Computational systems approach for drug target discovery

Importance of the field: The shift in focus from ligand based design approaches to target based discovery over the last two to three decades has been a major milestone in drug discovery research. Currently, it is witnessing another major paradigm shift by leaning towards the holistic systems based approaches rather the reductionist single molecule based methods. The effect of this new trend is likely to be felt strongly in terms of new strategies for therapeutic intervention, new targets individually and in combinations, and design of specific and safer drugs. Computational modeling and simulation form important constituents of new-age biology because they are essential to comprehend the large-scale data generated by high-throughput experiments and to generate hypotheses, which are typically iterated with experimental validation. Areas covered in this review: This review focuses on the repertoire of systems-level computational approaches currently available for target identification. The review starts with a discussion on levels of abstraction of biological systems and describes different modeling methodologies that are available for this purpose. The review then focuses on how such modeling and simulations can be applied for drug target discovery. Finally, it discusses methods for studying other important issues such as understanding targetability, identifying target combinations and predicting drug resistance, and considering them during the target identification stage itself. What the reader will gain: The reader will get an account of the various approaches for target discovery and the need for systems approaches, followed by an overview of the different modeling and simulation approaches that have been developed. An idea of the promise and limitations of the various approaches and perspectives for future development will also be obtained. Take home message: Systems thinking has now come of age enabling a `bird's eye view' of the biological systems under study, at the same time allowing us to `zoom in', where necessary, for a detailed description of individual components. A number of different methods available for computational modeling and simulation of biological systems can be used effectively for drug target discovery.

Environment Education for Ecosystem Conservation

Conservation of natural resources through sustainable ecosystem management and development is the key to our secured future. The management of ecosystem involves inventorying and monitoring, and applying integrated technologies, methodologies and interdisciplinary approaches for its conservation. Hence, now it is even more critical than ever before for the humans to be environmentally literate. To realise this vision, both ecological and environmental education must become a fundamental part of the education system at all levels of education. Currently, it is even more critical than ever before for the humankind as a whole to have a clear understanding of environmental concerns and to follow sustainable development practices. The degradation of our environment is linked to continuing problems of pollution, loss of forest, solid waste disposal, and issues related to economic productivity and national as well as ecological security. Environmental management has gained momentum in the recent years with the initiatives focussing on managing environmental hazards and preventing possible disasters. Environmental issues make better sense, when one can understand them in the context of one’s own cognitive sphere. Environmental education focusing on real-world contexts and issues often begins close to home, encouraging learners to understand and forge connections with their immediate surroundings. The awareness, knowledge, and skills needed for these local connections and understandings provide a base for moving out into larger systems, broader issues, and a more sophisticated comprehension of causes, connections, and consequences. Environmental Education Programme at CES in collaboration with Karnataka Environment Research Foundation (KERF) referred as ‘Know your Ecosystem’ focuses on the importance of investigating the ecosystems within the context of human influences, incorporating an examination of ecology, economics, culture, political structure, and social equity as well as natural processes and systems. The ultimate goal of environment education is to develop an environmentally literate public. It needs to address the connection between our conception and practice of education and our relationship as human cultures to life-sustaining ecological systems. For each environmental issue there are many perspectives and much uncertainty. Environmental education cultivates the ability to recognise uncertainty, envision alternative scenarios, and adapt to changing conditions and information. These knowledge, skills, and mindset translate into a citizenry who is better equipped to address its common problems and take advantage of opportunities, whether environmental concerns are involved or not.

Environment Education for Ecosystem Conservation

Conservation of natural resources through sustainable ecosystem management and development is the key to our secured future. The management of ecosystem involves inventorying and monitoring, and applying integrated technologies, methodologies and interdisciplinary approaches for its conservation. Hence, now it is even more critical than ever before for the humans to be environmentally literate. To realise this vision, both ecological and environmental education must become a fundamental part of the education system at all levels of education. Currently, it is even more critical than ever before for the humankind as a whole to have a clear understanding of environmental concerns and to follow sustainable development practices. The degradation of our environment is linked to continuing problems of pollution, loss of forest, solid waste disposal, and issues related to economic productivity and national as well as ecological security. Environmental management has gained momentum in the recent years with the initiatives focussing on managing environmental hazards and preventing possible disasters. Environmental issues make better sense, when one can understand them in the context of one’s own cognitive sphere. Environmental education focusing on real-world contexts and issues often begins close to home, encouraging learners to understand and forge connections with their immediate surroundings. The awareness, knowledge, and skills needed for these local connections and understandings provide a base for moving out into larger systems, broader issues, and a more sophisticated comprehension of causes, connections, and consequences. Environmental Education Programme at CES in collaboration with Karnataka Environment Research Foundation (KERF) referred as ‘Know your Ecosystem’ focuses on the importance of investigating the ecosystems within the context of human influences, incorporating an examination of ecology, economics, culture, political structure, and social equity as well as natural processes and systems. The ultimate goal of environment education is to develop an environmentally literate public. It needs to address the connection between our conception and practice of education and our relationship as human cultures to life-sustaining ecological systems. For each environmental issue there are many perspectives and much uncertainty. Environmental education cultivates the ability to recognise uncertainty, envision alternative scenarios, and adapt to changing conditions and information. These knowledge, skills, and mindset translate into a citizenry who is better equipped to address its common problems and take advantage of opportunities, whether environmental concerns are involved or not.

Environment Education for Ecosystem Conservation

Conservation of natural resources through sustainable ecosystem management and development is the key to our secured future. The management of ecosystem involves inventorying and monitoring, and applying integrated technologies, methodologies and interdisciplinary approaches for its conservation. Hence, now it is even more critical than ever before for the humans to be environmentally literate. To realise this vision, both ecological and environmental education must become a fundamental part of the education system at all levels of education. Currently, it is even more critical than ever before for the humankind as a whole to have a clear understanding of environmental concerns and to follow sustainable development practices. The degradation of our environment is linked to continuing problems of pollution, loss of forest, solid waste disposal, and issues related to economic productivity and national as well as ecological security. Environmental management has gained momentum in the recent years with the initiatives focussing on managing environmental hazards and preventing possible disasters. Environmental issues make better sense, when one can understand them in the context of one’s own cognitive sphere. Environmental education focusing on real-world contexts and issues often begins close to home, encouraging learners to understand and forge connections with their immediate surroundings. The awareness, knowledge, and skills needed for these local connections and understandings provide a base for moving out into larger systems, broader issues, and a more sophisticated comprehension of causes, connections, and consequences. Environmental Education Programme at CES in collaboration with Karnataka Environment Research Foundation (KERF) referred as ‘Know your Ecosystem’ focuses on the importance of investigating the ecosystems within the context of human influences, incorporating an examination of ecology, economics, culture, political structure, and social equity as well as natural processes and systems. The ultimate goal of environment education is to develop an environmentally literate public. It needs to address the connection between our conception and practice of education and our relationship as human cultures to life-sustaining ecological systems. For each environmental issue there are many perspectives and much uncertainty. Environmental education cultivates the ability to recognise uncertainty, envision alternative scenarios, and adapt to changing conditions and information. These knowledge, skills, and mindset translate into a citizenry who is better equipped to address its common problems and take advantage of opportunities, whether environmental concerns are involved or not.

Give-and-take based peer-to-peer content distribution networks

Content Distribution Networks (CDNs) are widely used to distribute data to large number of users. Traditionally, content is being replicated among a number of surrogate servers, leading to high operational costs. In this context, Peer-to-Peer (P2P) CDNs have emerged as a viable alternative. An issue of concern in P2P networks is that of free riders, i.e., selfish peers who download files and leave without uploading anything in return. Free riding must be discouraged. In this paper, we propose a criterion, the Give-and-Take (G&T) criterion, that disallows free riders. Incorporating the G&T criterion in our model, we study a problem that arises naturally when a new peer enters the system: viz., the problem of downloading a `universe' of segments, scattered among other peers, at low cost. We analyse this hard problem, and characterize the optimal download cost under the G&T criterion. We propose an optimal algorithm, and provide a sub-optimal algorithm that is nearly optimal, but runs much more quickly; this provides an attractive balance between running time and performance. Finally, we compare the performance of our algorithms with that of a few existing P2P downloading strategies in use. We also study the computation time for prescribing the strategy for initial segment and peer selection for the newly arrived peer for various existing and proposed algorithms, and quantify cost-computation time trade-offs.

Evolution of bacterial transcription factors: how proteins take on new tasks, but do not always stop doing the old ones

Many bacterial transcription factors do not behave as per the textbook operon model. We draw on whole genome work, as well as reported diversity across different bacteria, to argue that transcription factors may have evolved from nucleoid-associated proteins. This view would explain a large amount of recent data gleaned from high-throughput sequencing and bioinformatic analyses.

Social optimum in social groups with give-and-take criterion

We consider a Social Group' of networked nodes, seeking a universe' of segments. Each node has a subset of the universe and access to an expensive resource for downloading data. Nodes can also acquire the universe by exchanging copies of segments among themselves, at low cost, using inter-node links. While exchanges over inter-node links ensure minimum cost, some nodes in the group try to exploit the system. We term such nodes as non-reciprocating nodes' and prohibit such behavior by proposing the give-and-take' criterion, where exchange is allowed if each node has segments unavailable with the other. Under this criterion, we consider the problem of maximizing the number of nodes with the universe at the end of local exchanges. First, we present a randomized algorithm that is shown to be optimal in the asymptotic regime. Then, we present greedy links algorithm, which performs well for most of the scenarios and yields an optimal result when the number of nodes is four. The polygon algorithm is proposed, which yields an optimal result when each of the nodes has a unique segment. After presenting some intuitive algorithms (e.g., greedy incremental algorithm and rarest first algorithm), we compare the performances of all proposed algorithms with the optimal. Copyright (c) 2015 John Wiley & Sons, Ltd.