Collective behaviours: from biochemical kinetics to electronic circuits

In this work we aim to highlight a close analogy between cooperative behaviors in chemical kinetics and cybernetics; this is realized by using a common language for their description, that is mean-field statistical mechanics. First, we perform a one-to-one mapping between paradigmatic behaviors in chemical kinetics (i.e., non-cooperative, cooperative, ultra-sensitive, anti-cooperative) and in mean-field statistical mechanics (i.e., paramagnetic, high and low temperature ferromagnetic, anti-ferromagnetic). Interestingly, the statistical mechanics approach allows a unified, broad theory for all scenarios and, in particular, Michaelis-Menten, Hill and Adair equations are consistently recovered. This framework is then tested against experimental biological data with an overall excellent agreement. One step forward, we consistently read the whole mapping from a cybernetic perspective, highlighting deep structural analogies between the above-mentioned kinetics and fundamental bricks in electronics (i.e. operational amplifiers, flashes, flip-flops), so to build a clear bridge linking biochemical kinetics and cybernetics.Comment: 15 pages, 6 figures; to appear on Scientific Reports: Nature Publishing Grou

Biosensors and CMOS Interface Circuits

abstract: Analysing and measuring of biological or biochemical processes are of utmost importance for medical, biological and biotechnological applications. Point of care diagnostic system, composing of biosensors, have promising applications for providing cheap, accurate and portable diagnosis. Owing to these expanding medical applications and advances made by semiconductor industry biosensors have seen a tremendous growth in the past few decades. Also emergence of microfluidics and non-invasive biosensing applications are other marker propellers. Analyzing biological signals using transducers is difficult due to the challenges in interfacing an electronic system to the biological environment. Detection limit, detection time, dynamic range, specificity to the analyte, sensitivity and reliability of these devices are some of the challenges in developing and integrating these devices. Significant amount of research in the field of biosensors has been focused on improving the design, fabrication process and their integration with microfluidics to address these challenges. This work presents new techniques, design and systems to improve the interface between the electronic system and the biological environment. This dissertation uses CMOS circuit design to improve the reliability of these devices. Also this work addresses the challenges in designing the electronic system used for processing the output of the transducer, which converts biological signal into electronic signal.Dissertation/ThesisM.S. Electrical Engineering 201

Extra-auditory effects of noise in laboratory animals: the relationship between noise and sleep

Noise has both auditory and extra-auditory effects. Some of the most deleterious extra-auditory effects of noise are those leading to sleep disturbances. These disturbances seem to be related to both endogenous (physical parameters) and exogenous (sex, age) factors of noise. Despite correlative relations between noise level and awakenings, the scientific community has not reached consensus regarding a specific action of these factors on the different sleep stages. In animal research, 2 complementary main fields of research exist. One is focused on the positive modulation of sleep by repeated tone stimulation. The other concerns noise-related sleep disturbances. The few studies that have investigated noise-related sleep disturbances suggest the following conclusions. First, sleep disturbances are greater upon exposure to environmental noise, whose frequency spectrum is characterized by high and ultrasonic sounds, than white noise. Second, unpredictability and pattern of noise events are responsible for extractions from both SWS and PS. Third, chronic exposure to noise permanently reduces and fragments sleep. Finally, in chronic noise exposure, an inter-individual variability in SWS deficits is observed and correlated to a psychobiological profile related to an incapability to face stressful situations. Based on results from other research, acute noise-related sleep perturbations could result from an imbalance in the sleep-wake cycle in favor of arousing ascending systems. Chronic noise-related sleep disturbances may arise due to imbalance of the sleep-wake cycle and malfunctioning of the hypothalamo-pituitary-adrenal axis which may both contribute to the development of pathology

Novel Simulation to Avoid Bias in Measurement of Hyperpolarized Pyruvate: Demonstrated in Phantom and In Vivo

Dynamic nuclear polarization creates a transient hyperpolarized nuclear state that can dramatically increase the signal detected by magnetic resonance imaging. This signal increase allows real-time spectroscopic imaging of specific metabolites in vivo by magnetic resonance. Real-time imaging of both the spatial and chemical fate of hyperpolarized metabolites is showing great promise to meaningfully benefit clinical care of cancer patients. Imaging of hyperpolarized agents will have a larger clinical impact if it can function as a quantitative modality upon which clinical decisions can be made. However, quantitative measurement of hyperpolarized agents is currently difficult due to the restrictions imposed by the transient hyperpolarized state and the complexity inherent in biological systems. As more advanced imaging and measurement techniques are developed for imaging hyperpolarized substrates, it is critical to characterize their effect on any relevant quantitative measure. To assist in accurate quantitative measurement of hyperpolarized agents, an infrastructure where acquisition strategies can be developed, compared, optimized and validated was critically need. A novel simulation architecture was developed that combines classical chemical kinetics with the basic physics of nuclear magnetic resonance and couples them to multiple perfusion models. Simulation results showed that changes in the acquisition strategy used will affect the resulting quantification of chemical exchange rates and suggested that any bias that is imposed by the acquisition strategy can be avoided by using optimized pulse sequences. To validate these predictions, a phantom system was developed that allows controllable chemical conversion of hyperpolarized pyruvate into lactate with a variability less than 20%. Using this phantom system, studies showed that poorly optimized pulse sequences significantly reduced the measured value of the chemical exchange rates, whereas optimized pulse sequences showed no significant difference in chemical exchange measurements. In order to test simulation predictions for a perfused system, an animal cohort with orthotropic anaplastic thyroid cancer was scanned with multiple sequences. Again, optimized sequences showed no significant difference in measured exchange rates while poorly designed sequences significantly underestimated the exchange rates, which is consistent with the simulation results. These validation studies suggest that this simulation architecture will be a powerful tool for developing and optimizing acquisition and quantization methods for hyperpolarized magnetic resonance imaging

Complete integrability of information processing by biochemical reactions

Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling -- based on spin systems -- has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis--Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy -- based on completely integrable hydrodynamic-type systems of PDEs -- which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions.Comment: 24 pages, 10 figures; accepted for publication in Scientific Report

Study on Integrated Redox Image Sensor Employing Square Wave Voltammetry

豊橋技術科学大

Advanced sensors technology survey

This project assesses the state-of-the-art in advanced or 'smart' sensors technology for NASA Life Sciences research applications with an emphasis on those sensors with potential applications on the space station freedom (SSF). The objectives are: (1) to conduct literature reviews on relevant advanced sensor technology; (2) to interview various scientists and engineers in industry, academia, and government who are knowledgeable on this topic; (3) to provide viewpoints and opinions regarding the potential applications of this technology on the SSF; and (4) to provide summary charts of relevant technologies and centers where these technologies are being developed

Circuits with broken fibration symmetries perform core logic computations in biological networks

We show that logic computational circuits in gene regulatory networks arise from a fibration symmetry breaking in the network structure. From this idea we implement a constructive procedure that reveals a hierarchy of genetic circuits, ubiquitous across species, that are surprising analogues to the emblematic circuits of solid-state electronics: starting from the transistor and progressing to ring oscillators, current-mirror circuits to toggle switches and flip-flops. These canonical variants serve fundamental operations of synchronization and clocks (in their symmetric states) and memory storage (in their broken symmetry states). These conclusions introduce a theoretically principled strategy to search for computational building blocks in biological networks, and present a systematic route to design synthetic biological circuits