Small Town

Granville Hicks was one of America\u27s most influential literary and social critics. Along with Malcolm Cowley, F. O. Matthiessen, Max Eastman, Alfred Kazin, and others, he shaped the cultural landscape of 20th-century America. In 1946 Hicks published Small Town, a portrait of life in the rural crossroads of Grafton, N.Y., where he had moved after being fired from Rensselaer Polytechnic Institute for his left-wing political views. In this book, he combines a kind of hand-crafted ethnographic research with personal reflections on the qualities of small town life that were being threatened by spreading cities and suburbs. He eloquently tried to define the essential qualities of small town community life and to link them to the best features of American culture. The book sparked numerous articles and debates in a baby-boom America nervously on the move. Long out of print, this classic of cultural criticism speaks powerfully to a new generation seeking to reconnect with a sense of place in American life, both rural and urban. An unaffected, deeply felt portrait of one such place by one of the best American critics, it should find a new home as a vivid reminder of what we have lost-and what we might still be able to protect

Mammalian Target of Rapamycin (mTOR) Regulates Cellular Proliferation and Tumor Growth in Urothelial Carcinoma

Mammalian target of rapamycin (mTOR) signaling has been associated with aggressive tumor growth in many cancer models, although its role in urothelial carcinoma (UCC) has not been extensively explored. Expression of phosphorylated mTOR (P-mTOR) and a downstream target, ribosomal S6 protein (P-S6), was identified in 74% (90/121) and 55% (66/121) of muscle-invasive UCCs, respectively. P-mTOR intensity and %positive cells were associated with reduced disease-specific survival (P = 0.04, P = 0.08, respectively). Moreover, P-mTOR intensity corresponded to increased pathological stage (P < 0.01), and mTOR activity was associated with cell migration in vitro. In addition, mTOR inhibition via rapamycin administration reduced cell proliferation in UCC cell lines RT4, T24, J82, and UMUC3 in a dose-dependent manner to 6% of control levels and was significant at 1 nmol/L in J82, T24, and RT4 cells (P < 0.01, P < 0.01, P = 0.03, respectively) and at 10 nmol/L in UMUC3 cells (P = 0.03). Reduced proliferation corresponded with reduced P-S6 levels by Western blot, and effects were ablated by pretreatment of cells with mTOR-specific siRNA. No effects of rapamycin on apoptosis were identified by TUNEL labeling or PARP cleavage. Administration of rapamycin to T24-xenografted mice resulted in a 55% reduction in tumor volume (P = 0.03) and a 40% reduction in proliferation (P < 0.01) compared with vehicle-injected mice. These findings indicate that mTOR pathway activation frequently occurs in UCC and that mTOR inhibition may be a potential means to reduce UCC growth