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| 2. |
- Kiencke, Uwe, et al.
(författare)
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ISIS Opening Talks
- 1996
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Rapport (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Lagriffoul, Fabien, 1977-
(författare)
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Combining Task and Motion Planning
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis addresses the problem of automatically computing, given a high-level goal description, a sequence of actions and motion paths for one or several robots to achieve that goal. Also referred to as CTAMP (Combining Task And Motion Planning), this problem may seem trivial at first glance, since efficient solutions have been found for its two underlying problems, namely task planning and motion planning. However, further consideration reveals that combining task and motion planning, in many cases, is not straightforward. We have identified two important issues which are addressed in this thesis.The first issue originates in the fact that symbolic actions can be geometrically instantiated in multiple ways. Choosing a geometric instance for each action is not trivial, because a “wrong” choice may compromise the feasibility of subsequent actions. To address this issue, in the first part of the thesis we propose a mechanism for backtracking over geometric choices in the context of a partial symbolic plan. This process may greatly increase the complexity of CTAMP. Therefore, we also present a constraint-based approach for pruning out geometric configurations which violate a number of geometric constraints imposed by the action sequence, and by the kinematic models of robots. This approach has been tested with success on the real humanoid robotic platform Justin in the context of the GeRT1 project.The second issue results from the necessity to interleave symbolic and geometric computations for taking geometric constraints into account at the symbolic level. Indeed, the symbolic search space forms an abstraction of the physical world, hence geometric constraints such as objects occlusions or kinematic constraints are not represented. However, interleaving both search processes is not a workable approach for large problem instances, because the resulting search space is too large. In the second part of the thesis, we propose a novel approach for decoupling symbolic and geometric search spaces, while keeping the symbolic level aware of geometric constraints. Culprit detection mechanisms are used for computing explanations for geometric failures, and these explanations are leveraged at the symbolic level for pruning the search space through inference mechanisms. This approach has been extensively tested in simulation, on different types of single and multiple robot systems.
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| 4. |
- Leist, Marcel, et al.
(författare)
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Adverse outcome pathways : opportunities, limitations and open questions
- 2017
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 91:11, s. 3477-3505
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Tidskriftsartikel (refereegranskat)abstract
- Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event erelationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field.
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| 5. |
- Schneider, K. M., et al.
(författare)
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Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling
- 2021
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 3:9, s. 1228-1241
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Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology for which there are no approved therapeutic options. Patients with PSC display changes in gut microbiota and in bile acid (BA) composition; however, the contribution of these alterations to disease pathogenesis remains controversial. Here we identify a role for microbiota-dependent changes in BA synthesis that modulates PSC pathophysiology. In a genetic mouse model of PSC, we show that loss of microbiota-mediated negative feedback control of BA synthesis results in increased hepatic BA concentrations, disruption of bile duct barrier function and, consequently, fatal liver injury. We further show that these changes are dependent on decreased BA signalling to the farnesoid X receptor, which modulates the activity of the rate-limiting enzyme in BA synthesis, CYP7A1. Moreover, patients with advanced stages of PSC show suppressed BA synthesis as measured by serum C4 levels, which is associated with poor disease prognosis. Our preclinical data highlight the microbiota-dependent dynamics of BA metabolism in cholestatic liver disease, which could be important for future therapies targeting BA and gut microbiome interactions, and identify C4 as a potential biomarker to functionally stratify patients with PSC and predict disease outcomes. Patients with primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease, display changes in the gut microbiota and in bile acid composition. Schneider, Candels and colleagues identify a role for microbiota-dependent regulation of bile acid synthesis through farnesoid X receptor signalling, which is relevant for PSC disease progression.
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| 6. |
- Vartak, Nachiket, et al.
(författare)
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Intravital Dynamic and Correlative Imaging of Mouse Livers Reveals Diffusion-Dominated Canalicular and Flow-Augmented Ductular Bile Flux
- 2021
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Ingår i: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 73:4, s. 1531-1550
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Small-molecule flux in tissue microdomains is essential for organ function, but knowledge of this process is scant due to the lack of suitable methods. We developed two independent techniques that allow the quantification of advection (flow) and diffusion in individual bile canaliculi and in interlobular bile ducts of intact livers in living mice, namely fluorescence loss after photoactivation and intravital arbitrary region image correlation spectroscopy.Approach and Results: The results challenge the prevailing "mechano-osmotic" theory of canalicular bile flow. After active transport across hepatocyte membranes, bile acids are transported in the canaliculi primarily by diffusion. Only in the interlobular ducts is diffusion augmented by regulatable advection. Photoactivation of fluorescein bis-(5-carboxymethoxy-2-nitrobenzyl)-ether in entire lobules demonstrated the establishment of diffusive gradients in the bile canalicular network and the sink function of interlobular ducts. In contrast to the bile canalicular network, vectorial transport was detected and quantified in the mesh of interlobular bile ducts.Conclusions: The liver consists of a diffusion-dominated canalicular domain, where hepatocytes secrete small molecules and generate a concentration gradient and a flow-augmented ductular domain, where regulated water influx creates unidirectional advection that augments the diffusive flux.
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| 7. |
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| 8. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 9. |
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