The Human Fragment

Nonfiction. Photography. "[Michael Ernest Sweet] is a genius at composition, finding the beauty in the shapes and surprises of everyday life. His works often look set up and arranged, but in reality they're capturing the stylistic sexiness of the urban jungle as it pops up in spontaneous ways that only a photo could let you ponder and dissect." Michael Musto, from the Foreword"

The universe may well have begun with an immense act of fragmentation, "the big bang," that sent particles flying in all directions to perform spectacular acts of creation and destruction. The fragment, volatile and unpredictable, is not simply the static part of a once-whole thing but itself something in motion. Drawing upon art history, archaeology, literature, numismatics, philosophy, and film, this book explores the significance of the fragment and addresses the powerful drives that have impelled it into the cultural mainstream. Book jacket.

Fragment-based drug discovery is a rapidly evolving area of research, which has recently seen new applications in areas such as epigenetics, GPCRs and the identification of novel allosteric binding pockets. The first fragment-derived drug was recently approved for the treatment of melanoma. It is hoped that this approval is just the beginning of the many drugs yet to be discovered using this fascinating technique. This book is written from a Chemist's perspective and comprehensively assesses the impact of fragment-based drug discovery on a wide variety of areas of medicinal chemistry. It will prove to be an invaluable resource for medicinal chemists working in academia and industry, as well as anyone interested in novel drug discovery techniques.

Answering the need to facilitate quantum-chemical calculations of systems with thousands of atoms, Kazuo Kitaura and his coworkers developed the Fragment Molecular Orbital (FMO) method in 1999. Today, the FMO method can be applied to the study of whole proteins and protein-ligand interactions, and is extremely effective in calculating the propertie

Today, as the large international genome sequence projects are gaining a great amount of public attention and huge sequence data bases are created it be comes more and more obvious that we are very limited in our ability to access functional data for the gene products -the proteins, in particular for enzymes. Those data are inherently very difficult to collect, interpret and standardize as they are highly distributed among journals from different fields and are often sub ject to experimental conditions. Nevertheless a systematic collection is essential for our interpretation of the genome information and more so for possible appli cations of that knowledge in the fields of medicine, agriculture, etc .. Recent pro gress on enzyme immobilization, enzyme production, enzyme inhibition, coen zyme regeneration and enzyme engineering has opened up fascinating new fields for the potential application of enzymes in a large range of different areas. It is the functional profile of an enzyme that enables a biologist of physician to analyze a metabolic pathway and its disturbance; it is the substrate specificity of an enzyme which tells an analytical biochemist how to design an assay; it is the stability, specificity and efficiency of an enzyme which determines its usefulness in the biotechnical transformation of a molecule. And the sum of all these data will have to be considered when the designer of artificial biocatalysts has to choose the optimum prototype to start with.

Rather than solid frames, some less than perfect aesthetic objects have permeable membranes which allow them to diffuse effortlessly into the everyday world. In the parallel universes of music and literature, Linda Cummins extols the poetry of such imperfection. She places Debussy's work within a tradition thriving on anti-Aristotelian principles: motley collections, crumbling ruins real or fake, monstrous hybrids, patchwork and palimpsest, hasty sketches, ellipses, truncated beginnings and endings, meandering arabesques, irrelevant digressions, auto-quotations. Sensitive to the intermittences of memory and experience and with a keen ear for ironic intrusion, Cummins draws the reader into the Western cultural past in search of the surprisingly ubiquitous aesthetic of the unfinished, negatively silhouetted against expectations of rational coherence. Theories popularized by Schlegel and embraced by the French Symbolists are only the first waypoint on an elaborately illustrated tour reaching back to Petrarch. Cummins meticulously applies the derived results to Debussy's scores and finds convincing correlations in this chiasmatic crossover.