Introduction: Orthostatic dysregulation occurs during exposure to an increased gravitational vector and is especially common upon re-entering standard Earth gravity (1 g) after an extended period in microgravity (0 g). External peripheral skin cooling (PSC) has recently been described as a potent countermeasure against orthostatic dysregulation during heat stress and in lower body negative pressure (LBNP) studies. We therefore hypothesized that PSC may also be an effective countermeasure during hyper-gravity exposure (+Gz).
Methods: To investigate this, we designed a randomized short-arm human centrifuge (SAHC) experiment ("Coolspin") to investigate whether PSC could act as a stabilizing factor in cardiovascular function during+Gz. Artificial gravity between +1 g and+4 gwas generated by a SAHC. 18 healthy male volunteers completed two runs in the SAHC. PSC was applied during one of the two runs and the other run was conducted without cooling. Each run consisted of a 10-min baseline trial followed by a +Gz step protocol marked by increasing g-forces, with each step being 3min long. The following parameters were measured: blood pressure (BP), heart rate (HR), stroke volume (SV), total peripheral resistance (TPR), cardiac output (CO). Furthermore, a cumulative stress index for each subject was calculated.
Results: +Gz led to significant changes in primary as well as in secondary outcome parameters such as HR, SV, TPR, CO, and BP. However, none of the primary outcome parameters (HR, cumulative stress-index, BP) nor secondary outcome parameters (SV, TPR, CO) showed any significant differences-whether the subject was cooled or not cooled. Systolic BP did, however, tend to be higher amongst the PSC group.
Conclusion: In conclusion, PSC during +Gz did not confer any significant impact on hemodynamic activity or orthostatic stability during +Gz. This may be due to lower PSC responsiveness of the test subjects, or an insufficient level of body surface area used for cooling. Further investigations are warranted in order to comprehensively pinpoint the exact degree of PSC needed to serve as a useful countermeasure system during +Gz.
View lessBackground: Muscle fatigue and pain are key symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Although the pathophysiology is not yet fully understood, there is ample evidence for hypoperfusion which may result in electrolyte imbalance and sodium overload in muscles. Therefore, the aim of this study was to assess levels of sodium content in muscles of patients with ME/CFS and to compare these to healthy controls.
Methods: Six female patients with ME/CFS and six age, BMI and sex matched controls underwent Na-23-MRI of the left lower leg using a clinical 3T MR scanner before and after 3 min of plantar flexion exercise. Sodium reference phantoms with solutions of 10, 20, 30 and 40 mmol/L NaCl were used for quantification. Muscle sodium content over 40 min was measured using a dedicated plugin in the open-source DICOM viewer Horos. Handgrip strength was measured and correlated with sodium content.
Results: Baseline tissue sodium content was higher in all 5 lower leg muscle compartments in ME/CFS compared to controls. Within the anterior extensor muscle compartment, the highest difference in baseline muscle sodium content between ME/CFS and controls was found (mean ± SD; 12.20 ± 1.66 mM in ME/CFS versus 9.38 ± 0.71 mM in controls, p = 0.0034). Directly after exercise, tissue sodium content increased in gastrocnemius and triceps surae muscles with + 30% in ME/CFS (p = 0.0005) and + 24% in controls (p = 0.0007) in the medial gastrocnemius muscle but not in the extensor muscles which were not exercised. Compared to baseline, the increase of sodium content in medial gastrocnemius muscle was stronger in ME/CFS than in controls with + 30% versus + 17% to baseline at 12 min (p = 0.0326) and + 29% versus + 16% to baseline at 15 min (p = 0.0265). Patients had reduced average handgrip strength which was associated with increased average muscle tissue sodium content (p = 0.0319, R-2 = 0.3832).
Conclusion: Muscle sodium content before and after exercise was higher in ME/CFS than in healthy controls. Furthermore, our findings indicate an inverse correlation between muscle sodium content and handgrip strength. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and may allow for potential therapeutic targeting.
View lessX-rays are invaluable for imaging and sterilization of bones, yet the resulting ionization and primary radiation damage mechanisms are poorly understood. Here we monitor in-situ collagen backbone degradation in dry bones using second-harmonic-generation and X-ray diffraction. Collagen breaks down by cascades of photon-electron excitations, enhanced by the presence of mineral nanoparticles. We observe protein disintegration with increasing exposure, detected as residual strain relaxation in pre-stressed apatite nanocrystals. Damage rapidly grows from the onset of irradiation, suggesting that there is no minimal ‘safe’ dose that bone collagen can sustain. Ionization of calcium and phosphorous in the nanocrystals yields fluorescence and high energy electrons giving rise to structural damage that spreads beyond regions directly illuminated by the incident radiation. Our findings highlight photoelectrons as major agents of damage to bone collagen with implications to all situations where bones are irradiated by hard X-rays and in particular for small-beam mineralized collagen fiber investigations.
View lessInfluenza A virus (IAV) causes pandemics and annual epidemics of severe respiratory infections. A better understanding of the molecular regulation in tissue and cells upon IAV infection is needed to thoroughly understand pathogenesis. We analyzed IAV replication and gene expression induced by IAV strain H3N2 Panama in isolated primary human alveolar epithelial type II cells (AECIIs), the permanent A549 adenocarcinoma cell line, alveolar macrophages (AMs) and explanted human lung tissue by bulk RNA sequencing. Primary AECII exhibit in comparison to AM a broad set of strongly induced genes related to RIG-I and interferon (IFN) signaling. The response of AECII was partly mirrored in A549 cells. In human lung tissue, we observed induction of genes unlike in isolated cells. Viral RNA was used to correlate host cell gene expression changes with viral burden. While relative induction of key genes was similar, gene abundance was highest in AECII cells and AM, while weaker in the human lung (due to less IAV replication) and A549 cells (pointing to their limited suitability as a model). Correlation of host gene induction with viral burden allows a better understanding of the cell-type specific induction of pathways and a possible role of cellular crosstalk requiring intact tissue.
View lessDeep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer’s Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neural circuits. To investigate this, we performed a post-hoc analysis on a multi-center cohort of 46 patients with DBS to the fornix (NCT00658125, NCT01608061). Using normative structural and functional connectivity data, we found that stimulation of the circuit of Papez and stria terminalis robustly associated with cognitive improvement (R = 0.53, p < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming.
View lessJahr eins des Enforcements der Unternehmensberichterstattung in der Alleinverantwortung der BaFin liegt hinter uns. Während es für eine fundierte Beurteilung von praktisch relevanten Veränderungen im Enforcement- Verfahren mangels hinreichender Erfahrungswerte noch zu früh ist, wendet sich der Blick bereits wieder nach vorne: Welche Schwerpunktthemen wird die BaFin in ihrer Überwachungstätigkeit im Jahr 2023 aufgreifen? Und wie können sich kapitalmarktorientierte Unternehmen bestmöglich darauf einstellen? Auf diese beiden Fragen gibt der folgende Beitrag gezielte Antworten.
View lessScrolling through a social media newsfeed has become almost ubiquitous. Yet, it remains unknown what specific post elements people pay attention to and whether this varies depending on how they access social media newsfeeds. In an eye-tracking experiment among university students (N = 201), we compare user attention to specific post elements like source, title, or picture, in a dynamic Facebook newsfeed by device (desktop vs. mobile) and smartphone usage environment (private vs. public). Significant attentional differences occur at the level of the newsfeed post elements. Users pay less attention to visual information on the mobile newsfeed and more attention to textual post elements in a public setting.
View lessTetrapyridyl-functionalized phosphinines were prepared and structurally characterized. The donor-functionalized aromatic phosphorus heterocycles react highly selectively and even reversibly with water. Calculations reveal P,N-cooperativity for this process, with the flanking pyridyl groups serving to kinetically enhance the formal oxidative addition process of H2O to the low-coordinate phosphorus atom via H-bonding. Subsequent tautomerization forms 1,2-dihydrophosphinine derivatives, which can be quantitatively converted back to the phosphinine by applying vacuum, even at room temperature. This process can be repeated numerous times, without any sign of decomposition of the phosphinine. In the presence of CuI·SMe2, dimeric species of the type ([Cu2I2(phosphinine)]2) are formed, in which each phosphorus atom shows the less common μ2-bridging 2e−-lone-pair-donation to two Cu(I)-centres. Our results demonstrate that fully unsaturated phosphorus heterocycles, containing reactive P[double bond, length as m-dash]C double bonds, are interesting candidates for the activation of E–H bonds, while the aromaticity of such compounds plays an appreciable role in the reversibility of the reaction, supported by NICS calculations.
View lessCompounds containing Mn–O bonds are of utmost importance in biological systems and catalytic processes. Nevertheless, mononuclear manganese complexes containing all O-donor ligands are still rare. Taking advantage of the low tendency of the pentafluoroorthotellurate ligand (teflate, OTeF5) to bridge metal centers, we have synthesized two homoleptic manganese complexes with monomeric structures and an all O-donor coordination sphere. The tetrahedrally distorted MnII anion, [Mn(OTeF5)4]2−, can be described as a high spin d5 complex (S = 5/2), as found experimentally (magnetic susceptibility measurements and EPR spectroscopy) and using theoretical calculations (DFT and CASSCF/NEVPT2). The high spin d4 electronic configuration (S = 2) of the MnIII anion, [Mn(OTeF5)5]2−, was also determined experimentally and theoretically, and a square pyramidal geometry was found to be the most stable one for this complex. Finally, the bonding situation in both complexes was investigated by means of the Interacting Quantum Atoms (IQA) methodology and compared to that of hypothetical mononuclear fluoromanganates. Within each pair of [MnXn]2− (n = 4, 5) species (X = OTeF5, F), the Mn–X interaction is found to be comparable, therefore proving that the similar electronic properties of the teflate and the fluoride are also responsible for the stabilization of these unique species.
View lessO-glycosylation is a common post-translational modification that is essential for the defensive properties of mucus barriers. Incomplete and altered O-glycosylation is often linked to severe diseases, such as cancer, cystic fibrosis, and chronic obstructive pulmonary disease. Originating from a nontemplate-driven biosynthesis, mucin-type O-glycan structures are very complex. They are often present as heterogeneous mixtures containing multiple isomers. Therefore, the analysis of complex O-glycan mixtures usually requires hyphenation of orthogonal techniques such as liquid chromatography (LC), ion mobility spectrometry, and mass spectrometry (MS). However, MS-based techniques are mainly qualitative. Moreover, LC separation of O-glycans often lacks reproducibility and requires sophisticated data treatment and analysis. Here we present a mucin-type O-glycomics analysis workflow that utilizes hydrophilic interaction liquid chromatography for separation and fluorescence labeling for detection and quantification. In combination with mass spectrometry, a detailed analysis on the relative abundance of specific mucin-type O-glycan compositions and features, such as fucose, sialic acids, and sulfates, is performed. Furthermore, the average number of monosaccharide units of O-glycans in different samples was determined. To demonstrate universal applicability, the method was tested on mucins from different tissue types and mammals, such as bovine submaxillary mucins, porcine gastric mucins, and human milk mucins. To account for day-to-day retention time shifts in O-glycan separations and increase the comparability between different instruments and laboratories, we included fluorescently labeled dextran ladders in our workflow. In addition, we set up a library of glucose unit values for all identified O-glycans, which can be used to simplify the identification process of glycans in future analyses.
View lessThe perfluorinated silylphosphinidene, F3SiP, in the triplet ground state is generated by the reaction of laser-ablated silicon atoms with PF3 in solid neon and argon matrices. The reactions proceed with the initial formation of a silicon trifluorophosphine complex, F3PSi, in the triplet ground state, and a more stable inserted phosphasilene, FPSiF2, in the singlet ground state upon deposition. The trifluorosilylphosphinidene was formed through F-migration reactions of FPSiF2 and F3PSi following a two-state mechanism under irradiation with visible light (λ = 470 nm) and full arc light (λ > 220 nm), respectively. High-level quantum-chemical methods support the identification of F3PSi, FPSiF2, and F3SiP by matrix-isolation IR spectroscopy.
View lessIn this article Cristoph Wulf examines the basic concepts of pedagogy and educational science in the German-speaking world, looking at education and socialization from the perspective of educational anthropology. He makes evident that the complex German concept of Bildung, in particular, can only be fully understood by means of a historical and philosophical analysis.
Polar surfaces in water typically repel each other at close separations, even if they are charge-neutral. This so-called hydration repulsion balances the van der Waals attraction and gives rise to a stable nanometric water layer between the polar surfaces. The resulting hydration water layer is crucial for the properties of concentrated suspensions of lipid membranes and hydrophilic particles in biology and technology, but its origin is unclear. It has been suggested that surface-induced molecular water structuring is responsible for the hydration repulsion, but a quantitative proof of this water-structuring hypothesis is missing. To gain an understanding of the mechanism causing hydration repulsion, we perform molecular simulations of different planar polar surfaces in water. Our simulated hydration forces between phospholipid bilayers agree perfectly with experiments, validating the simulation model and methods. For the comparison with theory, it is important to split the simulated total surface interaction force into a direct contribution from surface–surface molecular interactions and an indirect water-mediated contribution. We find the indirect hydration force and the structural water-ordering profiles from the simulations to be in perfect agreement with the predictions from theoretical models that account for the surface-induced water ordering, which strongly supports the water-structuring hypothesis for the hydration force. However, the comparison between the simulations for polar surfaces with different headgroup architectures reveals significantly different decay lengths of the indirect water-mediated hydration-force, which for laterally homogeneous water structuring would imply different bulk-water properties. We conclude that laterally inhomogeneous water ordering, induced by laterally inhomogeneous surface structures, shapes the hydration repulsion between polar surfaces in a decisive manner. Thus, the indirect water-mediated part of the hydration repulsion is caused by surface-induced water structuring but is surface-specific and thus nonuniversal.
View lessWe study the application of a tailored quasi-Monte Carlo (QMC) method to a class of optimal control problems subject to parabolic partial differential equation (PDE) constraints under uncertainty: the state in our setting is the solution of a parabolic PDE with a random thermal diffusion coefficient, steered by a control function. To account for the presence of uncertainty in the optimal control problem, the objective function is composed with a risk measure. We focus on two risk measures, both involving high-dimensional integrals over the stochastic variables: the expected value and the (nonlinear) entropic risk measure. The high-dimensional integrals are computed numerically using specially designed QMC methods and, under moderate assumptions on the input random field, the error rate is shown to be essentially linear, independently of the stochastic dimension of the problem—and thereby superior to ordinary Monte Carlo methods. Numerical results demonstrate the effectiveness of our method.
View lessEnergy is a central concept across the sciences and an important goal of science education is to support all students so that they develop a full understanding of the energy concept. However, given the abstract and complex nature of the energy concept, only a few students develop an understanding so that they can use energy ideas to make sense of phenomena. Research into energy learning progressions aims at developing models of learning about energy to guide instruction so that students can be best supported in developing competence and has provided a rich model of how students' understanding of energy develops over time. Being largely based on cross-section data, however, the extent to which this model can guide instruction is limited, especially concerning the continued learning of students about energy. To address this gap—the limited evidence regarding what supports students' continued learning about energy—it was investigated how holding non-normative ideas and the integratedness of students' energy knowledge affect students' continued learning about energy. Drawing on data from a 4-year longitudinal study covering Grades 6–9 on students' learning about energy, diagnostic classification models were used to characterize students' non-normative idea profiles and the integratedness of their knowledge and then related both to their continued learning. The results suggest no detrimental effects of holding non-normative ideas and strong positive effects of holding integrated knowledge for students' continued learning about energy. Implications for teaching and future research are discussed.
View lessTuning the optoelectronic properties of monolayer MoS2 (1L-MoS2) is highly desired for optoelectronic applications. Gaining profound insights into the fundamental mechanisms that govern optoelectronic properties is of utmost significance. Here, we demonstrate that the photoluminescence (PL) of 1L-MoS2 can be modulated by photochemically functionalized graphene (F-G), which is covalently modified by oligophenyl groups. More importantly, the layer stacking sequence of F-G and 1L-MoS2 brings different interface structures, resulting in a significant difference in the PL enhancement. MoS2 supported by F-G (F-G/MoS2) has a 5-fold PL enhancement, while it only shows a 1.8-fold PL enhancement if stacked underneath F-G (MoS2/F-G). Accordingly, the results indicate that the oligophenyl groups in F-G/MoS2 not only have a p-doping effect on MoS2 but also largely prevent electron donation from the graphene basal plane with an enlarged interlayer distance of 8 nm. Consequently, the PL enhancement is lost with the thermal defunctionalization of F-G. Thus, we conclude that the functional groups can be considered as separate molecular components with the vertical arrangement in the functionalized heterostructure system. The photoactive graphene acts as a template for perpendicular molecular alignment in the heterointerface construction. The F-G/MoS2 heterostructures bring new perspectives to the design and investigation of optoelectronic devices.
View lessNaturally acquired immunity to the different types of malaria in humans occurs in areas of endemic transmission and results in asymptomatic infection of peripheral blood. The current study examined the possibility of naturally acquired immunity in Bornean orangutans, Pongo pygmaeus, exposed to endemic Plasmodium pitheci malaria. A total of 2140 peripheral blood samples were collected between January 2017 and December 2022 from a cohort of 135 orangutans housed at a natural forested Rescue and Rehabilitation Centre in West Kalimantan, Indonesia. Each individual was observed for an average of 4.3 years during the study period. Blood samples were examined by microscopy and polymerase chain reaction for the presence of plasmodial parasites. Infection rates and parasitaemia levels were measured among age groups and all 20 documented clinical malaria cases were reviewed to estimate the incidence of illness and risk ratios among age groups. A case group of all 17 individuals that had experienced clinical malaria and a control group of 34 individuals having an event of >2000 parasites μL−1 blood but with no outward or clinical sign of illness were studied. Immature orangutans had higher-grade and more frequent parasitaemia events, but mature individuals were more likely to suffer from clinical malaria than juveniles. The case orangutans having patent clinical malaria were 256 times more likely to have had no parasitaemia event in the prior year relative to asymptomatic control orangutans. The findings are consistent with rapidly acquired immunity to P. pitheci illness among orangutans that wanes without re-exposure to the pathogen.
View lessThe remains of black henbane (Hyoscyamus niger) are relatively common at archaeological sites as it grows naturally around settlements in north-western Europe. All parts of the plant may be used as a medicine or a narcotic but its natural prevalence in built environments makes it difficult to interpret any intentionality behind its presence in the archaeological record. Evidence of the deliberate collection and use of black henbane seeds in the Roman Netherlands is presented here for the first time. Examination of Classical texts and interrogation of the archaeobotanical data allow the authors to place the discovery at Houten-Castellum of a hollowed bone containing hundreds of black henbane seeds within the context of the wider Roman understanding of the plant and its properties.
View lessContemporary capitalist societies use different institutions to manage economic risks. While different public welfare state and financial institutions (banks, capital markets) have been studied across coordinated and liberal market economies, the different worlds of private insurance institutions have been understudied. Building on new insurance data sets (1880–2017), we find that countries with a Maritime (USA, GBR, CAN) in contrast to the more backward Alpine (AUT, DEU, CHE) insurance tradition developed bigger life and nonlife insurance earlier, with less state-associated and reinsurance enterprises, but riskier investments steered toward financial markets. We argue that the larger and more “Maritime” the insurance sector, the more it made welfare states liberal and securities markets large. Insurance is thus a hidden factor for countries’ varieties of capitalism and worlds of welfare. The recent convergence on the Maritime model, however, implies that the riskier and risk-individualizing type of private insurance has added to privatization and securitization trends everywhere.
View lessThe business case constitutes an important instrumental motive for corporate social responsibility (CSR), but its relationship with other moral and relational motives remains controversial. In this article, we examine the articulation of motives for CSR among different stakeholders in Germany historically. On the basis of reports of German business associations, state agencies, unions, and nongovernmental organizations from 1970 to 2014, we show how the business case came to be a dominant motive for CSR by acting as a coalition magnet: the vocabulary was used strategically by key policy entrepreneurs, while being ambiguous for flexible interpretations by different stakeholders, and thereby growing in attractiveness. As a resulting discourse coalition emerged among business, state, and civil society actors, the moral and relational motives for CSR became increasingly marginalized. The article offers a new approach to studying motives and contributes to understanding the complementary or competing nature of different motives for CSR.
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