Integrating environmental responsibility into decision making in the manufacture of non-standard discrete products

Thesis (M.S.)--Massachusetts Institute of Technology, Sloan School of Management, 1995, and Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1995.Includes bibliographical references (p. 85).by William N. Anderson.M.S

p21 is decreased in polycystic kidney disease and leads to increased epithelial cell cycle progression: roscovitine augments p21 levels.

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease with few treatment options other than renal replacement therapy. p21, a cyclin kinase inhibitor which has pleiotropic effects on the cell cycle, in many cases acts to suppress cell cycle progression and to prevent apoptosis. Because defects in cell cycle arrest and apoptosis of renal tubular epithelial cells occur in PKD, and in light of earlier reports that polycystin-1 upregulates p21 and that the cyclin-dependent kinase inhibitor roscovitine arrests progression in a mouse model, we asked whether (1) p21 deficiency might underlie ADPKD and (2) the mechanism of the salutary roscovitine effect on PKD involves p21.Methodsp21 levels in human and animal tissue samples as well as cell lines were examined by immunoblotting and/or immunohistochemisty. Apoptosis was assessed by PARP cleavage. p21 expression was attenuated in a renal tubular epithelial cell line by antisense methods, and proliferation in response to p21 attenuation and to roscovitine was assessed by the MTT assay.ResultsWe show that p21 is decreased in human as well as a non-transgenic rat model of ADPKD. In addition, hepatocyte growth factor, which induces transition from a cystic to a tubular phenotype, increases p21 levels. Furthermore, attenuation of p21 results in augmentation of cell cycle transit in vitro. Thus, levels of p21 are inversely correlated with renal tubular epithelial cell proliferation. Roscovitine, which has been shown to arrest progression in a murine model of PKD, increases p21 levels and decreases renal tubular epithelial cell proliferation, with no affect on apoptosis.ConclusionThe novelty of our study is the demonstration in vivo in humans and rat models of a decrement of p21 in cystic kidneys as compared to non-cystic kidneys. Validation of a potential pathogenetic model of increased cyst formation due to enhanced epithelial proliferation and apoptosis mediated by p21 suggests a mechanism for the salutary effect of roscovitine in ADPKD and supports further investigation of p21 as a target for future therapy

Semiclassical charged black holes with a quantized massive scalar field

Semiclassical perturbations to the Reissner-Nordstrom metric caused by the presence of a quantized massive scalar field with arbitrary curvature coupling are found to first order in \epsilon = \hbar/M^2. The DeWitt-Schwinger approximation is used to determine the vacuum stress-energy tensor of the massive scalar field. When the semiclassical perturbation are taken into account, we find extreme black holes will have a charge-to-mass ratio that exceeds unity, as measured at infinity. The effects of the perturbations on the black hole temperature (surface gravity) are studied in detail, with particular emphasis on near extreme ``bare'' states that might become precisely zero temperature ``dressed'' semiclassical black hole states. We find that for minimally or conformally coupled scalar fields there are no zero temperature solutions among the perturbed black holes.Comment: 19 pages; 1 figure; ReVTe

Comparison of Performance of Experimental and Conventional Cage Designs and Materials for 75-millimeter-bore Cylindrical Roller Bearings at High Speed

The results of two investigations, one to determine the relative merits of four experimental and two conventional design 75-millimeter-bore (size 215) cylindrical roller bearings and one to determine the relative merits of nodular iron and bronze as cage materials for this size and type of bearing, are presented in this report. Nine test bearings were operated over a range of dn values (product of bearing bore in mm and shaft speed in r.p.m) from 0.3 x 10(6) to 2.3 x 20(6), radial loads for 7 to 1613 pounds, and oil flows from 2 to 8 pounds per minute with a single-jet circulatory oil feed. Of the six bearings used to evaluate designs, four were experimental types with outer-race-riding cages and inner-race-guided rollers, and two were conventional types, one with outer-race-guided rollers and cage and one with inner-race-guided rollers and cage. Each of these six test bearings was equipped with a different design cage made of nodular iron. The experimental combination of an outer-race-riding cage with a straight-through outer race and inner-race-guided rollers was found to give the best over-all performance based on limiting dn values and bearing temperatures