Institution
University of Stuttgart
Education•Stuttgart, Germany•
About: University of Stuttgart is a education organization based out in Stuttgart, Germany. It is known for research contribution in the topics: Laser & Finite element method. The organization has 27715 authors who have published 56370 publications receiving 1363382 citations. The organization is also known as: Universität Stuttgart.
Papers published on a yearly basis
Papers
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TL;DR: It is suggested that a cause–effect relationship between FMS and PA is suspected but has not been demonstrated yet and could provide aids for decision making for teachers and coaches, but also for therapists' decision guidance to create training, lessons and therapy adequate to the target group.
275 citations
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TL;DR: There is a clear correlation between the contribution of the different subunits to the cleavage of fluorogenic and long peptide substrates and most of the proteolytic activity of mammalian 20 S proteasomes leading to the generation of MHC class I ligands.
275 citations
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TL;DR: Direct observation of the conformational equilibria of ligand-dependent G-protein-coupled receptor and deduction of the underlying mechanisms of receptor activation will have wide-reaching implications for the understanding of the function of G- proteins in health and disease.
Abstract: Conformational selection and induced fit are two prevailing mechanisms to explain the molecular basis for ligand-based activation of receptors. G-protein-coupled receptors are the largest class of cell surface receptors and are important drug targets. A molecular understanding of their activation mechanism is critical for drug discovery and design. However, direct evidence that addresses how agonist binding leads to the formation of an active receptor state is scarce. Here we use (19)F nuclear magnetic resonance to quantify the conformational landscape occupied by the adenosine A2A receptor (A2AR), a prototypical class A G-protein-coupled receptor. We find an ensemble of four states in equilibrium: (1) two inactive states in millisecond exchange, consistent with a formed (state S1) and a broken (state S2) salt bridge (known as 'ionic lock') between transmembrane helices 3 and 6; and (2) two active states, S3 and S3', as identified by binding of a G-protein-derived peptide. In contrast to a recent study of the β2-adrenergic receptor, the present approach allowed identification of a second active state for A2AR. Addition of inverse agonist (ZM241385) increases the population of the inactive states, while full agonists (UK432097 or NECA) stabilize the active state, S3', in a manner consistent with conformational selection. In contrast, partial agonist (LUF5834) and an allosteric modulator (HMA) exclusively increase the population of the S3 state. Thus, partial agonism is achieved here by conformational selection of a distinct active state which we predict will have compromised coupling to the G protein. Direct observation of the conformational equilibria of ligand-dependent G-protein-coupled receptor and deduction of the underlying mechanisms of receptor activation will have wide-reaching implications for our understanding of the function of G-protein-coupled receptor in health and disease.
274 citations
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TL;DR: T NF-R2 triggering can interfere with TNF-R1-induced apoptosis by inhibition of NF-kappaB-dependent production ofAnti-apoptotic factors and by blocking the action of anti-ap optotic factors at the post-transcriptional level.
Abstract: We have recently shown that stimulation of TNF-R2 selectively enhances apoptosis induction by the death receptor TNF-R1. Here, we demonstrate that stimulation of CD30 or CD40 also leads to selective enhancement of TNF-R1-induced cell death. Enhancement of apoptosis was correlated with the depletion of endogenous TRAF2 within 1 to 6 hours. Selective prestimulation of TNF-R2 for several hours inhibited TNF-R2-induced activation of the anti-apoptotic NF-kappaB pathway up to 90% and dramatically enhanced apoptosis induction by this receptor. When both TNF-receptors were stimulated simultaneously, TNF-R1-induced NF-kappaB activation remained unaffected but TNF-R1-induced apoptosis was still significantly enhanced. Compared with FasL-induced cell death TNF-R1-induced activation of caspase-8 was significantly weaker and delayed. Costimulation or prestimulation of TNF-R2 enhanced caspase-8 processing. Life cell imaging and confocal microscopy revealed that both TNF-R1 and TNF-R2 recruited the anti-apoptotic factor cIAP1 in a TRAF2-dependent manner. Thus, TNF-R2 may compete with TNF-R1 for the recruitment of newly synthesized TRAF2-bound anti-apoptotic factors, thereby promoting the formation of a caspase-8-activating TNF-R1 complex. Hence, TNF-R2 triggering can interfere with TNF-R1-induced apoptosis by inhibition of NF-kappaB-dependent production of anti-apoptotic factors and by blocking the action of anti-apoptotic factors at the post-transcriptional level.
274 citations
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11 Jun 2003TL;DR: This paper shows how weighted PDSs yield new algorithms for certain classes of interprocedural dataflow-analysis problems.
Abstract: Recently, pushdown systems (PDSs) have been extended to weighted PDSs, in which each transition is labeled with a value, and the goal is to determine the meet-over-all-paths value (for paths that meet a certain criterion). This paper shows how weighted PDSs yield new algorithms for certain classes of interprocedural dataflow-analysis problems.
274 citations
Authors
Showing all 28043 results
Name | H-index | Papers | Citations |
---|---|---|---|
Yi Chen | 217 | 4342 | 293080 |
Robert J. Lefkowitz | 214 | 860 | 147995 |
Michael Kramer | 167 | 1713 | 127224 |
Andrew G. Clark | 140 | 823 | 123333 |
Stephen D. Walter | 112 | 513 | 57012 |
Fedor Jelezko | 103 | 413 | 42616 |
Ulrich Gösele | 102 | 603 | 46223 |
Dirk Helbing | 101 | 642 | 56810 |
Ioan Pop | 101 | 1370 | 47540 |
Niyazi Serdar Sariciftci | 99 | 591 | 54055 |
Matthias Komm | 99 | 832 | 43275 |
Hans-Joachim Werner | 98 | 317 | 48508 |
Richard R. Ernst | 96 | 352 | 53100 |
Xiaoming Sun | 96 | 382 | 47153 |
Feng Chen | 95 | 2138 | 53881 |