Thesis (M.Eng.)--Massachusetts Institute of Technology, Engineering Systems Division, 2000. / Includes bibliographical references (leaves 48-51). / The Information Era has brought along a myriad of revolutionary changes. The Internet in particular has given new forms to old paradigms. It is quite a challenge for companies to decide which of all these options best suit their business model and their strategies, hopefully one that also provides them with a competitive edge. One of these new alternatives is online auctions used as a procurement tool. And because of their novelty, it is still unclear whether they are a flawless method of decreasing costs. Although there are many issues concerning this topic, the one addressed here is how the bidders' behavior during the auction (the strategy used to place their bids) affects the outcome, for them as well as for the company setting up the event; and how managers on both sides can maximize the benefits. The basis for the study was a recent auction conducted by autoparts maker Visteon for the procurement of a plastic hose. On the supplier side, the results show that those companies that had a target price before entering the auction, would obtain the most benefits (less sacrifice in profits), since Visteon did not award the projects solely based on price. On the buyer side, having a rich mixture of bidders (diverse in size, location, quality concern for example) enables a more dynamic process (lower prices). / by Michel Galland Lopez. / M.Eng.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004. / Includes bibliographical references (leaves 124-140). / Understanding the hepatotoxicity of drugs and chemicals is essential for progress in academic research, medical science and in the development of new pharmaceuticals. Studying hepatotoxicity in vitro is a challenging task because hepatocytes, the metabolically active cells of the liver, are very difficult to maintain in culture. After just 24 hours, the cells detach from the plate and die, and even if they survive they usually do not express the metabolic functions which they have in vivo. It has been observed by others that culturing hepatocytes between two layers of collagen type I maintains in vivo-like morphology and also many drug metabolizing enzymes for weeks. In spite of the research examining drug metabolism in collagen sandwiches, there are very few studies evaluating this system for investigating hepatotoxicity. We cultured primary rat hepatocytes in the collagen sandwich configuration and our goal was to optimize this system for long-term studies and to examine toxicity of a variety of hepatotoxins. By measuring secretions of urea and albumin, and P4501A activity, we determined the optimal cell density to be 50,000 cells/cm2. We also evaluated the need for epidermal growth factor (EGF) in our cultures, by comparing urea and albumin secretions in cultures grown with and without EGF. The cultures without EGF had significantly less secretion of both urea and albumin just two days after plating. Therefore, we decided to include EGF in the medium. The toxins we examined were aflatoxin B1, acetaminophen, carbon tetrachloride, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methyl methane sulfonate (MMS), cadmium, vinyl acetate and dimethylformamide (DMF). The cells were sensitive to aflatoxin B1, MMS, MNNG and cadmium. However, they were / (cont.) immune to acetaminophen, carbon tetrachloride, vinyl acetate and DMF. Our Western Blots showed that CYP1A, 2B and 3A were maintained in the culture for a week, but CYP2E1 was lost gradually over time. CYP2E1 is also the primary metabolic enzyme for acetaminophen, carbon tetrachloride and DMF. Thus, it is possible that the lack of toxicity is due to the loss of the enzyme responsible for the metabolism of these compounds. Immunity to vinyl acetate suggests that carboxylesterase is also lost in culture, since this enzyme is the one which converts vinyl acetate to acetaldehyde. The metabolism of acetaminophen was also examined with liquid chromatography and mass spectrometry. Liquid chromatography showed that acetaminophen is metabolized primarily to the sulfate and glucuronide metabolites. In order to investigate whether the glutathione adduct was formed, we synthesized the adduct and determined its retention time with liquid chromatography and its fragmentation pattern with mass spectrometry. We isolated the fraction with the same retention time from the medium of acetaminophen-treated cells, and showed that it contains a peak with the same mass to charge ratio and fragmentation pattern as the glutathione adduct. We also examined the conditioned medium from the hepatocytes to investigate the secreted protein profile, which could potentially be used to find toxicity biomarkers. We were able to remove most of the albumin from the medium using an immuno-affinity column containing anti-albumin antibodies bound to protein A-agarose beads ... / by Dóra Farkas. / Ph.D.

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2004. / Includes bibliographical references (leaves 46-47). / This thesis investigates financial results from RFID integration at product level in semiconductor manufacturing. The thesis explores how the technology might act in concert with other significant logistics tools to create return on investment. In this case, the use of RFID, along with postponement and Kanban practices, may help a manufacturer better align supply with central processing unit (CPU) demand. The resulting economic benefits are explored through yield scenarios. It is important to note that the thesis explores this topic without the benefit of empirical data. Consequently, a number of assumptions were made; these assumptions may affect the validity of the observations. Nonetheless, the study demonstrates an innovative approach that may contribute to new models of creative problem solving. / by John Dirk Kinley. / M.Eng.in Logistics

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2008. / Includes bibliographical references (leaves 62-63). / The object of the thesis is to develop a simple approach or heuristic for managing various types of uncertainty within a chemical production/inventory system. Later the company can use it to minimize the total cost at any required Cycle Service Level (CSL) under variable demand and production reliability. To solve this problem, we will base historical data to estimate the distribution type, the average demand and the standard deviation for the production line and initially assume that some factors like holding cost, penalty cost, demand and lead-time affect the production/inventory policy. Then, based on the above data and assumptions we build a model in Excel and then simulate some cases where change variables input. The model then is verified by Geert-Jan van Houtum Methodology. Finally, we will carry out the outcome analysis to capture the essence or insights of the multi-echelon problem. / by Nan Li & Guanghao Zhang. / M.Eng.in Logistics

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2012. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 90-92). / CPGCo, a global manufacturer of consumer packaged goods, has had tremendous difficulty in producing accurate forecasts for its products in developing markets. The problem was especially apparent during the global economic crisis in 2008, which caused demand for its products to become highly volatile. Its troubles have been aggravated by its long forecasting horizon, as it has not been able to adjust quickly enough to rapid market shifts due to fluctuations in various macroeconomic indicators. As a result, CPGCo faces heavy stockouts and excess inventories. This thesis explores the suitability of using macroeconomic indicators to forecast consumer demand for three developing countries in Asia as well as three separate product segments. A total of 27 macroeconomic models are constructed using stepwise multiple linear regression analysis employing three separate dependent variables: the firm's monthly wholesale shipment volume, retail market share by volume, and retail sales. The world oil price and country-specific exchange rates, stock indexes, interest rates, consumer price indexes, and consumer confidence indicators are used as independent variables. With our models, we are capable of producing extremely accurate forecasts for a small sample set with errors at or below 7.2%. Our findings also indicate that the consumer price index has the most influence on consumer demand, appearing in 81% of our models; thus, we recommend that CPGCo tracks the consumer price index of each country to complement its current forecasting processes. / by Jonathan Mau and Bryan P. McFadden. / M.Eng.in Logistics

Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, 2012. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 138-144). / Occupancy-moderated zonal space-conditioning (OZS) refers to the partitioning of a residence into different zones and independently operating the space-conditioning equipment of each zone based on its occupancy. OZS remains largely unexplored in spite of its potential to reduce the cost of space-conditioning. Despite the excitement surrounding cloud-connected devices like mobile phones and tablet computers, the benefit of using them to aid energy management agents (EMAs) in reducing space-conditioning cost under demand-driven pricing of electricity is not well understood. We develop a novel framework and the algorithms to enable an EMA to implement OZS for multiple inhabitants under a demand-driven pricing scheme for electricity. We further investigate the effects that influencing factors can have on the effectiveness of OZS under different scenarios using Monte Carlo simulations. The simulation results demonstrate that OZS is realizable on a simple home computer and can achieve significant space-conditioning cost reductions in practice. In our studies, both the financial operating cost of space-conditioning and the cost associated with discomfort are included in a single aggregate cost function. We then expand the simulations to study the cost reduction that is achievable when using cloud-connected devices to provide remote schedule updates to an EMA. This part of the study reveals that reduction in space-conditioning cost is appreciable if a working resident remotely updates an EMA at mid-day of his return time in the evening. In addition, we establish a directly proportional relationship between the level of space-conditioning cost reduction achievable and the variance of return time. Based on the research findings, we further offer recommendations and ideas for future research on the use of OZS and remote schedule updates to different stakeholders like policy-makers and homeowners. / by Woei Ling Leow. / Ph.D.

Thesis (M. Eng.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004. / Includes bibliographical references (p. 70-73). / Comb polymer, which consists of a hydrophobic poly(methyl methacrylate) (PMMA) backbone with hydrophilic hydroxy-poly(ethylene oxide) (HPOEM) side chains, is a tool that has many possible applications for the study of liver cell adhesion and signaling. This polymer has the unique properties of being cell resistant and chemically versatile such that various cell ligands can be coupled to its side chains. These properties allow adhesion through specific cell receptors to be studied without the effect of background adhesion to adsorbed proteins. By taking advantage of the ability to target specific receptors the comb polymer could be used as a powerful sorting tool. Sorting could be accomplished by finding cell type specific adhesion ligands. Several possible such ligands were screened. A ligand containing the tripeptide sequence RGD was found to elicit a strong cell adhesion response. However, this ligand is adherent to many cell types of the liver and would not be suitable for sorting purposes. Other cell type specific ligands tested showed little to no affinity for liver cell adhesion. Additionally, the comb was utilized to study α₅β₁ integrin-specific hepatocyte adhesion and the effect of Epidermal Growth Factor on adhesion. α₅β₁ integrin adhesion was mediated using a novel branched peptide, SynKRGD. This peptide consists of a linear peptide sequence containing RGDSP and the synergy site sequence PHSRN connected by the sequence GGKGGG. By utilizing the amine side group of Lysine a GGC branch was added. The terminal cysteine was used to conjugate SynKRGD to comb polymer surfaces using N-(p-Maleimidophenyl) isocyanate (PMPI) chemistry. EGF has a great potential to benefit the field of tissue engineering due to its influence on cell / (cont.) proliferation, migration, and differentiation. EGF is also known to have a de-adhesive effect in some cell types. Hepatocytes were studied on comb surfaces of variable SynKRGD densities with and without the presence of EGF in the media. Distinct morphological differences were observed for hepatocytes on substrates of varying adhesivity with and without the presence of EGF. EGF was found to have a de-adhesive effect on α₅β₁ integrin adhesion in hepatocytes. This effect became more pronounced as substrate adhesiveness increased. / by David Yin. / M.Eng.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004. / Includes bibliographical references. / (cont.) phosphoproteomics technology, IMAC/LC/MS/MS, [approximately] 200 phosphosites were identified from HT-29 cells, some of which were detected only from insulin-treated cells. Our phosphoproteomics approach also enabled us to detect alteration of both known and unknown phosphorylation states of apoptosis-related proteins at two time points during early apoptosis induced by tumor necrosis factor-α / Apoptosis, a physiologically regulated cell death, plays critical roles in development and immune system by maintaining tissue homeostasis. The thesis project investigates regulations of apoptosis in a human colon adenocarcinoma cell line, HT-29, exposed to diverse cellular stimuli, focusing on a specific protein as well as global level of proteins. The first part of the thesis demonstrated S-nitrosation of procaspase-9. S-nitrosation is a novel protein modification to regulate protein-protein interaction or protein activity. This modification has been implied to inactivate caspases. We could visualize S-nitrosation of an initiator caspase, procaspase-9, by enriching low-abundant procaspase-9 with immunoprecipitation and stabilizing S-nitroso-cysteine with biotin labeling. Nitric oxide synthase inhibitors and tumor necrosis factor-α (TNF-α) reduced the S-nitrosation level of procaspase-9, suggesting that S-nitrosation may be regulated by a nitric oxide synthase and denitrosation is likely a mechanism of apoptosis. The second part of the thesis is to examine survival effects of insulin on cells undergoing TNF-α-induced apoptosis. Insulin decreased the TNF-α-induced cleavage of key apoptotic mediators, caspases, and their substrates as well as apoptosis, in part, depending on phosphatidylinositol-3 kinase (PI-3K)/Akt pathway. One of protective mechanisms by insulin is likely to decrease the TNF-α-induced dissociation of a potent inhibitor of caspases, X-chromosome linked inhibitor of apoptosis protein (XIAP), from procaspase-9 via PI-3K/Akt pathway. Lack of phosphoproteomics data in HT-29 cells led the third part of the thesis to focus on investigating global level regulation of phosphoproteins during apoptosis. With a / by Ji-Eun Kim. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007. / Includes bibliographical references. / Our understanding of glycosaminoglycan (GAG) biology has been limited by a lack of sensitive and efficient analytical tools designed to deal with these complex molecules. GAGs are heterogeneous and often sulfated linear polys accharides found throughout the extracellular environment, and available to researchers only in limited mixtures. A series of sensitive label-free analytical tools were developed to provide sequence information and to quantify whole epitopes from GAG mixtures. Three complementary sets of tools were developed to provide GAG sequence information. Two novel exolytic sulfatases from Flavobacterium heparinum that degrade heparan/heparan sulfate glycosaminoglycans (HSGAGs) were cloned and characterized. These exolytic enzymes enabled the exo-sequencing of a HSGAG oligosaccharide. Phenylboronic acids (PBAs) were specifically reacted with unsulfated chondroitin sulfate (CS) disaccharides from within a larger mixture. The resulting cyclic esters were easily detected in mass spectrometry (MS) using the distinct isotopic abundance of boron. Electrospray ionization tandem mass spectrometry (ESI-MSn) was employed to determine the fragmentation patterns of HSGAG disaccharides. These patterns were used to quantify relative amounts of isomeric disaccharides in a mixture. Fragmentation information is valuable for building methods for oligosaccharide sequencing, and the general method can be applied to quantify any isomers using MSn. Three other tools were developed to quantify GAG epitopes. Two microfluidic devices were characterized as HSGAG sensors. Sensors were functionalized either with protamine to quantify total HSGAGs or with antithrombin-III (AT-III) to quantify a specific anticoagulant epitope. / (cont.) A charge sensitive silicon field effect sensor accurately quantified clinically relevant anticoagulants including low molecular weight heparins (LMWH), even out of serum. A mass sensitive suspended microchannel resonator (SMR) measured the same clinically relevant HSGAGs. When these two sensors were compared, the SMR proved more robust and versatile. The SMR signal is more stable, it can be reused ad infinitum, and surface modifications can be automated and monitored. The field effect sensor provided an advantage in selectivity by preferentially detecting highly charged HSGAGs instead of any massive, non-specifically bound proteins. Lastly, anti-HSGAG single chain variable fragments (scFv) were evolved using yeast surface display towards generating antibodies for HSGAG epitope sensing and clinical GAG neutralization. / by Jonathan Robert Behr. / Ph.D.

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2003. / Includes bibliographical references (leaf 46). / The freight brokerage industry in North America was born of the deregulation of the trucking industry in 1982. In the two decades since, the industry has grown from nothing to $50 Billion in revenue. In the beginning, freight brokers used T-card systems to record, track, and bill orders. Technology advances over those two decades have driven many of the operational changes throughout the freight transportation industry as a whole, with shipment data visibility, asset utilization, and supply chain planning leading the way. The use of optimization tools in transportation and supply chain management has proliferated. Network analysis, inventory planning and deployment, fleet routing, and warehouse planning are important examples of areas in which these tools have had a major impact. However, the freight brokerage sub-industry itself has largely ignored the use of these tools. This research proposes pragmatic uses for optimization techniques in the freight brokerage industry. Three tools are proposed, with justifications for need, mathematical formulations, and exemplary situations and savings described. The three tools are: 1) optimal truckload freight tenders to multiple carriers, 2) optimal LTL consolidation, and 3) optimal matching of loads and trucks. / by Jeffrey L. Silver. / M.Eng.in Logistics