management at FSJC, a top player in EMS industry, with the aim of gain deeper understanding on dynamics within FSJC's supply chain network and between suppliers and FSJC. We find out that to maintain its market position, FSJC must concentrate on small number of qualified suppliers and put effort to build strong partnership with these suppliers. This requires a better understanding of the impact of key parameters of partnership and manufacturing process of both suppliers and FSJC. Developing this sort of understanding can help FSJC continue to provide worldwide responsiveness to its customers by improving time-to-market, scalability and manufacturing efficiency and foster long-term partnership with both customers and suppliers by improving communications both upstream and downstream in the supply chain. / by Lihua Zhai. / M.Eng.in Logistics