Eluate derived by extracorporal antibody-based immunoadsorption elevates the cytosolic Ca2+ concentration in podocytes via B-2 kinin receptors

Background/Aim: Patients with idiopathic focal segmental glomerulosclerosis (FSGS) often develop a recurrence of the disease after kidney transplantation. In a number of FSGS patients, plasmapheresis and immunoadsorption procedures have been shown to transiently reduce proteinuria and are thought to do this by eliminating a circulating factor. Direct cellular effects of eluates from immunoadsorption procedures on podocytes, the primary target of injury in FSGS, have not yet been reported. Methods: Eluates were derived from antibody-based immunoadsorption of a patient suffering from primary FSGS, a patient with systemic lupus erythematosus, and a healthy volunteer. The cytosolic free Ca2+ concentration ({[}Ca2+](i)) of differentiated podocytes was measured by single-cell fura-2 microfluorescence measurements. Free and total immunoreactive kinin levels were measured by radioimmunoassay. Results: FSGS eluates increased the {[}Ca2+](i) levels concentration dependently (EC50 0.14 mg/ml; n = 3-19). 1 mg/ml eluate increased the {[}Ca2+](i) values reversibly from 82 +/- 12 to 1,462 +/- 370 nmol/l, and then they returned back to 100 16 nmol/l (n = 19). The eluate-induced increase of {[}Ca2+](i) consisted of an initial Ca2+ peak followed by a Ca2+ plateau which depended on the extracellular Ca2+ concentration. The eluate-induced increase of {[}Ca2+](i) was inhibited by the specific B-2 kinin receptor antagonist Hoe 140 in a concentration-dependent manner (IC50 2.47 nmol/l). In addition, prior repetitive application of bradykinin desensitized the effect of eluate on {[}Ca2+](i). A colonic epithelial cell line not reacting to bradykinin did not respond to eluate either (n = 6). Similar to FSGS eluates, the eluate preparations of both the systemic lupus patient and the healthy volunteer led to a biphasic, concentration-dependent {[}Ca2+](i) increase in poclocytes which again was inhibited by Hoe 140. Free kinins were detected in all eluate preparations. Conclusion: The procedure of antibody-based immunoadsorption leads to kinin in the eluate which elevates the {[}Ca2+](i) level of podocytes via B-2 kinin receptors. Copyright (C) 2002 S. Karger AG, Basel

The application of eye-tracking in music research

Though eye-tracking is typically a methodology applied in the visual research domain, recent studies suggest its relevance in the context of music research. There exists a community of researchers interested in this kind of research from varied disciplinary backgrounds scattered across the globe. Therefore, in August 2017, an international conference was held at the Max Planck Institute for Empirical Aesthetics in Frankfurt, Germany, to bring this research community together. The conference was dedicated to the topic of music and eye-tracking, asking the question: what do eye movements, pupil dilation, and blinking activity tell us about musical processing? This special issue is constituted of top-scoring research from the conference and spans a range of music-related topics. From tracking the gaze of performers in musical trios to basic research on how eye movements are affected by background music, the contents of this special issue highlight a variety of experimental approaches and possible applications of eye-tracking in music research

Towards efficient calibration for webcam eye-tracking in online experiments

Calibration is performed in eye-tracking studies to map raw model outputs to gaze-points on the screen and improve accuracy of gaze predictions. Calibration parameters, such as user-screen distance, camera intrinsic properties, and position of the screen with respect to the camera can be easily calculated in controlled offline setups, however, their estimation is non-trivial in unrestricted, online, experimental settings. Here, we propose the application of deep learning models for eye-tracking in online experiments, providing suitable strategies to estimate calibration parameters and perform personal gaze calibration. Focusing on fixation accuracy, we compare results with respect to calibration frequency, the time point of calibration during data collection (beginning, middle, end), and calibration procedure (fixation-point or smooth pursuit-based). Calibration using fixation and smooth pursuit tasks, pooled over three collection time-points, resulted in the best fixation accuracy. By combining device calibration, gaze calibration, and the best-performing deep-learning model, we achieve an accuracy of 2.580−a considerable improvement over reported accuracies in previous online eye-tracking studies

Time reversal in thermoacoustic tomography - an error estimate

The time reversal method in thermoacoustic tomography is used for approximating the initial pressure inside a biological object using measurements of the pressure wave made on a surface surrounding the object. This article presents error estimates for the time reversal method in the cases of variable, non-trapping sound speeds.Comment: 16 pages, 6 figures, expanded "Remarks and Conclusions" section, added one figure, added reference

Solution to the twin image problem in holography

While the invention of holography by Dennis Gabor truly constitutes an ingenious concept, it has ever since been troubled by the so called twin image problem limiting the information that can be obtained from a holographic record. Due to symmetry reasons there are always two images appearing in the reconstruction process. Thus, the reconstructed object is obscured by its unwanted out of focus twin image. Especially for emission electron as well as for x- and gamma-ray holography, where the source-object distances are small, the reconstructed images of atoms are very close to their twin images from which they can hardly be distinguished. In some particular instances only, experimental efforts could remove the twin images. More recently, numerical methods to diminish the effect of the twin image have been proposed but are limited to purely absorbing objects failing to account for phase shifts caused by the object. Here we show a universal method to reconstruct a hologram completely free of twin images disturbance while no assumptions about the object need to be imposed. Both, amplitude and true phase distributions are retrieved without distortion

Towards a time-reversal mirror for quantum systems

The reversion of the time evolution of a quantum state can be achieved by changing the sign of the Hamiltonian as in the polarization echo experiment in NMR. In this work we describe an alternative mechanism inspired by the acoustic time reversal mirror. By solving the inverse time problem in a discrete space we develop a new procedure, the perfect inverse filter. It achieves the exact time reversion in a given region by reinjecting a prescribed wave function at its periphery.Comment: 6 pages, 4 figures. Introduction modified, references added, one figure added to improve the discussio

Mitochondrial Targeted Coenzyme Q, Superoxide, and Fuel Selectivity in Endothelial Cells

Background Previously, we reported that the “antioxidant” compound “mitoQ” (mitochondrial-targeted ubiquinol/ubiquinone) actually increased superoxide production by bovine aortic endothelial (BAE) cell mitochondria incubated with complex I but not complex II substrates. Methods and Results To further define the site of action of the targeted coenzyme Q compound, we extended these studies to include different substrate and inhibitor conditions. In addition, we assessed the effects of mitoquinone on mitochondrial respiration, measured respiration and mitochondrial membrane potential in intact cells, and tested the intriguing hypothesis that mitoquinone might impart fuel selectivity in intact BAE cells. In mitochondria respiring on differing concentrations of complex I substrates, mitoquinone and rotenone had interactive effects on ROS consistent with redox cycling at multiple sites within complex I. Mitoquinone increased respiration in isolated mitochondria respiring on complex I but not complex II substrates. Mitoquinone also increased oxygen consumption by intact BAE cells. Moreover, when added to intact cells at 50 to 1000 nM, mitoquinone increased glucose oxidation and reduced fat oxidation, at doses that did not alter membrane potential or induce cell toxicity. Although high dose mitoquinone reduced mitochondrial membrane potential, the positively charged mitochondrial-targeted cation, decyltriphenylphosphonium (mitoquinone without the coenzyme Q moiety), decreased membrane potential more than mitoquinone, but did not alter fuel selectivity. Therefore, non-specific effects of the positive charge were not responsible and the quinone moiety is required for altered nutrient selectivity. Conclusions In summary, the interactive effects of mitoquinone and rotenone are consistent with redox cycling at more than one site within complex I. In addition, mitoquinone has substrate dependent effects on mitochondrial respiration, increases repiration by intact cells, and alters fuel selectivity favoring glucose over fatty acid oxidation at the intact cell level.This work was supported by Veterans Affairs Medical Research Funds and grant DK25295 from the National Institutes of Health

Exact time-reversal focusing of acoustic and quantum excitations in open cavities: The perfect inverse filter

The time-reversal mirror (TRM) prescribes the reverse playback of a signal to focalize an acoustic excitation as a Loschmidt echo. In the quantum domain, the perfect inverse filter (PIF) processes this signal to ensure an exact reversion provided that the excitation originated outside the cavity delimited by the transducers. We show that PIF takes a simple form when the initial excitation is created inside this cavity. This also applies to the acoustical case, where it corrects the TRM and improves the design of an acoustic bazooka. We solve an open chaotic cavity modeling a quantum bazooka and a simple model for a Helmholtz resonator, showing that the PIF becomes decisive to compensate the group velocities involved in a highly localized excitation and to achieve subwavelength resolution.Comment: 6 pages, 2 figure

Power train for three-stage potassium test turbine. Volume 1 - Final design

Final design for power train for three stage potassium test turbin