Thesis (M. Eng.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007. / Includes bibliographical references (leaves 60-61). / Idiosyncratic drug reactions are a subset of adverse reactions frequently targeting the liver, which become obvious only in large sample populations. Drug-induced hepatotoxicity, occurring in a very small fraction of patients, poses a major challenge to pharmaceutical companies due to its unknown mechanism(s) of action and deficient models for study. In vitro model systems may have the potential to predict this liver injury by generating conditions possibly representing key processes involved, both directly and indirectly, in drug effects on cellular physiology. Our ultimate goal is to develop an in vitro model effectively mimicking certain relevant aspects of the in vivo response of the human liver. In our initial effort described herein, we have designed a novel cell-based system using alternatively in both a human hepatoma cell line and primary rat hepatocytes to study toxic effects in a background reflecting in vivo inflammatory conditions. This background incorporates bacterial lipopolysaccharide (LPS) administration along with inflammatory cytokines (tumor necrosis factor, interferon y, interleukin-1 a, interleukin-113, and interleukin-6) previously shown to increase in LPS-administrated rats. Our study began with an investigation of toxicities that are induced by combinations of five cytokines and LPS in HepG2 and C3A human hepatoma cell lines and in primary rat hepatocytes. Informed by the results of these experiments, we selected representative cytokine/LPS treatments and cell systems to examine drug-cytokine synergies in vitro and were able to identify multiple idiosyncratic hepatotoxins that induced synergistic toxicity in either the HepG2 cell line or primary rat hepatocytes. / (cont.) Finally, we measured the sensitization of these cell systems to a panel of these drugs, given an inflammatory background induced by an abbreviated set of cytokine treatments including four cytokines and LPS. Analysis of this multivariate drug-cytokine toxicity data set yielded a subset of representative cytokine treatments for future drug-cytokine synergy investigations. This subset will be used to characterize the differences between cell systems, including cultured human hepatocytes, and to hopefully develop a data-driven partial least squares regression model that predicts idiosyncratic liver injury. The implications are two-fold. First, this model could provide direction to pharmaceutical companies in focusing their drug discovery and development. Second, it could help physicians design better treatment plans for their patients. / by Maya Hasan. / M.Eng.

Pun Siu Yi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 126-128). / Abstracts in English and Chinese. / List of Figure / List of Table / Chapter 1 --- Introduction --- p.11 / Chapter 2 --- Capacity of Single-Cell S-CDMA System --- p.15 / Chapter 2.1 --- Preliminary --- p.16 / Chapter 2.1.1 --- Information measure --- p.16 / Chapter 2.1.2 --- Capacity of a channel --- p.20 / Chapter 2.1.3 --- Capacity of multiple access Gaussian DS-CDMA channel --- p.22 / Chapter 2.2 --- Evaluation of the sum capacity for selected sequence sets --- p.26 / Chapter 2.2.1 --- Walsh Code --- p.28 / Chapter 2.2.2 --- M-Sequence --- p.34 / Chapter 2.2.3 --- Binary Almost Perfect Sequence --- p.42 / Chapter 2.3 --- Asymptotic Upper Bound of the sum capacity for 2 sequence sets --- p.50 / Chapter 2.3.1 --- Upper Bound of the sum capacity for selected sequence sets --- p.50 / Chapter 2.3.2 --- Asymptotic Upper Bound --- p.52 / Chapter 2.4 --- Optimal dynamic code allocation scheme for ad-hoc S-CDMA System --- p.62 / Chapter 2.4.1 --- Ad-hoc S-CDMA System --- p.62 / Chapter 2.4.2 --- Code Allocation Scheme --- p.63 / Chapter 2.4.3 --- Proof of Optimality --- p.66 / Chapter 3 --- Simulation of code adaptation schemes for mobile CDMA System --- p.72 / Chapter 3.1 --- Introduction of mobile CDMA System --- p.72 / Chapter 3.2 --- Simulation of code adaptation scheme --- p.77 / Chapter 3.2.1 --- System Model --- p.77 / Chapter 3.2.2 --- Description of 3 schemes --- p.78 / Chapter 3.2.3 --- Simulation Results --- p.96 / Conclusion and Future Work --- p.108 / Appendix --- p.110 / Bibliography --- p.126

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. 139-143). / Conventional criticality-assessment methods drawn from the existing literature are often limited to evaluations of scarcity risks, or rely on price as an indicator of criticality. Such approaches, however, are ill-suited to a firm's material procurement planning. A simulation tool - the m:5 model - has been developed to model the behavior and dynamics of materials markets. Grounded on economic theory, the model also draws upon the characteristics of mining economics and market imperfections, while offering a flexible structure adaptable to different markets and requiring few inputs. The m:5 model has been designed to enable manufacturers and policy-makers to compare the outcomes of different scenarios, informing decisions about material purchasing and market regulation. Model results illustrate common behaviors of materials markets viewed as critical, such as those of Rare Earth Elements and Platinum Group Metals. Analyses illustrate the interaction between demand growth rate and market concentration, as well as the impact of price elasticity of demand on market behaviors. Moreover, an effective recycling stream is shown to be an efficient policy to mitigate price excursions, especially in the presence of disruptive events. A variety of potential private and public mitigating policies are assessed in light of model results, to address common risks encountered in critical materials markets. In addition, this thesis presents how the model can be used to actually develop and compare such policies. While the initial purposes of the model - namely, enabling scenario comparisons and gaining qualitative insights on specific materials markets - has been fulfilled in this work, future developments on the model could include the endogenous treatment of recycling and adding price-responsiveness to the handling of stock, so as to refine its correspondence to actual markets' behaviors. / by Claire Marie Franc̦oise Poulizac. / S.M.in Technology and Policy

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2004. / "June 2004." / Includes bibliographical references (leaves 67-68). / An important topic in the Third Party Logistics (3PL) industry is the extent to which customers view 3PL services as pure-commodities to be re-bid. The trend towards commoditization has been one of the causes for current pricing pressures on the 3PLs. The 3PLs gearing towards "strategic partnerships" and the addition of Value-Added Services to their portfolio could decelerate the trend towards commoditization and could also otherwise differentiate them from their competitors. This study investigates the categories of relationships that 3PLs have and specifically the presence of strategic relationships in the 3PL industry. The study also examines the contexts in which they exist and highlights the factors that have contributed to the formation of the strategic relationships. The study concludes by proposing steps that 3PLs can take to better position themselves as candidates for strategic relationships. / by Madhu Ranjan [and] Richard Tonui. / M.Eng.in Logistics

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2004. / Includes bibliographical references (leaves 87-88). / The objective of this thesis is to find an appropriate analytical method for scheduling the daily driver tasks in the grocery industry. The goal is to maximize driver utilization. A "Bin-packing" approach is employed to solve the problem. A Bin-packing problem concerns packing a list of items into the minimal number of unit capacity bins. In our problem, the drivers correspond to the bins and the daily delivery tasks are equivalent to the items, where we use time units to measure bin capacity. The model is applied to characterize the operation of a grocery company. Several bin-packing algorithms are implemented on two weeks of delivery data, which represent the company's transportation demand. The driver requirements are calculated and compared with their actual assets. Driver requirements are assessed on a per-day basis, considering the volatility in transportation demand over the course of the week. The performance of a given bin-packing algorithm is measured by how well it maximizes driver utilization and balances the workload among the drivers. The model's solution generated labor savings and proved that better resource allocation is possible by considering the demands of the various dispatching locations and the days of the week. Extension of the current model to capture the time window constraints of the delivery locations is proposed for future further research. / by Arzum Akkas. / M.Eng.in Logistics

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2006. / Includes bibliographical references (leaves 99-100). / A convergence of factors including a strong economy, changing demographics and increased regulatory control has resulted in a U.S. For-Hire Truckload (TL) industry that is increasingly pressed to meet shippers' needs for freight services. As demand now exceeds supply, the buyer/seller relationship has swung to favor TL providers who wield much more power than they have historically enjoyed. TL carriers are now able to negotiate higher rates, increase charges for providing additional services and decrease service levels as shippers are unable to find suitable replacement carriers. Many shippers have responded to these changing market dynamics by increasing the use of private and/or dedicated fleets within their distribution networks. This provides them with guaranteed capacity, increased leverage with carriers during rate negotiations and increased overall operational control of their networks. In this thesis, I will propose a methodology for the creation of a shipper's overall transportation policy in a distribution network that uses an internally managed fleet in conjunction with TL contract carriers. / (cont.) This approach constructs transportation policy in a manner that recognizes the differences in costing between an internally owned and managed fleet versus that of a contract TL carrier. It seeks to maximize savings by leveraging internal economies of scope through the assignment of fleet resources to closed loop tours. Additionally, the approach will go beyond the standard deterministic methods that are commonly employed in the creation of transportation policy. Instead, an iterative process that incorporates both optimization and simulation is proposed that ensures variability inherent within the network is taken into account when defining the best transportation policy for an organization. / by Michael Jay Mulqueen, Jr. / M.Eng.in Logistics

Thesis (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 241-249). / The field of Engineering Systems maintains that fundamental engineering principles exist, which apply across different domains of complex socio-technical systems. In this thesis, a state-of-the art decision and design evaluation method developed using aerospace cases, Multi-Attribute Tradespace Exploration (MATE), is applied for the first time to a transportation design problem. Through the application process across domains, differences between the aerospace and transportation domain are characterized: (1) a "mission objective" has not emerged as a welldefined, integral concept for transportation project planning in the same way it did in the military and space communities; (2) a simple stakeholder structure for the purpose of the analysis is not a reasonable assumption, (3) inheritance (legacy structures and legacy expectations) in transportation planning brings with it the stickiness of the status quo and people's attachment to things they possess; (4) several cost types exist in addition to monetary costs, e.g. harmful effects to life and spending of scarce resources (time, money); (5) decisions about the welfare of stakeholders in transportation planning are inextricably linked to technical decisions. It follows that fundamental engineering systems design principles need to be general enough to encompass these domain differences. Decisions about the welfare of stakeholders (public, future generations, environment) by a legitimized representative decision maker raise the question about the desirability of prescriptive guiding principles for decision making, in order to ensure consideration for the represented constituency when their interests need to be traded off with personal and organizational interests of the decision maker. Decision makers themselves seek such guidance to help them in trading off and justifying decisions about multiple competing goals in complex situations. One established method to provide such guidance is Cost-Benefit Analysis (CBA). CBA is a central, established, prescriptive evaluation method used in several domains, including transportation. In order to compare insights gained through the emerging method MATE and the established method CBA, two case studies, a Chicago Airport Express and a High-Speed Rail link between Portugal and Spain, are evaluated using those two methods. CBA assumes a broad view over all affected stakeholders, decision making or not, and seeks to ensure that net benefits to society outweigh net costs. MATE seeks to best meet decision makers' expectations for a system. Attributes (tangible and intangible) that are valuable to individual stakeholders, but not to society as a whole, are captured in the value-based approach in MATE. They are purposefully excluded in CBA. A challenge that the value-based approach in MATE brings about are framing issues that can arise when utility theory is applied to decision making stakeholders who have mandates to represent other stakeholders. For both aerospace and transportation domains, political vision and technical understanding of properties of different designs are important for decision making. A real feedback cycle between goal capture and low-fidelity technical modeling of different design options as suggested in MATE does not seem to exist in transportation planning. MATE seems useful as a tool to support improved communication about system expectations and technical options. Future research will need to address how value-based attribute capture can be performed in the typical complex stakeholder structure of transportation systems. Recognizing that problems of equity and value judgments are an inherent part of (some) technical decisions, the question of how to support a decision maker in expressing those attributes (even if difficult and controversial) and understanding different design concepts' impact on technical properties becomes part of the design engineer's job. / by Julia Nickel. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, 2008. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 81-86). / This thesis recommends an experimentation methodology which can be used to improve systems, processes and products. The proposed technique borrows insights from statistical prediction practices referred to as Ensemble Methods, to extend Adaptive One-Factor-at-a-Time (aOFAT) experimentation. The algorithm is developed for an input space where each variable assumes two or more discrete levels. Ensemble methods are common data mining procedures in which a set of similar predictors is created and the overall prediction is achieved through the aggregation of these units. In a methodologically similar way this study proposes to plan and execute multiple aOFAT experiments on the same system with minor differences in experimental setup, such as starting points, or order of variable changes. Experimental conclusions are arrived at by aggregating the multiple, individual aOFATs. Different strategies for selecting starting points, order of variable changes, and aggregation techniques are explored. The proposed algorithm is compared to the performance of a traditional form of experimentation, namely a single orthogonal array (full and fractional factorial designs), which is equally resource intensive. Comparisons between the two experimental algorithms are conducted using a hierarchical probability meta-model (HPM) and an illustrative case study. The case is a wet clutch system with the goal of minimizing drag torque. Across both studies (HPM and case study), it is found that the proposed procedure is superior in performance to the traditional method. / (cont.) This is consistent across various levels of experimental error, comparisons at different resource intensities, and through a wide array of response surfaces generated by the meta-model. At best, the proposed algorithm provides an expected value of improvement that is 15% higher than the traditional approach, at worst, the two methods are equally effective, and on average the improvement is about 10% higher. These findings suggest that the ensemble of aOFATs can be an effective and often preferred alternative to the use of orthogonal arrays for experimentation. This thesis also shows that it more effective to apply ensemble procedures to aOFAT versus applying ensemble techniques on multiple, highly-fractioned orthogonal designs (each being as resource intensive as a single aOFAT). A theoretical discussion explaining the reasons for the superior performance of the proposed algorithm supports the empirical findings. / by Nandan Sudarsanam. / Ph.D.

Thesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004. / Includes bibliographical references (leaves 66-75). / (cont.) of transcription factors and subsequently, induction of RNA processing (35% of genes incrementally induced) and kinases involved in protein phosphorylation. In the WT, the response was restricted to a transient repression of fundamental biochemical processes. Interestingly, a gene whose repression is known to mimic apoptosis was found to be repressed in the WT. The overwhelming induction of ribosomal protein synthesis genes in both WT and mgtl in response to MNNG is an unexpected result that could signify a successful recovery following wide-spread cellular damage. / Damage to DNA can occur by means of endogenous biochemical processes or exogenous chemicals such as alkylating agents. If left unrepaired, alkylated bases, most notably, O⁶ Methylguanine (O⁶MeG) can be mutagenic and cytotoxic to the cell. Luckily, DNA methyltransferase (encoded by the gene MGT1 in yeast), repairs this damage. By using transcriptional profiling as a tool, an attempt to elucidate the role of MGT1 has been made. First, the basal expression profile of the mgtl was established. Then, the response of wild-type (WI) yeast and yeast lacking MGT1 (mgt1) to the alkylating agent, MNNG was studied using exponentially growing WT and mgti cultures which were exposed to 30[mu]g/ml of MNNG for 10 to 60 minutes. Basal expression profile of yeast lacking MGT1 showed up-regulation of RETV7, a gene implicated in spontaneous mutagenesis. Response to MNNG was invoked immediately and was dramatic and widespread involving 30% of the genome in both WT and mgt1. Cell-cycle checkpoints, damage signal amplifiers, DNA repair genes (nucleotide excision repair, photoreactive repair, mismatch repair) and chromatin remodeling genes were induced. Genes involved in maintaining mitochondrial structure and mitochondrial genome were also induced. Intriguingly, RPN4, a key regulator of proteasomal system was found to be repressed. Environmental stress response genes were culled out to examine the effects of MNNG on WT and mgtl, more carefully. Temporal gene expression profiles in WT and mgtl were informative in delineating differences in the distinct responses mounted by WT and mgtl. The magnitude of response in mgt1 is more profound than in WT. The differences in the dynamic trends between the two suggest that mgt1 initiates a coordinated response involving repression / by Anoop Rao. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, 2006. / Includes bibliographical references (p. 313-330). / We explore corporate decisions and their solutions under uncertainty using engineering methods. Corporate decisions tend to be complex; they are interdisciplinary and defy programmable solutions. To address these challenges, we take an engineering approach. Our proposition is that as in an engineering system, corporate problems and their potential solutions deal with the behavior of systems. Since systems can be studied with experiments, we use Design of Experiments (DOE) to understand the behavior of systems within which decisions are made and to estimate the consequences of candidate decisions as scenarios. The experiments are a systematically constructed class of gedanken experiments comparable to "what if' studies, but organized to span the entire space of controllable and uncontrollable options. In any experiment, the quality of data is important. Grounded on the work of scholars, we develop a debiasing process for eliciting data. And consistent with our engineering approach, we consider the composite consisting of the organization, their knowledge, data bases, formal and informal procedures as a measurement system. We then use Gage theory from Measurement Systems Analysis (MSA) to analyze the quality of the measuring composite. / (cont.) To test this engineering approach to decision analysis, we perform four experiments. The first two are a set of simulations using a company surrogate. Using a progression of experiments, we simulate two major corporate decisions. Simulation data show that there is support for the validity of our decision analysis method. We then perform two in situ experiments: with a manufacturing company and with a technology services company. Findings from these company experiments also support the validity and efficacy of our decision analysis method. The company executives were very satisfied with our findings. Finally, we evaluate our method using method-evaluation criteria. The evaluation suggests that our DOE-based decision analysis method is valid. Unexpectedly every experiment resulted in near-decomposable systems at the scale we formulated our problems. Scaling of corporate decision problems at the appropriate level of abstraction and the resultant properties of their dynamic behavior are identified as areas of future work. This research breaks new ground in corporate decision-analysis as engineering and it furthers DOE and MSA research to a new domain and a new class of problems. / by Victor Tang. / Ph.D.