Cisplatin in yeast--repair of DNA adducts and binding of HMG domain proteins

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1995.Vita.Includes bibliographical references.by Megan Moore McA'Nulty.Ph.D

The khmer software package: enabling efficient nucleotide sequence analysis

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/

Unconventional Potential: An Analysis of Glacier Meltwater as a Means of Energy Generation

There are underutilized natural and renewable energy resources in Alaska. Glaciers are like rechargeable batteries, fueled by the snow of past eons, they provide a virtually endless supply of running water via the hydrocycle. In addressing the methods that Alaskan communities generate power now, sustainable technologies should be implemented to lessen the impacts that fossil fuels have had on Alaska’s pristine environment

Blackboard Agents for Mixed Initiative Management of Integrated Process-Planning/Production-Scheduling Solutions Across the Supply Chain

As companies increasingly customize their products, move towards smaller lot production and experiment with more flexible customer/supplier arrangements, they increasingly require the ability to respond quickly, accurately and competitively to customer requests for bids on new products and efficiently work out supplier/subcontractor arrangements for these new products. This in turn requires the ability to rapidly convert standard-based product specifications into process plans and quickly integrate new orders with their process plans into existing production schedules across the supply chain. This paper describes IP3S, a blackboard-based agent for supporting integrated process planning/production scheduling across the supply chain. IP3S agents support concurrent development and dynamic revision of integrated process-planning/productionscheduling solutions across the supply chain, maintenance of multiple problem instances and solutions across the supply chain, flexible user-oriented decision making, declarative representation of control information, the use of a common representation for exchanging information, coordination with other planning/scheduling agents and information sources, and ease of integration with legacy systems. The IP3S agent has been customized for and validated in the context of a large and highly dynamicmachine shop at Raytheon’s Andover manufacturing facility. Empirical results show an average performance improvement of 23% in solution quality over a decoupled approach to building process-planning/production-scheduling solutions

A Blackboard Architecture for Integrating Process Planning and Production Scheduling

As companies attempt to increase customization levels in their product offerings, move towards smaller lot production, and experiment with more flexible customer/supplier arrangements such as those made possible by electronic data interchange (EDI), they increasingly require the ability to (1) respond quickly, accurately, and competitively to customer requests for bids on new or modified products and (2) efficiently work out supplier/subcontractor arrangements for these products. This in turn requires the ability to (1) rapidly convert standard-based product specifications into process plans and (2) quickly integrate process plans for new orders into the existing production schedule to best accommodate the current state of the manufacturing enterprise. This paper describes the IP3S system, an Integrated Process Planning/Production Scheduling shell for agile manufacturing. IP3S is based on a blackboard architecture that supports concurrent development and dynamic revision of integrated process planning/production scheduling solutions along with powerful workflow management functionalities for “what-if ” development and maintenance of multiple problem assumptions and associated solutions. The IP3S blackboard architecture is designed to support coordinated development and revisions of solutions across the supply chain. The architecture is further shown to facilitate portability and integration with legacy systems. IP3S has been validated in the context of a large and highly dynamicmachine shop at Raytheon’s Andover manufacturing facility. Empirical evaluation shows an average performance improvement of 23% in solution quality over a decoupled approach to building process planning/production scheduling solutions

Development of an Integrated Process Planning/Production Scheduling Shell for Agile Manufacturing

Increased reliance on agilemanufacturing techniques has created a demand for systems to solve integrated process-planning and production-scheduling problems in large-scale dynamic environments. To be effective, these systems should provide user-oriented interactive functionality for managing the various user tasks and objectives and reacting to unexpected events. This paper describes the mixed-initiative problem-solving features of IP3S, an Integrated Process-Planning/Production-Scheduling shell for agile manufacturing. IP3S is a blackboard -based system that supports the concurrent development and dynamic revision of integrated process-planning and production-scheduling solutions and the maintenance of multiple problem instances and solutions, as well as other flexible user-oriented decision-making capabilities, allowing the user to control the scope of the problem and explore alternate tradeoffs (“what-if ” scenarios) interactively. The system is scheduled for initial deployment and evaluation in a large and highly dynamic machine shop at Raytheon’s Andover manufacturing facility

Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals

Cisplatin is a chemotherapeutic drug used to treat a variety of cancers. Both intrinsic and acquired resistance to cisplatin, as well as toxicity, limit its effectiveness. Molecular mechanisms that underlie cisplatin resistance are poorly understood. Here we demonstrate that deletion of the yeast CTR1 gene, which encodes a high-affinity copper transporter, results in increased cisplatin resistance and reduced intracellular accumulation of cisplatin. Copper, which causes degradation and internalization of Ctr1 protein (Ctr1p), enhances survival of wild-type yeast cells exposed to cisplatin and reduces cellular accumulation of the drug. Cisplatin also causes degradation and delocalization of Ctr1p and interferes with copper uptake in wild-type yeast cells. Mouse cell lines lacking one or both mouse Ctr1 (mCtr1) alleles exhibit increased cisplatin resistance and decreased cisplatin accumulation in parallel with mCtr1 gene dosage. We propose that cisplatin uptake is mediated by the copper transporter Ctr1p in yeast and mammals. The link between Ctr1p and cisplatin transport may explain some cases of cisplatin resistance in humans and suggests ways of modulating sensitivity and toxicity to this important anticancer drug