Managing Laboratory Automation: Integration and Informatics in Drug Discovery

Drug discovery today requires the focused use of lab automation and other resources in Combinatorial Chemistry and High-Throughput Screening (HTS). The ultimate value of both Combinatorial Chemistry and High-Throughput Screening technologies and the lasting impact they will have on the drug discovery process is a chapter that remains to be written. Central to their success and impact is how well they are integrated with each other and with the rest of Drug Discovery - and Informatics is key to this success. This presentation will focus on Informatics and the integration of the disciplines of combinatorial chemistry and HTS in modern drug discovery. Examples from experiences at Neurogen from the last five years will be described.     

Definition of the Linear Region of X-Ray -Induced Cable Response

Cable response to X-rays is linear with incident fluence, provided the deposited charge in cable dielectrics is directly proportional to the X-ray flux. To estimate the level at which the linear region ends, we discuss three nonlinear processes that modify the deposited charge profile in a hypothetical cable model: field-limiting in vacuum gaps, ionization effects in air-filled gaps, and radiation-induced dielectric conductivity. The exact level at which limiting of the Norton driver in an elemental length of cable begins depends on the cable geometry and the X-ray source. Estimates of the onset of nonlinearities caused by field-limiting and by dielectric conductivity are found in terms of cable and source parameters. With air-filled gaps, the Norton driver is always nonlinear. In addition to limiting of the Norton drivers, the load response of a long cable may be limited because propagating currents are attenuated by the induced conductivity of the bulk of the dielectric.     

Identification of the female-produced sex pheromone of the scarab beetle,Hoplia equina

Hoplia equina LeConte (Coleoptera: Scarabaeidae: Melolonthinae) is a beetle pest of cranberry beds in Massachusetts. Larvae feed on the roots of the cranberry plant, reducing yield as well as vine density. The female sex pheromone was identified as 2-tetradecanone. There were eight compounds found in the airborne volatiles collected from females that elicited antennal responses from males. Of the eight compounds tested (nonanal, decanal, dodecanal, 2-dodecanone, 2-tridecanone, 2-tetradecanone, 2-pentadecanone, and 2-hexadecanone), 2-tetradecanone was the only one that attracted male beetles in the field. Combining any of the other seven antennally active compounds with 2-tetradecanone did not increase male capture.     

Emotion understanding and performance during computer-supported collaboration

Individuals collaborating around and through computers benefit from receiving information that helps them understand one another, which is often termed awareness. This article explores what collaborators understand about each other’s emotions and the potential benefits for performance that might come from raising this understanding. In Experiment 1 co-located collaborators judged each other’s emotions after playing a game that required cooperative data collection and analysis. Their judgements were largely inaccurate and based on their own emotions, suggesting limited emotion understanding. Experiment 2 explored if this could be overcome by making collaborators aware of each other’s emotions. Co-located and remote collaborators played a cooperative puzzle-solving game under conditions of awareness or no awareness. Awareness was manipulated by making collaborators share their self-reported emotions during key moments of their game play. Both remote and co-located collaborators improved their performance after sharing their emotions. However, unlike co-located collaborators, remote collaborators also improved their understanding of each other’s emotions and experienced more positive affect. We conclude by discussing the content of collaborators’ emotion understanding and the probable mechanisms underlying the observed effects of being made aware of a partner’s emotions.     

Physical Scale Keypoints: Matching and Registration for Combined Intensity/Range Images

We present a new framework for detecting, describing, and matching keypoints in combined range-intensity data, resulting in what we call physical scale keypoints. We first produce an image mesh by backprojecting associated 2D intensity images onto the 3D range data. We detect and describe keypoints on the image mesh using an analogue of the SIFT algorithm for images with two key modifications: the process is made insensitive to viewpoint and structural discontinuities using a novel bilinear filter, and a physical scale space is constructed that exploits the reliable range measurements. Keypoints are matched between scans only when their physical scales agree, avoiding many potential false matches. Finally, the matches are rank-ordered using a new quality measure and supplied to a registration algorithm that refines each match into a rigid transformation for the entire scan pair. We report experimental results on keypoint detection and matching and range scan registration and verification in a set of difficult real-world scan pairs, showing that the new physical scale keypoints are demonstrably better than a competing approach based on backprojected SIFT keypoints.     

Improving the Parameterization of Approximate Subdivision Surfaces

We provide a method for improving the parameterization of patching schemes that approximate Catmull‐Clark subdivision surfaces, such that the new parameterization conforms better to that of the original subdivision surface. We create this reparameterization in real‐time using a method that only depends on the topology of the surface and is independent of the surface's geometry. Our method can handle patches with more than one extraordinary vertex and avoids the combinatorial increase in both complexity and storage associated with multiple extraordinary vertices. Moreover, the reparameterization function is easy to implement and fast.     

Tensile strength characteristics of GFRP bars in concrete beams with work cracks under sustained loading and severe environments

To investigate the effect of different environmental conditions of GFRP bars in concrete beams with work cracks subjected to sustained loads, the beams were exposed in indoor, freeze/thaw cycles and immersed in alkaline solution at elevated temperature. The bars were carefully extracted from the beams and tested in order to evaluate residual tensile properties. The results show that the tensile strength decreased significantly in the highly aggressive conditions but not in the natural conditions. The effect of GFRP bars casting in concrete beams demonstrated approximately 2.5% decrease of tensile strength caused by pore water environment in concrete beams on basis of those of the original bars. The effect of sustained loading plus work cracks demonstrated about 10.5% tensile strength decrease on basis of those of the bars only casted in concrete beams. The effect of environments under sustained loading plus work cracks demonstrated about 17% tensile strength decrease caused by a saturated solution of Ca(OH)₂ and 60±2 °C tap water (pH=12–13) and about 8% tensile strength decrease caused by freezing and thawing cycle (F/T), both on basis of those of the bars of the indoor beams only under sustained loading plus work cracks. The results demonstrate the effects of the tensile strengths under different environmental conditions of GFRP bars in concrete beams with work cracks subjected to sustained loads.