Nachhaltige regionale Integration in Westafrika und Europa ZEI Forschungskooperation mit dem West Africa Institute (WAI) von 2007 bis 2016 C237 2016 = Sustainable regional integration in West Africa and Europe ZEI Research cooperation with the West Africa Institute (WAI) from 2007 to 2016

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Sensitive superoxide detection in vascular cells by the new chemiluminescence dye L-012

The detection superoxide production in vascular cells is usually limited by a low sensitivity of available assays, We tested the applicability of the luminol derivate L-012 {[}8-amino-5-chloro-7-phenylpyridol{[}3,4-d]pyridazine-l,4(2H,3H)dione] to measure superoxide production in cultured endothelial cells (human umbilical vein endothelial cells) and rat aortic segments. Following stimulation with the protein kinase stimulator phorbol 12-myristate 13-acetate (PMA, 1 mu M) there was an 2,8-fold increase of L-012 chemiluminescence, whereas incubation with angiotensin II (100 nM) did not result in a measurable increase. Addition of vanadate (100 mu M) considerably increased the chemiluminescence (up to 17-fold) after PMA and made possible the detection of an enhanced superoxide production after stimulation with angiotensin II (by 1.7-fold). This was due to a similar to 9-fold increase in signal intensity of L-012 in the presence of vanadate, Prolonged incubation with vanadate also led to a tyrosine phosphorylation-dependent increase in superoxide formation which was predominantly produced by an NAD(P)H oxidase. Short-Term vanadate-enhanced L-012 chemiluminescence represents a highly sensitive assay making it possible to detect small changes of superoxide formation in intact vascular cells. Copyright(C) 1999 S. Karger AG. Basel

Earnings management and managerial honesty: the investors’ perspectives

This paper studies how investors infer CEO commitment to honesty from earnings management and how these perceptions – in conjunction with investors’ own social and moral preferences – shape their investment choices. We conduct two laboratory experiments simulating investment choices. Our results show that participants perceive a CEO to be more committed to honesty when they infer that the CEO engaged less in earnings management. For investment decisions, a one standard deviation increase in a CEO's perceived commitment to honesty compared to another CEO reduces the relevance of differences in the CEOs’ claimed future returns by 40%. This effect is most prominent among investors with a proself value orientation. To prosocial investors, their own honesty values and those attributed to the CEO matter directly, while returns only play a secondary role. Overall, our results suggest that moral motives are not a niche concern for norm-constrained investors, but instead matter to different categories of investors for distinct reasons

Crucial role of local peroxynitrite formation in neutrophil-induced endothelial cell activation

Introduction and methods: The reaction of superoxide anions and NO not only results in a decreased availability of NO, but also leads to the formation of peroxynitrite, the role of which in the cardiovascular system is still discussed controversially. In cultured human endothelial cells, we studied whether there is a significant interaction between endothelial NO and neutrophil-derived superoxide anions in terms of endothelial peroxynitrite formation. We particularly studied whether a significantly higher redox-stress can be found in those endothelial cells directly adjacent to an activated neutrophil. Results: A considerable part of the 2,7-dihydrodichlorofluoresceine signal in endothelial cells was due to oxidation by peroxynitrite. Providing superoxide radicals by enzymatic source or by the neutrophil respiratory burst increased the fluorescence, which was attenuated by blockade of endothelial NO-synthase, suggesting that peroxynitrite was formed from neutrophil- or extracellular enzyme-derived superoxide and endothelial NO. Considerably higher fluorescence intensity was observed in endothelial cells in direct neighborhood to a neutrophil. This was particularly pronounced in the presence of a NO-donor and was accompanied by a strong activation of NF-κB and increased expression of E-selectin in these cells. Conclusion: Endothelial cells adjacent to neutrophils may have elevated levels of peroxynitrite that result in an increased expression of adhesion molecules. Such cells might represent a preferential site for adhesion and migration of additional neutrophils when simultaneously high concentrations of NO and neutrophil-derived superoxide are present

The InfraRed Imaging Spectrograph (IRIS) for TMT: photometric precision and ghost analysis

The InfraRed Imaging Spectrograph (IRIS) is a first-light instrument for the Thirty Meter Telescope (TMT) that will be used to sample the corrected adaptive optics field by NFIRAOS with a near-infrared (0.8 - 2.4 $\mu$m) imaging camera and Integral Field Spectrograph (IFS). In order to understand the science case specifications of the IRIS instrument, we use the IRIS data simulator to characterize photometric precision and accuracy of the IRIS imager. We present the results of investigation into the effects of potential ghosting in the IRIS optical design. Each source in the IRIS imager field of view results in ghost images on the detector from IRIS's wedge filters, entrance window, and Atmospheric Dispersion Corrector (ADC) prism. We incorporated each of these ghosts into the IRIS simulator by simulating an appropriate magnitude point source at a specified pixel distance, and for the case of the extended ghosts redistributing flux evenly over the area specified by IRIS's optical design. We simulate the ghosting impact on the photometric capabilities, and found that ghosts generally contribute negligible effects on the flux counts for point sources except for extreme cases where ghosts coalign with a star of $\Delta$m$>$2 fainter than the ghost source. Lastly, we explore the photometric precision and accuracy for single sources and crowded field photometry on the IRIS imager.Comment: SPIE 2018, 14 pages, 14 figures, 4 tables, Proceedings of SPIE 10702-373, Ground-based and Airborne Instrumentation for Astronomy VII, 10702A7 (16 July 2018

Platelet mitochondrial membrane depolarization reflects disease severity in patients with sepsis and correlates with clinical outcome

Introduction: Sepsis is still a leading cause of morbidity and mortality, even in modern times, and thrombocytopenia has been closely associated with unfavorable disease outcome. Decreases in mitochondrial membrane potential (depolarization) were found in different tissues during sepsis. Previous work suggests that mitochondrial dysfunction of platelets correlates with clinical disease activity in sepsis. However, platelet mitochondrial membrane potential (Mmp) has not been investigated in a clinical follow-up design and not with regard to disease outcome. Methods: In this study, platelet mitochondrial membrane depolarization was assessed by means of a fluorescent Mmp-Index with flow cytometry in 26 patients with sepsis compared with control patients. Platelet Mmp-Index on admission was correlated with the clinical disease scores Acute Physiology and Chronic Health Evaluation Score II (APACHE II), Sequential Organ Failure Score (SOFA), and Simplified Acute Physiology Score II (SAPS II). Finally, platelet Mmp-Index on admission and follow-up were compared in the group of sepsis survivors and nonsurvivors. Expression of the prosurvival protein Bcl-xL in platelets was quantified by immunoblotting. Results: Platelet mitochondrial membrane depolarization correlated significantly with the simultaneously assessed clinical disease severity by APACHE II (r = -0.867; P < 0.0001), SOFA (r = -0.857; P < 0.0001), and SAPS II score (r = -0.839; P < 0.0001). Patients with severe sepsis showed a significant reduction in platelet Mmp-Index compared with sepsis without organ failure (0.18 (0.12 to 0.25) versus 0.79 (0.49 to 0.85), P < 0.0006) or with the control group (0.18 (0.12 to 0.25) versus 0.89 (0.68 to 1.00), P < 0.0001). Platelet Mmp-Index remained persistently low in sepsis nonsurvivors (0.269 (0.230 to 0.305)), whereas we observed recovery of platelet Mmp-Index in the survivor group (0.9 (0.713 to 1.017)). Furthermore, the level of prosurvival protein Bcl-xL decreased in platelets during severe sepsis. Conclusion: In this study, we demonstrated that mitochondrial membrane depolarization in platelets correlates with clinical disease severity in patients with sepsis during the disease course and may be a valuable adjunct parameter to aid in the assessment of disease severity, risk stratification, and clinical outcome

Neutrophil Granulocytes in Ovarian Cancer - Induction of Epithelial-To- Mesenchymal-Transition and Tumor Cell Migration

Background: Ovarian cancer (OvCa) is a highly aggressive malignoma with a tumor-promoting microenvironment. Infiltration of polymorphonuclear neutrophils (PMN) is frequently seen, raising the question of their impact on tumor development. In that context, effects of PMN on human ovarian cancer cells were assessed. Methods: Human epithelial ovarian cancer cells were incubated with human PMN, lysate of PMN, or neutrophil elastase. Morphological alterations were observed by time-lapse video-microscopy, and the underlying molecular mechanism was analyzed by flow cytometry and Western blotting. Functional alternations were assessed by an in vitro wound healing assay. In parallel, a large cohort of n=334 primary OvCa tissue samples of various histological subtypes was histologically evaluated. Results: Co-cultivation of cancer cells with either PMN or PMN lysate causes a change of the polygonal epithelial phenotype of the cells towards a spindle shaped morphology, causing a cribriform cell growth. The PMN-induced alteration could be attributed to elastase, a major protease of PMN. Elastase-induced shape change was most likely due to the degradation of membranous E-cadherin, which results in loss of cell contacts and polarity. Moreover, in response to elastase, epithelial cytokeratins were downmodulated, in parallel with a nuclear translocation of β-catenin. These PMN-elastase induced alterations of cells are compatible with an epithelial-to-mesenchymal transition (EMT) of the cancer cells. Following EMT, the cells displayed a more migratory phenotype. In human biopsies, neutrophil infiltration was seen in 72% of the cases. PMN infiltrates were detected preferentially in areas with low E-cadherin expression. Conclusion: PMN in the microenvironment of OvCa can alter tumor cells towards a mesenchymal and migratory phenotype

The InfraRed Imaging Spectrograph (IRIS) for TMT: photometric characterization of anisoplanatic PSFs and testing of PSF-Reconstruction via AIROPA

The InfraRed Imaging Spectrograph (IRIS) is a first-light instrument for the Thirty Meter Telescope (TMT) that will be used to sample the corrected adaptive optics field by the Narrow-Field Infrared Adaptive Optics System (NFIRAOS) with a near-infrared (0.8 - 2.4 µm) imaging camera and integral field spectrograph. To better understand IRIS science specifications we use the IRIS data simulator to characterize relative photometric precision and accuracy across the IRIS imaging camera 34”x34” field of view. Because the Point Spread Function (PSF) varies due to the effects of anisoplanatism, we use the Anisoplanatic and Instrumental Reconstruction of Off-axis PSFs for AO (AIROPA) software package to conduct photometric measurements on simulated frames using PSF-fitting as the PSF varies in single-source, binary, and crowded field use cases. We report photometric performance of the imaging camera as a function of the instrumental noise properties including dark current and read noise. Using the same methods, we conduct comparisons of photometric performance with reconstructed PSFs, in order to test the veracity of the current PSF-Reconstruction algorithms for IRIS/TMT

The velocity dispersion and mass function of the outer halo globular cluster Palomar 4

We obtained precise line-of-sight radial velocities of 23 member stars of the remote halo globular cluster Palomar 4 (Pal 4) using the High Resolution Echelle Spectrograph (HIRES) at the Keck I telescope. We also measured the mass function of the cluster down to a limiting magnitude of V~28 mag using archival HST/WFPC2 imaging. We derived the cluster's surface brightness profile based on the WFPC2 data and on broad-band imaging with the Low-Resolution Imaging Spectrometer (LRIS) at the Keck II telescope. We find a mean cluster velocity of 72.55+/-0.22 km/s and a velocity dispersion of 0.87+/-0.18 km/s. The global mass function of the cluster, in the mass range 0.55<=M<=0.85 M_solar, is shallower than a Kroupa mass function and the cluster is significantly depleted in low-mass stars in its center compared to its outskirts. Since the relaxation time of Pal 4 is of the order of a Hubble time, this points to primordial mass segregation in this cluster. Extrapolating the measured mass function towards lower-mass stars and including the contribution of compact remnants, we derive a total cluster mass of 29800 M_solar. For this mass, the measured velocity dispersion is consistent with the expectations of Newtonian dynamics and below the prediction of Modified Newtonian Dynamics (MOND). Pal 4 adds to the growing body of evidence that the dynamics of star clusters in the outer Galactic halo can hardly be explained by MOND.Comment: 17 pages, accepted for publication in MNRAS; Fig. 8 surface brightness/density data at github.com/matthiasjfrank/pal4_surface_brightnes

The InfraRed Imaging Spectrograph (IRIS) for TMT: photometric characterization of anisoplanatic PSFs and testing of PSF-Reconstruction via AIROPA

The InfraRed Imaging Spectrograph (IRIS) is a first-light instrument for the Thirty Meter Telescope (TMT) that will be used to sample the corrected adaptive optics field by the Narrow-Field Infrared Adaptive Optics System (NFIRAOS) with a near-infrared (0.8 - 2.4 µm) imaging camera and integral field spectrograph. To better understand IRIS science specifications we use the IRIS data simulator to characterize relative photometric precision and accuracy across the IRIS imaging camera 34”x34” field of view. Because the Point Spread Function (PSF) varies due to the effects of anisoplanatism, we use the Anisoplanatic and Instrumental Reconstruction of Off-axis PSFs for AO (AIROPA) software package to conduct photometric measurements on simulated frames using PSF-fitting as the PSF varies in single-source, binary, and crowded field use cases. We report photometric performance of the imaging camera as a function of the instrumental noise properties including dark current and read noise. Using the same methods, we conduct comparisons of photometric performance with reconstructed PSFs, in order to test the veracity of the current PSF-Reconstruction algorithms for IRIS/TMT