The ?eld of cellular responses to DNA damage has attained widespread recognition and interest in recent years commensurate with its fundamental role in the ma- tenance of genomic stability. These responses, which are essential to preventing cellular death or malignant transformation, are organized into a sophisticated s- tem designated the “DNA damage response”. This system operates in all living organisms to maintain genomic stability in the face of constant attacks on the DNA from a variety of endogenous by-products of normal metabolism, as well as exogenous agents such as radiation and toxic chemicals in the environment. The response repairs DNA damage via an intricate cellular signal transduction network that coordinates with various processes such as regulation of DNA replication, tr- scriptional responses, and temporary cell cycle arrest to allow the repair to take place. Defects in this system result in severe genetic disorders involving tissue degeneration, sensitivity to speci?c damaging agents, immunode?ciency, genomic instability, cancer predisposition and premature aging. The ?nding that many of the crucial players involved in DNA damage response are structurally and functionally conserved in different species spurred discoveries of new players through similar analyses in yeast and mammals. We now understand the chain of events that leads to instantaneous activation of the massive cellular responses to DNA lesions. This book summarizes several new concepts in this rapidly evolving ?eld, and the advances in our understanding of the complex network of processes that respond to DNA damage.

The March of medicine through Wisconsin is a fascinating story, full of triumph and failure, heroes and quacks, and -- overriding all -- stuttering steps toward a modern system of health care that has witnessed the doubling of life expectancies among Wisconsin citizens. This is the story of medicine in Wisconsin, told by professional historians, each speaking from his or her area of specialty. Since territorial times, the physician has risen from a position of marginal respectability to one of unparalleled admiration and trust. The hospital, unknown to residents just 150 years ago, has become a symbol of modern science and a source of civic pride. Knowledge of disease has revolutionized health practices. The purpose of this book is not to celebrate the achievements of Wisconsin's physicians, notable as they have been, but to look critically and sympathetically at the state's medical record. The contributors make no exaggerated claims for Wisconsin. Occasionally, the state led the nation in health matters, but more often it followed the example of others. With this book, the reader will come to understand how and why Wisconsin's medical practice evolved. - Jacket flap.