Improving Universality Results on Parallel Enzymatic Numerical P Systems

We improve previously known universality results on enzymatic numerical P systems (EN P systems, for short) working in all-parallel and one-parallel modes. By using a attening technique, we rst show that any EN P system working in one of these modes can be simulated by an equivalent one-membrane EN P system working in the same mode. Then we show that linear production functions, each depending upon at most one variable, su ce to reach universality for both computing modes. As a byproduct, we propose some small deterministic universal enzymatic numerical P systems

Open Problems, Research Topics, Recent Results on Numerical and Spiking Neural P Systems (The "Curtea de Arge s 2015 Series")

A series of open problems and research topics are formulated, about numer- ical and spiking neural P systems, initially prepared as a working material for a three months research stage of the second and the third co-author in Curtea de Arge s, Roma- nia, in the fall of 2015. Further problems were added during this period, while certain problems were addressed in this time; some details and references are provided for such cases

Frontiers of Membrane Computing: Open Problems and Research Topics

This is a list of open problems and research topics collected after the Twelfth Conference on Membrane Computing, CMC 2012 (Fontainebleau, France (23 - 26 August 2011), meant initially to be a working material for Tenth Brainstorming Week on Membrane Computing, Sevilla, Spain (January 30 - February 3, 2012). The result was circulated in several versions before the brainstorming and then modified according to the discussions held in Sevilla and according to the progresses made during the meeting. In the present form, the list gives an image about key research directions currently active in membrane computing

Numerical P Systems with Thresholds

Numerical P systems are a class of P systems inspired both from the structure of living cells and from economics. In this work, a control of using evolution programs is introduced into numerical P systems: a threshold is considered and a program can be applied only when the values of the variables involved in the production function of the program are greater than/equal to (lower-threshold) or smaller than/equal to (upper-threshold) the threshold. The computational power of numerical P systems with lower-threshold or upper-threshold is investigated. It is proved that numerical P systems with a lower-threshold, with one membrane and linear production functions, working both in the all-parallel mode and in the one-parallel mode are universal. The result is also extended to numerical P systems with an upperthreshold, by proving the equivalence of the numerical P systems with lower- and upper-thresholds

A new P-Lingua toolkit for agile development in membrane computing

Membrane computing is a massively parallel and non-deterministic bioinspired computing paradigm whose models are called P systems. Validating and testing such models is a challenge which is being overcome by developing simulators. Regardless of their heterogeneity, such simulators require to read and interpret the models to be simulated. To this end, P-Lingua is a high-level P system definition language which has been widely used in the last decade. The P-Lingua ecosystem includes not only the language, but also libraries and software tools for parsing and simulating membrane computing models. Each version of P-Lingua supported new types or variants of P systems. This leads to a shortcoming: Only a predefined list of variants can be used, thus making it difficult for researchers to study custom ones. Moreover, derivation modes cannot be user-defined, i.e, the way in which P system computations should be generated is determined by the simulation algorithm in the source code. The main contribution of this paper is a completely new design of the P-Lingua language, called P-Lingua 5, in which the user can define custom variants and derivation modes, among other improvements such as including procedural programming and simulation directives. It is worth mentioning that it has backward-compatibility with previous versions of the language. A completely new set of command-line tools is provided for parsing and simulating P-Lingua 5 files. Finally, several examples are included in this paper covering the most common P system types.Agencia Estatal de Investigación TIN2017-89842-

Lab-on-a-chip Thermoelectric and Solid-phase Immunodetection of Biochemical Analytes and Extracellular Vesicles: Experimental and Computational Analysis

Microfluidics is the technology of controlling and manipulating fluids at the microscale. Microfluidic platforms provide precise fluidic control coupled with low sample volume and an increase in the speed of biochemical reactions. Lab-on-a-chip platforms are used for detection and quantification of biochemical analytes, capture, and characterization of various proteins, sensitive analysis of cytokines, and isolation and detection of extracellular vesicles (EVs). This study focuses on the development of microfluidic and solid-phase capture pin platforms for the detection of cytokines, extracellular vesicles, and cell co-culture. The fabrication processes of the devices, experimental workflows, numerical analysis to identify optimal design parameters, and reproducibility studies have been discussed. Layer-by-layer assembly of polyelectrolytes has been developed to functionalize glass and stainless-steel substrates with biotin for the immobilization of streptavidinconjugated antibodies for selective capture of cytokines or EVs. Microstructure characterization techniques (SEM, EDX, and fluorescence microscopy) have been implemented to assess the efficiency of substrate functionalization. A detailed overview of current methods for purification and analysis of EVs is discussed as well. Additionally, the dissertation demonstrates the feasibility of a calorimetric microfluidic immunosensor with an integrated antimony-bismuth (Sb/Bi) thermopile sensor for the detection of cytokines with picomolar sensitivity. The developed platform can be used for the universal detection of both exothermic or endothermic reactions. A three-dimensional numerical model was developed to define the critical design parameters that enhance the sensitivity of the platform. Mathematical analyses identified the optimal combinations of substrate material and dimensions that will maximize the heat transfer to the sensor. Lab-on-a-chip cell co-culture platform with integrated pneumatic valve was designed, numerically characterized, and fabricated. This device enables the reversible separation of two cell culture chambers and serves as a tool for the effective analysis of cell-to-cell communication. Intercellular communication is mediated by extracellular vesicles. A protocol for the functionalization of stainless-steel probe with exosomespecific CD63 antibody was developed. The efficiency of the layer-by-layer deposition of polyelectrolytes and the effectiveness of biotin and streptavidin covalent boding were characterized using fluorescent and scanning electron microscopy

Real-time optical manipulation of cardiac conduction in intact hearts

Optogenetics has provided new insights in cardiovascular research, leading to new methods for cardiac pacing, resynchronization therapy and cardioversion. Although these interventions have clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies do not take into account cardiac wave dynamics in real time. Here, we developed an all‐optical platform complemented by integrated, newly developed software to monitor and control electrical activity in intact mouse hearts. The system combined a wide‐field mesoscope with a digital projector for optogenetic activation. Cardiac functionality could be manipulated either in free‐run mode with submillisecond temporal resolution or in a closed‐loop fashion: a tailored hardware and software platform allowed real‐time intervention capable of reacting within 2 ms. The methodology was applied to restore normal electrical activity after atrioventricular block, by triggering the ventricle in response to optically mapped atrial activity with appropriate timing. Real‐time intraventricular manipulation of the propagating electrical wavefront was also demonstrated, opening the prospect for real‐time resynchronization therapy and cardiac defibrillation. Furthermore, the closed‐loop approach was applied to simulate a re‐entrant circuit across the ventricle demonstrating the capability of our system to manipulate heart conduction with high versatility even in arrhythmogenic conditions. The development of this innovative optical methodology provides the first proof‐of‐concept that a real‐time optically based stimulation can control cardiac rhythm in normal and abnormal conditions, promising a new approach for the investigation of the (patho)physiology of the heart

Towards Loosely-Coupled Programming on Petascale Systems

We have extended the Falkon lightweight task execution framework to make loosely coupled programming on petascale systems a practical and useful programming model. This work studies and measures the performance factors involved in applying this approach to enable the use of petascale systems by a broader user community, and with greater ease. Our work enables the execution of highly parallel computations composed of loosely coupled serial jobs with no modifications to the respective applications. This approach allows a new-and potentially far larger-class of applications to leverage petascale systems, such as the IBM Blue Gene/P supercomputer. We present the challenges of I/O performance encountered in making this model practical, and show results using both microbenchmarks and real applications from two domains: economic energy modeling and molecular dynamics. Our benchmarks show that we can scale up to 160K processor-cores with high efficiency, and can achieve sustained execution rates of thousands of tasks per second.Comment: IEEE/ACM International Conference for High Performance Computing, Networking, Storage and Analysis (SuperComputing/SC) 200

A control-theoretic approach to dynamic optimization of metabolic networks

The characterization of general control principles that underpin metabolic dynamics is an important part of systems analysis in biology. It has been long argued that many biological regulatory mechanisms have evolved so as to optimize cellular adaptation in response to external stimuli. In this thesis we use an optimal control framework to solve dynamic optimization problems associated with metabolic dynamics. The analysis is based on a nonlinear control-ane model of a metabolic network with the enzyme concentrations as control inputs. We consider the optimization of time-dependent enzyme concentrations to activate an unbranched network and reach a prescribed metabolic ux. The solution accounts for time-resource optimality under constraints in the total enzymatic abundance. We identify a temporal pattern in the solution that is consistent with previous experimental and numerical observations. Our analysis suggests that this behaviour may appear in a broader class of networks than previously considered. In addition, we address the optimization of time-dependent enzyme expression rates for a metabolic network coupled with a model of enzyme dynamics. The formulation accounts for the transition between two metabolic steady states in networks with arbitrary stoichiometries and enzyme kinetics. We consider a nite horizon quadratic cost function that weighs the deviations of metabolites, enzymes and their expression rates from their target values, together with the time-derivative of the expression rates. The problem is recast as an iterative sequence of Linear Quadratic Tracking problems, and we derive conditions under which the iterations converge to a suboptimal solution of the original problem. Additionally, if constant metabolite concentrations are enforced, the nonlinear system can be written as a linear Dierential-Algebraic system. In the innite horizon case the problem can be recast as a standard Linear Quadratic Regulator problem for a lower-dimensional system, the solution of which is readily available