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Strategic performance can be linked to shareholder value by measuring the positive spread between a company's return on capital employed and the cost of capital. If managers see a significant performance gap in their spread, compared with that of a premier company, they should redefine their strategic goals.
Companies in the cost- and price-conscious commodity field can achieve clear bottom-line gains through a detailed assessment of competitive alternates for use in purchasing negotiations, price setting, and development priorities.
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Sequence profiling is used routinely to predict the location of B-cell epitopes. In the postgenomic era, the need for reliable epitope prediction is clear. We assessed 484 amino acid propensity scales in combination with ranges of plotting parameters to examine exhaustively the correlation of peaks and epitope location within 50 proteins mapped for polyclonal responses. After examining more than 10(6) combinations, we found that even the best set of scales and parameters performed only marginally better than random. Our results confirm the null hypothesis: Single-scale amino acid propensity profiles cannot be used to predict epitope location reliably. The implication for studies using such methods is obvious.
We present a novel, continuous approach aimed at the large-scale assessment of the performance of available fold-recognition servers. Six popular servers were investigated: PDB-Blast, FFAS, T98-lib, GenTHREADER, 3D-PSSM, and INBGU. The assessment was conducted using as prediction targets a large number of selected protein structures released from October 1999 to April 2000. A target was selected if its sequence showed no significant similarity to any of the proteins previously available in the structural database. Overall, the servers were able to produce structurally similar models for one-half of the targets, but significantly accurate sequence-structure alignments were produced for only one-third of the targets. We further classified the targets into two sets: easy and hard. We found that all servers were able to find the correct answer for the vast majority of the easy targets if a structurally similar fold was present in the server's fold libraries. However, among the hard targets--where standard methods such as PSI-BLAST fail--the most sensitive fold-recognition servers were able to produce similar models for only 40% of the cases, half of which had a significantly accurate sequence-structure alignment. Among the hard targets, the presence of updated libraries appeared to be less critical for the ranking. An "ideally combined consensus" prediction, where the results of all servers are considered, would increase the percentage of correct assignments by 50%. Each server had a number of cases with a correct assignment, where the assignments of all the other servers were wrong. This emphasizes the benefits of considering more than one server in difficult prediction tasks. The LiveBench program (http://BioInfo.PL/LiveBench) is being continued, and all interested developers are cordially invited to join.
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The cervical smear test, like all screening tests, is not 100% effective in detecting abnormality. In order to prevent 80-90% of invasive cancers, cervical screening requires cervical smears to be taken competently at regular intervals and correctly interpreted. With laboratories following the guidelines in this report, the NHSCSP should be able to meet the Health of the Nation target to reduce the incidence of invasive cervical cancer to less than 12 cases per 100 000 women in the UK by the year 2000.
Methods for evaluating the hazards associated with noncancer responses with epidemiologic data are considered. The methods for noncancer risk assessment have largely been developed for experimental data, and are not always suitable for the more complex structure of epidemiologic data. In epidemiology, the measurement of the response and the exposure is often either continuous or dichotomous. For a continuous noncancer response modeled with multiple regression, a variety of endpoints may be examined: (1) the concentration associated with absolute or relative decrements in response; (2) a threshold concentration associated with no change in response; and (3) the concentration associated with a particular added risk of impairment. For a dichotomous noncancer response modeled with logistic regression, concentrations associated with specified added/extra risk or with a threshold responses may be estimated. No-observed-effect concentrations may also be estimated for categorizations of exposures for both continuous and dichotomous responses but these may depend on the arbitrary categories chosen. Respiratory function in miners exposed to coal dust is used to illustrate these methods.
In this study, the within-animal variation in routinely studied continuous toxicological parameters was estimated from temporal fluctuations in individual healthy nonexposed animals. Assuming that these fluctuations are nonadverse, this within-animal variation may be indicative of the minimal magnitude of the critical effect size (CES). The CES is defined as the breaking point between adverse and nonadverse changes in a continuous toxicological parameter, at the level of the individual organism. The total variation in the data from individual nonexposed animals was divided in variation parts due to known factors (differences in sex, animal, and day) and a residual variation, by means of analysis of variance. Using the residual variation and the estimated analytical measurement error of a toxicological parameter, the within-animal variation can be estimated. The data showed within-animal variations ranging between 0.6% and 34% for different clinical chemistry and hematological parameters in 90-day rat studies. This indicates that different (minimal) CES values may be applicable for different parameters.
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A comprehensive set of measurements and calculations has been conducted to investigate the accuracy of the Dose Planning Method (DPM) Monte Carlo code for dose calculations from 10 and 50 MeV scanned electron beams produced from a racetrack microtron. Central axis depth dose measurements and a series of profile scans at various depths were acquired in a water phantom using a Scanditronix type RK ion chamber. Source spatial distributions for the Monte Carlo calculations were reconstructed from in-air ion chamber measurements carried out across the two-dimensional beam profile at 100 cm downstream from the source. The in-air spatial distributions were found to have full width at half maximum of 4.7 and 1.3 cm, at 100 cm from the source, for the 10 and 50 MeV beams, respectively. Energy spectra for the 10 and 50 MeV beams were determined by simulating the components of the microtron treatment head using the code MCNP4B. DPM calculations are on average within +/- 2% agreement with measurement for all depth dose and profile comparisons conducted in this study. The accuracy of the DPM code illustrated in this work suggests that DPM may be used as a valuable tool for electron beam dose calculations.
Conservationists have long contended, largely in impressionistic terms, that 70 years of American dam building and water diversion have destroyed the biological richness of the Colorado River delta, a key nursery of marine life at the end of the Southwest's great watercourse. Now researchers have confirmed those suspicions, using an important ecological player--clams--as a quantitative marker.
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