Computer automated lanes detection and profiles evaluation of one-dimensional gel electrophoretic autoradiograms

A new fast, precise and reproducible method for lanes detection and profiles evaluation of one-dimensional gel electrophoretic autoradiograms is presented. It is fully automated, and its principles are based on image and signal processing techniques. The operator usually has only to specify the number of lanes that are present in the preparation, but still may retain overall control. In the first phase, the program automatically locates the lateral position of the lanes, and approximates their left and right boundaries by polynomials (which allow curved as well as straight lanes). The operator can then intervene, if necessary, to adjust these positions. In the second phase, the background variations are corrected; two types of density profiles are computed, representing the average density as well as the total amount of material in the lanes. This calculation is carried out with correction for tilt or curvature for each lane. Finally, prinouts are produced that contain graphs of the profiles together with quantitative measurements. Use of this method is illustrated by analysis of electrophoretic gels containing proteins and lipopolysaccharides of varying mobilities. Experiments made on these gels as well as others yield accurate quantitation of the relative amount of each component

Trick or treat: The effect of placebo on the power of pharmacogenetic association studies

<p>Abstract</p> <p>The genetic mapping of drug-response traits is often characterised by a poor signal-to-noise ratio that is placebo related and which distinguishes pharmacogenetic association studies from classical case-control studies for disease susceptibility. The goal of this study was to evaluate the statistical power of candidate gene association studies under different pharmacogenetic scenarios, with special emphasis on the placebo effect. Genotype/phenotype data were simulated, mimicking samples from clinical trials, and response to the drug was modelled as a binary trait. Association was evaluated by a logistic regression model. Statistical power was estimated as a function of the number of single nucleotide polymorphisms (SNPs) genotyped, the frequency of the placebo 'response', the genotype relative risk (GRR) of the response polymorphism, the strategy for selecting SNPs for genotyping, the number of individuals in the trial and the ratio of placebo-treated to drugtreated patients. We show that: (i) the placebo 'response' strongly affects the statistical power of association studies -- even a highly penetrant drug-response allele requires at least a 500-patient trial in order to reach 80 per cent power, several-fold more than the value estimated by standard tools that are not calibrated to pharmacogenetics; (ii) the power of a pharmacogenetic association study depends primarily on the penetrance of the response genotype and, when this penetrance is fixed, power decreases for larger placebo effects; (iii) power is dramatically increased when adding markers; (iv) an optimal study design includes a similar number of placebo- and drugtreated patients; and (v) in this setting, straightforward haplotype analysis does not seem to have an advantage over single marker analysis.</p

Neural adaptation in pSTS correlates with perceptual aftereffects to biological motion and with autistic traits

The adaptive nature of biological motion perception has been documented in behavioral studies, with research showing that prolonged viewing of an action can bias judgments of subsequent actions towards the opposite of its attributes. However, the neural mechanisms underlying action adaptation aftereffects remain unknown. We examined adaptation-induced changes in brain responses to an ambiguous action after adapting to walking or running actions within two bilateral regions of interest: 1) human middle temporal area (hMT. +), a lower-level motion-sensitive region of cortex, and 2) posterior superior temporal sulcus (pSTS), a higher-level action-selective area. We found a significant correlation between neural adaptation strength in right pSTS and perceptual aftereffects to biological motion measured behaviorally, but not in hMT. +. The magnitude of neural adaptation in right pSTS was also strongly correlated with individual differences in the degree of autistic traits. Participants with more autistic traits exhibited less adaptation-induced modulations of brain responses in right pSTS and correspondingly weaker perceptual aftereffects. These results suggest a direct link between perceptual aftereffects and adaptation of neural populations in right pSTS after prolonged viewing of a biological motion stimulus, and highlight the potential importance of this brain region for understanding differences in social-cognitive processing along the autistic spectrum.</p