A sentence of first-order logic is satisfiable if it is true in some structure, and finitely satisfiable if it is true in some finite structure. The question arises as to whether there exists an algorithm for determining whether a given formula of first-order logic is satisfiable, or indeed finitely satisfiable. This question was answered negatively in 1936 by Church and Turing (for satisfiability) and in 1950 by Trakhtenbrot (for finite satisfiability).In contrast, the satisfiability and finite satisfiability problems are algorithmically solvable for restricted subsets—-or, as we say, fragments—-of first-order logic, a fact which is today of considerable interest in Computer Science. This book provides an up-to-date survey of the principal axes of research, charting the limits of decision in first-order logic and exploring the trade-off between expressive power and complexity of reasoning. Divided into three parts, the book considers for which fragments of first-order logic there is an effective method for determining satisfiability or finite satisfiability. Furthermore, if these problems are decidable for some fragment, what is their computational complexity? Part I focusses on fragments defined by restricting the set of available formulas. Topics covered include the Aristotelian syllogistic and its relatives, the two-variable fragment, the guarded fragment, the quantifier-prefix fragments and the fluted fragment. Part II investigates logics with counting quantifiers. Starting with De Morgan's numerical generalization of the Aristotelian syllogistic, we proceed to the two-variable fragment with counting quantifiers and its guarded subfragment, explaining the applications of the latter to the problem of query answering in structured data. Part III concerns logics characterized by semantic constraints, limiting the available interpretations of certain predicates. Taking propositional modal logic and graded modal logic as our cue, we return to the satisfiability problem for two-variable first-order logic and its relatives, but this time with certain distinguished binary predicates constrained to be interpreted as equivalence relations or transitive relations. The work finishes, slightly breaching the bounds of first-order logic proper, with a chapter on logics interpreted over trees.

From its origins as a niche technique more than 15 years ago, fragment-based approaches have become a major tool for drug and ligand discovery, often yielding results where other methods have failed. Written by the pioneers in the field, this book provides a comprehensive overview of current methods and applications of fragment-based discovery, as well as an outlook on where the field is headed. The first part discusses basic considerations of when to use fragment-based methods, how to select targets, and how to build libraries in the chemical fragment space. The second part describes established, novel and emerging methods for fragment screening, including empirical as well as computational approaches. Special cases of fragment-based screening, e. g. for complex target systems and for covalent inhibitors are also discussed. The third part presents several case studies from recent and on-going drug discovery projects for a variety of target classes, from kinases and phosphatases to targeting protein-protein interaction and epigenetic targets.

Examines the life of the Russian author known for his writings depicting working class life in the pre- and post-revolutionary era

Fragment-based drug discovery (FBDD) is a new paradigm in drug discovery that utilizes very small molecules - fragments of larger molecules. It is a faster, cheaper, smarter way to do drug discovery, as shown by the number of pharmaceutical companies that have embraced this approach and the biotechnology companies who use fragments as their sole source of drug discovery. Fragment-Based Drug Discovery: A Practical Approach is a guide to the techniques and practice of using fragments in drug screening. The emphasis is on practical guidance, with procedures, case studies, practical tips, and contributions from industry. Topics covered include: an introduction to fragment based drug discovery, why using fragments is a more efficient process than predominant models, and what it means to have a successful FBDD effort. setting up an FBDD project library building and production NMR in fragment screening and follow up application of protein-ligand NOE matching to the rapid evaluation of fragment binding poses target immobilized NMR screening: validation and extension to membrane proteins in situ fragment-based medicinal chemistry: screening by mass spectrometry computational approaches to fragment and substructure discovery and evaluation virtual fragment scanning: current trends, applications and web based tools fragment-based lead discovery using covalent capture methods case study from industry: the identification of high affinity beta-secretase inhibitors using fragment-based lead generation With contributions from industry experts who have successfully set up an industrial fragment-based research program, Fragment-Based Drug Discovery: A Practical Approach offers essential advice to anyone embarking on drug discovery using fragments and those looking for a new approach to screening for drugs.

Between the independence of the colonies and the start of the Jacksonian age, American readers consumed an enormous number of literary texts called "fragments."American Fragments argues that this archive of deliberately unfinished writing reimagined the place of marginalized individuals in a country that was itself still unfinished.