| 1. |
- Roth, Lynn, et al.
(author)
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Pharmacological modulation of vascular ageing: a review from VascAgeNet
- 2023
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In: Ageing Research Reviews. - 1872-9649.
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Research review (peer-reviewed)abstract
- Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation.
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| 2. |
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| 3. |
- Fischer, Debra A., et al.
(author)
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M2K. II. A Triple-Planet System Orbiting Hip 57274
- 2012
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 745:1, s. 21-
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Journal article (peer-reviewed)abstract
- Doppler observations from Keck Observatory have revealed a triple-planet system orbiting the nearby K4V star, HIP 57274. The inner planet, HIP 57274b, is a super-Earth with M sin i = 11.6 M-circle plus (0.036 M-Jup), an orbital period of 8.135 +/- 0.004 days, and slightly eccentric orbit e = 0.19 +/- 0.1. We calculate a transit probability of 6.5% for the inner planet. The second planet has M sin i = 0.4 M-Jup with an orbital period of 32.0 +/- 0.02 days in a nearly circular orbit (e = 0.05 +/- 0.03). The third planet has M sin i = 0.53 M-Jup with an orbital period of 432 +/- 8 days (1.18 years) and an eccentricity e = 0.23 +/- 0.03. This discovery adds to the number of super-Earth mass planets with M sin i < 12 M-circle plus that have been detected with Doppler surveys. We find that 56% +/- 18% of super-Earths are members of multi-planet systems. This is certainly a lower limit because of observational detectability limits, yet significantly higher than the fraction of Jupiter mass exoplanets, 20% +/- 8%, that are members of Doppler-detected, multi-planet systems.
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| 4. |
- Hagelbäck, Johan, 1977-
(author)
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Multi-Agent Potential Field based Architectures for Real-Time Strategy Game Bots
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Real-Time Strategy (RTS) is a sub-genre of strategy games which is running in real-time, typically in a war setting. The player uses workers to gather resources, which in turn are used for creating new buildings, training combat units, build upgrades and do research. The game is won when all buildings of the opponent(s) have been destroyed. The numerous tasks that need to be handled in real-time can be very demanding for a player. Computer players (bots) for RTS games face the same challenges, and also have to navigate units in highly dynamic game worlds and deal with other low-level tasks such as attacking enemy units within fire range.This thesis is a compilation grouped into three parts. The first part deals with navigation in dynamic game worlds which can be a complex and resource demanding task. Typically it is solved by using pathfinding algorithms. We investigate an alternative approach based on Artificial Potential Fields and show how an APF based navigation system can be used without any need of pathfinding algorithms.In RTS games players usually have a limited visibility of the game world, known as Fog of War. Bots on the other hand often have complete visibility to aid the AI in making better decisions. We show that a Multi-Agent PF based bot with limited visibility can match and even surpass bots with complete visibility in some RTS scenarios. We also show how the bot can be extended and used in a full RTS scenario with base building and unit construction.In the next section we propose a flexible and expandable RTS game architecture that can be modified at several levels of abstraction to test different techniques and ideas. The proposed architecture is implemented in the famous RTS game StarCraft, and we show how the high-level architecture goals of flexibility and expandability can be achieved.In the last section we present two studies related to gameplay experience in RTS games. In games players usually have to select a static difficulty level when playing against computer oppo- nents. In the first study we use a bot that during runtime can adapt the difficulty level depending on the skills of the opponent, and study how it affects the perceived enjoyment and variation in playing against the bot.To create bots that are interesting and challenging for human players a goal is often to create bots that play more human-like. In the second study we asked participants to watch replays of recorded RTS games between bots and human players. The participants were asked to guess and motivate if a player was controlled by a human or a bot. This information was then used to identify human-like and bot-like characteristics for RTS game players.
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| 6. |
- Thompson, Samantha J., et al.
(author)
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HARS3 for a Roboticized Isaac Newton Telescope
- 2016
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In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY VI. - : SPIE. - 9781510601963
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Conference paper (peer-reviewed)abstract
- We present a description of a new instrument development, HARPS3, planned to be installed on an upgraded and roboticized Isaac Newton Telescope by end-2018. HARPS3 will be a high resolution (R similar or equal to 115,000) echelle spectrograph with a wavelength range from 380-690 nm. It is being built as part of the Terra Hunting Experiment {a future 10 year radial velocity measurement programme to discover Earth-like exoplanets. The instrument design is based on the successful HARPS spectrograph on the 3.6m ESO telescope and HARPS-N on the TNG telescope. The main changes to the design in HARPS3 will be: a customised fibre adapter at the Cassegrain focus providing a stabilised beam feed and on-sky fibre diameter approximate to 1.4 arcsec, the implementation of a new continuous flow cryostat to keep the CCD temperature very stable, detailed characterisation of the HARPS3 CCD to map the effective pixel positions and thus provide an improved accuracy wavelength solution, an optimised integrated polarimeter and the instrument integrated into a robotic operation. The robotic operation will optimise our programme which requires our target stars to be measured on a nightly basis. We present an overview of the entire project, including a description of our anticipated robotic operation.
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| 7. |
- van Rijn, Jorik M., et al.
(author)
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Enhanced Collagen Deposition in the Duodenum of Patients with Hyaline Fibromatosis Syndrome and Protein Losing Enteropathy
- 2020
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:21
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Journal article (peer-reviewed)abstract
- Hyaline fibromatosis syndrome (HFS), resulting from ANTXR2 mutations, is an ultra-rare disease that causes intestinal lymphangiectasia and protein-losing enteropathy (PLE). The mechanisms leading to the gastrointestinal phenotype in these patients are not well defined. We present two patients with congenital diarrhea, severe PLE and unique clinical features resulting from deleterious ANTXR2 mutations. Intestinal organoids were generated from one of the patients, along with CRISPR-Cas9 ANTXR2 knockout, and compared with organoids from two healthy controls. The ANTXR2-deficient organoids displayed normal growth and polarity, compared to controls. Using an anthrax-toxin assay we showed that the c.155C>T mutation causes loss-of-function of ANTXR2 protein. An intrinsic defect of monolayer formation in patient-derived or ANTXR2(KO) organoids was not apparent, suggesting normal epithelial function. However, electron microscopy and second harmonic generation imaging showed abnormal collagen deposition in duodenal samples of these patients. Specifically, collagen VI, which is known to bind ANTXR2, was highly expressed in the duodenum of these patients. In conclusion, despite resistance to anthrax-toxin, epithelial cell function, and specifically monolayer formation, is intact in patients with HFS. Nevertheless, loss of ANTXR2-mediated signaling leads to collagen VI accumulation in the duodenum and abnormal extracellular matrix composition, which likely plays a role in development of PLE.
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