The spinning top

Several mathematicians have solved the problems of motion of the top and gyroscope most completely, but none of them have considered in their solutions the effects of the supporting gimbal rings upon the motion or the effects of a variable rotor speed. It is the purpose of this paper to investigate the top equations by two well known methods; namely, by the method of Lagrange and by the method of Jacobi; considering in both the dynamics of the gimbal rings and varying rotor speed --Introduction, page 3

Generalized Root-loci Theory For The Static Scherbius Drive

Generalized root-loci techniques, developed in the mid 70\u27s for squirrel cage motors, have been extended in the static Scherbius configuration to wound rotor, slip energy, recovery systems. This arrangement is now applied to large power drives in the 0.5 to 50 MW range. In this paper, general results applicable to all machines are presented for the open-loop control scheme, but only the sub synchronous mode of operation in which a voltage source type inverter is used is addressed. Copyright © 1984 by The Institute of Electrical and Electronics Engineers, Inc

CLOSED-LOOP DYNAMIC RESPONSE OF A STATIC SCHERBIUS DRIVE.

Generalized root-loci techniques, for squirrel-cage motors have been extended to wound-rotor, slip-energy-recovery systems (static Scherbius drive). The influence of a feedback control loop on these root loci is considered. General conclusions on Scherbius drive dynamics, as well as supporting experimental results, are presented

The Receptor AXL Diversifies EGFR Signaling and Limits the Response to EGFR-Targeted Inhibitors in Triple-Negative Breast Cancer Cells

The relationship between drug resistance, changes in signaling, and emergence of an invasive phenotype is well appreciated, but the underlying mechanisms are not well understood. Using machine learning analysis applied to the Cancer Cell Line Encyclopedia database, we identified expression of AXL, the gene that encodes the epithelial-to-mesenchymal transition (EMT)–associated receptor tyrosine kinase (RTK) AXL, as exceptionally predictive of lack of response to ErbB family receptor–targeted inhibitors. Activation of EGFR (epidermal growth factor receptor) transactivated AXL, and this ligand-independent AXL activity diversified EGFR-induced signaling into additional downstream pathways beyond those triggered by EGFR alone. AXL-mediated signaling diversification was required for EGF (epidermal growth factor)–elicited motility responses in AXL-positive TNBC (triple-negative breast cancer) cells. Using cross-linking coimmunoprecipitation assays, we determined that AXL associated with EGFR, other ErbB receptor family members, MET (hepatocyte growth factor receptor), and PDGFR (platelet-derived growth factor receptor) but not IGF1R (insulin-like growth factor 1 receptor) or INSR (insulin receptor). From these AXL interaction data, we predicted AXL-mediated signaling synergy for additional RTKs and validated these predictions in cells. This alternative mechanism of receptor activation limits the use of ligand-blocking therapies and indicates against therapy withdrawal after acquired resistance. Further, subadditive interaction between EGFR- and AXL-targeted inhibitors across all AXL-positive TNBC cell lines may indicate that increased abundance of EGFR is principally a means to transactivation-mediated signaling.United States. Dept. of Defense (Congressionally Directed Medical Research Programs, Breast Cancer Research Program (W81XWH-11-1-0088))National Science Foundation (U.S.) (Graduate Research Fellowship)Repligen Corporation (Fellowship in Cancer Research)National Cancer Institute (U.S.). Integrative Cancer Biology Program (1-U54-CA112967)David H. Koch Institute for Integrative Cancer Research at MIT (Frontier Research Program Initiator Award)National Institutes of Health (U.S.) (NIH R01-CA96504

Mixing in the North Atlantic tracer release experiment : observations and numerical simulations of Lagrangian particles and passive tracer

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Earth, Atmospheric, and Planetary Sciences, 1995.Includes bibliographical references (leaves 89-90).by Miles Aaron Sundermeyer.M.S

Understanding and targeting network-level sheddase regulation in invasive disease

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (p. 197-212).Regulated cell-surface proteolysis underpins key processes of cellular growth and motility in both physiological and pathological contexts. However, comprehending how multiple proteolytic events cohesively integrate to yield context-dependent cellular behavior remains a challenge in the fields of both protease biology and systems biology in general. This work begins to address that challenge by quantitatively investigating the integrated effect of multiple diverse proteolytic events and their interaction with cell-signaling pathways from a computational network perspective, particularly focusing on A Disintegrin and Metalloproteinases (ADAMs). ADAMs have been studied for decades as the principal cell-surface "sheddases" responsible for cleaving growth factor ligands and receptor tyrosine kinase ectodomains from the cell surface. However, activity regulation, feedback, and catalytic promiscuity impede our understanding of context-dependent sheddase function, and clinical trials targeting metalloproteinases in cancer have failed in part due to a poor understanding of the complex functions they mediate. This thesis outlines a conceptual framework for studying protease network biology (Chapter 1), describes novel experimental methods designed for such a framework (Chapters 2-3), and applies both to understand protease regulation in invasive disease (Chapter 4). Using combined measurement and computational modeling, we present a paradigm for monitoring and analyzing complex networks of protease activities that interface with signaling pathways to influence cellular migration in the invasive diseases of cancer and endometriosis. We find sheddase activity integrates with signaling pathways to direct cell migration, especially through concomitant proteolysis of both ligands and receptors. We find that indirect reduction of sheddase activity through kinase inhibition can lead to an accumulation of growth-factor receptors on the cell surface, consequently producing undesired compensatory signaling feedback. Thus, here we present a novel mechanism of rapid, protease-driven resistance to kinase inhibitors, and we subsequently demonstrate strategies for overcoming resistance through drug combinations. We develop a novel microfluidic platform to study protease activities in clinical samples, and apply the technology to study the peritoneal fluid from endometriosis patients. Results indicate joint dysregulation of sheddase activity with disease. Overall, this work provides a model for measuring, understanding, and targeting networks of proteases and the kinases with which they interact.by Miles Aaron Miller.Ph.D

The effect of initial conditions on the nonlinear evolution of perturbed interfaces driven by strong blast waves

In core-collapse supernovae, strong blast waves drive interfaces susceptible to Rayleigh-Taylor (RT), Richtmyer-Meshkov (RM), and Kelvin-Helmholtz (KH) instabilities. In addition, perturbation growth can result from material expansion in large-scale velocity gradients behind the shock front. Laser-driven experiments are designed to produce a strongly shocked interface whose evolution is a scaled version of the unstable hydrogen-helium interface in core-collapse supernovae such as SN 1987A. The ultimate goal of this research is to develop an understanding of the effect of hydrodynamic instabilities and the resulting transition to turbulence on supernovae observables that remain as yet unexplained. In this dissertation, we present a computational study of unstable systems driven by high Mach number shock and blast waves. Using multi-physics radiation hydrodynamics codes and theoretical models, we consider the late nonlinear instability evolution of single mode, few mode, and multimode interfaces. We rely primarily on 2D calculations but present recent 3D results as well. For planar multimode systems, we show that compressibility effects preclude the emergence of a regime of self-similar instability growth independent of the initial conditions (IC's) by allowing for memory of the initial conditions to be retained in the mix-width at all times. The loss of transverse spectral information is demonstrated, however, along with the existence of a quasi-self-similar regime over short time intervals. Aspects of the IC's are shown to have a strong effect on the time to transition to the quasi-self-similar regime. With higher-dimensional blast waves, divergence restores the properties necessary for establishment of the self-similar state, but achieving it requires very high initial characteristic mode number and high Mach number for the incident blast wave. We point to recent stellar calculations that predict IC's we find incompatible with self-similarity, and emphasize the consequent importance of developing a sound understanding of the initial modal structure in the supernova progenitor. For divergent and planar systems, the time-dependence of the drive is shown to impose an "effective box size" on the systems that limits the inverse cascade to large-scales. Our model explains the weak IC-dependence of this scale observed in some supernova calculations

Studies of lateral dispersion in the ocean

Thesis (Ph.D.)--Joint Program in Physical Oceanography (Massachusetts Institute of Technology, Dept. of Earth, Atmospheric, and Planetary Sciences, and the Woods Hole Oceanographic Institution), September 1998.Includes bibliographical references (p. 209-215).This thesis is written in two parts. The first part deals with the problem of lateral dispersion due to mesoscale eddies in the open ocean, and the interaction between the mesoscale strain and horizontal diffusion on spatial scales less than 10 km. The second and major part examines lateral dispersion over the continental shelf on scales of 100 m to 10 km and over time scales of 1-5 days. PART I: Lateral Dispersion and the North Atlantic Tracer Release Experiment Mixing and stirring of Lagrangian particles and a passive tracer were studied by comparison of float and tracer observations from the North Atlantic Tracer Release Experiment. Statistics computed from the NATRE floats were found to be similar to those estimated by Ledwell et al. (1998) from the tracer dispersion. Mean velocities computed from the floats were .. The NATRE observations were used to evaluate theoretical models of tracer and particle dispersal. The tracer dispersion observed by Ledwell et al. (1998) was consistent with an exponential growth phase for about the first 6 months and a linear growth at larger times. A numerical model of mesoscale turbulence that was calibrated with float statistics also showed an exponential growth phase of tracer and a reduced growth for longer times. Numerical results further show that Garrett's (1983) theory, relating the effective small-scale diffusivity to the rms strain rate and tracer streak width, requires a scale factor of 2 when the observed growth rate of streak length is used as a measure of the strain rate. This scale factor will be different for different measures of the strain rate, and may also be affected by temporal and spatial variations in the mesoscale strain field. PART II: Lateral Dispersion over the New England Continental Shelf Lateral dispersion over the continental shelf was examined using dye studies of the Coastal Mixing and Optics (CMO) program. Four experiments performed at intermediate depths and lasting 3 to 5 days were examined. In some cases, the dye patches remained fairly homogeneous both vertically and horizontally throughout an experiment. In other cases, significant patchiness was observed on scales ranging from 2-10 m vertically and a few hundred meters to a few kilometers horizontally. The observations also showed that the dye distributions were significantly influenced by shearing and straining on scales of 5-10 m in the vertical and 1-10 km in the horizontal. Superimposed on these larger-scale distortions were simultaneous increases in the horizontal second moments of the dye patches, with corresponding horizontal diffusivities based on a Fickian diffusion model of 0.3 to 4.9 m2 s-1. Analysis of the dye data in concert with shear estimates from shipboard ADCP observations showed that the existing paradigms of shear dispersion and dispersion by interleaving water-masses can not account for the observed diffusive spreading of the dye patches. This result suggests that some other mechanisms provided an additional diffusivity of order 0.15 to 4.0 m2 s-1. An alternative mechanism, dispersion by vortical motions caused by the relaxation of diapycnal mixing events, was proposed which could explain the observed dispersion in some cases. Order-of-magnitude estimates of the effective lateral dispersion due to vortical motions showed that this mechanism could account for effective horizontal diffusivities of order 0.01 to 1.1 m2 s-1. The upper range of these estimates were within the range required by the observations for two of the four experiments examined.by Miles Aaron Sundermeyer.Ph.D