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Research on novel and advanced biomaterials is an indispensable step towards their applications in desirable fields such as tissue engineering, regenerative medicine, cell culture, or biotechnology. The work presented here focuses on such a promising material: polyelectrolyte multilayer (PEM) composed of hyaluronic acid (HA) and poly(L-lysine) (PLL). This gel-like polymer surface coating is able to accumulate (bio-)molecules such as proteins or drugs and release them in a controlled manner. It serves as a mimic of the extracellular matrix (ECM) in composition and intrinsic properties. These qualities make the HA/PLL multilayers a promising candidate for multiple bio-applications such as those mentioned above. The work presented aims at the development of a straightforward approach for assessment of multi-fractional diffusion in multilayers (first part) and at control of local molecular transport into or from the multilayers by laser light trigger (second part).
The mechanism of the loading and release is governed by the interaction of bioactives with the multilayer constituents and by the diffusion phenomenon overall. The diffusion of a molecule in HA/PLL multilayers shows multiple fractions of different diffusion rate. Approaches, that are able to assess the mobility of molecules in such a complex system, are limited. This shortcoming motivated the design of a novel evaluation tool presented here.
The tool employs a simulation-based approach for evaluation of the data acquired by fluorescence recovery after photobleaching (FRAP) method. In this approach, possible fluorescence recovery scenarios are primarily simulated and afterwards compared with the data acquired while optimizing parameters of a model until a sufficient match is achieved. Fluorescent latex particles of different sizes and fluorescein in an aqueous medium are utilized as test samples validating the analysis results. The diffusion of protein cytochrome c in HA/PLL multilayers is evaluated as well.
This tool significantly broadens the possibilities of analysis of spatiotemporal FRAP data, which originate from multi-fractional diffusion, while striving to be widely applicable. This tool has the potential to elucidate the mechanisms of molecular transport and empower rational engineering of the drug release systems.
The second part of the work focuses on the fabrication of such a spatiotemporarily-controlled drug release system employing the HA/PLL multilayer. This release system comprises different layers of various functionalities that together form a sandwich structure. The bottom layer, which serves as a reservoir, is formed by HA/PLL PEM deposited on a planar glass substrate. On top of the PEM, a layer of so-called hybrids is deposited. The hybrids consist of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) -based hydrogel microparticles with surface-attached gold nanorods. The layer of hybrids is intended to serve as a gate that controls the local molecular transport through the PEM–solution-interface. The possibility of stimulating the molecular transport by near-infrared (NIR) laser irradiation is being explored.
From several tested approaches for the deposition of hybrids onto the PEM surface, the drying-based approach was identified as optimal. Experiments, that examine the functionality of the fabricated sandwich at elevated temperature, document the reversible volume phase transition of the PEM-attached hybrids while sustaining the sandwich stability. Further, the gold nanorods were shown to effectively absorb light radiation in the tissue- and cell-friendly NIR spectral region while transducing the energy of light into heat. The rapid and reversible shrinkage of the PEM-attached hybrids was thereby achieved. Finally, dextran was employed as a model transport molecule. It loads into the PEM reservoir in a few seconds with the partition constant of 2.4, while it spontaneously releases in a slower, sustained manner. The local laser irradiation of the sandwich, which contains the fluorescein isothiocyanate tagged dextran, leads to a gradual reduction of fluorescence intensity in the irradiated region.
The release system fabricated employs renowned photoresponsivity of the hybrids in an innovative setting. The results of the research are a step towards a spatially-controlled on-demand drug release system that paves the way to spatiotemporally controlled drug release.
The approaches developed in this work have the potential to elucidate the molecular dynamics in ECM and to foster engineering of multilayers with properties tuned to mimic the ECM. The work aims at spatiotemporal control over the diffusion of bioactives and their presentation to the cells.
In this paper, we move from the large strand of research that looks at evidence of climate migration to the questions: who are the climate migrants? and where do they go? These questions are crucial to design policies that mitigate welfare losses of migration choices due to climate change. We study the direct and heterogeneous associations between weather extremes and migration in rural India. We combine ERAS reanalysis data with the India Human Development Survey household panel and conduct regression analyses by applying linear probability and multinomial logit models. This enables us to establish a causal relationship between temperature and precipitation anomalies and overall migration as well as migration by destination. We show that adverse weather shocks decrease rural-rural and international migration and push people into cities in different, presumably more prosperous states. A series of positive weather shocks, however, facilitates international migration and migration to cities within the same state. Further, our results indicate that in contrast to other migrants, climate migrants are likely to be from the lower end of the skill distribution and from households strongly dependent on agricultural production. We estimate that approximately 8% of all rural-urban moves between 2005 and 2012 can be attributed to weather. This figure might increase as a consequence of climate change. Thus, a key policy recommendation is to take steps to facilitate integration of less educated migrants into the urban labor market.
Reading requires the assembly of cognitive processes across a wide spectrum from low-level visual perception to high-level discourse comprehension. One approach of unravelling the dynamics associated with these processes is to determine how eye movements are influenced by the characteristics of the text, in particular which features of the words within the perceptual span maximise the information intake due to foveal, spillover, parafoveal, and predictive processing. One way to test the generalisability of current proposals of such distributed processing is to examine them across different languages. For Turkish, an agglutinative language with a shallow orthography-phonology mapping, we replicate the well-known canonical main effects of frequency and predictability of the fixated word as well as effects of incoming saccade amplitude and fixation location within the word on single-fixation durations with data from 35 adults reading 120 nine-word sentences. Evidence for previously reported effects of the characteristics of neighbouring words and interactions was mixed. There was no evidence for the expected Turkish-specific morphological effect of the number of inflectional suffixes on single-fixation durations. To control for word-selection bias associated with single-fixation durations, we also tested effects on word skipping, single-fixation, and multiple-fixation cases with a base-line category logit model, assuming an increase of difficulty for an increase in the number of fixations. With this model, significant effects of word characteristics and number of inflectional suffixes of foveal word on probabilities of the number of fixations were observed, while the effects of the characteristics of neighbouring words and interactions were mixed.
Based on an analysis of continuous monitoring of farm animal behavior in the region of the 2016 M6.6 Norcia earthquake in Italy, Wikelski et al., 2020; (Seismol Res Lett, 89, 2020, 1238) conclude that animal activity can be anticipated with subsequent seismic activity and that this finding might help to design a "short-term earthquake forecasting method." We show that this result is based on an incomplete analysis and misleading interpretations. Applying state-of-the-art methods of statistics, we demonstrate that the proposed anticipatory patterns cannot be distinguished from random patterns, and consequently, the observed anomalies in animal activity do not have any forecasting power.
Zwaag, Jelle ; Horst, Rob ter ; Blaženović, Ivana ; Stößel, Daniel ; Ratter, Jacqueline ; Worseck, Josephine M. ; Schauer, Nicolas ; Stienstra, Rinke ; Netea, Mihai G. ; Jahn, Dieter ; Pickkers, Peter ; Kox, Matthijs
We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1 beta and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects.
Zwaag, Jelle ; Horst, Rob ter ; Blaženović, Ivana ; Stößel, Daniel ; Ratter, Jacqueline ; Worseck, Josephine M. ; Schauer, Nicolas ; Stienstra, Rinke ; Netea, Mihai G. ; Jahn, Dieter ; Pickkers, Peter ; Kox, Matthijs
We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1 beta and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects.
Zu, Fengshuo ; Schultz, Thorsten ; Wolff, Christian Michael ; Shin, Dongguen ; Frohloff, Lennart ; Neher, Dieter ; Amsalem, Patrick ; Koch, Norbert
The remarkable progress of metal halide perovskites in photovoltaics has led to the power conversion efficiency approaching 26%. However, practical applications of perovskite-based solar cells are challenged by the stability issues, of which the most critical one is photo-induced degradation. Bare CH3NH3PbI3 perovskite films are known to decompose rapidly, with methylammonium and iodine as volatile species and residual solid PbI2 and metallic Pb, under vacuum under white light illumination, on the timescale of minutes. We find, in agreement with previous work, that the degradation is non-uniform and proceeds predominantly from the surface, and that illumination under N-2 and ambient air (relative humidity 20%) does not induce substantial degradation even after several hours. Yet, in all cases the release of iodine from the perovskite surface is directly identified by X-ray photoelectron spectroscopy. This goes in hand with a loss of organic cations and the formation of metallic Pb. When CH3NH3PbI3 films are covered with a few nm thick organic capping layer, either charge selective or non-selective, the rapid photodecomposition process under ultrahigh vacuum is reduced by more than one order of magnitude, and becomes similar in timescale to that under N-2 or air. We conclude that the light-induced decomposition reaction of CH3NH3PbI3, leading to volatile methylammonium and iodine, is largely reversible as long as these products are restrained from leaving the surface. This is readily achieved by ambient atmospheric pressure, as well as a thin organic capping layer even under ultrahigh vacuum. In addition to explaining the impact of gas pressure on the stability of this perovskite, our results indicate that covalently "locking" the position of perovskite components at the surface or an interface should enhance the overall photostability.
Zozulya, Dmitry R. ; Kullerud, Kare ; Ribacki, Enrico ; Altenberger, Uwe ; Sudo, Masafumi ; Savchenko, Yevgeny E.
During the period 750-600 Ma ago, prior to the final break-up of the supercontinent Rodinia, the crust of both the North American Craton and Baltica was intruded by significant amounts of rift-related magmas originating from the mantle. In the Proterozoic crust of Southern Norway, the 580 Ma old Fen carbonatite-ultramafic complex is a representative of this type of rocks. In this paper, we report the occurrence of an ultramafic lamprophyre dyke which possibly is linked to the Fen complex, although Ar-40/Ar-39 data from phenocrystic phlogopite from the dyke gave an age of 686 +/- 9 Ma. The lamprophyre dyke was recently discovered in one of the Kongsberg silver mines at Vinoren, Norway. Whole rock geochemistry, geochronological and mineralogical data from the ultramafic lamprophyre dyke are presented aiming to elucidate its origin and possible geodynamic setting. From the whole-rock composition of the Vinoren dyke, the rock could be recognized as transitional between carbonatite and kimberlite-II (orangeite). From its diagnostic mineralogy, the rock is classified as aillikite. The compositions and xenocrystic nature of several of the major and accessory minerals from the Vinoren aillikite are characteristic for diamondiferous rocks (kimberlites/lamproites/UML): Phlogopite with kinoshitalite-rich rims, chromite-spinel-ulvospinel series, Mg- and Mn-rich ilmenites, rutile and lucasite-(Ce). We suggest that the aillikite melt formed during partial melting of a MARID (mica-amphibole-rutile-ilmenite-diopside)-like source under CO2 fluxing. The pre-rifting geodynamic setting of the Vinoren aillikite before the Rodinia supercontinent breakup suggests a relatively thick SCLM (Subcontinental Lithospheric Mantle) during this stage and might indicate a diamond-bearing source for the parental melt. This is in contrast to the about 100 Ma younger Fen complex, which were derived from a thin SCLM.
Zouita, Sghaier ; Zouhal, Hassane ; Ferchichi, Habiba ; Paillard, Thierry ; Dziri, Catherine ; Hackney, Anthony C. ; Laher, Ismail ; Granacher, Urs ; Ben Moussa Zouita, Amira
Objective: We investigated the effects of combined balance and strength training on measures of balance and muscle strength in older women with a history of falls.
Methods: Twenty-seven older women aged 70.4 ± 4.1 years (age range: 65 to 75 years) were randomly allocated to either an intervention (IG, n = 12) or an active control (CG, n = 15) group. The IG completed 8 weeks combined balance and strength training program with three sessions per week including visual biofeedback using force plates. The CG received physical therapy and gait training at a rehabilitation center. Training volumes were similar between the groups. Pre and post training, tests were applied for the assessment of muscle strength (weight-bearing squat [WBS] by measuring the percentage of body mass borne by each leg at different knee flexions [0°, 30°, 60°, and 90°], sit-to-stand test [STS]), and balance. Balance tests used the modified clinical test of sensory interaction (mCTSIB) with eyes closed (EC) and opened (EO), on stable (firm) and unstable (foam) surfaces as well as spatial parameters of gait such as step width and length (cm) and walking speed (cm/s).
Results: Significant group × time interactions were found for different degrees of knee flexion during WBS (0.0001 < p < 0.013, 0.441 < d < 0.762). Post hoc tests revealed significant pre-to-post improvements for both legs and for all degrees of flexion (0.0001 < p < 0.002, 0.697 < d < 1.875) for IG compared to CG. Significant group × time interactions were found for firm EO, foam EO, firm EC, and foam EC (0.006 < p < 0.029; 0.302 < d < 0.518). Post hoc tests showed significant pre-to-post improvements for both legs and for all degrees of oscillations (0.0001 < p < 0.004, 0.753 < d < 2.097) for IG compared to CG. This study indicates that combined balance and strength training improved percentage distribution of body weight between legs at different conditions of knee flexion (0°, 30°, 60°, and 90°) and also decreased the sway oscillation on a firm surface with eyes closed, and on foam surface (with eyes opened or closed) in the IG.
Conclusion: The higher positive effects of training seen in standing balance tests, compared with dynamic tests, suggests that balance training exercises including lateral, forward, and backward exercises improved static balance to a greater extent in older women.
Zouita, Sghaier ; Zouhal, Hassane ; Ferchichi, Habiba ; Paillard, Thierry ; Dziri, Catherine ; Hackney, Anthony C. ; Laher, Ismail ; Granacher, Urs ; Ben Moussa Zouita, Amira
Objective: We investigated the effects of combined balance and strength training on measures of balance and muscle strength in older women with a history of falls.
Methods: Twenty-seven older women aged 70.4 ± 4.1 years (age range: 65 to 75 years) were randomly allocated to either an intervention (IG, n = 12) or an active control (CG, n = 15) group. The IG completed 8 weeks combined balance and strength training program with three sessions per week including visual biofeedback using force plates. The CG received physical therapy and gait training at a rehabilitation center. Training volumes were similar between the groups. Pre and post training, tests were applied for the assessment of muscle strength (weight-bearing squat [WBS] by measuring the percentage of body mass borne by each leg at different knee flexions [0°, 30°, 60°, and 90°], sit-to-stand test [STS]), and balance. Balance tests used the modified clinical test of sensory interaction (mCTSIB) with eyes closed (EC) and opened (EO), on stable (firm) and unstable (foam) surfaces as well as spatial parameters of gait such as step width and length (cm) and walking speed (cm/s).
Results: Significant group × time interactions were found for different degrees of knee flexion during WBS (0.0001 < p < 0.013, 0.441 < d < 0.762). Post hoc tests revealed significant pre-to-post improvements for both legs and for all degrees of flexion (0.0001 < p < 0.002, 0.697 < d < 1.875) for IG compared to CG. Significant group × time interactions were found for firm EO, foam EO, firm EC, and foam EC (0.006 < p < 0.029; 0.302 < d < 0.518). Post hoc tests showed significant pre-to-post improvements for both legs and for all degrees of oscillations (0.0001 < p < 0.004, 0.753 < d < 2.097) for IG compared to CG. This study indicates that combined balance and strength training improved percentage distribution of body weight between legs at different conditions of knee flexion (0°, 30°, 60°, and 90°) and also decreased the sway oscillation on a firm surface with eyes closed, and on foam surface (with eyes opened or closed) in the IG.
Conclusion: The higher positive effects of training seen in standing balance tests, compared with dynamic tests, suggests that balance training exercises including lateral, forward, and backward exercises improved static balance to a greater extent in older women.