Role of feedback and dynamics in a gene regulatory network

Cells exhibit a diverse repertoire of dynamic behaviors. These dynamic functions are implemented by circuits of interacting biomolecules. Although these regulatory networks function deterministically by executing specific programs in response to extracellular signals, molecular interactions are inherently governed by stochastic fluctuations. This molecular noise can manifest as cell-to-cell phenotypic heterogeneity in a well-mixed environment. Single-cell variability may seem like a design flaw but the coexistence of diverse phenotypes in an isogenic population of cells can also serve a biological function by increasing the probability of survival of individual cells upon an abrupt change in environmental conditions. Decades of extensive molecular and biochemical characterization have revealed the connectivity and mechanisms that constitute regulatory networks. We are now confronted with the challenge of integrating this information to link the structure of these circuits to systems-level properties such as cellular decision making. To investigate cellular decision-making, we used the well studied galactose gene-regulatory network in \textit{Saccharomyces cerevisiae}. We analyzed the mechanism and dynamics of the coexistence of two stable on and off states for pathway activity. We demonstrate that this bimodality in the pathway activity originates from two positive feedback loops that trigger bistability in the network. By measuring the dynamics of single-cells in a mixed sugar environment, we observe that the bimodality in gene expression is a transient phenomenon. Our experiments indicate that early pathway activation in a cohort of cells prior to galactose metabolism can accelerate galactose consumption and provide a transient increase in growth rate. Together these results provide important insights into strategies implemented by cells that may have been evolutionary advantageous in competitive environments.

Complex behavior and perception in Drosophila emerges from iterative feedback-regulated reflexes

For a hungry fruit fly, locating and landing on a fermenting fruit where it can feed, find mates, and lay eggs, is an essential and difficult task requiring the integration of both olfactory and visual cues. Understanding how flies accomplish this will help provide a comprehensive ethological context for the expanding knowledge of their neural circuits involved in processing olfaction and vision, as well as inspire novel engineering solutions for control and estimation in computationally limited robotic applications. In this thesis, I use novel high throughput methods to develop a detailed overview of how flies track odor plumes, land, and regulate flight speed. Finally, I provide an example of how these insights can be applied to robotic applications to simplify complicated estimation problems. To localize an odor source, flies exhibit three iterative, reflex-driven behaviors. Upon encountering an attractive plume, flies increase their flight speed and turn upwind using visual cues. After losing the plume, flies begin zigzagging crosswind, again using visual cues to control their heading. After sensing an attractive odor, flies become more attracted to small visual features, which increases their chances of finding the plume source. Their changes in heading are largely controlled by open-loop maneuvers called saccades, which they direct towards and away from visual features. If a fly decides to land on an object, it begins to decelerate so as to maintain a stereotypical ratio of expansion to retinal size. Once they reach a stereotypical distance from the target, flies extend their legs in preparation for touchdown. Although it is unclear what cues they use to trigger this behavior, previous studies have indicated that it is likely under visual control. In Chapter 3, I use a nonlinear control theoretic analysis and robotic testbed to propose a novel and putative mechanism for how a fly might visually estimate distance by actively decelerating according to a visual control law. Throughout these behaviors, a common theme is the visual control of flight speed. Using genetic tools I show that the neuromodulator octopamine plays an important role in regulating flight speed, and propose a neural circuit for how this controller might be implemented in the flies brain. Two general biological and engineering principles are evident across my experiments: (1) complex behaviors, such as foraging, can emerge from the interactions of simple independent sensory-motor modules; (2) flies control their behavior in such a way that simplifies complex estimation problems.

Optimal feedback control of two-photon fluorescence based on genetic algorithm

An optimal feedback control of two-photon fluorescence in the ethanol solution of 4-dicyanomethylene-2-methyl-6-p-dimethyl-amiiiostryryl-4H-pyran (DCM) using pulse-shaping technique based on genetic algorithm is demonstrated experimentally. The two-photon fluorescence of the DCM ethanol solution is enhanced in intensity of about 23%. The second harmonic generation frequency-resolved optical gating (SHG-FROG) trace indicates that the effective population transfer arises from the positively chirped pulse. The experimental results appear the potential applications of coherent control to the complicated molecular system.

Optimal feedback control of two-photon fluorescence in Coumarin 515 based on genetic algorithm

An optimal feedback control of two-photon fluorescence in the Coumarin 515 ethanol solution excited by shaping femtosecond laser pulses based on genetic algorithm is demonstrated experimentally. The two-photon fluorescence intensity can be enhanced by similar to 20%. Second harmonic generation frequency-resolved optical gating traces indicate that the optimal laser pulses are positive chirp, which are in favor of the effective population transfer of two-photon transitions. The dependence of the two-photon fluorescence signal on the laser pulse chirp is investigated to validate the theoretical model for the effective population transfer of two-photon transitions. The experimental results appear the potential applications in nonlinear spectroscopy and molecular physics. (c) 2005 Elsevier B.V. All rights reserved.

Análisis y mejora de la gestión y organización del equipo Formula Student Bizkaia usando como referencia el modelo EFQM

[ES]El presente trabajo de fin de grado tiene como objetivo analizar y mejorar la gestión y organización del equipo Formula Student Bizkaia, de tal manera que le permita ser más competitivo frente al resto de universidades. Para su realización, en primer lugar, se exponen las distintas alternativas que existen para evaluar la calidad de gestión del equipo. En segundo lugar, una vez se haya escogido el modelo más conveniente, se prosigue al estudio de los distintos criterios clave en los que se basa. En tercer lugar, cuando se haya llevado a cabo el estudio de los puntos fuertes, así como evidencias y áreas a mejorar, se procede a realizar una evaluación que permita determinar las fortalezas y debilidades, para de esta manera potenciarlas y solventarlas, respectivamente. Por último, se presenta un desglose de los gastos que conlleva realizar la elaboración de un estudio de estas características, así como un desglose de las diferentes tareas a llevar a cabo y su respectiva duración.

Stimulated Raman adiabatic passage from atomic to molecular Bose-Einstein condensates: Feedback laser-detuning control and suppression of dynamical instability

We present a feedback control scheme that designs time-dependent laser-detuning frequency to suppress possible dynamical instability in coupled free-quasibound-bound atom-molecule condensate systems. The proposed adaptive frequency chirp with feedback is shown to be highly robust and very efficient in the passage from an atomic to a stable molecular Bose-Einstein condensate.

Acceleration Sensing, Feedback Cooling, and Nonlinear Dynamics with Nanoscale Cavity-Optomechanical Devices

Light has long been used for the precise measurement of moving bodies, but the burgeoning field of optomechanics is concerned with the interaction of light and matter in a regime where the typically weak radiation pressure force of light is able to push back on the moving object. This field began with the realization in the late 1960's that the momentum imparted by a recoiling photon on a mirror would place fundamental limits on the smallest measurable displacement of that mirror. This coupling between the frequency of light and the motion of a mechanical object does much more than simply add noise, however. It has been used to cool objects to their quantum ground state, demonstrate electromagnetically-induced-transparency, and modify the damping and spring constant of the resonator. Amazingly, these radiation pressure effects have now been demonstrated in systems ranging 18 orders of magnitude in mass (kg to fg).

In this work we will focus on three diverse experiments in three different optomechanical devices which span the fields of inertial sensors, closed-loop feedback, and nonlinear dynamics. The mechanical elements presented cover 6 orders of magnitude in mass (ng to fg), but they all employ nano-scale photonic crystals to trap light and resonantly enhance the light-matter interaction. In the first experiment we take advantage of the sub-femtometer displacement resolution of our photonic crystals to demonstrate a sensitive chip-scale optical accelerometer with a kHz-frequency mechanical resonator. This sensor has a noise density of approximately 10 micro-g/rt-Hz over a useable bandwidth of approximately 20 kHz and we demonstrate at least 50 dB of linear dynamic sensor range. We also discuss methods to further improve performance of this device by a factor of 10.

In the second experiment, we used a closed-loop measurement and feedback system to damp and cool a room-temperature MHz-frequency mechanical oscillator from a phonon occupation of 6.5 million down to just 66. At the time of the experiment, this represented a world-record result for the laser cooling of a macroscopic mechanical element without the aid of cryogenic pre-cooling. Furthermore, this closed-loop damping yields a high-resolution force sensor with a practical bandwidth of 200 kHZ and the method has applications to other optomechanical sensors.

The final experiment contains results from a GHz-frequency mechanical resonator in a regime where the nonlinearity of the radiation-pressure interaction dominates the system dynamics. In this device we show self-oscillations of the mechanical element that are driven by multi-photon-phonon scattering. Control of the system allows us to initialize the mechanical oscillator into a stable high-amplitude attractor which would otherwise be inaccessible. To provide context, we begin this work by first presenting an intuitive overview of optomechanical systems and then providing an extended discussion of the principles underlying the design and fabrication of our optomechanical devices.

Estudio del comportamiento aerodinámico de un alerón trasero de un monoplaza tipo Formula Student

[ES]El proyecto investigador tiene el objeto el estudio del comportamiento de un perfil aerodinámico frente a un flujo turbulento, en este caso el aire. Se trata de evaluar las presiones que se ejercen sobre dicho perfil, que será un alerón de monoplaza tipo Formula Student, para comprobar si aporta alguna mejora en el comportamiento del monoplaza la introducción de este paquete aerodinámico. Con la introducción de este perfil en el monoplaza se pretende ganar un mayor agarre en el paso por curva siendo la resistencia al avance en recta la mínima posible, ya que lo que se pretende es hacer el recorrido del circuito en el menor tiempo posible. Por tanto hay dos variables a tener en cuenta a la hora de diseñar el alerón, por un lado esta mejorar el agarre de los neumáticos sobre el asfalto al tomar una curva, lo que nos permitirá tomar la curva a mayor velocidad y por tanto en menos tiempo, y por otro lado, la oposición que el alerón ejerce en el avance en recta disminuyendo su velocidad máxima. En resumen, se trata de comparar la fuerza horizontal y la fuerza vertical que el aire ejerce sobre el perfil aerodinámico a introducir en el monoplaza y evaluar si es beneficioso para este, es decir, si añadiendo dicho perfil se realiza el trazado del circuito en menor tiempo que sin él. Para ello se realizarán simulaciones con un software de modelado físico de flujos y turbulencias sobre un diseño de un alerón dado, con diferentes tipos de flujo, de forma que se asemeje de mejor forma a las condiciones de la pista y se obtendrán los resultados de las presiones que el flujo de aire ejerce sobre las superficies del perfil. Después se obtendrán las fuerzas puntuales vertical y horizontal y se analizaran los datos obtenidos. Deberán tenerse en cuenta, además de los resultados obtenidos, los materiales a emplear a la hora de su fabricación, el proceso de dicha fabricación y el coste que supone tanto el proceso como los materiales empleados.

Optimum linear coding for additive noise systems using information feedback

The feedback coding problem for Gaussian systems in which the noise is neither white nor statistically independent between channels is formulated in terms of arbitrary linear codes at the transmitter and at the receiver. This new formulation is used to determine a number of feedback communication systems. In particular, the optimum linear code that satisfies an average power constraint on the transmitted signals is derived for a system with noiseless feedback and forward noise of arbitrary covariance. The noisy feedback problem is considered and signal sets for the forward and feedback channels are obtained with an average power constraint on each. The general formulation and results are valid for non-Gaussian systems in which the second order statistics are known, the results being applicable to the determination of error bounds via the Chebychev inequality.