Observations of cosmic ray electrons between 2.7 and 21.5 MeV

Intensity of 2.7 to 21.5 MeV electrons in interplanetary space from Explorer 34 measurement

Role of a Conserved Glutamate Residue in the \u3cem\u3eEscherichia coli\u3c/em\u3e SecA ATPase Mechanism

Escherichia coli SecA uses ATP to drive the transport of proteins across cell membranes. Glutamate 210 in the “DEVD” Walker B motif of the SecA ATP-binding site has been proposed as the catalytic base for ATP hydrolysis (Hunt, J. F., Weinkauf, S., Henry, L., Fak, J. J., McNicholas, P., Oliver, D. B., and Deisenhofer, J. (2002) Science 297, 2018–2026). Consistent with this hypothesis, we find that mutation of glutamate 210 to aspartate results in a 90-fold reduction of the ATP hydrolysis rate compared with wild type SecA, 0.3 s–1versus 27 s–1, respectively. SecA-E210D also releases ADP at a slower rate compared with wild type SecA, suggesting that in addition to serving as the catalytic base, glutamate 210 might aid turnover as well. Our results contradict an earlier report that proposed aspartate 133 as the catalytic base (Sato, K., Mori, H., Yoshida, M., and Mizushima, S. (1996) J. Biol. Chem. 271, 17439–17444). Re-evaluation of the SecA-D133N mutant used in that study confirms its loss of ATPase and membrane translocation activities, but surprisingly, the analogous SecA-D133A mutant retains full activity, revealing that this residue does not play a key role in catalysis

Data Mining and Quantitative Structure-Activity Relationships of Inhibitors for Treating Alzheimer's Disease

poster abstractAmyloid cleaving enzyme-1 (BACE1) is a target of interest for treating patients with Alzheimer’s disease (AD). As of 2007, more than 37 million people worldwide are afflicted with the disease. Incidence of the disease keeps increasing as the population ages and fewer people die of other diseases. ß-Amyloid precursor protein (APP) is a natural protein associated with neurons of the brain. In Alzheimer's disease, APP is cleaved by BACE1 at the beta-site, resulting in short 42 amino acid segments called amyloid-ß (Aß). Aggregation of Aß into plaques results in the death of neurons and is associated with AD. Inhibition of the BACE1 enzyme may prevent Aß formation and prevent the development or progression of AD. Known BACE1 inhibitors are analyzed using computational chemistry techniques, and quantitative structure-activity relationships (QSAR) are developed

Simple Structure-Based Approach for Predicting the Activity of Inhibitors of Beta-Secretase (BACE1) Associated with Alzheimer's Disease

poster abstractBeta-site amyloid precursor protein cleaving enzyme-1 (BACE1) is a target of interest for treating patients with Alzheimer’s disease (AD). Inhibition of BACE1 may prevent amyloid-ß (Aß) plaque formation and the development or progression of Alzheimer’s disease. Known BACE1 inhibitors were analyzed using computational chemistry and cheminformatics techniques to search for quantitative structure− activity relationships (QSAR). A remarkable relationship was found with only two simple descriptors with a square of the linear correlation coefficient r2 of 0.75. The main descriptor is the number of hydrophobic contacts in the range 4−5 Å between the atoms of the ligand and active site. The other descriptor is the number of short (<2.8 Å) hydrogen bonds. Our approach uses readily available structural data on protein- inhibitor complexes in the Protein Data Bank (PDB) but would be equally applicable to proprietary structural biology data. The findings can aid structure-based design of improved BACE-1 inhibitors. If an inhibitor has less observed activity than predicted by our correlation, the compound should be retested because the first assay may have underestimated the compound’s true activity

Earthquake forecasting and its verification

No proven method is currently available for the reliable short time prediction of earthquakes (minutes to months). However, it is possible to make probabilistic hazard assessments for earthquake risk. These are primarily based on the association of small earthquakes with future large earthquakes. In this paper we discuss a new approach to earthquake forecasting. This approach is based on a pattern informatics (PI) method which quantifies temporal variations in seismicity. The output is a map of areas in a seismogenic region (``hotspots'') where earthquakes are forecast to occur in a future 10-year time span. This approach has been successfully applied to California, to Japan, and on a worldwide basis. These forecasts are binary--an earthquake is forecast either to occur or to not occur. The standard approach to the evaluation of a binary forecast is the use of the relative operating characteristic (ROC) diagram, which is a more restrictive test and less subject to bias than maximum likelihood tests. To test our PI method, we made two types of retrospective forecasts for California. The first is the PI method and the second is a relative intensity (RI) forecast based on the hypothesis that future earthquakes will occur where earthquakes have occurred in the recent past. While both retrospective forecasts are for the ten year period 1 January 2000 to 31 December 2009, we performed an interim analysis 5 years into the forecast. The PI method out performs the RI method under most circumstances.Comment: 10(+1) pages, 5 figures, 2 tables. Submitted to Nonlinearl Processes in Geophysics on 5 August 200

A deep sea docking station for ODYSSEY class autonomous underwater vehicles

Under subcontract to the Massachusetts Institute of Technology's (MIT) Sea Grant Autonomous Ocean Sampling Network (AOSN) program, engineers and researchers at the Woods Hole Oceanographic Institution (WHOI) designed, fabricated and operated a deep sea Docking Station for ODYSSEY-class autonomous underwater vehicles (AUVs). The docking station provides shelter as well as power transfer and data exchange services for an AUV that is between autonomous midwater missions. The Station is integrated into the main tension member of a deep sea mooring system. A large subsea flotation sphere supports the mass of the Station above the seafoor. A surface expression connected by an umbilcal to the Station was capable of bi-directional satellite or radio frequency communications. Primary subsystems of the Docking Station described in this report include a dock controller with multi-sensor support, long-duration battery packs, a docking pole with a moving carage, an inductive link for power and data transfer, and information about how the Station was deployed, operated and recovered.Funding was provided by the Offce of Naval Research under Grant No. NOOO-14-95-1-1316

Predicting Returns in the Stock and Bond Markets

Several predetermined variables that reflect levels of bond and stock prices appear to predict returns on common stocks of firms of various sizes, long-term bonds of various default risks, and default-free bonds of various maturities. The returns on small-firm stocks and low-grade bonds are more highly correlated in January than in the rest of the year with previous levels of asset prices, especially prices of small-firm stocks. Seasonality is found in several conditional risk measures, but such seasonality is unlikely to explain, and in some cases is opposite to, the seasonal found in mean returns