Place learning overrides innate behaviors in Drosophila

Animals in a natural environment confront many sensory cues. Some of these cues bias behavioral decisions independent of experience, and action selection can reveal a stimulus–response (S–R) connection. However, in a changing environment it would be a benefit for an animal to update behavioral action selection based on experience, and learning might modify even strong S–R relationships. How animals use learning to modify S–R relationships is a largely open question. Three sensory stimuli, air, light, and gravity sources were presented to individual Drosophila melanogaster in both naïve and place conditioning situations. Flies were tested for a potential modification of the S–R relationships of anemotaxis, phototaxis, and negative gravitaxis by a contingency that associated place with high temperature. With two stimuli, significant S–R relationships were abandoned when the cue was in conflict with the place learning contingency. The role of the dunce (dnc) cAMP-phosphodiesterase and the rutabaga (rut) adenylyl cyclase were examined in all conditions. Both dnc1 and rut2080 mutant flies failed to display significant S–R relationships with two attractive cues, and have characteristically lower conditioning scores under most conditions. Thus, learning can have profound effects on separate native S–R relationships in multiple contexts, and mutation of the dnc and rut genes reveal complex effects on behavior.</jats:p

Rapid and Precise Semi-Automatic Axon Quantification in Human Peripheral Nerves

We developed a time-efficient semi-automated axon quantification method using freeware in human cranial nerve sections stained with paraphenylenediamine (PPD). It was used to analyze a total of 1238 facial and masseteric nerve biopsies. The technique was validated by comparing manual and semi-automated quantification of 129 (10.4%) randomly selected biopsies. The software-based method demonstrated a sensitivity of 94% and a specificity of 87%. Semi-automatic axon counting was significantly faster (p<0.001) than manual counting. It took 1hour and 47minutes for all 129 biopsies (averaging 50sec per biopsy, 0.04seconds per axon). The counting process is automatic and does not need to be supervised. Manual counting took 21hours and 6minutes in total (average 9minutes and 49seconds per biopsy, 0.52seconds per axon). Our method showed a linear correlation to the manual counts (R=0.944 Spearman rho). Attempts have been made by several research groups to automate axonal load quantification. These methods often require specific hard- and software and are therefore only accessible to a few specialized laboratories. Our semi-automated axon quantification is precise, reliable and time-sparing using publicly available software and should be useful for an effective axon quantification in various human peripheral nerves

Continuous bunch-by-bunch spectroscopic investigation of the micro-bunching instability

Electron accelerators and synchrotrons can be operated to provide short emission pulses due to longitudinally compressed or sub-structured electron bunches. Above a threshold current, the high charge density leads to the micro-bunching instability and the formation of sub-structures on the bunch shape. These time-varying sub-structures on bunches of picoseconds-long duration lead to bursts of coherent synchrotron radiation in the terahertz frequency range. Therefore, the spectral information in this range contains valuable information about the bunch length, shape and sub-structures. Based on the KAPTURE readout system, a 4-channel single-shot THz spectrometer capable of recording 500 million spectra per second and streaming readout is presented. First measurements of time-resolved spectra are compared to simulation results of the Inovesa Vlasov-Fokker-Planck solver. The presented results lead to a better understanding of the bursting dynamics especially above the micro-bunching instability threshold.Comment: 12 pages, 11 figure

Valsartan Improves Insulin Sensitivity without Altering Vascular Function in Healthy Overweight Adults without the Metabolic Syndrome

Background. We investigated hyperactivity of the renin-angiotensin system (RAS) as a cause of endothelial dysfunction in obese humans. Methods. Thirty five healthy overweight (BMI = 33.6 ± 6.6 kg m −2) adults (33 ± 10 years old) without cardiovascular risk factors received valsartan (160 mg) orally daily or a matching placebo for 6 weeks each. Results. Baseline flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were not altered by placebo or valsartan. However, fasting plasma insulin was significantly decreased by valsartan compared to placebo (−4.6 ± 16.0 μUmL−1 versus −0.4 ± 11.6 μUmL−1, P = 0.032) with no changes in glucose. A secondary analysis in patients with elevated waist to hip ratios (ÿ0.85, n = 18) showed an increase in FMD with valsartan. Conclusions. Our findings suggest that angiotensin 2 receptor blockade may aid in the prevention of diabetes even at the earliest stages of risk due solely to uncomplicated obesity. The lack of an improvement in FMD does not support a central role of RAS-hyperactivity in the etiology of the vascular dysfunction due solely to obesity. However, it is possible that obese patients with central adiposity may improve FMD with RAS blockade, and future investigation is warranted in this subgroup.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63259/1/met.2007.0002.pd

Fast Mapping of Terahertz Bursting Thresholds and Characteristics at Synchrotron Light Sources

Dedicated optics with extremely short electron bunches enable synchrotron light sources to generate intense coherent THz radiation. The high degree of spatial compression in this so-called low-alpha optics entails a complex longitudinal dynamics of the electron bunches, which can be probed studying the fluctuations in the emitted terahertz radiation caused by the micro-bunching instability ("bursting"). This article presents a "quasi-instantaneous" method for measuring the bursting characteristics by simultaneously collecting and evaluating the information from all bunches in a multi-bunch fill, reducing the measurement time from hours to seconds. This speed-up allows systematic studies of the bursting characteristics for various accelerator settings within a single fill of the machine, enabling a comprehensive comparison of the measured bursting thresholds with theoretical predictions by the bunched-beam theory. This paper introduces the method and presents first results obtained at the ANKA synchrotron radiation facility.Comment: 7 pages, 7 figures, to be published in Physical Review Accelerators and Beam

Simultaneous Detection of Longitudinal and Transverse Bunch Signals at a Storage Ring

To understand and control the dynamics in the longitudinal phase space, time-resolved measurements of different bunch parameters are required. For a reconstruction of this phase space, the detector systems have to be synchronized. This reconstruction can be used e.g. for studies of the micro-bunching instability. It occurs if the interaction of the bunch with its own radiation leads to the formation of sub-structures on the longitudinal bunch profile. These sub-structures can grow rapidly -- leading to a sawtooth-like behaviour of the bunch. At KARA, we use a fast-gated intensified camera for energy spread studies, Schottky diodes for coherent synchrotron radiation studies as well as electro-optical spectral decoding for longitudinal bunch profile measurements. For a synchronization, a hardware synchronization scheme is used which compensates for eventual hardware delays. In this paper, the different experimental setups and their synchronization are discussed and first results of synchronous measurements are presented

Irinotecan pharmacokinetics-pharmacodynamics: the clinical relevance of prolonged exposure to SN-38

We have shown previously that the terminal disposition half-life of SN-38, the active metabolite of irinotecan, is much longer than earlier thought. Currently, it is not known whether this prolonged exposure has any relevance toward SN-38-induced toxicity. Here, we found that SN-38 concentrations present in human plasma for up to 3 weeks after a single irinotecan infusion induce significant cytotoxicity in vitro. Using pharmacokinetic data from 26 patients, with sampling up to 500 h, relationships were evaluated between systemic exposure (AUC) to SN-38 and the per cent decrease in absolute neutrophil count (ANC) at nadir, or by taking the entire time course of ANC into account (AOC). The time course of SN-38 concentrations (AUC500 h) was significantly related to this AOC (P<0.001). Based on these findings, a new limited-sampling model was developed for SN-38 AUC500 h using only two timed samples: AUC500 h=(6.588×C2.5 h)+(146.4×C49.5 h)+15.53, where C2.5 h and C49.5 h are plasma concentrations at 2.5 and 49.5 h after start of infusion, respectively. The use of this limited-sampling model may open up historic databases to retrospectively obtain information about SN-38-induced toxicity in patients treated with irinotecan