Active alignment for two-beam interferometers

An active control system is described for the automatic alignment of the mirrors in a two-beam interferometer. From an initial unaligned position the active control system determines the degree of misalignment and adjusts the relative mirror positions accordingly. An embodiment of the system is described for a Michelson interferometer in which one of the mirrors is mounted upon three piezoelectric transducers PZT arranged so that they can both tilt and retard the mirror. Laser sources and corresponding photodetectors are also incorporated such that a control system can use the PZT actuators to produce a series of mirror movements relative to the fixed mirror and give a set of two-dimensional diffraction patterns one for each of the laser photodetectors. Amplitude and phase information is extracted from these patterns which enables the control system to align the mirrors such that the diffraction pattern maxima is at the center of the instrument central photodetector. In a further stage of the control algorithm, the alignment accuracy is refined using information from the laser photodetectors during retardation of the mirror. In this manner, the initial mirror alignment, maintaining that alignment during retardation and diagnosis of possible misalignment, become part of a single active control technology for instrument alignment

Optimal metabolic pathway activation

This paper deals with temporal enzyme distribution in the activation of biochemical pathways. Pathway activation arises when production of a certain biomolecule is required due to changing environmental conditions. Under the premise that biological systems have been optimized through evolutionary processes, a biologically meaningful optimal control problem is posed. In this setup, the enzyme concentrations are assumed to be time dependent and constrained by a limited overall enzyme production capacity, while the optimization criterion accounts for both time and resource usage. Using geometric arguments we establish the bang-bang nature of the solution and reveal that each reaction must be sequentially activated in the same order as they appear in the pathway. The results hold for a broad range of enzyme dynamics which includes, but is not limited to, Mass Action, Michaelis-Menten and Hill Equation kinetics.Comment: 14 pages, 3 figures. Paper to be presented at the 17th IFAC World Congress, Seoul, Korea, July 200

Control structure and limitations of biochemical networks

Biochemical networks typically exhibit intricate topologies that hinder their analysis with control-theoretic tools. In this work we present a systematic methodology for the identification of the control structure of a reaction network. The method is based on a bandwidth reduction technique applied to the incidence matrix of the network’s graph. In addition, in the case of mass-action and stable networks we show that it is possible to identify linear algebraic dependencies between the time-domain integrals of some species’ concentrations. We consider the extrinsic apoptosis pathway and an activation– inhibition mechanism to illustrate the application of our result

ALISSA: an automated live-cell imaging system for signal transduction analyses

Probe photobleaching and a specimen’s sensitivity to phototoxicity severely limit the number of possible excitation cycles in time-lapse fluorescent microscopy experiments. Consequently, when a study of cellular processes requires measurements over hours or days, temporal resolution is limited, and spontaneous or rapid events may be missed, thus limiting conclusions about transduction events. We have developed ALISSA, a design framework and reference implementation for an automated live-cell imaging system for signal transduction analysis. It allows an adaptation of image modalities and laser resources tailored to the biological process, and thereby extends temporal resolution from minutes to seconds. The system employs online image analysis to detect cellular events that are then used to exercise microscope control. It consists of a reusable image analysis software for cell segmentation, tracking, and time series extraction, and a measurement-specific process control software that can be easily adapted to various biological settings. We have applied the ALISSA framework to the analysis of apoptosis as a demonstration case for slow onset and rapid execution signaling. The demonstration provides a clear proof-of-concept for ALISSA, and offers guidelines for its application in a broad spectrum of signal transduction studies

Automatic quality assessment for fluorescence microscopy images

Fluorescence microscopy imaging is a constant trade off between signal to noise ratio, total observation time and spatio-temporal resolution due to photo toxicity. In this paper, we propose a method to estimate the quality of a fluorescent image acquisition, from a single image, taking into account both signal dependent and signal independent noise. We propose a method for the calculation of the signal to noise ratio globally and locally. We validated our algorithm on real experimental data and data with known simulated noise.Results allow us to conclude that this fully automatic method provides a good quantification of the image quality

Active alignment for two-beam interferometers

An active control system is described for the automatic alignment of the mirrors in a two-beam interferometer. From an initial unaligned position the active control system determines the degree of misalignment and adjusts the relative mirror positions accordingly. An embodiment of the system is described for a Michelson interferometer in which one of the mirrors is mounted upon three piezoelectric transducers PZT arranged so that they can both tilt and retard the mirror. Laser sources and corresponding photodetectors are also incorporated such that a control system can use the PZT actuators to produce a series of mirror movements relative to the fixed mirror and give a set of two-dimensional diffraction patterns one for each of the laser photodetectors. Amplitude and phase information is extracted from these patterns which enables the control system to align the mirrors such that the diffraction pattern maxima is at the center of the instrument central photodetector. In a further stage of the control algorithm, the alignment accuracy is refined using information from the laser photodetectors during retardation of the mirror. In this manner, the initial mirror alignment, maintaining that alignment during retardation and diagnosis of possible misalignment, become part of a single active control technology for instrument alignment

Active alignment for two-beam interferometers

An active control system is described for the automatic alignment of the mirrors in a two-beam interferometer. From an initial unaligned position the active control system determines the degree of misalignment and adjusts the relative mirror positions accordingly. An embodiment of the system is described for a Michelson interferometer in which one of the mirrors is mounted upon three piezoelectric transducers PZT arranged so that they can both tilt and retard the mirror. Laser sources and corresponding photodetectors are also incorporated such that a control system can use the PZT actuators to produce a series of mirror movements relative to the fixed mirror and give a set of two-dimensional diffraction patterns one for each of the laser photodetectors. Amplitude and phase information is extracted from these patterns which enables the control system to align the mirrors such that the diffraction pattern maxima is at the center of the instrument central photodetector. In a further stage of the control algorithm, the alignment accuracy is refined using information from the laser photodetectors during retardation of the mirror. In this manner, the initial mirror alignment, maintaining that alignment during retardation and diagnosis of possible misalignment, become part of a single active control technology for instrument alignment

Active alignment for two-beam interferometers

An active control system is described for the automatic alignment of the mirrors in a two-beam interferometer. From an initial unaligned position the active control system determines the degree of misalignment and adjusts the relative mirror positions accordingly. An embodiment of the system is described for a Michelson interferometer in which one of the mirrors is mounted upon three piezoelectric transducers PZT arranged so that they can both tilt and retard the mirror. Laser sources and corresponding photodetectors are also incorporated such that a control system can use the PZT actuators to produce a series of mirror movements relative to the fixed mirror and give a set of two-dimensional diffraction patterns one for each of the laser photodetectors. Amplitude and phase information is extracted from these patterns which enables the control system to align the mirrors such that the diffraction pattern maxima is at the center of the instrument central photodetector. In a further stage of the control algorithm, the alignment accuracy is refined using information from the laser photodetectors during retardation of the mirror. In this manner, the initial mirror alignment, maintaining that alignment during retardation and diagnosis of possible misalignment, become part of a single active control technology for instrument alignment

Cell Death: Linear Control Analysis of Eissing's Model

We deconstruct Eissing's intrinsic apoptosis model using linear control theory. In the life steady state the linearised dynamics are shown to be a tightly coupled but unstable multi- variable system. The life steady state is stabilized biochemically by decentralised XIAP and CARP acting as lead controllers. The small gain theorem is used to analyse stability and to give insight into how the inhibitors naturally modulate cell death and highlighting the role played by positive and negative feedback. Finally we use simulations to examine the extent to which recovery is possible once apoptosis has been initiated