Elektrisches Verhalten von Maschinenelementen im Antriebsstrang

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Empirical formulae for the influence of real film thickness distribution on the capacitance of an EHL point contact and application to rolling bearings

Electrical bearing capacitance plays an important role in the prediction of harmful bearing currents, which could lead to premature failure of the bearing and the entire drive system. The effect of rolling speed, force, and material parameters on the electrical capacitance of an elliptical contact in elastohydrodynamic lubrication has been studied numerically. An empirical equation that describes the relationship between the areas of central film thickness and minimum film thickness of the HERTZ'ian contact area has been derived. Additional, another formula to calculate the total capacitance of a rolling bearing, based only on the HERTZ'ian contact capacitance with the central film thickness as single parameter, has been developed. Finally, a comparison was made between the calculated capacities and measured values

Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.

Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells. Co-culturing CD4 <sup>+</sup> with autologous CD8 <sup>+</sup> T cells from ART-suppressed HIV <sup>+</sup> donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8 <sup>+</sup> T cells. This trispecific antibody mediates CD4 <sup>+</sup> and CD8 <sup>+</sup> T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection

Analyzing multitarget activity landscapes using protein-ligand interaction fingerprints: interaction cliffs.

This is the original submitted version, before peer review. The final peer-reviewed version is available from ACS at http://pubs.acs.org/doi/abs/10.1021/ci500721x.Activity landscape modeling is mostly a descriptive technique that allows rationalizing continuous and discontinuous SARs. Nevertheless, the interpretation of some landscape features, especially of activity cliffs, is not straightforward. As the nature of activity cliffs depends on the ligand and the target, information regarding both should be included in the analysis. A specific way to include this information is using protein-ligand interaction fingerprints (IFPs). In this paper we report the activity landscape modeling of 507 ligand-kinase complexes (from the KLIFS database) including IFP, which facilitates the analysis and interpretation of activity cliffs. Here we introduce the structure-activity-interaction similarity (SAIS) maps that incorporate information on ligand-target contact similarity. We also introduce the concept of interaction cliffs defined as ligand-target complexes with high structural and interaction similarity but have a large potency difference of the ligands. Moreover, the information retrieved regarding the specific interaction allowed the identification of activity cliff hot spots, which help to rationalize activity cliffs from the target point of view. In general, the information provided by IFPs provides a structure-based understanding of some activity landscape features. This paper shows examples of analyses that can be carried out when IFPs are added to the activity landscape model.M-L is very grateful to CONACyT (No. 217442/312933) and the Cambridge Overseas Trust for funding. AB thanks Unilever for funding and the European Research Council for a Starting Grant (ERC-2013- StG-336159 MIXTURE). J.L.M-F. is grateful to the School of Chemistry, Department of Pharmacy of the National Autonomous University of Mexico (UNAM) for support. This work was supported by a scholarship from the Secretariat of Public Education and the Mexican government

C. ELEGANS RESPONSE TO COMBINED STRESS

Cellular stress has been shown to increase with age, but the human body’s ability to respond to this stress decreases with age. Various forms of stress, including osmotic and heavy metal stress, are linked to a broad range of human disease. Age is the leading risk factors for many of these major morbidities, including cardiovascular disease and cancer, among others. Developing a better understanding of stress response pathways will allow targeted therapy for better treatment. Developing a better understanding of stress response pathways will allow targeted therapy for better treatment. Using the roundworm Caenorhabditis elegans as a model of study, I investigated the osmotic and heavy metal stress pathways by treating worms with sodium chloride (NaCl) and cadmium chloride (CdCl2), respectively. I first identified a target dose for each stressors that reduced lifespan by 50%, then I combined the stressors in order to observe their interaction. I found that 250mM NaCl and 1mM CdCl2 reduced C. elegans lifespan by roughly 50% individually. When these two stressors were combined, I observed an 85% reduction in lifespan, indicating that the stressors are activating different responses within the worms

Evaluation of Oil-Film Thickness Along the Path of Contact in a Gear Mesh by Capacitance Measurement

This paper presents a new method to evaluate the oil-film thickness in gears. By using high speed capacitance measurements in combination with an exact timing it is possible to detect the changes in capacitance along the path of contact. With knowledge of the contact area, the oil-film thickness can be calculated from the capacitance measurements. The design of the test rig relies on a good electrical insulation and accurate speed measurements. First test results show that the changing conditions in the contact can be detected by the measurement of the capacitance

Comprehensive knowledge base of two- and three-dimensional activity cliffs for medicinal and computational chemistry [v1; ref status: indexed, http://f1000r.es/5ir]

Activity cliffs are formed by pairs or groups of structurally similar or analogous active compounds with large differences in potency. They can be defined in two or three dimensions by comparing graph-based molecular representations or compound binding modes, respectively. Through systematic analysis of publicly available compound activity data and ligand-target X-ray structures we have in a series of studies determined all currently available two- and three-dimensional activity cliffs (2D- and 3D-cliffs, respectively). Furthermore, we have systematically searched for 2D extensions of 3D-cliffs. Herein, we specify different categories of activity cliffs we have explored and introduce an open access data deposition in ZENODO (doi: 10.5281/zenodo.18490) that makes the entire knowledge base of current activity cliffs freely available in an organized form

Classification of Binding Modes for Kinase-Inhibitor Complex Structures, 3D Activity Cliffs Formed by Kinase Inhibitors, and Structural Analogues of 3D-Cliff Compounds

<p>The classification of crystallographic binding modes is provided for 884 kinase-inhibitor complex structures that were assembled from PDB. In addition, a total of 105 three-dimensional activity cliffs formed by 3D kinase inhibitors are listed. Their corresponding potency information is also given. Furthermore, the 2D structural analogues of 3D cliff-forming inhibitors were identified from ChEMBL database, on the basis of matched molecular pairs. These analogs and their activity information are also provided.</p

Current Compound Coverage of the Kinome

Publicly available kinase inhibitors have been analyzed in detail. Nearly 19000 inhibitors have been identified with activity against 266 different kinases. Thus, about half of the human kinome is currently covered with active small molecules. The distribution of inhibitors across the kinome is uneven. Most available kinase inhibitors are likely to be type I inhibitors. By contrast, type II inhibitors are rare but usually have high potency. Kinase inhibitors generally display high scaffold diversity. Activity cliffs with an at least 100-fold difference in potency are only found for inhibitors of 106 kinases, which is partly due to only small numbers of compounds available for many kinases, in addition to scaffold diversity. Moreover, kinase inhibitors are less promiscuous than often thought. More than 70% of available inhibitors are only annotated with a single kinase activity, and only ∼1% of the inhibitors are active against five or more kinases