Activity-Directed Synthesis: A Flexible Approach for Lead Generation

Activity-directed synthesis (ADS) is a structure-blind, functional-driven molecular discovery approach. In this Concept, four case studies highlight the general applicability of ADS and showcase its flexibility to support different medicinal chemistry strategies. ADS deliberately harnesses reactions with multiple possible outcomes, and allows many chemotypes to be evaluated in parallel. Resources are focused on bioactive molecules, which emerge in tandem with associated synthetic routes. Some of the future challenges for ADS are highlighted, including the realisation of an autonomous molecular discovery platform. The prospects for ADS to become a mainstream lead generation approach are discussed.     

Improving narrow bandgap a-SiGe:H alloys grown by hot-wire chemical vapor deposition

We have improved the electronic properties of narrow-bandgap (Tauc gap below 1.5 eV) amorphous-silicon germanium alloys (a-SiGe:H) grown by hot-wire chemical vapor deposition (HWCVD) by lowering the substrate temperature and deposition rate. Prior to this work, we were unable to grow a-SiGe:H alloys with bandgaps below 1.5 eV that had photo-to-dark conductivity ratios comparable with our plasma-enhanced CVD (PECVD) grown materials [B.P. Nelson et al., Mater. Res. Soc. Symp. 507 (1998) 447]. Decreasing the filament diameter from our standard configuration of 0.5 mm to 0.38 or 0.25 mm provides first big improvements in the photoresponse of these alloys. Lowering the substrate temperature from our previous optimal temperatures (T_sub starting at 435 °C) to at 250 °C provides additional photo-to-dark conductivity ratio increasing by two orders of magnitude for growth conditions containing 20–30% GeH₄ in the gas phase (relative to the total GeH₄+SiH₄ flow).     

Predicting Forest Age Classes from High Spatial Resolution Remotely Sensed Imagery Using Voronoi Polygon Aggregation

Efficient identification of forest age is useful for forest management and ecological applications. Here we propose a user-assisted method for determining forest age using high spatial resolution remotely sensed imagery. This method requires individual trees to be extracted from imagery and represented as points. We use a local maximum filter to generate points that are converted to Voronoi polygons. Properties of the Voronoi polygons are correlated with forest age and used to aggregate points (trees) into areas (stands) based on three forest age classes. Accuracy of the aggregation ranges from approximately 68% to 78% and identification of the mature class is more consistent and accurate than the younger classes.     

High dynamic range InP HBT delta-sigma analog-to-digital converters

To date, the development of multifunction multicarrier digital receivers for cellular base station and military communications applications has been limited by the demanding dynamic range requirements for the analog-to-digital converter (ADC). The use of oversampling delta-sigma modulators provides a promising approach to overcoming the dynamic range barriers Nyquist-rate converters face in the same applications. This paper discusses issues involved in the design of high-speed high dynamic range wide-band delta-sigma ADCs for such communications applications. Test results of prototype designs are also presented. The delta-sigma modulators described in this paper operate at sampling frequencies ranging from 1 to 2.5 GHz with center frequencies ranging from dc to 100 MHz, providing between 74 and 84.2 dB signal-to-noise ratio (12 and 13.7 bits) for bandwidths of 25 and 12.5 MHz, respectively. The loop filters are continuous-time low-pass and bandpass implementations of order 6 and 10, and were fabricated in an InP heterojunction bipolar (HBT) technology. A typical tenth-order design consumes 6 W of power and occupies a die area of 23.5 mm/sup 2/.     

Improved RNS FIR filter architectures

A new architecture for implementing finite-impulse response (FIR) filters using the residue number system (RNS) is detailed. The design is based on using a restricted modulus set, with moduli of the form 2/sup n/,2/sup n/-1, and 2/sup n/+1. This does not restrict the modulus set to the common 3 modulus set {2/sup n/-1,2/sup n/,2/sup n/+1}, but any number of pairwise relatively prime moduli of this form, for example, {5,7,17,31,32,33}. Based on a comparison with a 2's complement design, the new RNS design can offer a significant speed improvement. The gain is obtained by using a set of small moduli, selected so as to minimize critical path delay and area. An algorithmic approach is used to obtain full adder based architectures that are optimized for area and delay. The modulus set is optimum based on cost parameters for each modulus. This new architecture presents a practical approach to implementing a fast RNS FIR filter.     

A Revised Methodology for Research on Metamemory: Pre-judgment Recall And Monitoring (PRAM).

A revised methodology is described for research on metacognitive monitoring, especially judgments of learning (JOLs), to investigate psychological processing that previously has been only hypothetical and unobservable. During data collection a new stage of recall occurs just prior to the JOL, so that during data analysis the items can be partitioned into subcategories to measure the degree of JOL accuracy in ways that are more analytic than was previously possible. A weighted-average combinatorial rule allows the component measures of JOL accuracy to be combined into the usual overall measure of metacognitive accuracy. An example using the revised methodology offers a new explanation for the delayed-JOL effect, in which delayed JOLs are more accurate than immediate JOLs for predicting recall. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

National survey of mammographic facilities in 1985, 1988, and 1992

PURPOSE: To determine trends in mammography in the United States. MATERIALS AND METHODS: A sample of mammographic facilities was selected for each year of the Nationwide Evaluation of X-ray Trends. The same protocol was followed for the 1985, 1988, and 1992 surveys. Data were collected with use of the same imaging phantom for all three surveys and also with a different phantom in the 1988 and 1992 surveys. RESULTS: Of the 356 facilities surveyed in 1992, 59% claimed to be in compliance with the Health Care Financing Administration (HCFA) mammography requirements, 42% were accredited by the American College of Radiology (ACR), and 23% did not hold credentials from either the HCFA or the ACR. Since 1985, there has been a 34% improvement in acceptable phantom image quality score and a 20% decrease in the mean glandular dose. CONCLUSION: Mammography as practiced today is essentially a screen-film technique. Mammographic phantom image quality has improved considerably. The overall mean glandular dose has decreased primarily because of the elimination of xeroradiography.     

Apoptosis and delayed neuronal damage after carbon monoxide poisoning in the rat

Delayed neurological damage after CO hypoxia was studied in rats to determine whether programmed cell death (PCD), in addition to necrosis, is involved in neuronal death. In rats exposed to either air or CO (2500 ppm), microdialysis in brain cortex and hippocampus was performed to determine the extent of glutamate release and hydroxyl radical generation during the exposures. Groups of control and CO-exposed rats also were tested in a radial maze to assess the effects of the CO exposures on learning and memory. At 3, 7, and 21 days after CO exposure brains were perfusion-fixed and hematoxylin-eosin (H&E) was used to assess injury and to select regions for further examination. DNA fragmentation was sought by examining cryosections with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) reaction. We found significant increases in glutamate release and .OH generation during and immediately after CO hypoxia. CO-exposed rats showed learning and memory deficits after exposure associated with heterogeneous cell loss in cortex, globus pallidus, and cerebellum. The frontal cortex was affected most seriously; the damage was slight at Day 3, increased at Day 7, and persistent at Day 21 after CO exposure. TUNEL staining was positive at all three time points, and TUNEL-labeled cells were distributed similarly to eosinophilic cells. The number of cells stained by TUNEL was less than by H&E and amounted to 2 to 5% of all cell nuclei in regions of injury. Ultrastructural features of both neuronal necrosis and apoptosis also were observed readily by electron microscopy. These findings indicate that both necrosis and apoptosis (PCD) contribute to CO poisoning-induced brain cell death.