Dissertations / Theses on the topic 'Spatial control'

Microtubules are long linear polymers that switch randomly between periods of growth and shrinkage, in a process known as dynamic instability. In vivo, dynamic instability is regulated by microtubule associated proteins (MAPs). One class of MAPS, the kinesins, move actively along microtubules, and some regulate microtubule dynamics. Kinesin-8, a kinesin, regulates microtubule dynamics in a wide range of eukaryotic cells. Schizosaccharomyces pombe (S. pombe) provides a well-characterised system in which to study microtubule regulation by MAPs. During interphase, microtubules grow from the centre of the rod-shaped cell until their plus ends reach and pause at the cell end, before undergoing catastrophe and shrinking. Shrinkage occurs predominantly at cell ends, even as the cell grows longer. I have studied the cell biology of kinesin-8-dependent interphase microtubule dynamics in S. pombe. I have identified an interphase-specific binding partner of S. pombe kinesin-8 (Klp5/Klp6); Mcp1. Mcp1 was required for Klp5/Klp6 accumulation at interphase microtubule plus ends and for Klp5/Klp6 induced interphase microtubule shrinkage. Tea2 (a kinesin) and Tip1 (CLIP170 orthologue) were found to stabilise interphase microtubules. Cells lacking Tea2 or Tip1 displayed interphase microtubules which, after reaching cell ends, underwent shrinkage sooner than wild type cells. Cells lacking Klp5/Klp6 or Mcp1 showed the opposite phenotype, microtubules which dwelt at cell ends longer than control cells before shrinking. Klp5/Klp6 accumulation on interphase microtubule plus ends steadily increased, peaking just before microtubule shrinkage. In contrast, Tea2 accumulated rapidly to newly nucleated interphase microtubule plus ends and was lost before microtubule shrinkage. I propose a model in which Tea2 prevents Klp5/Klp6 induced microtubule shrinkage until the interphase microtubule has grown to the cell end, where Tea2 is lost. At the cell end Klp5/Klp6 now induce shrinkage.

Virtual camera control is nowadays an essential component in many computer graphics applications. Despite its importance, current approaches remain limited in their expressiveness, interactive nature and performances. Typically, elements of directorial style and genre cannot be easily modeled nor simulated due to the lack of simultaneous control in viewpoint computation, camera path planning and editing. Second, there is a lack in exploring the creative potential behind the coupling of a human with an intelligent system to assist users in the complex task of designing cinematographic sequences. Finally, most techniques are based on computationally expensive optimization techniques performed in a 6D search space, which prevents their application to real-time contexts. In this thesis, we first propose a unifying approach which handles four key aspects of cinematography (viewpoint computation, camera path planning, editing and visibility computation) in an expressive model which accounts for some elements of directorial style. We then propose a workflow allowing to combine automated intelligence with user interaction. We finally present a novel and efficient approach to virtual camera control which reduces the search space from 6D to 3D and has the potential to replace a number of existing formulations.

The stabilization of a hip-actuated spatial double inverted pendulum can be considered as a problem of postural control of a humanoid robot. Based on an existing model of this underactuated mechanical system with four degrees of freedom, the ultimate objective is to design a suitable controller to achieve global stabilization around the unstable upright equilibrium position. This thesis presents a number of control algorithms and simulation results that provide either local stabilization or semi-global swing-up. For the effort of local stabilization in the vicinity of the upright equilibrium position, both an lqr controller and three types of linearization-based sliding mode control algorithms are presented. The region of convergence of the lqr controller is investigated. System performance and robustness against disturbances are compared for all controllers.In order to realize semi-global swing-up, two types of nonlinear sliding mode control approaches are explored for the swing up of the system in an attempt to bring the system into the region of convergence of the local linear controllers. The hybrid approach is proposed to switch from the swing-up controller to a local linear controller under certain conditions in the vicinity of the upright equilibrium to complete the stabilization effort. However, despite extensive tuning of the controllers, it has not been possible to achieve global stabilization with such an approach. Further investigation is needed in order to resolve this issue. The main contribution of this thesis is a successful extension of existing 2-dimensional sliding mode control algorithms into 3-D for the control of the spatial double inverted pendulum. The linearization-based sliding mode controllers serve as alternatives to lqr for local stabilization. The nonlinear sliding mode controllers are able bring the system from a configuration far from the upright equilibrium to the vicinity of the unstable upright equilibrium in semi-global swing-up.
La stabilisation d'un double pendule spatiale inversé actionné à la hanche peut-être considérée comme un problème de contrôle de la posture d'un robot humanoïde. Basé sur un modèle existant de ce système mécanique sous-actionné avec quatre degrés de liberté, l'ultime objectif est de concevoir un régulateur approprié pour obtenir une stabilisation globale autour de l'instable position d'équilibre debout. Cette thèse présente un certain nombre d'algorithmes de contrôle et les résultats de simulation qui permettent une stabilisation locale ou semi-globale pivoter-vers-le-haut. Pour l'effort de stabilisation locale dans le voisinage de la position d'équilibre en position verticale, à la fois un contrôleur lqr et trois types de linéarisation basée sur des algorithmes de contrôle de mode glissant sont présentés. La région de la convergence du contrôleur lqr est étudiée. La performance et la robustesse du système sont comparées pour tous les contrôleurs. Afin de réaliser la strateǵie semi-globale pivoter-vers-le-haut, deux types d'approches de commande non linéaire de mode glissant sont explorés pour le balancement du système dans un essai pour amener le système dans la région de convergence locale des contrôleurs linéaires. L'approche hybride est proposée pour passer du contrôleur pour pivoter-vers-le-haut à un contrôleur linéaire local sous certaines conditions dans le voisinage de l'équilibre en position verticale afin de compléter l'effort de stabilisation. Toutefois, malgré des ajustements des contrôleurs, il n'a pas été possible de parvenir à une stabilisation globale avec une telle approche. Une enquête plus profonde est nécessaire pour résoudre ce problème. La contribution principale de cette thèse est la réussite une d'extension d'algorithmes de commande de 2-dimensions de mode glissant qui existent pour le cas de 3-D pour le contrôle du double pendule inversé spatial. Les contrôleurs de mode glissant basés sur un modèle du système linéarisé servent comme alternatives au contrôleur lqr pour la stabilisation locale. Les contrôleurs de mode glissant non-linéaires sont capables, à partir d'une configuration loin de l'équilibre de mettre le système dans la proximité de l'équilibre debout vertical utilisant le principe semi-global pivoter-vers-le-haut.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.
Includes bibliographical references (p. 60-65).
Inertial cavitation has been implicated as the primary mechanism for a host of emerging applications. In all these applications, the main concern is to induce cavitation in perfectly controlled locations in the field; this means specifically to be able to achieve cavitation threshold at the geometrical focus of the transducer without stimulating its near field. In this study, we make use of dual-frequency methods to preferentially lower the cavitation threshold at the focus relative to the rest of the field. One family of dual-frequency driving waveforms is evaluated in a bubble model incorporating rectified diffusion. Theoretical predictions based on Sokka's work (Sokka 2003a) are confirmed in vitro using Optison[TM], a commercially available contrast agent. The performance of the rest of acoustic field in suppressing cavitation when cavitation is induced at the focus is investigated theoretically and checked experimentally. This first part shows that dual-frequency phased arrays could be used to precisely control cavitation. Cavitation threshold is proved to be 1.2 times higher in the near field than at the focus. One of the main limitations of the aforementioned protocol is that it is tightly controlled. As an example, Optison[TM] has a mean bubble size of 2 - 4.5 [micro]m, which means that the initial bubble radii will fall in this range. Since cavitation threshold has been proved to depend on this parameter, using ultrasound contrast agents allows for more predictable results. Therefore, in the second half of this study, we propose a focused ultrasound protocol that induces and monitors gas bubbles at the focus and allows for ex vivo validation of the aforementioned theoretical results. The experiments involve fresh rabbit tissue and a statistical analysis is performed over data collected from back muscle.
(cont.) Moreover, the experimental apparatus is designed to be MRI-compatible to make future in vivo assessments feasible. This second half of the study demonstrates that the theoretical predictions made earlier can reliably be used to predict dual-frequency cavitation thresholds. It also suggests that clinical use of dual-frequency excitations might be a solution to the problem of spatial control of cavitation.
by Thomas P. Gauthier.
S.M.

Iterative learning control (ILC) is a high performance method for systems operating in a repetitive manner, which aims to improve tracking performance by learning from previous trial information. In recent years research interest has focused on generalizing the task description in order to achieve greater performance and flexibility. In particular, researchers have addressed the ease of tracking only at a single, or a collection of time instants. However, there still remain substantial open problems, such as the choice of the time instants, the need for system constraint handling, and the ability to release explicit dependence on time. A number of ILC methods have tackled the latter problem, loosely termed spatial ILC, but are all application specific and limited in scope. The aim of this thesis is to unlock this potential, and the specific contributions are as follows: first a mechanism to optimize the time instants at the critical tracking positions within point-to-point tracking is developed. This is achieved by embedding an additional cost function and deriving a ‘Two Stage’ design framework to yield an iterative algorithm which minimizes control effort as well as guaranteeing high performance tracking. This approach is based on norm optimal ILC and gradient minimization. Then the task description is further generalized by expanding the formulation to embed via-point constraint and linear planar constraints. This embeds the incorporation of various design objectives including spatial path tracking in a general class of systems, and a mixed form of system constraints are added into this framework. An algorithmic ILC solution is derived using the successive projection method to achieve high performance tracking of the design objectives. Finally, the Two Stage design framework and the generalized ILC framework are combined together to yield the first spatial ILC algorithm capable of optimizing an additional cost function whilst completing the spatial path tracking objective for a general class of systems. All proposed algorithms are verified experimentally on a gantry robot platform, whose experimental results demonstrate their practical efficacy and ability to substantially widen the scope of the current ILC framework.

The life-history and infection parameters of the entomopathogenic nematodes Steinernema feltiae (Filipjev)(Nematoda:Rhabditida) and Heterorhahditis megidis (Poinar, Jackson & Klein)(Nematoda:Rhabditida) were examined to provide specific details for the construction of mathematical SI models for biological control of soil insect pests. Laboratory experiments using the Greater Waxmoth, Galleria mellonella as the model host were undertaken to specifically examine the transmission behaviour of infective juvenile nematodes. The proportion of infective juveniles of S. feltiae which infected hosts was dependent on time. Previous studies declared that the proportion of infective juveniles which can infect is static, however, over a period of 5 days most of the infective juveniles infected hosts, demonstrating that the proportion infecting is dynamic. Infection of hosts by both species of nematode was compared using two mathematical representations of the transmission rate. Whereas the most parsimonious form of transmission for H. megidis was the linear Mass Action function, it was evident that, when measured at the individual nematode scale, S. feltiae transmission was non-linear. I postulated that this functional difference is due to the biology of the two species of nematodes. The subsequent effect of including the non-linear response on model predictions were investigated and it was demonstrated that the dynamics of the host nematode interaction became less stable. Spatial models of S. feltiae infection were parameterised from laboratory experiments, and control prediction of these models examined. The horizontal rate of dispersal through sand columns was determined in the presence and absence of hosts. Infective juveniles were found to disperse preferentially towards hosts. The predicted dynamics of pest control using the spatial moqel were highly dependent on the degree of nematode dispersal, host dispersal and the attraction of nematode infective juveniles towards hosts. The overall findings of this thesis have been placed in the context of epidemiological models created elsewhere, and predict that entomopathogenic nematodes may be targeted to specific pest systems with a high degree of success. An understanding of the infection biology of these nematode species is crucial in determining how and when pests may be controlled, and equally importantly, which systems successful control is not predicted.

This thesis represents the work that has been done by the author during his Master of Engineering Science candidature in the area of vibration control of flexible structures at the School of Mechanical Engineering, The University of Adelaide, between March 2003 and June 2004. The aim of this research is to further extend the application of the Spatial Control Approach for two-dimensional flexible structures for attenuating global structural vibration with the possible implication of reduction in noise radiation. The research was concentrated on a simply supported thin flexible plate, using piezoelectric ceramic materials as actuators and sensors. In this work, active controllers were designed for the purpose of controlling only the first five vibration modes (0-500Hz) of the plate. A spatial controller was designed to minimize the total energy of the spatially distributed signal, which is reflected by the spatial H2 norm of the transfer function from the disturbance signal to the vibration output at every point over the plate. This approach ensures the vibration contributed by all the in bandwidth (0-500 Hz) vibration modes is minimized, and hence is capable of minimizing vibration throughout the entire plate. Within the control framework, two cases were considered here; the case when the prior knowledge of the incoming disturbance in terms of reference signal is vailable and the case when it is not available. For the case when the reference signal is available, spatial feedforward controller was designed; whereas for the case when the reference signal is not available, spatial feedback controller was designed to attenuate the global disturbance. The effectiveness of spatial controllers was then compared with that of the standard point-wise controllers numerically and experimentally. The experimental results were found to reflect the numerical results, and the results demonstrated that spatial controllers are able to reduce the energy transfer from the disturbance to the structural output across the plate in a more uniform way than the point-wise controllers. The research work has demonstrated that spatial controller managed to minimize the global plate vibrations and noise radiation that were due to the first five modes.
Thesis (M.Eng.Sc.)--School of Mechanical Engineering, 2005.

El control dinámico y determinístico de la luz en una escala espacial por debajo de la longitud de onda es un requisito clave para ampliar los conceptos y las funcionalidades de la macro-óptica hasta la escala nanométrica. Un mayor nivel de control también tendrá implicaciones importantes en nuestra comprensión de los fenómenos ópticos en la nanoescala. Uno de los principales problemas en nano-óptica tiene como objetivo describir cómo y con qué precisión es posible controlar la distribución espacial de la luz de forma dinámica en la nanoescala. Desafortunadamente, un límite fundamental de la física – el límite de difracción de la luz – afecta nuestra capacidad de seleccionar ópticamente puntos separados por menos de media longitud de onda de la luz. El campo de la plasmónica ofrece una oportunidad única para cerrar la brecha entre el límite de difracción y la escala nanométrica. Nanoantenas metálicas pueden acoplarse eficientemente a luz propagante y focalizarla en volúmenes nanométricos, y viceversa. Además, estas nanoantenas prometen mejorar significativamente la eficiencia de procesos como le fotodetección, la emisión de luz, sensores, transferencia de calor, y espectroscopía a la escala nanométrica. Aprender a controlar de forma precisa la respuesta óptica de estas nanoantenas representa un enfoque muy prometedor para controlar la distribución espacial y temporal de la luz a la escala nanométrica. Tradicionalmente, se han desarrollado dos principales estrategias para el control de la respuesta óptica de nanoantenas plasmónicas: la primer estrategia (estrategia estática) tiene como objetivo la optimización del diseño geométrico de las nanoantenas acorde a su aplicación, mientras que la segunda estrategia (estrategia dinámica) tiene como objetivo la modulación reversible del campo cercano de una nanoestructura dada a través de la manipulación de la luz de excitación en el tiempo y el espacio. El trabajo presentado en esta Tesis extiende el estado del arte de estas dos estrategias, y desarrolla nuevas herramientas, tanto experimentales como teóricas, para ampliar el nivel de control que tenemos sobre la distribución espacial de la luz debajo del límite de difracción. Después de presentar una visión general de los principios básicos de nano-óptica y de la óptica de lo plasmones de superficie, el Capítulo 1 repasa los avances en el control de la respuesta óptica de nanoestructuras metálicas – sea por una estrategia estática o dinámica – en el momento en que se inició este trabajo de investigación. La modificación de la geometría y las dimensiones de las nanpartículas metálicas sigue siendo un ingrediente fundamental para controlar las resonancias plasmónicas y los campos de luz a la escala nanométrica. Como ejemplos novedosos de control estático, por lo tanto, los Capítulos 2 y 3 estudian nuevos diseños de estructuras plasmónicas con capacidades sin precedentes de modelar campos de luz a la escala nanométrica, en particular un diseño fractal y una nanoantena unidireccional tipo Yagi-Uda. Los Capítuols 4 y 5 describen una nueva herramienta teórica y experimental para el control dinámico y determinístico de la respuesta óptica de nanoantenas basada en la modulación espacial de la fase de la luz de excitación: el campo óptico cercano, que resulta de la interacción entre la luz y las nanoestructuras plasmónicas, es normalmente determinado por la geometría del sistema metálico y las propiedades de la luz incidente, como su longitud de onda y su polarización; sin embargo, el control exacto y dinámico del campo óptico cercano debajo de límite de difracción de la luz – independientemente de la geometría de la nanoestructura – es también un ingrediente importante para el desarrollo de futuros dispositivos nano-ópticos y para ampliar los conceptos y las funcionalidades de la óptica macroscópica a la escala nanométrica. Finalmente, la Conclusión resume los resultados de este trabajo y ofrece una visión general de algunos estudios paralelos a esta tesis. Algunas de las observaciones finales permiten echar un vistazo a las perspectivas y estrategias futuras para complementar el control estático y el control dinámico en una única herramienta, que podría avanzar enormemente nuestra capacidad de controlar la respuesta óptica de nanoantennas debajo del límite de difracción.
El control dinámico y determinístico de la luz en una escala espacial por debajo de la longitud de onda es un requisito clave para ampliar los conceptos y las funcionalidades de la macro-óptica hasta la escala nanométrica. Un mayor nivel de control también tendrá implicaciones importantes en nuestra comprensión de los fenómenos ópticos en la nanoescala. Uno de los principales problemas en nano-óptica tiene como objetivo describir cómo y con qué precisión es posible controlar la distribución espacial de la luz de forma dinámica en la nanoescala. Desafortunadamente, un límite fundamental de la física – el límite de difracción de la luz – afecta nuestra capacidad de seleccionar ópticamente puntos separados por menos de media longitud de onda de la luz. El campo de la plasmónica ofrece una oportunidad única para cerrar la brecha entre el límite de difracción y la escala nanométrica. Nanoantenas metálicas pueden acoplarse eficientemente a luz propagante y focalizarla en volúmenes nanométricos, y viceversa. Además, estas nanoantenas prometen mejorar significativamente la eficiencia de procesos como le fotodetección, la emisión de luz, sensores, transferencia de calor, y espectroscopía a la escala nanométrica. Aprender a controlar de forma precisa la respuesta óptica de estas nanoantenas representa un enfoque muy prometedor para controlar la distribución espacial y temporal de la luz a la escala nanométrica. Tradicionalmente, se han desarrollado dos principales estrategias para el control de la respuesta óptica de nanoantenas plasmónicas: la primer estrategia (estrategia estática) tiene como objetivo la optimización del diseño geométrico de las nanoantenas acorde a su aplicación, mientras que la segunda estrategia (estrategia dinámica) tiene como objetivo la modulación reversible del campo cercano de una nanoestructura dada a través de la manipulación de la luz de excitación en el tiempo y el espacio. El trabajo presentado en esta Tesis extiende el estado del arte de estas dos estrategias, y desarrolla nuevas herramientas, tanto experimentales como teóricas, para ampliar el nivel de control que tenemos sobre la distribución espacial de la luz debajo del límite de difracción. Después de presentar una visión general de los principios básicos de nano-óptica y de la óptica de lo plasmones de superficie, el Capítulo 1 repasa los avances en el control de la respuesta óptica de nanoestructuras metálicas – sea por una estrategia estática o dinámica – en el momento en que se inició este trabajo de investigación. La modificación de la geometría y las dimensiones de las nanpartículas metálicas sigue siendo un ingrediente fundamental para controlar las resonancias plasmónicas y los campos de luz a la escala nanométrica. Como ejemplos novedosos de control estático, por lo tanto, los Capítulos 2 y 3 estudian nuevos diseños de estructuras plasmónicas con capacidades sin precedentes de modelar campos de luz a la escala nanométrica, en particular un diseño fractal y una nanoantena unidireccional tipo Yagi-Uda. Los Capítuols 4 y 5 describen una nueva herramienta teórica y experimental para el control dinámico y determinístico de la respuesta óptica de nanoantenas basada en la modulación espacial de la fase de la luz de excitación: el campo óptico cercano, que resulta de la interacción entre la luz y las nanoestructuras plasmónicas, es normalmente determinado por la geometría del sistema metálico y las propiedades de la luz incidente, como su longitud de onda y su polarización; sin embargo, el control exacto y dinámico del campo óptico cercano debajo de límite de difracción de la luz – independientemente de la geometría de la nanoestructura – es también un ingrediente importante para el desarrollo de futuros dispositivos nano-ópticos y para ampliar los conceptos y las funcionalidades de la óptica macroscópica a la escala nanométrica. Finalmente, la Conclusión resume los resultados de este trabajo y ofrece una visión general de algunos estudios paralelos a esta tesis. Algunas de las observaciones finales permiten echar un vistazo a las perspectivas y estrategias futuras para complementar el control estático y el control dinámico en una única herramienta, que podría avanzar enormemente nuestra capacidad de controlar la respuesta óptica de nanoantennas debajo del límite de difracción.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1999.
Includes bibliographical references (leaves 201-211).
Adhesion of many cell types to the extracellular matrix or to synthetic bioactive surfaces is mediated by transmembrane integrin receptors. Integrin clustering is believed to be closely associated with focal contact formation and signaling, as assessed by the behavior of cells on surfaces presenting relatively uniform ligand distributions. It has therefore been hypothesized that controlled clustering of 2, 3.....n integrins might be achieved by controlling the spatial distribution of adhesion ligands on biomaterial surfaces. Substrates were prepared on which cell-surface interactions are controlled by modifying non-adhesive poly(ethylene oxide) (PEO) hydrogels with the minimal cell-adhesion peptide sequence GRGDY (RGD). The peptide is tethered to the hydrogel surfaces via star PEO molecules, producing surfaces on which the ligands are presented to cells in "clusters", or domains of high concentration. The substrates are compared with others on which the RGD peptide is uniformly distributed. Control of the RGD cluster size was achieved by varying the relative concentrations of reactants in solution. The binding of RGD-modified stars to surfaces was found to be a non-linear function of its concentration in solution and degree of modification, and is reasonably explained by a Langmuir model of competitive adsorption. Quantitative techniques for visualizing the ligand distribution on the surface were developed, and indicated that surfaces to which ligands had been tethered via star molecules showed a significant deviation from normal, random distribution. Thus, control of the ligand spatial distribution was achieved. In addition, preliminary biological testing suggests that substrates on which adhesion ligands are presented to cells in a clustered format produces more physiological behaviour than those on which ligands are uniformly distributed at the same average ligand density. Thus, we have fabricated surfaces which, because of their resistance to non-specific cell interactions and the control of specific interactions at the molecular level, can serve as a model for artificial matrix development and can be used for fundamental in vitro studies.
by Gillian L. Brown.
Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.
DVD-ROM contains 4 supplemental movies (mov.) for Chapter III.
Both MIT Institute Archives and Science Library copy: with DVD-ROM.
Cataloged from PDF version of thesis.
Includes bibliographical references.
During mitosis, cells must accurately segregate their genome in order to produce healthy daughter cells. In budding yeast, cells align their anaphase spindle along a predetermined axis of division in order to partition their genome into the daughter cells. In the event that the spindle becomes mispositioned, cells will prevent exit from mitosis by inhibiting the mitotic exit network (MEN). The MEN functions to regulate the localization of the essential phosphatase Cdc 4. Control of the MEN by spindle position is established through MEN inhibitory signals in the mother cell compartment (such as the kinase Kin4), MEN promoting signals in the bud (such as Ltel) and a GTPase sensor (Tem1) that moves between them. While the molecular functions of Kin4 and Tem1 are well defined, the function of Ltel has remained unclear. In the first part of this thesis I attribute a function to Ltel in promoting exit from mitosis. I show that Ltel functions to prevent Kin4 from inappropriately localizing to SPBs (spindle pole bodies) in the bud cell compartment. I find that these two proteins interact and that the Nterminus of Kin4 mediates this interaction. This work highlights the importance of spatial restriction of Ltel in the bud and Kin4 in the mother for the proper execution of chromosome segregation in anaphase. In the second part of this thesis I investigate the role of cytoplasmic microtubules in spatial regulation of the MEN. It has been proposed that spatial regulation of the MEN functions as a checkpoint that requires contact between cytoplasmic microtubules (cMTs) and the budneck to arrest cells in anaphase. Loss of cMT-budneck contact was reported to lead to checkpoint failure resulting in anucleate and multinucleate cells. In contradiction to these results, I find that Cdc14 release is responsible for the loss of cMT-budneck interactions that precede inappropriate exit from mitosis. Lastly, through the generation of cells with two nuclei, I show that the coupling of spindle position to exit from mitosis is established in a dual manner through both inhibitory signals in mother cell compartment and through activating signals in the bud.
by Jill E. Falk.
Ph. D.

It is now widely acknowledged that spatial structure and hence the spatial position of host populations plays a vital role in the spread of infection. In this work I investigate an ensemble of techniques for understanding the stochastic dynamics of spatial and discrete epidemic processes, with especial consideration given to SIR disease dynamics for the Levins-type metapopulation. I present a toolbox of techniques for the modeller of spatial epidemics. The highlight results are a novel form of moment closure derived directly from a stochastic differential representation of the epidemic, a stochastic simulation algorithm that asymptotically in system size greatly out-performs existing simulation methods for the spatial epidemic and finally a method for tackling optimal vaccination scheduling problems for controlling the spread of an invasive pathogen.

ITC/USA 2010 Conference Proceedings / The Forty-Sixth Annual International Telemetering Conference and Technical Exhibition / October 25-28, 2010 / Town and Country Resort & Convention Center, San Diego, California
Direct spatial antenna modulation (DSAM) is a new approach to phased array control that opens up new "smart antenna" architecture possibilities. The DSAM technique leverages the inherent spatial differences of excitation in an antenna in a novel way to achieve the equivalent of conventional modulation and beam control effects. Smart antenna techniques are of potentially increasing importance to test range operations given a trend toward more flexible, internetworked, and autonomous test activities. The DSAM technique has been demonstrated through several generations of analysis, simulation, and prototyping, but has previously only been applied to narrowband antenna designs. Furthermore, the IQ DSAM approach in particular has not been previously implemented in hardware. This paper details the application of IQ DSAM to achieve wideband phase control using a commercial off the shelf (COTS) antenna. The phase control performance of IQ DSAM over a range of 1.5 GHz to 4 GHz is measured across relative field control angles of +/- 45 degrees. The measured IQ DSAM performance is compared to what could be expected from a conventional phased array element control architecture.

Functional surfaces interact with surrounding substances, such as another solid, a liquid, gas, acoustic or electromagnetic waves etc., in order to achieve a required effect. Surfaces are increasingly required with complex forms and ever-increasing precision, can be very challenging to make. In particular, mid-spatial frequency (MSF) ripples are difficult to avoid for various reasons, but especially the changing misfit between a polishing tool as it moves across a complex workpiece surface. Current surface processing techniques are limited in their ability effectively to control or remove MSF errors for the reasons: i) lack of the ability to conform to the complex working surfaces, including grinding and lapping; ii) low material removal rate, such as Magnetorheological finishing and fluid jet polishing; iii) high cost (typically for ion beam figuring); iv) constrains for the size of the workpiece, such as stressed lap polishing and stressed mirror polishing. This thesis reports on the development of enhanced techniques, both to understand the formation of MSF errors on aspherical surfaces, and to mitigate them, increasing overall production efficiency. This has been achieved by: 1) Development of a novel stressed mirror technique providing a universal platform for aspheric experiments. 2) Results and analysis of kinetic simulations to understand the working mechanism of the non-Newtonian material under different stress conditions. 3) Developing a non-Newtonian tool, used in a novel way, to manage misfit between an aspherical workpiece and the tool surface. Peak-to-valley MSF error on an off-axis aspheric part better than 10 nm has been achieved. 4) Using bonded diamond pads, with various diamond sizes in a ‘grolishing’ (hybrid between grinding and polishing) procedure to achieve extremely high material removal rates (up to 267 mm3 /min), and control MSF errors 10 nm peak-to-valley, on flat and spherical surfaces. 5) Providing an aspherical surface after grolishing by a 3-microns diamond pad, with texture of sufficiently quality to be measured directly by an interferometer, which usually be achieved only after polishing.

Thesis advisor: Mary T. Crane
Thesis advisor: Andrew Sofer
Spatial Dramaturgy and Domestic Control in Early Modern Drama explores the social components of early modern domestic architecture and the spatial practices that helped to dramatize them. Each chapter examines a particular domestic feature—doors, windows, galleries, studies—and considers its role in a variety of early modern plays. Methodologically, I bridge the gaps between literary study, dramaturgy, and history by analyzing the palimpsest of the physical stage (e.g., the upper playing balcony) and the fictional spaces produced in performance (e.g., Juliet’s window). My work takes its influence from literary scholars, primarily Lena Cowen Orlin and Patricia Fumerton; theater historians, primarily Tim Fitzpatrick, Alan Dessen, Leslie Thompson, and Mariko Ichikawa; and architectural historians, primarily Mark Girouard and Alice T. Friedman. Bringing together these fields of study allows me to reconsider the theory of the unlocalized early modern stage that has largely dominated scholarly and theatrical approaches to early modern theater for half a century. In my first chapter, “Doors and Keys: Enclosure and Spatial Control,” I argue that doors and keys operate in productive tension with the spatial flexibility of the “unlocalized” stage, troubling the fantasy of domestic spatial control in plays such as A Woman Killed With Kindness and The Comedy of Errors. In my second chapter, “Windows: Locus, Platea, and Contested Authority,” I explore the way window scenes in plays such as Romeo and Juliet and Women Beware Women provide a liminal space between house and street where the tiring house façade and the apron of the stage could intersect. My third chapter, “Galleries: Feigned Soliloquy and Interiority,” shows how playwrights used gallery settings to stage feigned soliloquy, exposing the limits of private speech and the struggle to access another person’s most inner thoughts. My final chapter, “Studies: Hauntings and Impossible Privacy,” looks at plays that feature ghosts or devils in studies, such as Doctor Faustus and Friar Bacon and Friar Bungay, to argues that these supernatural elements reflect the ease with which playwrights could violate presumably protected spaces. In turn, these hauntings explore the danger presented in early modern humanism: that the most haunted place of all is one’s own mind
Thesis (PhD) — Boston College, 2015
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: English

In this thesis, a mathematical model for tissue growth under curvature control and directed cell guidance is derived. The model extends previous mathematical work by adding a tangential cell velocity. A numerical solver is implemented to solve the model and the solutions show that new cases of tissue growth can now be simulated thanks to the extension derived in this thesis. Finally, the model is fit to data on bone pore infilling and is used to examine hypotheses about atypical tissue growth.

As demanded by applications such as GIS, CAD, ecology analysis, and space research, efficient spatial data access methods have attracted much research. Especially, moving object management and continuous spatial queries are becoming highlighted in the spatial database area. However, most of the existing spatial query processing approaches were designed for single-user environments, which may not ensure correctness and data consistency in multiple-user environments. This research focuses on designing efficient concurrent operations on spatial datasets. Current multidimensional data access methods can be categorized into two types: 1) pure multidimensional indexing structures such as the R-tree family and grid file; 2) linear spatial access methods, represented by the Space-Filling Curve (SFC) combined with B-trees. Concurrency control protocols have been designed for some pure multidimensional indexing structures, but none of them is suitable for variants of R-trees with object clipping, which are efficient in searching. On the other hand, there is no concurrency control protocol designed for linear spatial indexing structures, where the one-dimensional concurrency control protocols cannot be directly applied. Furthermore, the recently designed query processing approaches for moving objects have not been protected by any efficient concurrency control protocols. In this research, solutions for efficient concurrent access frameworks on both types of spatial indexing structures are provided, as well as for continuous query processing on moving objects, for multiple-user environments. These concurrent access frameworks can satisfy the concurrency control requirements, while providing outstanding performance for concurrent queries. Major contributions of this research include: (1) a new efficient spatial indexing approach with object clipping technique, ZR+-tree, that outperforms R-tree and R+-tree on searching; (2) a concurrency control protocol, GLIP, to provide high throughput and phantom update protection on spatial indexing with object clipping; (3) efficient concurrent operations for indices based on linear spatial access methods, which form up the CLAM protocol; (4) efficient concurrent continuous query processing on moving objects for both R-tree-based and linear spatial indexing frameworks; (5) a generic access framework, Disposable Index, for optimal location update and parallel search.
Ph. D.

La prochaine génération de télescopes spatiaux devra repousser les limites des technologies actuelles afin d’accroitre les performances techniques et opérationnelles. Dans le cas d’observations difficiles, l'utilisation de plus grandes ouvertures des miroirs primaires est essentielle pour obtenir la résolution optique et la sensibilité requises. Toutefois, les grandes ouvertures primaires induisent un certain nombre de défis techniques tels que la masse, le volume et la raideur du miroir. La masse et le volume doivent rester acceptables par rapport au lanceur et la raideur du miroir, qui diminue avec l’augmentation du diamètre du miroir, doit être suffisante afin que les performances ne soient pas altérées par les déformations statiques et dynamiques. Pour surmonter ces limitations, des configurations de miroirs déformables comportant des éléments de contrôle actifs sont étudiées pour les futurs télescopes spatiaux. Les actionneurs piézoélectriques, qui répondent aux exigences de puissance massique et de bande passante, peuvent être utilisés comme éléments de contrôle actifs intégrés dans la structure de miroir. Toutefois, ces actionneurs montrent en fonctionnement en boucle ouverte des comportements non linéaires indésirables, comme le fluage et l'hystérésis, qui peuvent conduire à des inexactitudes indésirables et limiter les performances des systèmes. Par conséquent, pour les miroirs déformables activés par des actionneurs piézoélectriques, la compensation des non linéarités dans les actionneurs piézoélectriques est indispensable.La conception d’un miroir léger, compact et déformable à raideur adéquate est un défi très important pour les télescopes spatiaux mais n'est pas abordée dans cette thèse. Cette thèse porte sur le contrôle de surfaces de miroirs déformables actionnés par des actionneurs piézoélectriques et en particulier sur la compensation du fluage et de l'hystérésis dans les actionneurs piézoélectriques. La technologie de miroir actif étudié (avec des pieds activés, type miroir fakir) requiert un grand nombre d’actionneurs afin de tenir les exigences en termes de planéité de surface et ne permet pas un contrôle en boucle fermée de chaque actionneur (ce type de contrôle est trop exigeant en nombre de capteurs). La compensation du fluage et de l’hystérésis est donc réalisée en boucle ouverte et s’appuie sur des modèles précis des non linéarités à compenser et sur l’implémentation de modèles inverses. Un support d’étude expérimental a été élaboré au cours de la thèse afin de valider les études théoriques par des résultats expérimentaux. Il représente une partie d’un miroir de grande taille et consiste en une plaque de verre circulaire de diamètre 300mm dont la surface peut être actionnée par 7 actionneurs piézoélectriques annulaires.Les premières chapitres de la thèse concernent l’étude de la compensation en boucle ouverte du fluage et de l’hystérésis dans un seul actionneur qui est alors considéré comme un système SISO (single input – single output). Dans le dernier chapitre de la thèse, le fluage et de l’hystérésis sont compensés dans 3 actionneurs simultanément, ceux-ci formant un système MIMO (multi input – multi output). Les apports de la thèse concernent le développement de nouveaux modèles directs et inverses de fluage et d’hystérésis qui ont été validés par des expérimentations réalisées dans un contexte difficile de par la faible étendue des amplitudes de déplacement ( de l’ordre du micromètre)
The next generation of space-based observation systems will make use of larger primary mirrors to achieve higher image resolution. Large primary mirrors lead to the increase of structural flexibility and are more susceptible to distortions. Thus maintaining optical tolerances across the mirror surface becomes increasingly difficult. The techniques of active shape control may be required for spatial mirror surfaces in future space observation systems. Piezoelectric actuators are often studied as embedded elements for the active control of mirror structures due to their excellent properties. However, unwanted nonlinear effects in piezoelectric actuators, i.e., hysteresis and creep, severely limit the service performance. This thesis aims at developing openloopcontrol laws to compensate hysteresis and creep effects in piezoelectric actuators. The studies led during this thesis are applied to the shape control of spatial mirror surfaces. An experimental setup with a small-scale mirror test structure involving multiple piezoelectric actuators is first developed and is used as support for all the measurements conducted during this thesis. Then the open-loop control methodologies of creep compensation, hysteresis compensation, and simultaneous compensation of both the nonlinear effects in a single piezoelectric actuator are respectively developed. To compensate creep, a nonlinear viscoelastic model is used to portray creep, and a new inverse model of creep based on the concept of “voltage relaxation” is proposedRegarding the hysteresis compensation, the classical Preisach model is modified by adding a derivative term in parallel to describe hysteresis more accurately with relatively few measurements, and the new inverse model is constructed in the similar way. For the simultaneous compensation of the two nonlinear effects, the hysteresis is first compensated and then, the creepof the hysteresis-compensated piezoelectric actuator is attenuated by open-loop control. The methodology is first developed for a single actuator. Finally, the shape control of a mirror surface with several piezoelectric actuators is achieved by actuating the points on the mirror surface in such a way as to reach the required displacements. The mirror test structure involving multiplepiezoelectric actuators compensated in hysteresis and creep is considered as a linear system on which the superposition principle can be applied. The influence coefficients characterizing the coupling effect between the piezoelectric actuators are determined by measurements. The influence coefficient matrix is first constructed using the superposition principle, and is then inverted. By insertion of the inverse matrix in cascade with multiple piezoelectric actuators with hysteresis and creep compensation, a feed-forward control approach to actuate the multiple interesting points of the mirror surface is developed. A number of experimental results demonstrate that the developed control methodologies are effective and feasible in practice

"It is not about the product. It is about the total experience." My aim with this project is to explore the interaction between technology, brand, space and the human being in designing an overall experience. We are moving towards a reality where intelligent technology is getting embedded in our homes and our lives. How can we make technology not just intelligent, but also more empathic and sensual? Can we create a relationship to a company, just as if it was a real person? Considering design as communication/conversation, I like to think of the product as a presence of a subject rather than an object, in this case as a spatial presence of a personality that we can reach through our senses. With a design method influenced by thoughts from interpersonal communication and rhetoric, I believe this experience can become more emotional and human. By thinking of products as the most important messengers of brand communication, In this case, I believe the acting and behaviour of the products become crucial in terms of authenticity and trust to the brand message. "A spatial presence of thoughtfulness" is my thesis project sponsored by Electrolux. It is about using these ideas to bring the Electrolux brand philosophy "thinking of you" into life through an emotional experience of thoughtfulness in the home atmosphere. An ambience not only created by the presence of technology, but in dialog with the participatory presence of humans and their actions.
Examensarbete Industridesign kandidatexamensarbete

This study presented the design and implementation of a spatial Hinf controller to suppress the free and forced vibrations of a cantilevered smart beam. The smart beam consists of a passive aluminum beam with surface bonded PZT (Lead-Zirconate-Titanate) patches. In this study, the PZT patches were used as the actuators and a laser displacement sensor was used as the sensor. In the first part of the study, the modeling of the smart beam by the assumed-modes method was conducted. The model correction technique was applied to include the effect of out-of-range modes on the dynamics of the system. Later, spatial system identification work was performed in order to clarify the spatial characteristics of the smart beam. In the second part of the study, a spatial Hinf controller was designed for suppressing the first two flexural vibrations of the smart beam. The efficiency of the controller was verified both by simulations and experimental implementation. As a final step, the comparison of the spatial and pointwise Hinf controllers was employed. A pointwise Hinf controller was designed and experimentally implemented. The efficiency of the both controllers was compared by simulations.

Cylindrical shells are common structures that are often used in industry, such as pipes, ducts, aircraft fuselages, rockets, submarine pressure hulls, electric motors and generators. In many applications it is desired to attenuate the sound radiated from the vibrating structure. There are both active and passive methods to achieve this purpose. However, at low frequencies passive methods are less effective and often an excessive amount of material is needed to achieve acceptable results. There have been a number of works regarding active control methods for this type of structure. In most cases a considerable number of error sensors and secondary sources are needed. However, in practice it is much preferred to have the fewest number of error sensors and control forces possible. Most methods presented have shown considerable dependence on the error sensor location. The goal of this dissertation is to develop an active noise control method that is able to attenuate the radiated sound effectively at low frequencies using only a small number of error sensors and secondary sources, and with minimal dependence on error sensor location. The Weighted Sum of Spatial Gradients control metric has been developed both theoretically and experimentally for simply supported cylindrical shells. The method has proven to be robust with respect to error sensor location. In order to quantify the performance of the control method, the radiated sound power has been chosen. In order to calculate the radiated sound power theoretically, the radiation modes have been developed for cylindrical shells. Experimentally, the radiated sound power without and with control has been measured using the ISO 3741 standard. The results show comparable, or in some cases better, performance in comparison with other known methods. Some agreement has been observed between model and experimental results. However, there are some discrepancies due to the fact that the actual cylinder does not appear to behave as an ideal simply supported cylindrical shell.

Thesis advisor: Willie J. Padilla
Progress in the field of metamaterials has started coming to a point where the field may finally begin to emerge as a viable solution to many electromagnetic challenges facing the community. No where is that more true then at terahertz frequencies where there lies an immense opportunity for growth. The development of mature technologies within this region of the electromagnetic spectrum would provide a valuable resource to become available for a multitude of applications. In order to achieve this, the necessary first steps of identifying viable materials and paths to integrate these with metamaterials will need to be completed. In this dissertation, we examine several different paths to achieve dynamic metamaterial electromagnetic response at terahertz frequencies, and demonstrate several paths to package these devices into imaging systems. In Chapter 1, we introduce the basic theory and design principles of metamaterials. We also describe the experimental techniques involved in the study of terahertz metamaterials. Chapter 2 presents a computational and experimental study investigating the integration of high electron mobility transistors with metamaterials allowing for high speed modulation of incident terahertz radiation. In Chapters 3 and 4, we investigate several different paths to create tunable terahertz metamaterial absorbers. Chapter 3 presents an investigation where we encapsulate a metametarial absorber unit cell with liquid crystals. We study both computationally and experimentally the tuning mechanism of the absorber as the liquid crystal refractive index is controlled as a function of the applied electric field strength and modulation frequency. In Chapter 4, we form a doped semiconducting metamaterial spatial light modulator with multi-color super-pixels composed of arrays of electronically controlled terahertz metamaterial absorbers. We computationally and experimentally study the independent tunability of each pixel in the spatial array and demonstrate high speed modulation. Chapter 5 introduces a multiplex imaging approach by using a terahertz spatial light modulator to enable terahertz imaging with a single pixel detector. We demonstrate the capability for high speed image acquisition, currently only limited by the commerical software used to reconfigure the spatial masks. We also configure the system to capture high fidelity images of varying complexity. In Chapter 6, we show how a metamaterial absorber can be implemented into a detector focal plane array for high sensitivity, low mutual coupling, and broad angle performance. Finally, we summarize in Chapter 7 the achievments of the research presented and highlight the direction of future work
Thesis (PhD) — Boston College, 2013
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Physics

Recently, technological advancement and the promise of next-generation devices have created an overwhelming push for the continued miniaturization of active systems to the micro- and nanometer scale. In this regime, traditional mechanical systems are largely inaccessible and as a result new active or stimuli-responsive materials are required. The work presented in this dissertation provides an understanding of the responsive nature of polymer and biopolymer interfaces especially in contact with metal nanoparticles. This understanding was utilized in conjunction with top-down template-based and self-assembly fabrication strategies to create hybrid protein based films and active polymer-metal hybrids that exhibit large and well-defined modulation of mechanical and optical properties. These materials processing developments represent advancement in the current state of the art specifically in three major areas: 1. template-based top-down control of protein chain conformation, 2. high-throughput synthesis and assembly of strongly coupled plasmonic nanoparticles with modulated optical properties (both near- and far-field), 3. field-assisted assembly of highly mobile and non-close packed magnetic nanorods with capabilities for rapid actuation.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2013.
Cataloged from PDF version of thesis.
Includes bibliographical references.
Living systems are composed of complex multicellular organizations containing various cell types spatially distributed in defined microenvironments. The intricate cell-cell and cell-matrix interactions in these microenvironments regulate the cell fate, differentiation of the cells, and functions of the associated tissues. Recreating these complex associations in vitro can be highly useful for fabricating biomimetic tissues for regenerative medicine, disease models for drug discovery, and models to study embryogenesis. This thesis focused on developing microscale responsive platforms for spatial and geometrical control of multicellular organizations. The first part of the thesis describes methods to fabricate spherical and stripe microtissues of single cell types and their temperature-controlled retrieval. These microtissues were scaffold-free and can potentially produce homotypic cell-cell interactions. Microwells fabricated from poly(Nisopropylacrylamide) (PNIPAAm) responded to temperature by changing their shapes. Spherical microtissues of a single cell type were formed in responsive microwells and recovered by using shape changing properties of microwells. Elastomeric microgrooves were conformally coated with PNIPAAm to first generate stripe microtissues of a single cell type, and then harvest them by exploiting the temperature-dependent hydrophilicity and swelling change of PNIPAAm film. The second part of the thesis introduces techniques to control spatial and geometrical distribution of multiple cell types in scaffold-free and scaffold-based tissues. Shape changing properties of dynamic microwells facilitated the sequential patterning of multicompartment hydrogels. Different cell types were spatially arranged in different compartments of microgels which may lead to complex cell-matrix interactions replicating native tissues. Shape changing properties of dynamic microwells were also employed to seed different cell types at different temperatures within defined geometries to control spatial and geometrical organization of multiple cell types. Resulting scaffold-free tissues can potentially produce homotypic and heterotypic cell-cell interactions. Dynamic microstructures with different geometries could be used to recapitulate complex native tissues with controlled cell-cell and cell-matrix interactions. The techniques presented in this thesis are versatile and may potentially be useful for replicating biological complexities for a wide range of applications in tissue engineering, regenerative medicine, drug discovery, developmental biology, and cancer biology.
by Halil Tekin.
Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2009.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references (p. 195-201).
Sphingomyelinase (SMase) has been shown to be involved in a variety of cell regulation processes. It can convert sphingomyelin (SM) to ceramide (Cer) and has been suggested to influence the cellular processes by reorganizing the cell membrane morphology. This thesis aims at a more comprehensive understanding of how sphingomyelinase (SMase) can regulate lipid membrane heterogeneity. We develop corralled model raft membranes in a microfluidic device to study the complex phase phenomena induced by SMase. The mass balance of lipid molecules in each confined corral greatly helps us to interpret results. By using the corralled membrane arrays, we are able to obtain the overall statistical distribution of the induction time of a slow domain nucleation and therefore fairly compare the membrane responses caused by different factors. In addition, the flow control by a microfluidic device solves the difficulty of distributing SMase uniformly to membrane systems. Furthermore, the laminar flow in a microchannel allows us to create model membrane arrays with a variety of lipid membrane compositions or solution conditions, which can serve as a screening tool to study a broad range of parameters associated with the interactions between lipid membranes and SMase or other peripheral proteins. We report that SMase can induce both a reaction-induced and a solvent-mediated phase transformation, causing switches of three stationary membrane morphologies and multiple-time-domain ceramide generation in model raft membranes.
(cont.) During the reaction-induced phase transformation, the ceramide generated by SMase causes the disintegration of pre-existing rafts rich in sphingomyelin and cholesterol, and recruit sphingomyelin to form SM-enriched domains which are relatively inaccessible to SMase. Once most of the sphingomyelin is physically trapped in SM-enriched domains and the SM concentration in the SMase-accessible region becomes low, the morphology pauses. The pause situation is resolved after the formation of a 3-D feature, rich in SMase, sphingomyelin (SMase's substrate), and ceramide (SMase's product), which triggers the solvent-mediated phase transformation. This 3-D feature is hypothesized as a slowly nucleating SMase-enriched phase where SMase processes sphingomyelin at low concentration more efficiently. The disparate time-scales of the formation of these SMase-features and the SM-enriched domains allow for the development of a significant duration of the middle pause morphology between the two transformations. The results show that SMase can be actively involved in the lipid membrane phase changes. The SMase-induced multi-stage morphology evolution is not only due to the membrane compositional changes caused by SMase,but also due to the selective binding of SMase, and SMase's special phase behavior during the solvent-mediated phase transformation. We further demonstrate that lipid membrane composition and SMase concentration can be used to tune the two phase transformations and therefore the intervals and spatial patterns of Smase-induced multi-stage morphology evolution.
(cont.) At a physiologically relevant concentration of SMase, we observe that membrane composition can influence the formation of SM-enriched domains and the nucleation of SMase-features at different extents of time scale and thus significantly tune the stable duration of the middle pause morphology. More importantly, the induction time of SMase-feature nucleation can be significantly decreased by increasing the supersaturating level of its three components in the membrane system. We further model the spatio-temporal morphology change during the solvent-mediated phase transformation. Three major kinetic processes are described in the model: the consumption of SM by the enzymatic reaction at an SMase-feature, the diffusion of SM from SM-enriched domains to an SMase-feature, and the release of SM due to the dissolution of SM-enriched domains. We combine MATLAB coding with Comsol, a software using finite element method to solve partial differential equations, to solve the model numerically due to the complex geometry and the moving boundary of our membrane systems. The non-dimensionality of the model allows the system to be characterized by three non-dimensional parameters. We show all of the possible scenarios of spatial pattern change during the phase transformation. The modeling results are shown to be consistent with our experimental results and can provide insights into the system parameters which are difficult to measure.
by Ling Chao.
Ph.D.

The mechanical properties of the extracellular matrix (ECM) have shown to regulate key cellular processes. However, current tools studying cell-ECM biophysical interactions revolve around cell-mediated traction forces, which, as I will show, are not appropriate in natural matrices due to matrix remodeling. I used active microrheology (AMR) to, instead, measure ECM stiffness in order to quantify these interactions in various cell-ECM systems.

In the first system, I evaluated a commonly used 3D cell-culture method in breast cancer research. I show that this model produces a large physical asymmetry in ECM stiffness, which resulted in altered cellular morphology, adhesion-mediated signaling, and phenotype. Importantly, a hallmark result obtained in this culture method was not repeatable once the asymmetry was removed, highlighting the importance of considering biophysical interactions in cell-culture models.

In the second system, my work, in collaboration with Dr. Stephen Weiss, led to the discovery that stem cells are not passive recipients of ECM stiffness signals as previously thought. Rather they can deliberately alter local (pericellular) stiffness with matrix metalloproteinases as a control for cellular functions. In particular, we found that skeletal stem cells competent in their ability to degrade collagen, increased pericellular stiffness via matrix remodeling to activate ?1 integrin signaling pathways and thus controlled their own lineage commitment to osteogenic fates. Cells without the ability to degrade their local matrix lost this functionality and were restricted in lineage commitment to adipogenic or chondrogenic fates.

For the third system, I quantified the contributions of cell contractility and matrix metalloproteinases in matrix remodeling for developing a normal mechanical topography in smooth muscle cells. I also provide evidence that it is the distribution of pericellular stiffness rather than a bulk value that instructs cellular behavior. In order to accomplish this task, I automated the AMR system (aAMR) for a tenfold decrease in measurement time. Importantly, aAMR reduces the complexity of AMR to a few mouse clicks, can create stiffness maps over large distances and provides metrics to assess the distribution of stiffness in the pericellular space within the volume of a natural, fibrous hydrogel.

In the state of Virginia, population growth and the associated increases in municipal wastewater, along with the threat of EPA regulations, will increase the need for reductions in phosphorous (P) loads in surface waters in order to meet and maintain water quality standards for the Chesapeake Bay. Agriculture contributes 49% of P entering the Bay; therefore, it can be expected that agriculture will be targeted as a source of P reductions. Spatially variable physical and socioeconomic characteristics of a watershed and its occupant farms affect both the decisions made by farmers and the transport of nutrients. Evidence suggests that spatially variable characteristics should be considered when designing policies to control nonpoint sources of water pollution. However, spatial information can be expensive to collect and the evidence is not conclusive as to the level of information required to analyze specific pollution-control policies. The objective of this study was to estimate the accuracy of predicted compliance costs and changes in P deliveries resulting from mandatory buffer installation and mandatory nutrient management for three alternative levels of information, relative to the population of farms in a Virginia watershed. For each information case, an economic model, FARMPLAN, was used to determine the profit maximizing levels of inputs, outputs and gross margins. Selected crop rotations and P applications were used as inputs to the physical model, PDM, which estimated the levels of P delivered to the watershed outlet. The compliance cost and P reduction estimates for the three alternative cases were compared to those of the population to determine their accuracy. The inclusion of greater levels of spatial information will lead to more accurate estimates of compliance costs and pollution reductions. Estimates of livestock capacity are more important to making accurate predictions than are farm boundaries. Differences in estimates made using different levels of information will be greater when the farmers have greater flexibility in meeting the policy requirements. The implications are that additional spatial information does not aid in the selection of one policy over the other, but can be useful in when estimating costs for budgeting purposes, or when evaluating how farmers will respond to the policy.
Master of Science

A major challenge in nanotechnology is the spatially controlled transport of cargo on the nanometer scale. The use of a nanoscale transport system based on molecular motors and filaments of the cytoskeleton proved as a promising approach to this problem. Therefore, the objective of this work was to pattern planar surfaces with motor proteins in a way that allows controlled and guided movement of microtubule-shuttles. The first part of the work was in particular focused on generating nanometer–sized tracks of motor proteins on unstructured surfaces. Specifically, microtubules themselves were used as biological templates for the stamping and alignment of motor proteins. Compared to other soft lithography techniques like microcontact printing this approach circumvented protein denaturation due to drying and conformational changes caused by mechanical stress. Given the large persistence length of microtubules their encounters with the boundaries of the nanotracks are limited to shallow approach angles. This way, the generated structures proved very efficient for the guiding of microtubules without topographical barriers. Topography-free guiding, as demonstrated in this work, is expected to significantly ease the design and fabrication of microtubule-transport systems and opens up the possibility to transport cargo of unlimited size, i.e. without any constraints by the dimensions of topographic guiding channels. Moreover, the biotemplated patterning is a promising tool for in vitro studies on the individual and cooperative action of motor proteins. In particular it might be helpful for the reconstitution of complex subcellular machineries in synthetic environments. As an example, microtubule-microtubule sliding by the biomolecular motor ncd has been shown to induce directional sliding between antiparallel microtubules and static cross-linking between parallel ones. The second part of the work explored an in-situ patterning technique for motor proteins to enable user-defined pattern designs, and investigated the achievable resolution. Photothermal patterning, based on localized light-to-heat conversion combined with a thermoresponsive polymer layer, was presented as a novel method. Specifically, the conformation of poly(N-isopropylacrylamide) (PNIPAM) molecules in aqueous solution was switched between the swollen state at T < 30°C (protein-repelling conformation) to the collapsed state at T > 33°C (protein-binding conformation) by optical signals of visible light to generate heat in a highly-localized manner. Upon heating of a light-absorbing layer on the substrate, the surface-grafted PNIPAM molecules collapsed locally and allowed motor proteins in solution to bind in the illuminated areas. To confirm the successful patterning of kinesin-1 molecules and their functionality microtubule-based gliding motility assays were performed. It was shown that the microtubules bind to the patterned kinesin-1 molecules and are transported exclusively in the patterned areas. While the achieved pattern sizes were currently in the range of ten micrometers, finite element modeling (implemented in COMSOL) showed that increased optical intensities possibly combined with cooling of the sample allow to significantly scale down the pattern dimensions. The produced patterns can be reversibly activated and deactivated at high and low temperature, respectively. Moreover, sequential patterning of multiple kinds of proteins on the same surface will be possible in a similar way without the need for specific linker molecules or elaborate surface preparation. Another advantage of the method is the use of visible light, which is versatile as any wavelength can be applied. In addition visible light is in comparison to other UV-based photopatterning techniques non-damaging to proteins
Der räumlich kontrollierte Transport von nanoskaligen Objekten ist eine große Herausforderung auf dem Gebiet der Nanotechnologie. Ein auf molekularen Motoren und Filamenten des Zellskeletts basierendes Nanotransportsystem hat sich dabei als ein viel versprechender Ansatz erwiesen. Das Ziel der vorgelegten Arbeit war es daher, ebene Oberflächen so mit Motorproteinen zu strukturieren, dass eine kontrollierte und geführte Bewegung von Mikrotubuli-Transportern ermöglicht wird. Der erste Teil der Arbeit war insbesondere darauf fokussiert, Motorprotein-Spuren im Nanometerbereich zu erzeugen. Im zweiten Teil der Arbeit wurde eine Strukturierungsmethode zur Realisierung von benutzerdefinierten Musterdesigns untersucht und die erreichbare Auflösung bestimmt. Für die Nanometerstrukturierung von Oberflächen mit funktionalen Motorproteinen wurde ein neuer Ansatz demonstriert. Mit der Anwendung von Biotemplaten, wie hier der Mikrotubuli, konnte ein hoch-lokalisiertes und orientiertes Anbinden von Proteinen an Oberflächen sowie gleichzeitig geringer Proteindenaturierung erreicht werden. Durch spezifisches Stempeln beziehungsweise Binden von Motoren wurden Muster aus funktionellen Proteinen mit hoher Oberflächendichte hergestellt. Die erzeugten Motor-Spuren haben gezeigt, dass Nanometerstrukturierungen möglich sind und ohne topographische Barrieren zu zuverlässiger Führung von Mikrotubuli führen können. Bisher konnte die nicht-topographische Strukturierung von Oberflächen mit Kinesin-1-Motoren nur im Mikrometerbereich demonstriert werden. Wegen der hohen Steifigkeit der Mikrotubuli war die thermische Energie des Systems in diesen Fällen nicht ausreichend, um die führende Spitze der Mikrotubuli zurück auf das Gebiet mit den strukturierten Motoren zu biegen. Dieses Problem wird durch die kleine Breite der hier demonstrierten Motor-Nanospuren verhindert, da das Auftreffen der Mikrotubuli mit den Grenzlinien auf extrem flache Winkel begrenzt ist. Interessanterweise haben sich Spuren des nicht-prozessiven Motors Kinesin-14 für das Führen und den Transport im Nanometerbereich als noch zuverlässiger herausgestellt als Kinesin-1-Spuren. Es ist zu erwarten, dass nicht-topographisches Führen, wie es in dieser Arbeit gezeigt wurde, das Design und die Herstellung von Mikrotubuli-Transportsystemen deutlich vereinfacht und die Möglichkeit eröffnet, Cargo mit unlimitierter Größe, d.h. ohne Einschränkungen durch die Abmessungen der topographischen Führungskanäle, zu transportieren. Zusätzlich ist die biotemplierte Strukturierung ein viel versprechendes Werkzeug um das individuelle und das kooperative Arbeiten von Motorproteinen in vitro untersuchen und komplexe subzelluläre Maschinerien in synthetischer Umgebung rekonstituieren zu können. Dies wurde am Beispiel des gerichteten Gleitens des biomolekularen Motors Kinesin-14 gezeigt, der ein gerichtetes Gleiten zwischen antiparallelen Mikrotubuli und statisches Vernetzen zwischen parallelen Mikrotubuli hervorruft. Mit dem Ansatz des biotemplierten Strukturierens ist es jedoch nicht einfach möglich, benutzerdefinierte Spuren zu erzeugen. Daher wurde die photothermische Proteinstrukturierung als eine neue Methode für die frei programmierbare, hochauflösende und schnelle Herstellung von strukturierten Proteinoberflächen eingeführt. Auf diese Weise wurden Kinesin-1-Muster durch licht-induziertes Heizen einer licht-absorbierenden Substratschicht erzeugt. Die thermisch schaltbaren poly(N-isopropylacrylamid) (PNIPAM) Moleküle auf der Oberfläche kollabierten lokal und erlaubten es den Motorproteinen, in den beleuchteten Gebieten aus der Lösung an die Oberfläche zu binden. Die Bewegung gleitender Mikrotubuli bestätigte anschließend die erfolgreiche Strukturierung der Kinesin-1-Motoren und deren Funktionalität, da die Mikrotubuli an die strukturierten Motoren banden und ausschließlich in den strukturierten Gebieten transportiert wurden. Neben der Proteinstrukturierung wurde die lokalisierte Licht-zu-Wärme-Umwandlung kombiniert mit einer thermisch schaltbaren Polymerschicht auch für die lokale Aktivierung von Kinesin-1-Motoren auf der Oberfläche genutzt. Ein Vorteil der photothermischen Proteinstrukturierung ist die Möglichkeit, sichtbares Licht zu verwenden, da jede beliebige Wellenlänge angewendet werden kann und sichtbares Licht, im Vergleich zu anderen UV-basierten Photostrukturierungsmethoden, Proteine nicht schädigt. Modellierungen mit Hilfe der Finite-Elemente-Methode (implementiert in der Software COMSOL) haben gezeigt, dass die Lichtintensität und die Oberflächentemperatur speziell eingestellt werden müssen, um definierte Strukturgrößen zu erzielen. Während die derzeitig erzeugten Muster Größen im Bereich von zehn Mikrometern hatten, könnten durch höhere optische Intensitäten kombiniert mit Kühlung der Probe die Größenordnungen signifikant reduziert werden. Die reale experimentelle Auflösung wird jedoch auch von der Schaltcharakteristik des Polymers und der Proteinbindungsdynamik abhängen. Die hergestellten Muster können reversibel bei hohen beziehungsweise niedrigen Temperaturen aktiviert und deaktiviert werden. Zusätzlich können auf die gleiche Weise verschiedene Proteinsorten sequentiell auf einer Oberfläche strukturiert werden, ohne dass spezifische Bindungsmoleküle oder aufwändige Oberflächenpräparationen notwendig wären. Die Möglichkeit, Proteine reversibel an die Oberfläche zu binden, um geschriebene Muster wieder löschen zu können, wäre eine Weiterentwicklung und würde die Anwendungsmöglichkeiten der photothermischen Strukturierungsmethode erweitern. Außerdem würden optisch schaltbare Polymere das direkte Strukturieren von Motoren mit Licht ermöglichen und daher die Methode vereinfachen

Control over particle positioning is of particular importance in microfluidic systems. Acoustic techniques offer a low- power, minimally invasive method of achieving such control. This thesis discusses such control using surface acoustic waves. Mathematical models are first developed to describe the control over particles in liquids using acoustic radiation forces , which highlight the influence of acoustic power and particle size. The formation of both one and two dimensional particle arrays in fluidic channels are t hen demonstrated experimentally in a range of fluidic channels. Particle acceleration during array formation is shown by experiment to be directly proportional to the acoustic power level, indicating both fast and slow regimes of operation for this technique. Additionally, the time taken for particle arrays to form is shown to follow an inverse square relationship with particle size, allowing the possibility of sorting particles according to their size. A method of transporting particle arrays is reported, by sequential increments in the acoustic frequency. This is a cyclic process and the controlled transport of arrays of micron-sized particles by distances greater than 100 11m is demonstrated. A biocompatible microfluidic device is presented, which enables the use of the techniques presented here with biologically relevant samples. A significant biological application is demonstrated by the formation and transportation of arrays of microbubbles. This could allow the characterisation of individual micro bubbles in targeted drug delivery studies, for example.

Eye movements are a powerful tool to examine cognitive processes. However, in most paradigms little is known about the dynamics present in sequences of saccades and fixations. In particular, the control of fixation durations has been widely neglected in most tasks. As a notable exception, both spatial and temporal aspects of eye-movement control have been thoroughly investigated during reading. There, the scientific discourse was dominated by three controversies, (i), the role of oculomotor vs. cognitive processing on eye-movement control, (ii) the serial vs. parallel processing of words, and, (iii), the control of fixation durations. The main purpose of this thesis was to investigate eye movements in tasks that require sequences of fixations and saccades. While reading phenomena served as a starting point, we examined eye guidance in non-reading tasks with the aim to identify general principles of eye-movement control. In addition, the investigation of eye movements in non-reading tasks helped refine our knowledge about eye-movement control during reading. Our approach included the investigation of eye movements in non-reading experiments as well as the evaluation and development of computational models. I present three main results : First, oculomotor phenomena during reading can also be observed in non-reading tasks (Chapter 2 & 4). Oculomotor processes determine the fixation position within an object. The fixation position, in turn, modulates both the next saccade target and the current fixation duration. Second, predicitions of eye-movement models based on sequential attention shifts were falsified (Chapter 3). In fact, our results suggest that distributed processing of multiple objects forms the basis of eye-movement control. Third, fixation durations are under asymmetric control (Chapter 4). While increasing processing demands immediately prolong fixation durations, decreasing processing demands reduce fixation durations only with a temporal delay. We propose a computational model ICAT to account for asymmetric control. In this model, an autonomous timer initiates saccades after random time intervals independent of ongoing processing. However, processing demands that are higher than expected inhibit the execution of the next saccade and, thereby, prolong the current fixation. On the other hand, lower processing demands will not affect the duration before the next saccade is executed. Since the autonomous timer adjusts to expected processing demands from fixation to fixation, a decrease in processing demands may lead to a temporally delayed reduction of fixation durations. In an extended version of ICAT, we evaluated its performance while simulating both temporal and spatial aspects of eye-movement control. The eye-movement phenomena investigated in this thesis have now been observed in a number of different tasks, which suggests that they represent general principles of eye guidance. I propose that distributed processing of the visual input forms the basis of eye-movement control, while fixation durations are controlled by the principles outlined in ICAT. In addition, oculomotor control contributes considerably to the variability observed in eye movements. Interpretations for the relation between eye movements and cognition strongly benefit from a precise understanding of this interplay.
Blickbewegungen stellen ein wichtiges Instrument dar, um kognitive Prozesse zu untersuchen. In den meisten Paradigmen ist allerdings wenig über die Entstehung von Sakkaden und Fixationen bekannt. Insbesondere die Kontrolle der Fixationsdauern wurde häufig außer acht gelassen. Eine wesentliche Ausnahme stellt die Leseforschung dar, in der sowohl zeitlichliche als auch räumliche Aspekte der Blickbewegungssteuerung im Detail betrachtet wurden. Dabei war der wissenschaftliche Diskurs durch drei Kontroversen gekennzeichnet, die untersuchten, (i), welchen Einfluss okulomotorische bzw. kognitive Prozesse auf die Blicksteuerung haben, (ii), ob Worte seriell oder parallel verarbeitet werden und, (iii), wie Fixationsdauern kontrolliert werden. Die vorliegende Arbeit zielt im wesentlichen darauf ab, die Dynamik von Fixationssequenzen zu erforschen. Ausgehend von den Erkenntnissen beim Lesen untersuchten wir Blickbewegungen in Nichtlese-Aufgaben, mit dem Ziel allgemeine Prinzipien der Blicksteuerung zu identifizieren. Zusätzlich versuchten wir mit Hilfe dieser Aufgaben, Erkenntnisse über Prozesse beim Lesen zu vertiefen. Unser Vorgehen war sowohl von der Durchführung von Experimenten als auch der Entwicklung und Evaluation computationaler Modelle geprägt. Die Hauptbefunde zeigten: Erstens, okulomotorische Phänomene des Lesens lassen sich in Suchaufgaben ohne Wortmaterial replizieren (Kapitel 2 & 4). Dabei bestimmen okulomotorische Prozesse die Fixationsposition innerhalb eines Objektes. Diese wiederum beeinflusst das nächste Sakkadenziel sowie die Fixationsdauer. Zweitens, wesentliche Vorhersagen von Modellen, in denen Blickbewegungen von seriellen Aufmerksamkeitsverschiebungen abhängen, konnten falsifiziert werden (Kapitel 3). Stattdessen legen unsere Erkenntnisse nahe, dass die Blicksteuerung von der parallelen Verarbeitung mehrerer Objekte abhängt. Drittens, Fixationsdauern werden asymmetrisch kontrolliert (Kapitel 4). Während hohe Verarbeitungsanforderungen Fixationsdauern unmittelbar verlängern können, führen niedrige Verarbeitungsanforderungen nur zeitlich verzögert zu einer Reduktion. Wir schlagen ein computationales Modell ICAT vor, um asymmetrische Kontrolle zu erklären. Grundlage des Modells ist ein autonomer Zeitgeber, der unabhängig von der momentanen Verarbeitung nach zufälligen Zeitintervallen Sakkaden initiiert. Unerwartet hohe Verarbeitungsanforderungen können die Initiierung der nächsten Sakkade hinauszögern, während unerwartet niedrige Verarbeitungsanforderungen den Beginn der nächsten Sakkade nicht verändern. Der Zeitgeber passt sich allerdings von Fixation zu Fixation neuen Verarbeitungsanforderungen an, so dass es zu einer zeitlich verzögerten Reduktion der Fixationsdauern kommen kann. In einer erweiterten Version des Modells überprüfen wir die Kompatibilität ICATs mit einer realistischen räumlichen Blicksteuerung. Die Ähnlichkeit von Blickbewegungsphänomenen über Aufgaben hinweg legt nahe, dass sie auf allgemeinen Prinzipien basieren. Grundlage der Blicksteuerung ist die verteilte Verarbeitung des visuellen Inputs, während die Kontrolle der Fixationsdauer auf den Prinzipien von ICAT beruht. Darüber hinaus tragen okulomotorische Phänomene wesentlich zur Variabilität der Blicksteuerung bei. Ein Verständnis dieses Zusammenspiels hilft entscheidend den Zusammenhang von Blickbewegungen und Kognitionen besser zu verstehen.