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Quantitative analysis of signaling networks
 Progr. Biophys. Mol. Bio
"... The response of biological cells to environmental change is coordinated by protein based signaling networks. These networks are to be found in both prokaryotes and eukaryotes. In eukaryotes the signaling networks can be highly complex, some networks comprising of sixty or more proteins. The fundamen ..."
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The response of biological cells to environmental change is coordinated by protein based signaling networks. These networks are to be found in both prokaryotes and eukaryotes. In eukaryotes the signaling networks can be highly complex, some networks comprising of sixty or more proteins. The fundamental motif that has been found in all signaling networks is the protein phosphorylation/dephosphorylation cycle the cascade cycle. At this time, the computational function of many of the signaling networks is poorly understood. However, it is clear that it is possible to construct a huge variety of control and computational circuits, both analog and digital from combinations of the cascade cycle. In this review we will summarize the great versatility of the simple cascade cycle as a computational unit and towards the end give two examples, one prokaryotic chemotaxis circuit and the other, the eukaryotic MAPK
The computational versatility of proteomic signaling networks
 Current Proteomics
, 1993
"... Abstract: Almost all proteomic signaling networks in prokaryotes and eukaryotes are based on the simple phosphorylation/dephosporylation cycle; from this simple unit it is possible to construct a huge variety of control and computational circuits, both analog and digital. With the characterization o ..."
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Abstract: Almost all proteomic signaling networks in prokaryotes and eukaryotes are based on the simple phosphorylation/dephosporylation cycle; from this simple unit it is possible to construct a huge variety of control and computational circuits, both analog and digital. With the characterization of many signaling networks, researchers are turning to address the question of how a particular physiological response can be understood in terms of the proteins that make up the network; this is one of the central questions in “Systems Biology”. In this article I wish to summarize the great versatility of the basic protein cycle as a means to construct complex functional behaviors including the central role that feedback plays in determining the properties of protein based networks. 1.
Elements of a More Comprehensive Theory of Computing
 BioSystems
, 1999
"... Problems implementing DNA computers stem from the physical nature of molecules and their reactions. The present theory of computation requires assumptions that, at best, are extremely crude approximations of the physical chemistry. Here I consider the hypothesis that discarding those assumptions in ..."
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Problems implementing DNA computers stem from the physical nature of molecules and their reactions. The present theory of computation requires assumptions that, at best, are extremely crude approximations of the physical chemistry. Here I consider the hypothesis that discarding those assumptions in favor of more physically realistic descriptions would produce a more comprehensive theory of computing, yielding both theoretical insights and help in designing better molecular computers. I describe the discordances between the theories of physical biochemistry and computation, indicate some elements of a more comprehensive theory, and discuss some of the challenges the construction of a unified theory faces. keywords: molecular computing DNA computing physical biochemistry theory of computing 1 Hypothesis Molecular computing is justifiably exciting, not least for the alluring prospect of biologicallyinspired machines nicely handling NPcomplete problems. However, current molecular ...
Accurate and Precise Computation using Analog VLSI, with Applications to Computer Graphics and Neural Networks
, 1993
"... This thesis develops an engineering practice and design methodology to enable us to use CMOS analog VLSI chips to perform more accurate and precise computation. These techniques form the basis of an approach that permits us to build computer graphics and neural network applications using analog VLSI ..."
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This thesis develops an engineering practice and design methodology to enable us to use CMOS analog VLSI chips to perform more accurate and precise computation. These techniques form the basis of an approach that permits us to build computer graphics and neural network applications using analog VLSI. The nature of the design methodology focuses on defining goals for circuit behavior to be met as part of the design process. To increase the accuracy of analog computation, we develop techniques for creating compensated circuit building blocks, where compensation implies the cancellation of device variations, offsets, and nonlinearities. These compensated building blocks can be used as components in larger and more complex circuits, which can then also be compensated. To this end, we develop techniques for automatically determining appropriate parameters for circuits, using constrained optimization. We also fabricate circuits that implement multidimensional gradient estimation for a grad...
Neuromorphic Systems: past, present and future
"... Abstract Neuromorphic systems are implementations in silicon of elements of neural systems. The idea of electronic implementation is not new, but modern microelectronics has provided opportunities for producing systems for both sensing and neural modelling that can be mass produced straightforwardly ..."
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Abstract Neuromorphic systems are implementations in silicon of elements of neural systems. The idea of electronic implementation is not new, but modern microelectronics has provided opportunities for producing systems for both sensing and neural modelling that can be mass produced straightforwardly. We review the the history of neuromorphic systems, and discuss the range of neuromorphic systems that have ben developed. We discuss recent ideas for overcoming some of the problems, particularly providing effective adaptive synapses in large numbers. 1
Kholodenko: Quantitative analysis of signaling networks
 Progress in Biophysics & Molecular Biology 86
, 2004
"... The response of biological cells to environmental change is coordinated by proteinbased signaling networks. These networks are to be found in both prokaryotes and eukaryotes. In eukaryotes, the signaling networks can be highly complex, some networks comprising of 60 or more proteins. The fundamenta ..."
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The response of biological cells to environmental change is coordinated by proteinbased signaling networks. These networks are to be found in both prokaryotes and eukaryotes. In eukaryotes, the signaling networks can be highly complex, some networks comprising of 60 or more proteins. The fundamental motif that has been found in all signaling networks is the protein phosphorylation/dephosphorylation cycle—the cascade cycle. At this time, the computational function of many of the signaling networks is poorly understood. However, it is clear that it is possible to construct a huge variety of control and computational circuits, both analog and digital from combinations of the cascade cycle. In this review, we will summarize the great versatility of the simple cascade cycle as a computational unit and towards the end give two examples, one prokaryotic chemotaxis circuit and the other, the eukaryotic MAPK cascade.
After the Turing Machine
, 1999
"... Problems in implementing DNA and other types of molecular computers stem from the inherent physical nature of molecules and their reactions. The current theory of computation makes assumptions that at best are very crude approximations of the physical chemistry. A theory which took into account the ..."
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Problems in implementing DNA and other types of molecular computers stem from the inherent physical nature of molecules and their reactions. The current theory of computation makes assumptions that at best are very crude approximations of the physical chemistry. A theory which took into account the physical chemistry would likely be very different from what we have now and should help in designing more optimal molecular computing systems. In this paper I describe briefly the discordance between these assumptions and the physical chemistry; indicate some of the properties a more physically realistic model might have; and sketch some of the possibilities for a computing system which exploited the physical chemistry. We are developing a model for networks of biochemical reactions and molecules incorporating treatments of both continuous and discrete aspects of biochemical systems. The formal system of the model provides an example of what a CPC might be if the problems of encodi...
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"... Study of the thermal behavior of a synchronous motor with permanent magnets ..."
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Study of the thermal behavior of a synchronous motor with permanent magnets
A Review of Field Computation
, 2007
"... This report reviews the basic principles of field computation, a model of massively parallel analog computation, and discusses its applications in natural and artificial intelligence. We begin with the mathematical foundations and notation for field computation; Hilbert spaces provide the basic math ..."
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This report reviews the basic principles of field computation, a model of massively parallel analog computation, and discusses its applications in natural and artificial intelligence. We begin with the mathematical foundations and notation for field computation; Hilbert spaces provide the basic mathematical framework. Next we discuss examples of field computation in the brain, especially in its computational maps. Fields appear in a number of contexts, including activity at the axon hillocks, in patterns of axonal connection between areas, and in patterns of synaptic connection to dendrites. The following section presents examples of field computation in the brain and in other natural and artificial systems, including fields for sensorimotor processing, excitable media, and diffusion processes. Next we consider special topics in field computation in cognition, including the separation of information (semantics) from pragmatics, and the analysis of discrete symbols as field excitations. We also consider the relevance of universal mutivariate approximation theorems to generalpurpose
Metaphorical Uses of an Electric Power Network: Early Computations of Atomic Particles and Nuclear Reactors
"... To retrieve the constitutional importance of metaphors, analogies, and models in scientific computations of the immediate postWorld War II period, we shall investigate the uses of an understudied artifact known as the ‘network analyzer’. As an electrical model of an electric power network, it was i ..."
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To retrieve the constitutional importance of metaphors, analogies, and models in scientific computations of the immediate postWorld War II period, we shall investigate the uses of an understudied artifact known as the ‘network analyzer’. As an electrical model of an electric power network, it was introduced during the interwar period as the best option to compute the complex environment produced by lengthening and interconnecting electric power transmission lines. Now considered an exemplar of the devaluated analog computer, ostensibly limited by being a special purpose machine, the network analyzer was used for many purposes beyond electric power transmission computations, including that of sciencerelated computations. We shall consider the suggestive case of its use in computing atomic particles and nuclear reactions, based on the metaphoric consideration of both as analogous to an electric power network.