http://dspace.mit.edu:80 The DSpace@MIT digital repository system captures, stores, indexes, preserves, and distributes digital research material. http://hdl.handle.net/1721.1/49846 BA in Engineering - A Proposal Bucciarelli, Louis A proposal to provoke discussion of possibilities for the establishment of a Bachelor of Arts in Engineering at MIT. A proposal submitted to the d'Arbeloff Fund for Excellence in Education, MIT, Fall, 2008. Tue, 24 Nov 2009 20:26:35 GMT http://hdl.handle.net/1721.1/49845 Identifying Drug Effects via Pathway Alterations using an Integer Linear Programming Optimization Formulation on Phosphoproteomic Data Mitsos, Alexander Melas, Ioannis N. Siminelakis, Paraskeuas Chairakaki, Aikaterini D. Saez-Rodriguez, Julio Alexopoulos, Leonidas G. Understanding the mechanisms of cell function and drug action is a major endeavor in the pharmaceutical industry. Drug effects are governed by the intrinsic properties of the drug (i.e., selectivity and potency) and the specific signaling transduction network of the host (i.e., normal vs. diseased cells). Here, we describe an unbiased, phosphoproteomicbased approach to identify drug effects by monitoring drug-induced topology alterations. With the proposed method, drug effects are investigated under several conditions on a cell-type specific signaling network. First, starting with a generic pathway made of logical gates, we build a cell-type specific map by constraining it to fit 13 key phopshoprotein signals under 55 experimental cases. Fitting is performed via a formulation as an Integer Linear Program (ILP) and solution by standard ILP solvers; a procedure that drastically outperforms previous fitting schemes. Then, knowing the cell topology, we monitor the same key phopshoprotein signals under the presence of drug and cytokines and we re-optimize the specific map to reveal the drug-induced topology alterations. To prove our case, we make a pathway map for the hepatocytic cell line HepG2 and we evaluate the effects of 4 drugs: 3 selective inhibitors for the Epidermal Growth Factor Receptor (EGFR) and a non selective drug. We confirm effects easily predictable from the drugs’ main target (i.e. EGFR inhibitors blocks the EGFR pathway) but we also uncover unanticipated effects due to either drug promiscuity or the cell’s specific topology. An interesting finding is that the selective EGFR inhibitor Gefitinib is able to inhibit signaling downstream the Interleukin-1alpha (IL-1α) pathway; an effect that cannot be extracted from binding affinity based approaches. Our method represents an unbiased approach to identify drug effects on a small to medium size pathways and is scalable to larger topologies with any type of signaling perturbations (small molecules, 3 RNAi etc). The method is a step towards a better picture of drug effects in pathways, the cornerstone in identifying the mechanisms of drug efficacy and toxicity. Mon, 28 Sep 2009 22:58:59 GMT http://hdl.handle.net/1721.1/49844 A Unified Operating System for Clouds and Manycore: fos Modzelewski, Kevin Miller, Jason Belay, Adam Beckmann, Nathan Gruenwald, Charles, III Wentzlaff, David Youseff, Lamia Agarwal, Anant Single chip processors with thousands of cores will be available in the next ten years and clouds of multicore processors afford the operating system designer thousands of cores today. Constructing operating systems for manycore and cloud systems face similar challenges. This work identifies these shared challenges and introduces our solution: a factored operating system (fos) designed to meet the scalability, faultiness, variability of demand, and programming challenges of OSâ s for single-chip thousand-core manycore systems as well as current day cloud computers. Current monolithic operating systems are not well suited for manycores and clouds as they have taken an evolutionary approach to scaling such as adding fine grain locks and redesigning subsystems, however these approaches do not increase scalability quickly enough. fos addresses the OS scalability challenge by using a message passing design and is composed out of a collection of Internet inspired servers. Each operating system service is factored into a set of communicating servers which in aggregate implement a system service. These servers are designed much in the way that distributed Internet services are designed, but provide traditional kernel services instead of Internet services. Also, fos embraces the elasticity of cloud and manycore platforms by adapting resource utilization to match demand. fos facilitates writing applications across the cloud by providing a single system image across both future 1000+ core manycores and current day Infrastructure as a Service cloud computers. In contrast, current cloud environments do not provide a single system image and introduce complexity for the user by requiring different programming models for intra- vs inter-machine communication, and by requiring the use of non-OS standard management tools. Thu, 19 Nov 2009 22:58:59 GMT http://hdl.handle.net/1721.1/49843 Monitoring VIV fatigue damage on marine risers Mukundan, Harish Modarres-Sadeghi, Yahya Dahl, Jason Michael Hover, Franz S. Triantafyllou, Michael S. Long flexible cylinders (e.g., risers, tendons and mooring lines) exposed to the marine environment encounter ocean currents leading to vortex-induced vibration (VIV). These oscillations, often driven at high frequencies over extended periods of time, may result in structural failure of the member due to fatigue damage accumulation. Recent developments in instrumentation and installation of data acquisition systems on board marine risers have made accurate measurement of riser responses possible. This paper aims at using the data from these data acquisition devices (typically strain gages and accelerometers) in order to understand the evolution of the riser VIV, with the final aim of estimating the fatigue damage. For this purpose we employ systematic techniques to reconstruct riser VIV response using the data from the available sensors. The reconstructed riser response allows estimation of the dynamic axial stresses due to bending and consequently the estimates of the fatigue damage along the entire riser. The above methods can take into account the fatigue damage arising from complicated riser motions involving the presence of traveling waves even with the use of very few sensors. An alternate approach using a Van der Pol wake oscillator model is also explored to obtain fatigue life estimates caused by riser VIV. Tue, 28 Apr 2009 22:58:59 GMT