Flux balance analysis of biological systems: applications and challenges

Systems level modelling and simulations of biological processes are proving to be invaluable in obtaining a quantitative and dynamic perspective of various aspects of cellular function. In particular, constraint-based analyses of metabolic networks have gained considerable popularity for simulating cellular metabolism, of which flux balance analysis (FBA), is most widely used. Unlike mechanistic simulations that depend on accurate kinetic data, which are scarcely available, FBA is based on the principle of conservation of mass in a network, which utilizes the stoichiometric matrix and a biologically relevant objective function to identify optimal reaction flux distributions. FBA has been used to analyse genome-scale reconstructions of several organisms; it has also been used to analyse the effect of perturbations, such as gene deletions or drug inhibitions in silico. This article reviews the usefulness of FBA as a tool for gaining biological insights, advances in methodology enabling integration of regulatory information and thermodynamic constraints, and finally addresses the challenges that lie ahead. Various use scenarios and biological insights obtained from FBA, and applications in fields such metabolic engineering and drug target identification, are also discussed. Genome-scale constraint-based models have an immense potential for building and testing hypotheses, as well as to guide experimentation.

Solution NMR studies of acetohydroxy acid synthase I: Identification of the sites of inter-subunit interactions using multidimensional NMR methods

The novel multidomain organization in the multimeric Escherichia coli AHAS I (ilvBN) enzyme has been dissected to generate polypeptide fragments. These fragments when cloned, expressed and purified reassemble in the presence of cofactors to yield a catalytically competent enzyme. Structural characterization of AHAS has been impeded due to the fact that the holoenzyme is prone to dissociation leading to heterogeneity in samples. Our approach has enabled the structural characterization using high-resolution nuclear magnetic resonance methods. Near complete sequence specific NMR assignments for backbone H-N, N-15, C-13 alpha and C-13(beta) atoms of the FAD binding domain of ilvB have been obtained on samples isotopically enriched in H-2, C-13 and N-15. The secondary structure determined on the basis of observed C-13(alpha) secondary chemical shifts and sequential NOEs indicates that the secondary structure of the FAD binding domain of E. coli AHAS large Subunit (ilvB) is similar to the structure of this domain in the catalytic subunit of yeast AHAS. Protein-protein interactions involving the regulatory subunit (ilvN) and the domains of the catalytic subunit (ilvB) were studied using circular dichroic and isotope edited solution nuclear magnetic resonance spectroscopic methods. Observed changes in circular dichroic spectra indicate that the regulatory subunit (ilvN) interacts with ilvB alpha and ilvB beta domains of the catalytic subunit and not with the ilvB gamma domain. NMR chemical shift mapping methods show that ilvN binds close to the FAD binding site in ilvB beta and proximal to the intrasubunit ilvB alpha/ilvB beta domain interface. The implication of this interaction on the role of the regulatory subunit oil the activity of the holoenzyme is discussed. NMR studies of the regulatory domains show that these domains are structured in solution. Preliminary evidence for the interaction of ilvN with the metabolic end product of the pathway, viz., valine is also presented.

A new framework for solution of multidimensional population balance equations

A new framework is proposed in this work to solve multidimensional population balance equations (PBEs) using the method of discretization. A continuous PBE is considered as a statement of evolution of one evolving property of particles and conservation of their n internal attributes. Discretization must therefore preserve n + I properties of particles. Continuously distributed population is represented on discrete fixed pivots as in the fixed pivot technique of Kumar and Ramkrishna [1996a. On the solution of population balance equation by discretization-I A fixed pivot technique. Chemical Engineering Science 51(8), 1311-1332] for 1-d PBEs, but instead of the earlier extensions of this technique proposed in the literature which preserve 2(n) properties of non-pivot particles, the new framework requires n + I properties to be preserved. This opens up the use of triangular and tetrahedral elements to solve 2-d and 3-d PBEs, instead of the rectangles and cuboids that are suggested in the literature. Capabilities of computational fluid dynamics and other packages available for generating complex meshes can also be harnessed. The numerical results obtained indeed show the effectiveness of the new framework. It also brings out the hitherto unknown role of directionality of the grid in controlling the accuracy of the numerical solution of multidimensional PBEs. The numerical results obtained show that the quality of the numerical solution can be improved significantly just by altering the directionality of the grid, which does not require any increase in the number of points, or any refinement of the grid, or even redistribution of pivots in space. Directionality of a grid can be altered simply by regrouping of pivots.

On the L2 stability of linear multidimensional time varying systems

This paper analyzes the L2 stability of solutions of systems with time-varying coefficients of the form [A + C(t)]x′ = [B + D(t)]x + u, where A, B, C, D are matrices. Following proof of a lemma, the main result is derived, according to which the system is L2 stable if the eigenvalues of the coefficient matrices are related in a simple way. A corollary of the theorem dealing with small periodic perturbations of constant coefficient systems is then proved. The paper concludes with two illustrative examples, both of which deal with the attitude dynamics of a rigid, axisymmetric, spinning satellite in an eccentric orbit, subject to gravity gradient torques.

Bounded-input/bounded-output stability of linear multidimensional time- varying systems

The present study of the stability of systems governed by a linear multidimensional time-varying equation, which are encountered in spacecraft dynamics, economics, demographics, and biological systems, gives attention the lemma dealing with L(inf) stability of an integral equation that results from the differential equation of the system under consideration. Using the proof of this lemma, the main result on L(inf) stability is derived according; a corollary of the theorem deals with constant coefficient systems perturbed by small periodic terms. (O.C.)

IPCC:accomplishments,controversies and challenges

The Intergovernmental Panel on Climate Change (IPCC) has successfully produced four assessment reports since 1990 along with a number of special reports and greenhouse gas inventory guidelines. It has very rigorous and robust procedures and guidelines for preparing the assessment reports largely based on synthesis of peer-reviewed and published scientific literature. IPCC has attracted controversy since the Second Assessment Report of 1995. The recent controversies surrounding the IPCC reports surfaced nearly two years after the release of the report in 2007, especially in the wake of the crucial Copenhagen Climate Convention. Many of the controversies can be traced to the use of information sourced from reports published outside the scientific journals such as reports of the World Wildlife Fund. It is true that there are a few errors in the IPCC reports, which may have escaped the multilayered rigorous review process. Many of the errors found in the main reports, which are over a thousand page each, have not been quoted in the crucial and most referred Summary for Policy Makers. IPCC may have to develop a more robust policy for sourcing literature published outside the scientific journals. The United Nations Secretary General has requested the prestigious Inter-Academy Council to review the IPCC principles, procedures and guidelines. The controversies raised in the recent past do not in any way change the main conclusions of the IPCC Assessment Report.

Impact of dust on solar photovoltaic (PV) performance: Research status, challenges and recommendations

The peaking of most oil reserves and impending climate change are critically driving the adoption of solar photovoltaic's (PV) as a sustainable renewable and eco-friendly alternative. Ongoing material research has yet to find a breakthrough in significantly raising the conversion efficiency of commercial PV modules. The installation of PV systems for optimum yield is primarily dictated by its geographic location (latitude and available solar insolation) and installation design (tilt, orientation and altitude) to maximize solar exposure. However, once these parameters have been addressed appropriately, there are other depending factors that arise in determining the system performance (efficiency and output). Dust is the lesser acknowledged factor that significantly influences the performance of the PV installations. This paper provides an appraisal on the current status of research in studying the impact of dust on PV system performance and identifies challenges to further pertinent research. A framework to understand the various factors that govern the settling/assimilation of dust and likely mitigation measures have been discussed in this paper. (C) 2010 Elsevier Ltd. All rights reserved.

Climate change and forests in India: adaptation opportunities and challenges

Climate change is projected to lead to shift of forest types leading to irreversible damage to forests by rendering several species extinct and potentially affecting the livelihoods of local communities and the economy. Approximately 47% and 42% of tropical dry deciduous grids are projected to undergo shifts under A2 and B2 SRES scenarios respectively, as opposed to less than 16% grids comprising of tropical wet evergreen forests. Similarly, the tropical thorny scrub forest is projected to undergo shifts in majority of forested grids under A2 (more than 80%) as well as B2 scenarios (50% of grids). Thus the forest managers and policymakers need to adapt to the ecological as well as the socio-economic impacts of climate change. This requires formulation of effective forest management policies and practices, incorporating climate concerns into long-term forest policy and management plans. India has formulated a large number of innovative and progressive forest policies but a mechanism to ensure effective implementation of these policies is needed. Additional policies and practices may be needed to address the impacts of climate change. This paper discusses an approach and steps involved in the development of an adaptation framework as well as policies, strategies and practices needed for mainstreaming adaptation to cope with projected climate change. Further, the existing barriers which may affect proactive adaptation planning given the scale, accuracy and uncertainty associated with assessing climate change impacts are presented.

Challenges in Earth sciences: the 21st century

The 21st century poses many challenges for global sustainability. Among them, most importantly, the human race will encounter scarcity of raw materials and conventional energy resources. And, India may have to take the brunt of these problems as it is going to be the most populated region of the world with concomitant increase in energy demand and requirement of other resources. India will be the testing ground for introducing newer ways of green technology and innovative principles of resource management and utilization. With the vagaries of potential climate change gathering clouds in the background, Earth sciences will have a special and predominant role in guiding the society in prioritizing our resource discovery, utilization and their consumption and the upkeep of environment. On the fundamental level, Earth sciences are going through a most exciting phase of development as a born-again science. Technological breakthroughs including the satellite-based observations augur well for gaining new insights into Earth processes. A set of exciting fundamental problems that are globally identified will set the stage for an exhilarating period of new discoveries. Improvements in numerical and computer-based techniques will assist in modelling of Earth processes to unprecedented levels. India will have to take special effort in improving the existing experimentation facilities in the Earth science departments of the country, and also the general level of Earth science education to meet the global standards. This article presents an Earth science vision for the 21st century in an Indian context.

Biopolymers in nanopores: challenges and opportunities

We review the current status of various aspects of biopolymer translocation through nanopores and the challenges and opportunities it offers. Much of the interest generated by nanopores arises from their potential application to third-generation cheap and fast genome sequencing. Although the ultimate goal of single-nucleotide identification has not yet been reached, great advances have been made both from a fundamental and an applied point of view, particularly in controlling the translocation time, fabricating various kinds of synthetic pores or genetically engineering protein nanopores with tailored properties, and in devising methods (used separately or in combination) aimed at discriminating nucleotides based either on ionic or transverse electron currents, optical readout signatures, or on the capabilities of the cellular machinery. Recently, exciting new applications have emerged, for the detection of specific proteins and toxins (stochastic biosensors), and for the study of protein folding pathways and binding constants of protein-protein and protein-DNA complexes. The combined use of nanopores and advanced micromanipulation techniques involving optical/magnetic tweezers with high spatial resolution offers unique opportunities for improving the basic understanding of the physical behavior of biomolecules in confined geometries, with implications for the control of crucial biological processes such as protein import and protein denaturation. We highlight the key works in these areas along with future prospects. Finally, we review theoretical and simulation studies aimed at improving fundamental understanding of the complex microscopic mechanisms involved in the translocation process. Such understanding is a pre-requisite to fruitful application of nanopore technology in high-throughput devices for molecular biomedical diagnostics.

Training Young Minds for Nanoscience and Technology: Issues and Challenges

This article explores issues and challenges in the field of education in nanoscience and technology with special emphasis with respect to India, where an expanding programme of research in nano science and technology is in place. The article does not concentrate on actual curricula that are needed in nano science and technology education course. Rather it focuses on the desirability of nanoscience and technology education at different levels of education and future prospect of students venturing into this within the economic and cultural milieu of India. We argue that care is needed in developing the education programme in India. However, the risk is worth taking as the education on nanoscience and technology can bridge the man power gap not only in this area of technology but also related technologies of hardware and micro electronics for which the country is a promising destination at global level. This will also unlock the demographical advantage that India will enjoy in the next five decades.