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349 results on '"Grund, S"'

57. TCR-induced activation of Ras proceeds at the plasma membrane and requires palmitoylation of N-Ras

Author

RUBIO I, GRUND S, SONG SP, BISKUP C, BANDEMER S, FRICKE M, FÖRSTER M, A, WITTIG U, KLICHE S., GRAZIANI , ANDREA, Rubio, I, Grund, S, Song, Sp, Biskup, C, Bandemer, S, Fricke, M, Förster, M, Graziani, Andrea, A, Wittig, U, and Kliche, S.

Subjects
T cell, Lipoylation, Immunology, Receptors, Antigen, T-Cell, Biology, Oncogene Protein p21(ras), Endoplasmic Reticulum, Jurkat cells, Immunological synapse, Jurkat Cells, Palmitoylation, T-Lymphocyte Subsets, Anti-apoptotic Ras signalling cascade, Cell Line, Tumor, medicine, Immunology and Allergy, Animals, Guanine Nucleotide Exchange Factors, Humans, Fluorescent Dyes, T-cell receptor, Cell Membrane, Cell biology, Rats, DNA-Binding Proteins, Protein Transport, medicine.anatomical_structure, ras Proteins, ras Guanine Nucleotide Exchange Factors, Guanine nucleotide exchange factor, Protein Binding, Signal Transduction
Abstract

Ras transmits manifold signals from the TCR at various crossroads in the life of a T cell. For example, selection programs in the thymus or the acquisition of a state of hypo-responsiveness known as anergy are just some of the T cell features known to be controlled by TCR-sparked signals that are intracellularly propagated by Ras. These findings raise the question of how Ras can transmit such a variety of signals leading to the shaping of equally many T cell traits. Because Ras proteins transit through endomembrane compartments on their way to the plasma membrane (PM), compartmentalized Ras activation at distinct subcellular sites represents a potential mechanism for signal diversification in TCR signaling. This hypothesis has been nurtured by studies in T cells engineered to overexpress Ras that reported distinct activation of Ras at the PM and Golgi. Contrary to this scenario, we report in this study that activation of endogenous Ras, imaged in live Jurkat T cells using novel affinity probes for Ras-GTP, proceeds only at the PM even upon enforced signal flux through the diacylglycerol/RasGRP1 pathway. Physiological engagement of the TCR at the immunological synapse in primary T cells caused focalized Ras-GTP accumulation also only at the PM. Analysis of palmitoylation-deficient Ras mutants, which are confined to endomembranes, confirmed that the TCR does not activate Ras in that compartment and revealed a critical function for palmitoylation in N-Ras/H-Ras activation. These findings identify the PM as the only site of TCR-driven Ras activation and document that endomembranes are not a signaling platform for Ras in T cells.

Published
2010

60. Validation of biplane high‐speed fluoroscopy combined with two different noninvasive tracking methodologies for measuring <italic>in vivo</italic> distal limb kinematics of the horse.

Author

Geiger, S. M., Reich, E., Böttcher, P., Grund, S., and Hagen, J.

Abstract

Summary: Reason for performing study: Biplane high‐speed fluoroscopy is a new method for gait analysis of the equine distal extremity. This is the first study validating the noninvasive tracking possibilities (Autoscoping and Scientific Rotoscoping) taking equine anatomy into account. Objectives: To determine the resolution with which Autoscoping and Scientific Rotoscoping depict motion of the equine phalanges in comparison to the invasive gold standard marker‐based registration. Study design: Comparative ex vivo study. Methods: In 5 distal extremities of slaughtered ponies, 3 or 4 tantalum beads with 1 mm diameter were implanted in each of the proximal, middle and distal phalangeal bones. Three‐dimensional models of the bones were reconstructed using computed tomographic data (120 kV, 50 mA, slice thickness 1 mm, increment 0.5). The beads were digitally removed from the bone models. Biplane fluoroscopic videos were taken at 69.5 ± 3.5 kV, 102.5 ± 22.5 mA, 500 frames/s and 0.5 ms shutter speed. The 5 specimens were moved in the trial field of the biplane fluoroscopic setup in a step‐like motion (simulation of landing, main stance phase, lift‐off). Marker‐based registration, Autoscoping and Scientific Rotoscoping were carried out. For statistical analysis agreement was computed as percentiles, mean and s.d. Results: The medians of Scientific Rotoscoping ranged from 0.16 to 0.66 mm in translations and 0.43 to 2.78° in rotations, while values for Autoscoping were 0.13–0.70 mm and 0.28–2.39° respectively. With 2 exceptions, all differences between methods were statistically significant. Scientific Rotoscoping is more time efficient than Autoscoping and results in smaller maximum errors. Main limitations: The experimental set‐up was specifically designed to accommodate in vivo requirements. Autoscoping was not manually corrected but rather expected to work automatically. Conclusions: It is possible to noninvasively apply both Autoscoping and Scientific Rotoscoping for gait analysis of the equine phalanges with high precision. The summary is available in Chinese ‐ see supporting information. [ABSTRACT FROM AUTHOR]

Published
2018
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62. Mitoxantrone-loaded zeolite beta nanoparticles

Author

Grund, S., Doussineau, T., Fischer, D., Mohr, G.J., and Publica

Abstract

This article describes the preparation and the physico-chemical characterization of a new host-guest system consisting of zeolite beta nanoparticles as host and mitoxantrone as guest. The resulting host-guest system mitoxantrone@. beta is characterized in terms of morphology (transmission electron microscopy, dynamic light scattering), structure (powder wide-angle X-ray diffraction, nitrogen sorption), surface charge (-potential measurements), and optical properties (UV-visible absorption, steady-state fluorescence). Mitoxantrone@. beta particles are monodisperse in size with a mean diameter centered around 100. nm. Mitoxantrone guest molecules are adsorbed at the micropore entrances of zeolite host. Resulting nanoparticles retrieve the interesting optical properties of guest molecules with a fluorescence emission band in the near-infrared region. Mitoxantrone loading is comparatively evaluated by three different means (elemental analysis, direct and indirect UV-visible absorption studies) showing a loading level of 6.8. mol/g. Mitoxantrone@. beta nanoparticles also show a noticeable cytotoxic effect when applied to cancer cells.

Published
2012

71. Endocrine disrupting, mutagenic, and teratogenic effects of upper Danube River sediments using effect-directed analysis

Author

Higley, E., Grund, S., Jones, P.D., Schulze, Tobias, Seiler, T.-B., Lübcke-von Varel, Urte, Brack, Werner, Wölz, J., Zielke, H., Giesy, J.P., Hollert, H., Hecker, M., Higley, E., Grund, S., Jones, P.D., Schulze, Tobias, Seiler, T.-B., Lübcke-von Varel, Urte, Brack, Werner, Wölz, J., Zielke, H., Giesy, J.P., Hollert, H., and Hecker, M.

Abstract

Effect-directed analysis (EDA) can be useful in identifying and evaluating potential toxic chemicals in matrixes. Previous investigations of extracts of sediments from the upper Danube River in Germany revealed acute nonspecific and mechanism-specific toxicity as determined by several bioassays. In the present study, EDA was used to further characterize these sediments and identify groups of potentially toxic chemicals. Four extracts of sediments were subjected to a novel fractionation scheme coupled with identification of chemicals to characterize their ability to disrupt steroidogenesis, or cause mutagenic and/or teratogenic effects. All four whole extracts of sediment caused significant alteration of steroidogenesis, and were mutagenic as well as teratogenic. The whole extracts of sediments were separated into 18 fractions and these fractions were then subjected to the same bioassays as the whole extracts. Fractions 7 to 15 of all four extracts were consistently more potent in both the Ames fluctuation and H295R assays. Much of this toxicity could be attributed to polycyclic aromatic hydrocarbons, sterols, and in fraction 7-naphthoic acids. Because the fraction containing polychlorinated biphenyls, polychlorodibenzodioxin/furan, dichlorodiphenyltrichloroethane, and several organophosphates did not cause any observable effects on hormone production or a mutagenic response, or were not detected in any of the samples, these compounds could be eliminated as causative agents for the observed effects. These results demonstrate the value of using EDA, which uses multiple bioassays and new fractionation techniques to assess toxicity. Furthermore, to our knowledge this is the first study using the recently developed H295R assay within EDA strategies.

Published
2012

72. Evolution by Evaluation

Author

Mahlow, C, Hess, M, Grund, S, Mahlow, C, Hess, M, and Grund, S

Abstract

This paper describes the process of formally evaluating an E-Learning system that has been in use for several years. Professional usability evaluation offers deeper insight into user behaviour and needs than accidental feedback collection or introspection by system developers. A first analysis of the evaluation samples shows satisfaction of users with the general design of the system but also dissatisfaction with certain aspects of navigation that would otherwise have escaped our attention. State of the art formal evaluation turned out to be instrumental in making an existing system considerably more user-friendly.

Published
2007

88. The Effect of an Eroded Leading Edge on the Aerodynamic Performance of a Transonic Fan Blade Cascade.

Author

Hergt, Alexander, Klinner, J., Steinert, W., Grund, S., Beversdorff, M., Giebmanns, A., and Schnell, R.

Subjects
WIND turbine blades, LEADING edges (Aerodynamics), TRANSONIC aerodynamics, PARTICLE image velocimetry, LIQUID crystals, EROSION, DEFORMATIONS (Mechanics)
Abstract

Especially at transonic flow conditions the leading edge shape influences the performance of a fan profile. At the same time the leading edge of a fan profile is highly affected by erosion during operation. This erosion leads to a deformation of the leading edge shape and a reduction of the chord length. In the present experimental and numerical study, the aerodynamic performance of an original fan profile geometry is compared to an eroded fan profile with a blunt leading edge (BLE) and a chord length reduced by about 1%. The experiments are peiformed at a linear fan blade cascade in the Transonic Cascade Wind Tunnel of DLR in Cologne. The inflow Mach number during the tests is 1.25 and the Reynolds number 1.5 x 106. All tests are carried out at a low inflow turbulence level of 0.8%. The results of the investigation show that losses are increased over the whole operating range of the cascade. At the aerodynamic design point (ADP) the losses raise by 25%. This significant loss increase can be traced back to the increase of the shock losses at the leading edge. The change in shock structure is investigated and described in detail by means of particle image velocimetry (PIV) measurements and Schlieren imaging. Additionally, the unsteady fluctuation of the shock position is measured by a high-speed shadowgraphy. Then the frequency range of the fluctuation is obtained by a Fourier analysis of the time resolved shock position. Furthermore, liquid crystal measurements are performed in order to analyze the influence of the leading edge shape on the development of the suction side boundary layer. The results show that for the original fan blade the transition occurs at the shock position on the blade suction side by a separation bubble whereas the transition onset is shifted upstream for the fan blade with the BLE. [ABSTRACT FROM AUTHOR]

Published
2015
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