Circadian Rhythms in Visual Responsiveness in the Behaviorally Arrhythmic Drosophila Clock Mutant ClkJrk

An organism's biological day is characterized by a pattern of anticipatory physiological and behavioral changes that are governed by circadian clocks to align with the 24-h cycling environment. Here, we used flash electroretinograms (ERGs) and steady-state visually evoked potentials (SSVEPs) to examine how visual responsiveness in wild-type Drosophila melanogaster and the circadian clock mutant ClkJrk varies over circadian time. We show that the ERG parameters of wild-type flies vary over the circadian day, with a higher luminance response during the subjective night. The SSVEP response that assesses contrast sensitivity also showed a time-of-day dependence, including 2 prominent peaks within a 24-h period and a maximal response at the end of the subjective day, indicating a tradeoff between luminance and contrast sensitivity. Moreover, the behaviorally arrhythmic ClkJrk mutants maintained a circadian profile in both luminance and contrast sensitivity, but unlike the wild-types, which show bimodal profiles in their visual response, ClkJrk flies show a weakening of the bimodal character, with visual responsiveness tending to peak once a day. We conclude that the ClkJrk mutation mainly affects 1 of 2 functionally coupled oscillators and that the visual system is partially separated from the locomotor circadian circuits that drive bouts of morning and evening activity. As light exposure is a major mechanism for entrainment, our work suggests that a detailed temporal analysis of electrophysiological responses is warranted to better identify the time window at which circadian rhythms are most receptive to light-induced phase shifting

Method for Flavor Tagging in Neutral B Meson Decays

A method is proposed for tagging the flavor of neutral $B$ mesons in the study of CP-violating decay asymmetries. The method makes use of a possible difference in interactions in $B \pi$ or $B^* \pi$ systems with isospins 1/2 and 3/2, and would be particularly clean if the $I = 1/2$ systems can be detected as ``$B^{**}$'' resonances.Comment: Submitted to Phys. Rev. D. 11 pages, LaTeX, Technion-PH-92-40 / PITHA 92/39 / EFI 92-5

Data Mining at a major bank: Lessons from a large marketing application

. This paper summarizes experiences and results of productively using knowledge discovery and data mining technology in a large retail bank. We present data mining as part of a greater effort to develop and deploy an integrated IT-infrastructure for loyalty based customer management, combining data warehousing, and campaign management together with data mining technology. We have completed a first campaign where potential customers were selected using the new built data warehouse together with data mining. Because of the better insight we have used a decision tree as selection method. 1 Introduction Recent developments of technology, like for example storage management or the Internet, have made it very easy and cheap to collect tera bytes of data and make them on-line accessible in very large databases. However, these valuable assets are still not comprehensively and systematically exploited as part of daily business processes. The growing competition, the increased speed o..

Abnormal visual gain control in a Parkinson's disease model

Our understanding of Parkinson's disease (PD) has been revolutionized by the discovery of disease-causing genetic mutations. The most common of these is the G2019S mutation in the LRRK2 kinase gene, which leads to increased kinase activity. However, the link between increased kinase activity and PD is unclear. Previously, we showed that dopaminergic expression of the human LRRK2-G2019S transgene in flies led to an activity-dependent loss of vision in older animals and we hypothesized that this may have been preceded by a failure to regulate neuronal activity correctly in younger animals. To test this hypothesis, we used a sensitive measure of visual function based on frequency-tagged steady-state visually evoked potentials. Spectral analysis allowed us to identify signals from multiple levels of the fly visual system and wild-type visual response curves were qualitatively similar to those from human cortex. Dopaminergic expression of hLRRK2-G2019S increased contrast sensitivity throughout the retinal network. To test whether this was due to increased kinase activity, we fed Drosophila with kinase inhibitors targeted at LRRK2. Contrast sensitivity in both day 1 and day 14 flies was normalized by a novel LRRK2 kinase inhibitor 'BMPPB-32'. Biochemical and cellular assays suggested that BMPPB-32 would be a more specific kinase inhibitor than LRRK2-IN-1. We confirmed this in vivo, finding that dLRRK- null flies show large off-target effects with LRRK2-IN-1 but not BMPPB-32. Our data link the increased Kinase activity of the G2019S-LRRK2 mutation to neuronal dysfunction and demonstrate the power of the Drosophila visual system in assaying the neurological effects of genetic diseases and therapies

Data Mining at a major bank: Lessons from a large marketing application

This paper summarizes experiences and results of productively using knowledge discovery and data mining technology in a large retail bank. We present data mining as part of a greater effort to develop and deploy an integrated IT-infrastructure for loyalty based customer management, combining data warehousing, and campaign management together with data mining technology. We have completed a first campaign where potential customers were selected using the new built data warehouse together with data mining. Because of the better insight we have used a decision tree as selection method