Kinetic approaches to lactose operon induction and bimodality

The quasi-equilibrium approximation is acceptable when molecular interactions are fast enough compared to circuit dynamics, but is no longer allowed when cellular activities are governed by rare events. A typical example is the lactose operon (lac), one of the most famous paradigms of transcription regulation, for which several theories still coexist to describe its behaviors. The lac system is generally analyzed by using equilibrium constants, contradicting single-event hypotheses long suggested by Novick and Weiner (1957). Enzyme induction as an all-or-none phenomenon. Proc. Natl. Acad. Sci. USA 43, 553-566) and recently refined in the study of (Choi et al., 2008. A stochastic single-molecule event triggers phenotype switching of a bacterial cell. Science 322, 442-446). In the present report, a lac repressor (LacI)-mediated DNA immunoprecipitation experiment reveals that the natural LacI-lac DNA complex built in vivo is extremely tight and long-lived compared to the time scale of lac expression dynamics, which could functionally disconnect the abortive expression bursts and forbid using the standard modes of lac bistability. As alternatives, purely kinetic mechanisms are examined for their capacity to restrict induction through: (i) widely scattered derepression related to the arrival time variance of a predominantly backward asymmetric random walk and (ii) an induction threshold arising in a single window of derepression without recourse to nonlinear multimeric binding and Hill functions. Considering the complete disengagement of the lac repressor from the lac promoter as the probabilistic consequence of a transient stepwise mechanism, is sufficient to explain the sigmoidal lac responses as functions of time and of inducer concentration. This sigmoidal shape can be misleadingly interpreted as a phenomenon of equilibrium cooperativity classically used to explain bistability, but which has been reported to be weak in this system

Conditional Reliability in Uncertain Graphs

Network reliability is a well-studied problem that requires to measure the probability that a target node is reachable from a source node in a probabilistic (or uncertain) graph, i.e., a graph where every edge is assigned a probability of existence. Many approaches and problem variants have been considered in the literature, all assuming that edge-existence probabilities are fixed. Nevertheless, in real-world graphs, edge probabilities typically depend on external conditions. In metabolic networks a protein can be converted into another protein with some probability depending on the presence of certain enzymes. In social influence networks the probability that a tweet of some user will be re-tweeted by her followers depends on whether the tweet contains specific hashtags. In transportation networks the probability that a network segment will work properly or not might depend on external conditions such as weather or time of the day. In this paper we overcome this limitation and focus on conditional reliability, that is assessing reliability when edge-existence probabilities depend on a set of conditions. In particular, we study the problem of determining the k conditions that maximize the reliability between two nodes. We deeply characterize our problem and show that, even employing polynomial-time reliability-estimation methods, it is NP-hard, does not admit any PTAS, and the underlying objective function is non-submodular. We then devise a practical method that targets both accuracy and efficiency. We also study natural generalizations of the problem with multiple source and target nodes. An extensive empirical evaluation on several large, real-life graphs demonstrates effectiveness and scalability of the proposed methods.Comment: 14 pages, 13 figure

A Multi-Model Approach to Identification of Biosynthetic Pathways

We present an identification framework for biochemical systems that allows multiple candidate models to be compared. This framework is designed to select a model that fits the data while maintaining model simplicity. The model identification task is divided into a parameter estimation stage and a model comparison stage. Model selection is based on calculating Akaike's information criterion, which is a systematic method for determining the model that best represents a set of experimental data. Two case studies are presented: a simulated transcriptional control circuit and a system of oscillators that has been built and characterized in vitro. In both examples the multi-model framework is able to discriminate between model candidates to select the one that best describes the data

Efficient Control Approaches for Guaranteed Frequency Performance in Power Systems

Due to high penetration of renewable energy, converter-interfaced sources are increasing in power systems and degrading the grid frequency response. Synthetic inertia emulation and guaranteed primary frequency response is a challenging task. Still, there is high potential for application of highly controllable converter-interfaced devices to help performance. Renewable energy sources and demand side smart devices also need to be equipped with innovative frequency control approaches that contribute to frequency regulation operations. First, the wind turbine generator is chosen to represent an example of a converter- interfaced source. An augmented system frequency response model is derived, including the system frequency response model and a reduced-order model of the wind turbine generator representing the supportive active power due to supplementary inputs. An output feedback observer-based control is designed to provide guaranteed frequency performance. System performance is analyzed for different short circuit ratio scenarios where a lower bound to guarantee the performance is obtained. Second, the load side control for frequency regulation with its challenges is introduced. 5G technology and its potential application in smart grids are analyzed. The effect of communication delays and packet losses on inertia emulation are investigated to show the need of using improved communication infrastructure. Third, a robust delay compensation for primary frequency control using fast demand response is proposed. Possible system structured uncertainties and communication delays are considered to limit frequency variations using the proposed control approach. An uncertain governor dead-band model is introduced to capture frequency response characteristics. Guaranteed inertial response is achieved and compared with a PI-based Smith predictor controller to show the effectiveness of the proposed method. Fourth, set theoretic methods for safety verification to provide guaranteed frequency response are introduced. The Barrier certificate approach using a linear programming relaxation by Handelman’s representation is proposed with its application to power systems. Finally, the Handelman’s based barrier certificate approach for adequate frequency performance is studied. The computational algorithm is provided for the proposed method and validated using power system benchmark case studies with a discussion on a safety supervisory control (SSC)

Anaerobic digestion and biogas potential: simulation of lab and industrial-scale processes

In this study, simulation was carried out using BioWin to test the capability of the software in predicting biogas potential for two different anaerobic systems. The two scenarios included; 1) a laboratory scale batch reactor and 2) an industrial scale anaerobic continuous lagoon digester. Measured data relating to operating conditions, reactor design parameters, and chemical properties of influent wastewater were entered into BioWin. A sensitivity analysis was carried out to identify the sensitivity of the most important default parameters in the software's models. BioWin was then calibrated by matching the predicted data with measured data and used to simulate other parameters which were unmeasured or deemed uncertain. In addition, statistical analyses were carried out using evaluation indices such as coefficient of determination (R-squared), correlation coefficient (r) and its significance (P value), general standard deviation (SD) and Willmott index of agreement to evaluate the agreement between the software prediction and the measured data. The results have shown that after calibration, BioWin can be used reliably to simulating both small scale batch reactors and industrial scale digesters with an absolute relative error less than 10% and very good indexes' values. Also, by changing the default parameters in BioWin, which is a way of calibrating the models in the software as well, it may provide information about the performance of the digester. Furthermore, the results of this study showed there may be an over estimation for biogas generated from industrial scale digesters. More sophisticated analytical devices may be required for reliable measurements of biogas quality and quantity