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    Mothers of Young Children during the COVID-19 Pandemic: Depressive Symptoms and Perceived Stress

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    Objective: Due to the COVID-19 pandemic, psychosocial well-being of families and parents worldwide has been impaired. As part of a larger online survey, we analyzed maternal depressive symptoms and perceived stress. Method: A total of 666 mothers from Germany with young children (mostly aged 0–3 years) filled out the Edinburgh Postnatal Depression Scale (EPDS) and the Perceived Stress Scale (PSS) at 2 time points during the pandemic (T1: summer/fall 2020; T2: early spring 2021). We (1) calculated prevalence rates of a risk for depression and high perceived stress levels, (2) analyzed differences between time points via paired t tests, and (3) examined the reciprocal relation between the two constructs via cross-lagged panel modeling. Results: Considering cut-off values of the EPDS (≥10) and PSS (≥27), 33.8% carried a risk for depression and 15.2% high levels of stress at T1, whereas, respectively, 55.1% and 26.0% did so at T2. Depressive symptom severity and perceived stress levels significantly differed between measurement points with higher values at T2 (p < 0.001). Our cross-lagged panel analysis revealed large correlations (p < 0.001) within as well as small to medium (i.e., [0.21, 0.47]) auto-regressive (p < 0.001) and reciprocal (p < 0.001) predictions across time points between the severity of depressive symptoms and perceived stress. Conclusions: This work demonstrates how severely mothers of infants were affected by depressive symptoms and perceived stress in a time of pandemic crisis. Psychosocial support should focus on screening and treating mothers as early as possible to mitigate the risk for subsequent depressive symptoms and perceived stress. Aiming attention at both depressive symptom reduction and stress relief most successfully promotes maternal well-being

    Pre-Rift Orogenic Erosion Facilitates the Exhumation of Lower Crust at Rifted Margins

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    During the late-stage of continental rifting, lower crustal rocks can be exhumed to the Earth's surface. Such exposure has been identified especially in rifts that developed within former orogens. These rifts exploited zones of lithospheric weakness created during previous mountain-building events. Here we investigate whether lower crustal exhumation during rifting could result directly from structural inheritance of prior orogeny. To this aim we use Wilson-Cycle numerical models where we impose a prior shortening and subsequent extension. Our models incorporate the effects of thermal and structural inheritance as well as surface processes. We find that the erosion of mountain belts thins the upper crust, reducing the upper-to-lower crustal ratio prior to rifting. This process facilitates the exhumation of lower crustal material during extension, exposing them at the Earth's surface along the footwall of normal faults. We suggest a new conceptual model to explain lower crustal exhumation observed at rifted margins worldwide

    Dysregulation of monocytic PD-1-signalling in patients undergoing Immune-Checkpoint-Blockade-Therapy with immune-related adverse events

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    Einleitung: Immun-assoziierte Nebenwirkungen (irAE) sind eine wesentliche Limitation der Immun-Checkpoint-Inhibitor-Therapie (ICI), die in den vergangenen Jahren die Behandlung diverser Tumorentitäten revolutioniert hat. IrAE weisen große Ähnlichkeiten zu Autoimmunerkrankungen auf und betreffen die Hälfte der ICI- Patient:innen (IP), wobei die Inzidenz aufgrund neuer Indikationen und des Einsatzes von Kombinationstherapien, die ein erhöhtes Risiko für irAE aufweisen, vermutlich steigt. Die zugrunde liegende Pathophysiologie ist nach wie vor schlecht verstanden. Unsere Arbeitsgruppe hat bei der Untersuchung der Reaktivität peripherer Leukozytenpopulationen im Anschluss an zelltypspezifische Stimulationen bei IP eine erhöhte Toll-Like-Rezeptor-2-Reaktivität (TLR2) von Monozyten festgestellt. Diese blieb bei IP mit irAE (AE-IP) aus, was zu der Hypothese führte, dass schadensassoziierte molekulare Muster (DAMPs), welche zum Teil TLR2-Liganden sind, in Kontext von irAE relevant sein könnten, zumal ihnen bei Autoimmunerkrankungen eine Schlüsselrolle zugeschrieben werden. Methoden: Mithilfe FACS-basierter in vitro-Assays wurde erstens untersucht, welche Prozesse die PD-1-Expression auf Monozyten modulieren, zweitens wie eine PD-1- Blockade die Reaktivität von Monozyten beeinflusst und drittens die Monozyten- Reaktivität im Anschluss an verschiedene Ko-Kulturen mit DAMPs analysiert. Mittels ELISA- und Immunoplex-Assays sowie cfDNA-Isolierung wurden verschiedene TLR2- Liganden und Zytokine bei den IP quantifiziert, um mögliche Faktoren zu identifizieren, die die Monozytenreaktivität modulieren. Ergebnisse: Durch Inkubation von PBMC konnte PD-1 auf Monozyten von gesunden Spender:innen (HC) induziert werden. Der bei IP beobachtete Anstieg der monozytären Reaktivität konnte in vitro bestätigt werden. Darüber hinaus wiesen HC- Monozyten durch die Anwesenheit von AE-IP-Sera eine abgeschwächte Zytokinproduktion nach TLR2-Stimulation auf, was auf einen löslichen Faktor im Serum der AE-IP hinweist, der für diesen Mechanismus verantwortlich sein könnte. Bei den AE-IP wurden erhöhte Level zellfreier DNA (cfDNA) beobachtet, welche mit dem Grad der Desensibilisierung von HC-Monozyten durch die IP-Sera korrelierte. Auch führte isolierte cfDNA von IP zu einer reduzierten Zytokin-Produktion sowie zu einer Herunterregulierung von PD-1 auf HC-Monozyten. Die Quantifizierung von DAMPs und Zytokinen bei den IP ergab zudem einen Anstieg des anti-inflammatorischen Zytokins IL-10 und des TLR2-Agonisten HMGB-1 bei jenen IP, die keine irAE entwickelten. Diskussion: Zusammenfassend wurden funktionelle Auswirkungen der PD-1-Blockade auf Monozyten charakterisiert und cfDNA als DAMP identifiziert, welches potenziell die TLR2-Reaktivität bei AE-IP beeinträchtigt. Perspektivisch könnte cfDNA eine Rolle als prädiktiver Biomarker für irAE sowie als therapeutisches Ziel spielen.Introduction: Immune related adverse events (irAE) play a key role in immune checkpoint therapy (ICI), being one of the main limitations of this promising tool against cancer. Summarizing a variety of autoimmune disease-like side effects, mainly affecting skin, gastrointestinal tract and lung, but potentially any organ system, irAE occur in over half of patients receiving checkpoint therapy (IP) against PD-1, PD-L1 and CTLA-4 with numbers assumably rising due to a growing field of indications and the use of combination therapies which have an increased risk of causing irAE. The underlying mechanism remains unclear with some hypotheses being discussed, mainly referring to T cells as major disease drivers. Analyzing the reactivity of peripheral leukocyte populations upon cell-type-specific stimulation, our group found an increase of the Toll Like-Receptor 2-reactivity (TLR2) of monocytes in IP which was absent in patients with irAE (AE-IP). Therefore, we assumed a potential role of damage- associated molecular patterns (DAMPs), some of which are TLR2-Ligands, as they are being attributed a key role in autoimmune disease, which resemble irAE in its clinical characteristics. Methods: FACS based in vitro assays were established in order to first, examine mechanisms modulating the PD-1- expression, second, to characterize the effect of PD- 1-blockade on monocytes reactivity and third, to identify potential factors that could account for the altered TLR signaling patterns of AE-IP. By using ELISA- and Immunoplex-based assays as well as cfDNA isolation technique a variety of TLR2- Ligands were quantified in the IP aiming to identify possible factors dampening the monocyte reactivity. Results: PD-1-expression could be induced by incubating PBMC overnight. Also, the increase of monocytes reactivity following anti-PD-1-treatment observed in patients was validated in vitro. Furthermore AE-IP-sera led to a desensitization of TLR2-reactivity of healthy control (HC) monocytes, indicating a soluble factor that indeed accounts for this mechanism. Levels of cell free DNA (cfDNA) levels were found to be elevated in AE-IP and correlated with the degree in which the patients’ sera desensitized HC monocytes. Also, isolated cfDNA from IP led to a reduced production of cytokines and a downregulation of PD-1 in HC monocytes. In addition, quantification of cytokines and DAMPs in the IP revealed increasing levels of the anti-inflammatory cytokine IL-10 and the TLR2 agonist HMGB-1 in IP who didn’t develop irAE. Discussion: In conclusion, functional effects of blocking PD-1 on monocytes were characterized and cfDNA was identified as potential DAMP to hamper the TLR2 reactivity in AE-IP. Perspectively cfDNA could play a role as predictive biomarker for irAE as well as a therapeutic target to lower the negative effects of irAE without interfering with the effectiveness of ICI

    Two-dimensional infrared spectroscopy as a tool to reveal the vibrational and molecular structure of [FeFe] hydrogenases

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    [FeFe] hydrogenases are Nature's most efficient catalysts for the cleavage and evolution of molecular hydrogen. Despite decades of research, key aspects of the catalytic cycle and the underlying geometrical and electronic properties of the active-site cofactor, called the H-cluster, are not fully understood. Spectroscopic techniques have played a central role in establishing the current state of knowledge on [FeFe] hydrogenases, and further advances in the field depend critically on novel techniques that yield so-far inaccessible insights into structural and mechanistic aspects. Infrared (IR) absorption spectroscopy represents a well-established and versatile technique that can identify and characterize all active and inactive states of the H-cluster by means of structurally sensitive and spectrally isolated CO and CN stretching vibrations. However, the amount of information that can be extracted from these linear experiments is inherently limited. Here we introduce experimental and computational two-dimensional (2D-)IR spectroscopy for the characterization of [FeFe] hydrogenases. Utilizing the Hinact state of the H-cluster as a model system, we demonstrate that this nonlinear technique yields direct information about the nature and interactions of the CO and CN stretching vibrations. These insights allow, for the first time, to quantitatively describe the character of these widely used reporter vibrations, their spatial localization, and the way they change upon structural variation of the H-cluster. The strength of this approach is demonstrated by correctly identifying the proposed structure of the Hinact state, in solution and at ambient temperature. In conclusion, the introduced combination of experimental and computational 2D-IR spectroscopy represents a powerful approach for studying [FeFe] hydrogenases and other complex organometallic targets

    Synchrotron X-ray photoelectron spectroscopy study of sodium adsorption on vertically arranged MoS2 layers coated with pyrolytic carbon

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    Hybrid materials consisting of molybdenum disulfide (MoS2) and graphitic-like carbon have great potential for practical application as anodes in high-performance sodium-ion batteries. In this work, to reveal the effect of carbon coating on the interaction of sodium with the MoS2 layers located vertically relative to the substrate, model experiments were carried out using synchrotron-radiation-induced X-ray photoelectron spectroscopy (XPS). Sodium vapor obtained by heating a sodium source was simultaneously deposited in vacuum on the surfaces of MoS2, pyrolytic carbon, and a hybrid sample obtained by transferring a pyrolytic carbon film onto the MoS2 film. According to XPS data, sodium easily penetrates into the space between the vertical layers of the uncoated film, and its interaction with MoS2 leads to the transformation of the original hexagonal structure into a distorted tetragonal one. Under the experimental conditions, sodium is unable to diffuse through the carbon film consisting of horizontally oriented graphene domains and is almost completely removed by annealing the sample at 773 K in ultrahigh vacuum. The presence of the underlying MoS2 film facilitates the diffusion of sodium through the graphitic coating, but not all of the deposited sodium reaches MoS2. As a result, the sodium-induced rearrangement of the carbon-coated MoS2 is less than that of the free MoS2 film, and annealing of the sodiated sample restores its structure. The obtained results demonstrate the important role of the graphitic coating in the development of viable MoS2-based electrodes for energy storage systems

    Die Rolle von stromalem R-spondin 3 im Magencorpus im Kontext von epithelialer Differenzierung, Regeneration und Infektion mit Helicobacter pylori

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    The gastric epithelium contains a variety of differentiated cell types that are organized in epithelial units called glands. Despite their high cellular turnover, gastric glands maintain their compartmentalized architecture. Stem cells in the isthmus of the gland proliferate and their progenies are pushed toward the gland apex or gland base and differentiate into different epithelial cell types. The signals that regulate epithelial differentiation, glandular compartmentalization, and its reacquisition upon injury in the stomach corpus are poorly understood. R-spondin 3 (Rspo3) is a signaling molecule secreted from myofibroblasts adjacent to the gland basis and the Wnt/Rspo3 signaling pathway controls stem cell dynamics in the stomach antrum and intestine. To investigate its role in the stomach corpus, I used conditional mouse models that enable the manipulation of Rspo3 gene expression in myofibroblasts. I found that during homeostasis stromal Rspo3 acts as a morphogen and controls the differentiation into glandular cell populations such as chief cells. Loss of Rspo3 expression resulted in a shrinkage of the chief cell compartment, whereas overexpression of Rspo3 promoted its expansion. Tamoxifen injection into mice triggers epithelial injury that is characterized by the loss of glandular lineages. I found that epithelial recovery was initiated by the upregulation of Rspo3 expression which was required for the induction of proliferation and the coordinated regeneration of chief cells. The central role of Rspo3 for epithelial healing was confirmed in another mouse model that enables the simultaneous loss of Lgr5-expressing chief cells and stromal Rspo3 expression. The Yap signaling pathway controls epithelial proliferation and regeneration in the small intestine and colon. I found that the Rspo3-dependent induction of proliferation upon epithelial injury required active YAP. Accordingly, inhibition of YAP in the organoid system impeded the proliferation of epithelial cells despite the presence of an R-spondin supplement. Infection with Helicobacter pylori (H. pylori) is the main risk factor for the development of gastric cancer. Chronic infection with H. pylori results in a loss of chief cells in humans and mice. In Rspo3 overexpressing mice, H. pylori-induced pathology was more pronounced than in infected Rspo3 wild-type mice. In detail, I detected glandular hyperproliferation, the expression of metaplastic markers, and the activation of YAP in gland base cells. In conclusion, Rspo3 plays a dual role in the stomach corpus: While it promotes glandular differentiation during homeostasis, Rspo3 acts as a driver of proliferation and epithelial recovery upon injury, and amplifies epithelial transformation in the context of H. pylori infection.Das Magenepithel besteht aus einer Vielzahl differenzierter Zelltypen, die in epithelialen Einheiten, den Drüsen, organisiert sind. Trotz ihres hohen Zellumsatzes halten die Magendrüsen ihre kompartimentierte Architektur aufrecht. Stammzellen im Isthmus der Drüse proliferieren und deren Tochterzellen werden in Richtung Drüsenapex oder Drüsenbasis geschoben und differenzieren in verschiedene Epithelzelltypen. Die Signale, die die epitheliale Differenzierung, die Drüsenkompartimentierung und deren Wiederherstellung nach Schädigung im Magenkorpus regulieren, sind nur unzureichend bekannt. R-spondin 3 (Rspo3) ist ein Signalmolekül, das von Myofibroblasten nahe der Drüsenbasis sezerniert wird, und der Wnt/Rspo3-Signalweg reguliert die Stammzelldynamik im Magenantrum und im Darm. Um dessen Rolle im Magenkorpus zu untersuchen, habe ich konditionale Mausmodelle verwendet, die die Manipulation der Rspo3-Genexpression in Myofibroblasten ermöglichen. Ich fand heraus, dass stromales Rspo3 während der Homöostase als Morphogen wirkt und die Drüsendifferenzierung kontrolliert. Ein Verlust der Rspo3-Expression führte zu einer Verkleinerung des Hauptzellkompartiments, während die Überexpression von Rspo3 dessen Ausdehnung förderte. Die Injektion von Tamoxifen in Mäuse induziert eine Epithelschädigung, die durch den Verlust von Drüsenzellen gekennzeichnet ist. Ich fand heraus, dass die epitheliale Regeneration durch die Hochregulierung der Rspo3-Expression eingeleitet wurde. welche für die Induktion der Proliferation und die koordinierte Regeneration der Stammzellen erforderlich war. Die zentrale Rolle von Rspo3 für die epitheliale Heilung wurde in einem anderen Mausmodell bestätigt, das den gleichzeitigen Verlust von Lgr5-exprimierenden Hauptzellen und stromaler Rspo3-Expression ermöglicht. Der Yap-Signalweg kontrolliert die epitheliale Proliferation und Regeneration im Dünn- und Dickdarm. Ich fand heraus, dass die Rspo3-abhängige Induktion der Proliferation nach Epithelverletzungen aktives YAP erfordert. Dementsprechend verhinderte die Hemmung von YAP im Organoid-System die Proliferation von Epithelzellen trotz des Vorhandenseins von R-spondin-Supplement. Die Infektion mit Helicobacter pylori (H. pylori) ist der Hauptrisikofaktor für die Entstehung von Magenkrebs. Eine chronische Infektion mit H. pylori führt bei Menschen und Mäusen zu einem Verlust von Hauptzellen. Bei Rspo3-überexprimierenden Mäusen war die H. pylori-induzierte Pathologie stärker ausgeprägt als bei infizierten Rspo3 Wildtyp-Mäusen. Im Einzelnen konnte ich eine Hyperproliferation der Drüsen, die Expression metaplastischer Marker und die Aktivierung von YAP in den Zellen der Drüsenbasis feststellen. Zusammenfassend spielt Rspo3 im Magenkorpus eine duale Rolle: Während es die homeostatische Drüsendifferenzierung fördert, fungiert Rspo3 als Treiber der Proliferation und der epithelialen Regeneration nach Schädigung und verstärkt die epitheliale Transformation im Kontext einer H. pylori-Infektion

    Porous borders and the emergence of hybrid sovereignties

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    This article examines the condition of hybrid sovereignties in unstable borderlands characterised by conflict, crime and cross-border mobility as well as the competition and collusion between violent non-state actors and state authorities. While in political practice open borders are often associated with mobility (of people), closed borders are imagined as guarantors of security (of nation-states). This dichotomy, however, ignores porosity as a third dimension. The article theorises the link between the porosity of borders and complementary governance constellations and discusses its implications for hybrid sovereignty. We illustrate our argument with insights from the Colombian-Venezuelan borderlands

    Effect of alternating canal and marginal groundwater irrigation on banana yield, water use efficiency, and soil salinity under furrow plantation

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    Banana is one of the most important cash crops in Sindh, Pakistan; however, its production is increasingly compromised due to declining freshwater availability. Currently, banana is cultivated using conventional flat basin irrigation, which results in low water use efficiency (WUE). Groundwater in the region is predominantly marginal to saline in quality but could potentially supplement limited freshwater resources. Therefore, it is essential to evaluate the conjunctive use of marginal-quality groundwater and canal water to address freshwater shortages without compromising crop yields. In this study, the Dwarf Cavendish banana variety (locally known as Basrai) was cultivated over a four-year period (October 2015–June 2019) on furrows (0.90 m furrow width, 1.20 m bed width, and 0.23 m bed height). Alternate irrigation using canal and marginal groundwater was applied at three levels of available soil moisture depletion (ASMD): 50 %, 40 %, and 30 %. Traditional farmer irrigation practices were also monitored for comparison. At ASMD levels of 50 %, 40 %, and 30 %, annual water applications were 1228 mm, 1403 mm, and 1592 mm, respectively. In contrast, farmers applied 2866 mm of water annually. Irrigation at 50 % ASMD resulted in 12–23 % higher yield and 23–41 % higher WUE compared to 30 % and 40 % ASMD treatments. Compared to the 50 % ASMD treatment, farmer practices produced 24 % lower yield and 67 % lower WUE. Importantly, soil salinity remained within acceptable threshold limits across all treatments. These results suggest that banana can be successfully cultivated on furrows using alternate irrigation with canal and marginal groundwater at 50 % ASMD. This strategy offers substantial water savings while improving yield and WUE, making it a viable and sustainable solution for banana production in water-scarce regions

    Entwicklung und Validierung schneller Elastographie-Techniken für die klinische Anwendung

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    Magnetic resonance elastography (MRE) and ultrasound time-harmonic elas-tography (THE) are innovative imaging techniques mainly used for the in vivo quantifica-tion of viscoelastic properties of soft human tissues. Stiffness is measured as the shear wave propagation speed (SWS in m/s), which depends on the shear wave frequency; this dependence is known as dispersion. Time-averaged elastography methods have already been established as clinical standards, especially for the detection and staging of liver fibrosis. Time-resolved techniques are currently being developed to expand the potential applications of elastography. Such techniques can be used, for example, to analyze the influence of hemodynamics on the viscoelastic properties of the liver and brain. Therefore, a polymerized polyacrylamide (PAAm) liver phantom was developed, calibrated, and characterized over a frequency range of 5 to 3000 Hz. The phantom is an important tool for the comparative analysis of different elastography techniques, in-cluding THE and MRE. It allows the establishment of system-independent thresholds for disease detection. In a subsequent study, a rapid MRE sequence was developed to measure liver stiffness in vivo with an acquisition time of only 625 ms. This sequence was used to study a group of eleven healthy volunteers to determine how liver stiffness is affected by different breathing states, including end-inspiration (1.83 ± 0.22 m/s), end-expiration (1.49 ± 0.22 m/s), Valsalva maneuver (1.60 ± 0.22 m/s), and free breathing (1.62 ± 0.25 m/s). The third study introduced a novel real-time THE approach for investigating changes in cerebral stiffness resulting from cerebrovascular compli-ance and blood perfusion. Such changes are affected by the mechanical properties of the brain and the variations in arterial pressure that occur during cardiac pulsation. The aim of the study was to quantify the pulsatile characteristics of brain stiffness in a sam-ple of ten healthy volunteers. The results showed changes in SWS within the brain in synchrony with cerebral blood flow variation (4.8 % ± 1.8 % in the temporal parenchy-ma, 11 % ± 5 % in the basal cisterns, 13 % ± 9 % in the brain stem). These advances in the practical application of elastography techniques pave the way for future studies aimed at further exploring the impact of hemodynamic activity on the biomechanical properties of soft human tissues.Die Magnetresonanzelastographie (MRE) und die Zeit-Harmonische Elastographie (THE) sind innovative bildgebende Verfahren zur in vivo Quantifizierung viskoelastischer Eigenschaften, die primär zur Charakterisierung von menschlichem Weichgewebe eingesetzt werden. Die Steifigkeit wird dabei über die Ausbreitungsgeschwindigkeit von Scherwellen (SWS in m/s) gemessen, die von der Frequenz der Scherwellen abhängt; dieser Zusammenhang wird als Dispersion bezeichnet. Zeitgemittelte Elastographie-Methoden zur Erkennung und Stadieneinteilung von Fibrosen sind in der klinischen Praxis bereits etabliert. Derzeit werden zeitaufgelöste Techniken entwickelt, um die Anwendungsgebiete der Elastographie zu erweitern. Mit diesen Techniken kann zum Beispiel untersucht werden, wie die Hämodynamik die viskoelastischen Eigenschaften der Leber und des Gehirns beeinflusst. In dieser Arbeit wurde ein auf polymerisiertem Polyacrylamid (PAAm) basierendes Leberphantom entwickelt, kalibriert und über ein Frequenzspektrum von 5 bis 3000 Hz charakterisiert. Dieses neue Phantom dient als Referenzmaterial für den Vergleich verschiedener Elastographie-Techniken, einschließlich THE und MRE, und kann zur Etablierung von systemunabhängigen Schwellenwerten für die Diagnose von Krankheiten verwendet werden. In einer anschließenden Studie wurde eine schnelle MRE-Sequenz konzipiert, die in der Lage ist, die Lebersteifigkeit in vivo in nur 625 ms zu quantifizieren. Diese Sequenz wurde in einer Gruppe von elf gesunden Probanden eingesetzt, um die Auswirkungen verschiedener Atmungszustände auf die Lebersteifigkeit zu bestimmen, darunter Einatmung (1,83 ± 0,22 m/s), Ausatmung (1,49 ± 0,22 m/s), Valsalva-Manöver (1,60 ± 0,22 m/s) und freie Atmung (1,62 ± 0,25 m/s). In einer dritten Studie wurde eine neue Echtzeit-THE-Technik entwickelt, um Veränderungen der zerebralen Steifigkeit aufgrund der zerebrovaskulären Compliance und der Blutperfusion zu untersuchen. Diese Veränderungen beruhen auf der mechanischen Struktur des Gehirns und den durch die Herzpulsation verursachten arteriellen Druckschwankungen. Die Quantifizierung des pulsatilen Verhaltens der Hirnsteifigkeit bei zehn gesunden Probanden zeigte Veränderungen der SWS (4,8 % ± 1,8 % im temporalen Parenchym, 11 % ± 5 % in den basalen Zisternen, 13 % ± 9 % im Hirnstamm), die mit dem zerebralen Blutfluss synchronisiert waren. Die erzielten Ergebnisse stellen einen bedeutenden Fortschritt auf dem Weg zur klinischen Anwendung dieser Elastographie-Techniken dar. Sie ebnen den Weg für weitere Untersuchungen des Einflusses hämodynamischer Prozesse auf biomechanische Parameter in menschlichem Weichgewebe

    Biofunctionalization of ADA‐GEL Hydrogels Based on the Degree of Cross‐Linking and Polymer Concentration Improves Angiogenesis

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    The creation of bioartificial tissues is a promising option for the reconstruction of large‐volume defects. The vascularization of tissue engineering constructs, as well as the material properties of the carrier matrix, are important factors for successful clinical application. In this regard, hydrogels are promising biomaterials, providing an extracellular matrix‐like milieu that enables the possibility of cell transplantation and de novo tissue formation. Furthermore, biofunctionalization allows for a certain fine‐tuning of angiogenic properties. This study aims to investigate vascularization and tissue formation of highly cross‐linked alginate dialdehyde (ADA) and gelatin (GEL). This highly cross‐linked network is created using a dural cross‐linking mechanism combining ionic (Ca 2+ ions) and enzymatic (human transglutaminase (hTG)) cross‐linking, resulting in reduced swelling and moderate degradation rates. Vascularization of the ADA‐GEL‐hTG constructs is induced surgically using arteriovenous (AV) loops. Biocompatibility, tissue formation, and vascularization are analyzed by histology and X‐ray microscopy. After only 2 weeks, vascularization of the ADA‐GEL‐hTG constructs is already present. After 4 weeks, both de novo tissue formation and vascularization of the ADA‐GEL‐hTG matrix increase. In conclusion, ADA‐GEL‐hTG‐based hydrogels are shown to be promising scaffold materials for tissue engineering applications

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