Biochemical systems analysis: A study of function and design in molecular biology

When conditions cause bacterial growth to stop, extensive reprogramming of physiology and gene expression allows for the cell's survival. We used whole‐genome DNA arrays to determine the system response in Escherichia coli cells experiencing transient growth arrest caused by glucose–lactose diauxie and H2O2 treatment, and also entry into stationary phase. The results show that growth‐arrested cells induce stringent control of several gene systems. The vast majority of genes encoding the transcription and translation apparatus immediately downregulate, followed by a global return to steady state when growth resumes. Approximately one‐half of the amino acid biosynthesis genes downregulate during growth arrest, with the notable exception of the his operon, which transiently upregulates in the diauxie experiment. Nucleotide biosynthesis downregulates, a result that is again consistent with the stringent response. Likewise, aerobic metabolism downregulates during growth arrest, and the results led us to suggest a model for stringent control of the ArcA regulon. The stationary phase stress response fully induces during growth arrest, whether transient or permanent, in a manner consistent with known mechanisms related to stringent control. Cells similarly induce the addiction module anti‐toxin and toxin genes during growth arrest; the latter are known to inhibit translation and DNA replication. The results indicate that in all aspects of the response cells do not distinguish between transient and potentially permanent growth arrest (stationary phase). We introduce an expanded model for the stringent response that integrates induction of stationary phase survival genes and inhibition of transcription, translation and DNA replication. Central to the model is the reprogramming of transcription by guanosine tetraphosphate (ppGpp), which provides for the cell's rapid response to growth arrest and, by virtue of its brief half‐life, the ability to quickly resume growth as changing conditions allow.

Gene expression profiling of Escherichia coli growth transitions: an expanded stringent response model: an expanded stringent response model

The understanding, and even the description of protein folding is impeded by the complexity of the process. Much of this complexity can be described and understood by taking a statistical approach to the energetics of protein conformation, that is, to the energy landscape. The statistical energy landscape approach explains when and why unique behaviors, such as specific folding pathways, occur in some proteins and more generally explains the distinction between folding processes common to all sequences and those peculiar to individual sequences. This approach also gives new, quantitative insights into the interpretation of experiments and simulations of protein folding thermodynamics and kinetics. Specifically, the picture provides simple explanations for folding as a two-state first-order phase transition, for the origin of metastable collapsed unfolded states and for the curved Arrhenius plots observed in both laboratory experiments and discrete lattice simulations. The relation of these quantitative ideas to folding pathways, to uni-exponential {\em vs.} multi-exponential behavior in protein folding experiments and to the effect of mutations on folding is also discussed. The success of energy landscape ideas in protein structure prediction is also described. The use of the energy landscape approach for analyzing data is illustrated with a quantitative analysis of some recent simulations, and a qualitative analysis of experiments on the folding of three proteins. The work unifies several previously proposed ideas concerning the mechanism protein folding and delimits the regions of validity of these ideas under different thermodynamic conditions.

Funnels, Pathways and the Energy Landscape of Protein Folding: A Synthesis

Reversible logic has shown potential to have extensive applications in emerging technologies such as quantum computing, optical computing, quantum dot cellular automata as well as ultra low power VLSI circuits. Recently, several researchers have focused their efforts on the design and synthesis of efficient reversible logic circuits. In these works, the primary design focus has been on optimizing the number of reversible gates and the garbage outputs. The number of reversible gates is not a good metric of optimization as each reversible gate is of different type and computational complexity, and thus will have a different quantum cost and delay. The computational complexity of a reversible gate can be represented by its quantum cost. Further, delay constitutes an important metric, which has not been addressed in prior works on reversible sequential circuits as a design metric to be optimized. In this work, we present novel designs of reversible sequential circuits that are optimized in terms of quantum cost, delay and the garbage outputs. The optimized designs of several reversible sequential circuits are presented including the D Latch, the JK latch, the T latch and the SR latch, and their corresponding reversible master-slave flip-flop designs. The proposed master-slave flip-flop designs have the special property that they don't require the inversion of the clock for use in the slave latch. Further, we introduce a novel strategy of cascading a Fredkin gate at the outputs of a reversible latch to realize the designs of the Fredkin gate based asynchronous set/reset D latch and the master-slave D flip-flop. Finally, as an example of complex reversible sequential circuits, the reversible logic design of the universal shift register is introduced. The proposed reversible sequential designs were verified through simulations using Verilog HDL and simulation results are presented.

Design of reversible sequential circuits optimizing quantum cost, delay, and garbage outputs

Biochemical systems theory (BST) is the foundation for a set of analytical andmodeling tools that facilitate the analysis of dynamic biological systems. This paper depicts major developments in BST up to the current state of the art in 2012. It discusses its rationale, describes the typical strategies and methods of designing, diagnosing, analyzing, and utilizing BST models, and reviews areas of application. The paper is intended as a guide for investigators entering the fascinating field of biological systems analysis and as a resource for practitioners and experts.

https://downloads.hindawi.com/archive/2013/897658.pdf

Biochemical Systems Theory: A Review

Efficient approaches for designing reversible Binary Coded Decimal adders

A reversible gate has the equal number of inputs and outputs and one-to-one mappings between input vectors and output vectors; so that, the input vector states can be always uniquely reconstructed from the output vector states. This correspondence introduces a reversible full-adder circuit that requires only three reversible gates and produces least number of "garbage outputs ", that is two. After that, a theorem has been proposed that proves the optimality of the propounded circuit in terms of number of garbage outputs. An efficient algorithm is also introduced in this paper that leads to construct a reversible circuit.

Synthesis of full-adder circuit using reversible logic

Reversible logic is of the growing importance to many future technologies. A reversible circuit maps each output vector, into a unique input vector, and vice versa. This paper introduces an approach to synthesise the generalized multi-rail reversible cascades and minimizing the "garbage bit" and number of reversible gates, which is the main challenge of reversible logic synthesis. This proposed full-adder circuit contains only three gates and two garbage outputs whereas earlier full-adder circuit by M. Perkowski et al. (2001) requires four gates and produces two garbage outputs and another existing full-adder circuit by Md. H. H Azad Khan (2002) requires three gates but produces three garbage outputs. Thus, the proposed full-adder circuit is efficient in terms of number of gates with compared to M. Perkowski et al. (2001) as well as in terms of number of garbage outputs with compared to Md. H. H Azad Khan (2002).

Reversible logic synthesis for minimization of full-adder circuit

In this paper, we have proposed a design technique for the reversible circuit of binary coded decimal (BCD) adder. The proposed circuit has the ability to add two 4-bits binary variables and it transforms the addition into the appropriate BCD number with efficient error correcting modules where the operations are reversible. We also show that the proposed design technique generates the reversible BCD adder circuit with minimum number of gates as well as the minimum number of garbage outputs.

Ahsan Raja Chowdhury

Papers

Efficient approaches for designing reversible Binary Coded Decimal adders

Synthesis of full-adder circuit using reversible logic

Reversible logic synthesis for minimization of full-adder circuit

Design of a reversible binary coded decimal adder by using reversible 4-bit parallel adder

Design of a compact reversible binary coded decimal adder circuit