ing WS1S Systems to Verify Parameterized Networks . . . . . . . . . . . . 188 Kai Baukus, Saddek Bensalem, Yassine Lakhnech and Karsten Stahl FMona: A Tool for Expressing Validation Techniques over Infinite State Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 J.-P. Bodeveix and M. Filali Transitive Closures of Regular Relations for Verifying Infinite-State Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220 Bengt Jonsson and Marcus Nilsson Diagnostic and Test Generation Using Static Analysis to Improve Automatic Test Generation . . . . . . . . . . . . . 235 Marius Bozga, Jean-Claude Fernandez and Lucian Ghirvu Efficient Diagnostic Generation for Boolean Equation Systems . . . . . . . . . . . . 251 Radu Mateescu Efficient Model-Checking Compositional State Space Generation with Partial Order Reductions for Asynchronous Communicating Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266 Jean-Pierre Krimm and Laurent Mounier Checking for CFFD-Preorder with Tester Processes . . . . . . . . . . . . . . . . . . . . . . . 283 Juhana Helovuo and Antti Valmari Fair Bisimulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299 Thomas A. Henzinger and Sriram K. Rajamani Integrating Low Level Symmetries into Reachability Analysis . . . . . . . . . . . . . 315 Karsten Schmidt Model-Checking Tools Model Checking Support for the ASM High-Level Language . . . . . . . . . . . . . . 331 Giuseppe Del Castillo and Kirsten Winter Table of

Tools and Algorithms for the Construction and Analysis of Systems. Proc. TACAS 2009

1. (i) Suppose K is a conjugacy class of Sn contained in An; then K is called split if K is a union of two conjugacy classes of An. Show that the number of split conjugacy classes contained in An is equal to the number of characters χ ∈ Irr(Sn) such that χAn is not irreducible. (Hint. Consider the vector space of class functions on An which are invariant under conjugation by the transposition (12).)

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Character Theory of Finite Groups

Drug designing and development is an important area of research for pharmaceutical companies and chemical scientists. However, low efficacy, off-target delivery, time consumption, and high cost impose a hurdle and challenges that impact drug design and discovery. Further, complex and big data from genomics, proteomics, microarray data, and clinical trials also impose an obstacle in the drug discovery pipeline. Artificial intelligence and machine learning technology play a crucial role in drug discovery and development. In other words, artificial neural networks and deep learning algorithms have modernized the area. Machine learning and deep learning algorithms have been implemented in several drug discovery processes such as peptide synthesis, structure-based virtual screening, ligand-based virtual screening, toxicity prediction, drug monitoring and release, pharmacophore modeling, quantitative structure-activity relationship, drug repositioning, polypharmacology, and physiochemical activity. Evidence from the past strengthens the implementation of artificial intelligence and deep learning in this field. Moreover, novel data mining, curation, and management techniques provided critical support to recently developed modeling algorithms. In summary, artificial intelligence and deep learning advancements provide an excellent opportunity for rational drug design and discovery process, which will eventually impact mankind. The primary concern associated with drug design and development is time consumption and production cost. Further, inefficiency, inaccurate target delivery, and inappropriate dosage are other hurdles that inhibit the process of drug delivery and development. With advancements in technology, computer-aided drug design integrating artificial intelligence algorithms can eliminate the challenges and hurdles of traditional drug design and development. Artificial intelligence is referred to as superset comprising machine learning, whereas machine learning comprises supervised learning, unsupervised learning, and reinforcement learning. Further, deep learning, a subset of machine learning, has been extensively implemented in drug design and development. The artificial neural network, deep neural network, support vector machines, classification and regression, generative adversarial networks, symbolic learning, and meta-learning are examples of the algorithms applied to the drug design and discovery process. Artificial intelligence has been applied to different areas of drug design and development process, such as from peptide synthesis to molecule design, virtual screening to molecular docking, quantitative structure-activity relationship to drug repositioning, protein misfolding to protein-protein interactions, and molecular pathway identification to polypharmacology. Artificial intelligence principles have been applied to the classification of active and inactive, monitoring drug release, pre-clinical and clinical development, primary and secondary drug screening, biomarker development, pharmaceutical manufacturing, bioactivity identification and physiochemical properties, prediction of toxicity, and identification of mode of action.

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Artificial intelligence to deep learning: machine intelligence approach for drug discovery.

/pdf/uncertainty-and-information-foundations-of-generalized-2maw5bt1n4.pdf

Uncertainty and Information: Foundations of Generalized Information Theory

The task of predicting the interactions between drugs and targets plays a key role in the process of drug discovery. There is a need to develop novel and efficient prediction approaches in order to avoid costly and laborious yet not-always-deterministic experiments to determine drug-target interactions (DTIs) by experiments alone. These approaches should be capable of identifying the potential DTIs in a timely manner. In this article, we describe the data required for the task of DTI prediction followed by a comprehensive catalog consisting of machine learning methods and databases, which have been proposed and utilized to predict DTIs. The advantages and disadvantages of each set of methods are also briefly discussed. Lastly, the challenges one may face in prediction of DTI using machine learning approaches are highlighted and we conclude by shedding some lights on important future research directions.

Machine learning approaches and databases for prediction of drug-target interaction: a survey paper.

Type 2 diabetes mellitus (T2DM) is a challenging and progressive metabolic disease caused by insulin resistance. Skeletal muscle is the major insulin-sensitive tissue that plays a pivotal role in blood sugar homeostasis. Dysfunction of muscle metabolism is implicated in the disturbance of glucose homeostasis, the development of insulin resistance, and T2DM. Understanding metabolism reprogramming in newly diagnosed patients provides opportunities for early diagnosis and treatment of T2DM as a challenging disease to manage. Here, we applied a system biology approach to investigate metabolic dysregulations associated with the early stage of T2DM. We first reconstructed a human muscle-specific metabolic model. The model was applied for personalized metabolic modeling and analyses in newly diagnosed patients. We found that several pathways and metabolites, mainly implicating in amino acids and lipids metabolisms, were dysregulated. Our results indicated the significance of perturbation of pathways implicated in building membrane and extracellular matrix (ECM). Dysfunctional metabolism in these pathways possibly interrupts the signaling process and develops insulin resistance. We also applied a machine learning method to predict potential metabolite markers of insulin resistance in skeletal muscle. 13 exchange metabolites were predicted as the potential markers. The efficiency of these markers in discriminating insulin-resistant muscle was successfully validated.

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Kaveh Kavousi

Papers

A holistic view of muscle metabolic reprogramming through personalized metabolic modeling in newly diagnosed diabetic patients