In two studies we investigate the role of affective factors and top-down processes underlying production and deliberate control of emotional facial expressions and its neural underpinnings. In Study ...1 we examine facial expressions of joy, fear and disgust depending on the emotional content of the visual stimuli (upright faces, inverted faces, emotion inducing pictures without faces). In Study 2 we focus on expressions of joy and disgust depending on gaze direction (with and without eye contact) in a more natural setting with a real person as stimulus. We hypothesized that the more automatic processes are induced by stimuli (e.g., arousal, mimicry or social cues like eye contact) the harder it is to control facial expressions; particularly expressions of joy compared to fear and disgust. In both studies we used go/no-go tasks and showed faster RTs for conditions with upright faces or eye contact, respectively. We also found faster RTs for expressions of joy than of fear and disgust. In Study 1 participants showed more errors in no-go trials for expressions of joy than for expressions of fear and disgust, indicating worse top-down control for expressions of joy than of fear or disgust. An ERP analysis of the no-go P3 in Study 1 revealed larger amplitudes for upright faces compared with both inverted faces and emotion inducing pictures and larger amplitudes for expressions of joy than for disgust. This indicates greater demand of top-down control when automatic mimicry processes are activated and some degree of specificity to particular facial expressions. In Study 2 more errors in no-go trials in conditions with eye contact only for expressions of joy indicate mimicry could be larger for expressions with high affiliative intent like expressions of joy, and reduced mimicry for negative expressions. All results indicate that facial expressions buffered by automatic processes (e.g., mimicry) have a greater need for top-down control, especially expressions of joy compared to expressions of fear and disgust.
•We investigated deliberate control of emotional facial expressions in a go/no-go task.•We found differences for expressions of joy compared to those of fear and disgust.•ERPs indicate greater demand of control when automatic processes are activated.•Eye contact modulates automatic processes for expressions of joy.
Fibroblast growth factor 23 (FGF23) is secreted primarily by osteocytes and regulates phosphate and vitamin D metabolism. Elevated levels of FGF23 are clinically associated with endothelial ...dysfunction and arterial stiffness in chronic kidney disease (CKD) patients; however, the direct effects of FGF23 on endothelial function are unknown. We hypothesized that FGF23 directly impairs endothelial vasorelaxation by hindering nitric oxide (NO) bioavailability. We detected expression of all four subtypes of FGF receptors (Fgfr1-4) in male mouse aortas. Exogenous FGF23 (90-9,000 pg/ml) did not induce contraction of aortic rings and did not relax rings precontracted with PGF2α. However, preincubation with FGF23 (9,000 pg/ml) caused a ∼36% inhibition of endothelium-dependent relaxation elicited by acetylcholine (ACh) in precontracted aortic rings, which was prevented by the FGFR antagonist PD166866 (50 nM). Furthermore, in FGF23-pretreated (9,000 pg/ml) aortic rings, we found reductions in NO levels. We also investigated an animal model of CKD (Col4a3(-/-) mice) that displays highly elevated serum FGF23 levels and found they had impaired endothelium-dependent vascular relaxation and reduced nitrate production compared with age-matched wild types. To elucidate a mechanism for the FGF23-induced impairment, we measured superoxide levels in endothelial cells and aortic rings and found that they were increased following FGF23 treatment. Crucially, treatment with the superoxide scavenger tiron reduced superoxide levels and also restored aortic relaxation to ACh. Therefore, our data suggest that FGF23 increases superoxide, inhibits NO bioavailability, and causes endothelial dysfunction in mouse aorta. Together, these data provide evidence that high levels of FGF23 contribute to cardiovascular dysfunction.
Ultracold quantum gases provide a unique setting for studying and understanding the properties of interacting quantum systems. Here, we investigate a multi-component system of 87Rb-39K Bose-Einstein ...condensates (BECs) with tunable interactions both theoretically and experimentally. Such multi-component systems can be characterized by their miscibility, where miscible components lead to a mixed ground state and immiscible components form a phase-separated state. Here we perform the first full simulation of the dynamical expansion of this system including both BECs and thermal clouds, which allows for a detailed comparison with experimental results. In particular we show that striking features emerge in time-of-flight (TOF) for BECs with strong interspecies repulsion, even for systems which were separated in situ by a large gravitational sag. An analysis of the centre of mass positions of the BECs after expansion yields qualitative agreement with the homogeneous criterion for phase-separation, but reveals no clear transition point between the mixed and the separated phases. Instead one can identify a transition region, for which the presence of a gravitational sag is found to be advantageous. Moreover, we analyse the situation where only one component is condensed and show that the density distribution of the thermal component also shows some distinct features. Our work sheds new light on the analysis of multi-component systems after TOF and will guide future experiments on the detection of miscibility in these systems.
Fibroblast growth factor (FGF) 23 is a phosphaturic hormone that directly targets cardiac myocytes via FGF receptor (FGFR) 4 thereby inducing hypertrophic myocyte growth and the development of left ...ventricular hypertrophy (LVH) in rodents. Serum FGF23 levels are highly elevated in patients with chronic kidney disease (CKD), and it is likely that FGF23 directly contributes to the high rates of LVH and cardiac death in CKD. It is currently unknown if the cardiac effects of FGF23 are solely pathological, or if they potentially can be reversed. Here, we report that FGF23-induced cardiac hypertrophy is reversible in vitro and in vivo upon removal of the hypertrophic stimulus. Specific blockade of FGFR4 attenuates established LVH in the 5/6 nephrectomy rat model of CKD. Since CKD mimics a form of accelerated cardiovascular aging, we also studied age-related cardiac remodeling. We show that aging mice lacking FGFR4 are protected from LVH. Finally, FGF23 increases cardiac contractility via FGFR4, while known effects of FGF23 on aortic relaxation do not require FGFR4. Taken together, our data highlight a role of FGF23/FGFR4 signaling in the regulation of cardiac remodeling and function, and indicate that pharmacological interference with cardiac FGF23/FGFR4 signaling might protect from CKD- and age-related LVH.
Fibroblast growth factor 23 (FGF23) is a hormone released primarily by osteocytes that regulates phosphate and vitamin D metabolism. Recent observational studies in humans suggest that circulating ...FGF23 is independently associated with cardiac hypertrophy and increased mortality, but it is unknown whether FGF23 can directly alter cardiac function. We found that FGF23 significantly increased cardiomyocyte cell size in vitro, the expression of gene markers of cardiac hypertrophy, and total protein content of cardiac muscle. In addition, FGFR1 and FGFR3 mRNA were the most abundantly expressed FGF receptors in cardiomyocytes, and the coreceptor α-klotho was expressed at very low levels. We tested an animal model of chronic kidney disease (Col4a3(-/-) mice) that has elevated serum FGF23. We found elevations in common hypertrophy gene markers in Col4a3(-/-) hearts compared with wild type but did not observe changes in wall thickness or cell size by week 10. However, the Col4a3(-/-) hearts did show reduced fractional shortening (-17%) and ejection fraction (-11%). Acute exposure of primary cardiomyocytes to FGF23 resulted in elevated intracellular Ca(2+) (Ca(2+)(i); F/F(o) + 86%) which was blocked by verapamil pretreatment. FGF23 also increased ventricular muscle strip contractility (67%), which was inhibited by FGF receptor antagonism. We hypothesize that although FGF23 can acutely increase Ca(2+)(i), chronically this may lead to decreases in contractile function or stimulate cardiac hypertrophy, as observed with other stress hormones. In conclusion, FGF23 is a novel bone/heart endocrine factor and may be an important mediator of cardiac Ca(2+) regulation and contractile function during chronic kidney disease.
Cardiovascular disease is a major cause of morbidity and mortality among patients with chronic kidney disease (CKD). Trimethylamine-
-oxide (TMAO), a uremic metabolite that is elevated in the setting ...of CKD, has been implicated as a nontraditional risk factor for cardiovascular disease. While association studies have linked elevated plasma levels of TMAO to adverse cardiovascular outcomes, its direct effect on cardiac and smooth muscle function remains to be fully elucidated. We hypothesized that pathological concentrations of TMAO would acutely increase cardiac and smooth muscle contractility. These effects may ultimately contribute to cardiac dysfunction during CKD. High levels of TMAO significantly increased paced, ex vivo human cardiac muscle biopsy contractility (
< 0.05). Similarly, TMAO augmented contractility in isolated mouse hearts (
< 0.05). Reverse perfusion of TMAO through the coronary arteries via a Langendorff apparatus also enhanced cardiac contractility (
< 0.05). In contrast, the precursor molecule, trimethylamine (TMA), did not alter contractility (
> 0.05). Multiphoton microscopy, used to capture changes in intracellular calcium in paced, adult mouse hearts ex vivo, showed that TMAO significantly increased intracellular calcium fluorescence (
< 0.05). Interestingly, acute administration of TMAO did not have a statistically significant influence on isolated aortic ring contractility (
> 0.05). We conclude that TMAO directly increases the force of cardiac contractility, which corresponds with TMAO-induced increases in intracellular calcium but does not acutely affect vascular smooth muscle or endothelial function of the aorta. It remains to be determined if this acute inotropic action on cardiac muscle is ultimately beneficial or harmful in the setting of CKD.
We demonstrate for the first time that elevated concentrations of TMAO acutely augment myocardial contractile force ex vivo in both murine and human cardiac tissue. To gain mechanistic insight into the processes that led to this potentiation in cardiac contraction, we used two-photon microscopy to evaluate intracellular calcium in ex vivo whole hearts loaded with the calcium indicator dye Fluo-4. Acute treatment with TMAO resulted in increased Fluo-4 fluorescence, indicating that augmented cytosolic calcium plays a role in the effects of TMAO on force production. Lastly, TMAO did not show an effect on aortic smooth muscle contraction or relaxation properties. Our results demonstrate novel, acute, and direct actions of TMAO on cardiac function and help lay the groundwork for future translational studies investigating the complex multiorgan interplay involved in cardiovascular pathogenesis during CKD.
Hybrid adhesive joints of metal and composite parts are increasingly common features of lightweight structures. Efficient design of these joints requires computational methods for estimating the ...fatigue life of the adhesive as well as of the parts being joined – i. e. the adherends. The paper focuses on computational fatigue life prediction for carbon fiber reinforced polymer (CFRP) adherends in hybrid adhesive joints. After a brief description of the composite material considered, two modeling approaches for the fatigue life are presented. Subsequently, the experimental determination of the model parameters is discussed and the relevant values are presented. For validation, the models are applied to predict the fatigue lives of a multidirectional laminate as well as of the composite adherend in a hybrid single‐lap joint. Finally, the results for both models are compared and discussed with respect to the experimental results. Both models yield reasonable predictions for the cases considered here. For almost uniaxial stress states, the predictions of both models are very similar while for multiaxial stress states the difference is more pronounced.
Translation
Hybride Klebverbindungen zwischen Metall‐ und Faserverbundkomponenten sind zunehmend Bestandteil von modernen Leichtbaustrukturen. Die Auslegung dieser Verbindungen erfordert numerische Berechnungsverfahren zur Lebensdauerabschätzung sowohl des Klebstoffs als auch der jeweiligen Fügekomponenten. Die hier gezeigten Untersuchungen befassen sich mit der numerischen Lebensdauerabschätzung von Komponenten aus Kohlenstofffaser‐Kunststoff‐Verbundwerkstoff (CFK) in einer hybriden Klebverbindung. Nach einer kurzen Beschreibung des verwendeten Werkstoffes werden zwei Modellansätze zur Lebensdauerabschätzung vorgestellt. Des Weiteren werden die experimentelle Ermittlung der Modellparameter erläutert und die relevanten Parameter dargestellt. Zur Validierung werden die Modellansätze für die Lebensdauerabschätzung von multidirektionalen Laminaten und von einschnittig überlappten hybriden Klebverbindungen angewandt. Die Ergebnisse der beiden Ansätze werden miteinander verglichen und den experimentellen Untersuchungen gegenübergestellt. Beide Modellansätze ergeben für die hier untersuchten Fälle annehmbare Lebensdauerabschätzungen. Für vorwiegend uniaxiale Spannungszustände liefern beide Ansätze ähnliche Ergebnisse, wohingegen die Unterschiede bei multiaxialen Spannungszuständen stärker ausprägt sind.
In the present paper, fatigue life prediction for carbon fiber reinforced polymer (CFRP) adherends in hybrid adhesive joints is proposed using a stress‐ and energy‐based approach. The analyses are compared to results of fatigue experiments on single‐lap joints and effects such as the multiaxial stress state in the laminate and the stress magnitude at the notch root are discussed.
Innovative approaches for lightweight design of components can contribute significantly to reduced fuel consumption and emissions of future aircraft. Within the framework of the European aviation ...research program Clean Sky 2, an innovative design of an aircraft nose wheel for the A320 is developed using carbon fiber reinforced plastics (CFRP) in order to demonstrate a weight reduction potential of 27% compared to conventional designs. In the present paper, the approach of the development process and the final detailed design of the composite aircraft wheel as well as a manufacturing concept are presented, various design challenges are highlighted and the solutions developed to meet them are discussed. Within a concept phase different structural design principles for the wheel are analyzed, taking into account the challenging load cases during different phases of aircraft operation. The selected innovative design principle is further elaborated into a detailed design considering design challenges such as space, installation, and safety requirements, as well as integration of bearings, seals and joint solutions. Also, structural analysis of the composite components via FEA and experimental validation of the joints are discussed. In addition, the manufacturing concept for the complex wheel geometry via resin transfer molding (RTM) using carbon non-crimp fabrics is presented and an outlook on the future manufacturing and testing of wheel prototypes is given.
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