The design, computer modeling, solution structure, and biological evaluation of synthetic analogs of bryostatin 1

The bryostatins are a unique family of emerging cancer chemotherapeutic candidates isolated from marine bryozoa. Although the biochemical basis for their therapeutic activity is not known, these macrolactones exhibit high affinities for protein kinase C (PKC) isozymes, compete for the phorbol ester binding site on PKC, and stimulate kinase activity in vitro and in vivo. Unlike the phorbol esters, they are not first-stage tumor promoters. The design, computer modeling, NMR solution structure, PKC binding, and functional assays of a unique class of synthetic bryostatin analogs are described. These analogs (7b, 7c, and 8) retain the putative recognition domain of the bryostatins but are simplified through deletions and modifications in the C4-C14 spacer domain. Computer modeling of an analog prototype (7a) indicates that it exists preferentially in two distinct conformational classes, one in close agreement with the crystal structure of bryostatin 1. The solution structure of synthetic analog 7c was determined by NMR spectroscopy and found to be very similar to the previously reported structures of bryostatins 1 and 10. Analogs 7b, 7c, and 8 bound strongly to PKC isozymes with Ki = 297, 3.4, and 8.3 nM, respectively. Control 7d, like the corresponding bryostatin derivative, exhibited weak PKC affinity, as did the derivative, 9, lacking the spacer domain. Like bryostatin, acetal 7c exhibited significant levels of in vitro growth inhibitory activity (1.8–170 ng/ml) against several human cancer cell lines, providing an important step toward the development of simplified, synthetically accessible analogs of the bryostatins.

Benthic foraminiferal assemblage counts from the Gulf of California

Extensive CO2 vents have been discovered in the Wagner Basin, northern Gulf of California, where they create large areas with lowered seawater pH. Such areas are suitable for investigations of long-term biological effects of ocean acidification and effects of CO2 leakage from subsea carbon capture storage. Here, we show responses of benthic foraminifera to seawater pH gradients at 74-207 m water depth. Living (rose Bengal stained) benthic foraminifera included Nonionella basispinata, Epistominella bradyana and Bulimina marginata. Studies on foraminifera at CO2 vents in the Mediterranean and off Papua New Guinea have shown dramatic long-term effects of acidified seawater. We found living calcareous benthic foraminifera in low pH conditions in the northern Gulf of California, although there was an impoverished species assemblage and evidence of post-mortem test dissolution.

UM Men's Swimming Team, 1992

Front Row: swimming coach Jon Urbanchek, Steve Duttenhofer, Steve Bigelow, Jim Hume, Noel Strauss, Greg Gooch, Brian Gunn, diving coach Dick Kimball

Middle Row: Gustavo Borges, Tom Hay, Rodney VanTassell, Matt Jaffe, Steve West, Tim Bower Chris Veber

Back Row: Bill Pettit, Dan Abruzzi, Thomas Blake, Kevin Glass, Bill Kopas, Kent Tschannen, trainer J. Petter. Eric Lesser

Not Pictured: Eric Bailey, Alex Bogaerts, Jayson Field, R. Genova, Drew Hansz, Jeff Jozwiak, John Kiani, Brad Lambert, Chad McCloud, asst. coach Mark Noetzel, Scott Pjesky, Abel Sanchez, Rob Silverman, Dan Valdes

The Iowa homestead and weekly northwestern farmer.

Description based on: Vol. 9, no. 2 (Feb. 3, 1864).

... International exhibition, 1876. [Reports]

v.1. Report of the director-general, A.T. Goshorn. Reports of the bureaus of administration : Installation of Henry Pettit. Art by John Sartain. Machinery by John S. Albert. Agriculture by Burnet Landreth. Horticulture by Charles H. Miller. Engineering by H.J. Schwarzmann. Transportation by Dolphus Torrey. Admissions by David G. Yates. Awards by Francis A. Walker. Classification and catalogue by Dorsey Gardner. Medical service by William Pepper. Protection by A.T. Goshorn. Fire by Atwood Smith. Water-supply by Frederick Graff. Telegraphy by William J. Phillips.--v.2. Reports of the president, secretary, and Executive committee. Together with the Journal of the final session of the commission.--v.3-8. Reports and awards. Groups I-XXXVI and collective exhibits. Ed. by Francis A. Walker.--v.9. Grounds and buildings of the Centennial exhibition... Ed. by Dorsey Gardner.--v.10-11. Report of the Board on behalf of the United States executive departments.

Key to Orthoptera of Michigan with annotations,

Mode of access: Internet.

Turbine wheels : on the inapplicability of the theoretical investigations of the turbine wheel, as given by Rankine, Weisbach, Bresse and others, to the modern constructions introduced by Boyden and Francis /

Mode of access: Internet.

Memoirs of the life of the Rev. Charles Simeon ... with a selection from his writings and correspondence.

Mode of access: Internet.

Rev. Mr. M'Ilvaine in answer to the Rev. Henry U. Onderdonk, D. D.

Mode of access: Internet.

The history of Great Britain,

Mode of access: Internet.

The work of preaching Christ.

Mode of access: Internet.

The Christian minister's great work : the sermon at the consecration of the Right Rev. George Upfold, D. D., Bishop ... in the Diocese of Indiana ; preached in Christ Church, Indianapolis, Sunday, December 16, 1849 /

"Published by request of the Standing Committee of the Diocese of Indiana."

The sinner's justification before God; its nature and means.

Mode of access: Internet.

Electronic measurements /

First ed. published in 1935 under title: Measurements in radio engineering.

1879 University of Michigan Football Team