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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.
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.
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.
Lava domes are severely hazardous, mound-shaped extrusions of highly viscous lava and commonly erupt at many active stratovolcanoes around the world. Due to gradual growth and flank oversteepening, such lava domes regularly experience partial or full collapses, resulting in destructive and far-reaching pyroclastic density currents. They are also associated with cyclic explosive activity as the complex interplay of cooling, degassing, and solidification of dome lavas regularly causes gas pressurizations on the dome or the underlying volcano conduit. Lava dome extrusions can last from days to decades, further highlighting the need for accurate and reliable monitoring data.
This thesis aims to improve our understanding of lava dome processes and to contribute to the monitoring and prediction of hazards posed by these domes. The recent rise and sophistication of photogrammetric techniques allows for the extraction of observational data in unprecedented detail and creates ideal tools for accomplishing this purpose. Here, I study natural lava dome extrusions as well as laboratory-based analogue models of lava dome extrusions and employ photogrammetric monitoring by Structure-from-Motion (SfM) and Particle-Image-Velocimetry (PIV) techniques. I primarily use aerial photography data obtained by helicopter, airplanes, Unoccupied Aircraft Systems (UAS) or ground-based timelapse cameras. Firstly, by combining a long time-series of overflight data at Volcán de Colima, México, with seismic and satellite radar data, I construct a detailed timeline of lava dome and crater evolution. Using numerical model, the impact of the extrusion on dome morphology and loading stress is further evaluated and an impact on the growth direction is identified, bearing important implications for the location of collapse hazards. Secondly, sequential overflight surveys at the Santiaguito lava dome, Guatemala, reveal surface motion data in high detail. I quantify the growth of the lava dome and the movement of a lava flow, showing complex motions that occur on different timescales and I provide insight into rock properties relevant for hazard assessment inferred purely by photogrammetric processing of remote sensing data. Lastly, I recreate artificial lava dome and spine growth using analogue modelling under controlled conditions, providing new insights into lava extrusion processes and structures as well as the conditions in which they form.
These findings demonstrate the capabilities of photogrammetric data analyses to successfully monitor lava dome growth and evolution while highlighting the advantages of complementary modelling methods to explain the observed phenomena. The results presented herein further bear important new insights and implications for the hazards posed by lava domes.
This thesis aims to investigate the visualization approaches in the field of annotated discourse relations and to find a solution that meets the requirements best by comparing different programming tools. The subject of this research are coherence relations, which have several properties that can be challenging for many visualization methods. The thesis presents five different visualization options from both the application and the development perspective. The initially tested simple HTML approaches as well as the software package displaCy show the insufficient level for the visualization purposes of this work. The alternative implementation with D3 would optimally meet the requirements but goes beyond the scope of the project. The main method chosen in this thesis was implemented as a single web application and uses the brat annotation tool, which fulfills most of the defined requirements for the representation of the coherence relations. The application graphically displays the coherence relations annotated in the text and offers a filter function for different relation types.
Zoicas, Iulia ; Schumacher, Fabian ; Kleuser, Burkhard ; Reichel, Martin ; Gulbins, Erich ; Fejtova, Anna ; Kornhuber, Johannes ; Rhein, Cosima
Human and murine studies identified the lysosomal enzyme acid sphingomyelinase (ASM) as a target for antidepressant therapy and revealed its role in the pathophysiology of major depression. In this study, we generated a mouse model with overexpression of Asm (Asm-tg(fb)) that is restricted to the forebrain to rule out any systemic effects of Asm overexpression on depressive-like symptoms. The increase in Asm activity was higher in male Asm-tg(fb) mice than in female Asm-tg(fb) mice due to the breeding strategy, which allows for the generation of wild-type littermates as appropriate controls. Asm overexpression in the forebrain of male mice resulted in a depressive-like phenotype, whereas in female mice, Asm overexpression resulted in a social anxiogenic-like phenotype. Ceramides in male Asm-tg(fb) mice were elevated specifically in the dorsal hippocampus. mRNA expression analyses indicated that the increase in Asm activity affected other ceramide-generating pathways, which might help to balance ceramide levels in cortical brain regions. This forebrain-specific mouse model offers a novel tool for dissecting the molecular mechanisms that play a role in the pathophysiology of major depression.
Zoch-Lesniak, Beate ; Dobberke, Jeanette ; Schlitt, Axel ; Bongarth, Christa ; Glatz, Johannes ; Spörl-Dönch, Sieglinde ; Koran, Iryna ; Völler, Heinz ; Salzwedel, Annett
Objective: To determine immediate performance measures for short-term, multicomponent cardiac rehabilitation (CR) in clinical routine in patients of working age, taking into
account cardiovascular risk factors, physical performance, social medicine, and subjective health parameters and to explore the underlying dimensionality.
Design: Prospective observational multicenter register study in 12 rehabilitation centers throughout Germany.
Setting: Comprehensive 3-week CR.
Portal Wissen = Energy
(2020)
Energy – there is something to it. There is, of course, the matter-of-fact definition in every student encyclopedia: “the capacity to do mechanical work, transfer heat, or emit light.” In this way, energy accompanies us, often undetected, all day long: getting out of bed, turning on the heat, switching on the lights, taking a hot shower, getting dressed, making coffee, having breakfast – before we have even left the house, we have already released, transformed, applied, and refueled a lot of energy. And we haven’t even worked, at least not in the traditional sense.
But energy is not just a physical quantity that, due to its omnipresence, plays a key role in every natural science discipline, such as biology and chemistry, but also in almost every technical field. It is also indispensable when it comes to how we understand and describe our world and our activities – and it has been for a long time. How about an example? The Greek philosopher Aristotle was the first to speak of enérgeia, for him a rather nonphysical thing, a living “reality and effectiveness ” – that which makes the possible real. About 2,100 years later, the uncrowned king of German literature Johann Wolfgang von Goethe declared it to be a humanistic essence. “What can we call our own if not energy, strength, and will!” And for his contemporary Wilhelm von Humboldt, energy “was the human’s first and only virtue”. Although physics began to dominate the concept of energy when it became the leading science in the 19th century, energy remained significant in many areas.
Reason enough for us to take a look at energy-related matters at the University of Potsdam. We found them in a wide range of disciplines: While Iranian physicist Safa Shoaee is researching how organic materials can be used to manufacture the solar cells of the future, Swedish environmental researcher Johan Lilliestam is focusing on the different dimensions of the energy transition to learn what makes it successful. Slavicist Susanne Strätling, on the other hand, crosses the boundaries of her discipline as she examines a complex conceptual history and tries to find out why energy electrifies us today more than ever. And physicist Markus Gühr is able to use ultrashort flashes of light to investigate how molecules change under its influence and convert energy in the process.
Of course, we have enough energy to highlight the diversity of research at the University of Potsdam besides the feature topic of this issue. A cognitive researcher, for example, explains why our brain processes both music and language according to its own respective rhythm, while an environmental researcher presents a method that uses particles from outer space to measure soil moisture. Educational researchers have also launched a study on hate speech in schools and we introduce a palaeoclimatologist who is one of twelve researchers in the new postdoc program at the University of Potsdam. We have spared no energy!
Zimmermann, Matthias ; Schünzel, Julia ; Safoklov, Yury ; Lehmann, Louise ; Eilebrecht, Johanna ; Gölz, Leah ; Stegemann, Tim ; Wagner, Marlene ; Klimke, Romy ; Steinbach, Peter
Aus dem Inhalt:
• Gemeinschaftliches Eigentum indigener Völker – Recht und Rechtsdurchsetzung am Fall Lhaka Honhat gegen Argentinien
• „Spiel mir das Lied vom Tod“: Die Pflichten des Staates beim Umgang mit freiverantwortlicher Lebensbeendigung – Eine Untersuchung unter Berücksichtigung der deutschen und europäischen höchstrichterlichen Rechtsprechung
• Die Individualbeschwerde vor dem Kinderrechtsausschuss der Vereinten Nationen: Ein Instrument zur effektiven Durchsetzung der Kinderrechte?
Zimmermann, Matthias ; Horn-Conrad, Antje ; Scholz, Jana ; Elsner, Birgit ; Schubarth, Wilfried ; Engel, Silke ; Blaum, Niels ; Rößling, Claudia ; Mikulla, Stefanie
Corona. Schon mal gehört? Noch Weihnachten 2019 hätten viele ahnungslos geantwortet: „Nö.“ Besser Informierte hätten zurückgefragt: „Meinst du die Korona – den Hof um die Sonne?“ Und ganz Schlaue hätten gesagt: „Klar, trink ich gern.“ Doch spätestens seit Februar beherrscht das Virus die Nachrichten, seit März auch unser Leben. Nach und nach mussten wir alle lernen, uns (wieder) richtig die Hände zu waschen und die „Niesetikette“ zu befolgen, Abstand zu halten, zu Hause zu arbeiten oder zu lernen, Masken zu tragen oder gar zu nähen – und überhaupt: uns mit dem Ausnahmezustand, der zum Dauerzustand zu werden droht, zu arrangieren. Aber wie macht das eine ganze Universität – mit 21.000 Studierenden, mehr als 4.500 Beschäftigten, Tausenden Kursen, Praktika, Prüfungen und Forschungsprojekten? Wie hält man einen Tanker an – in voller Fahrt – und rüstet ihn um für einen pandemiesicheren Betrieb? Die zurückliegenden Wochen haben gezeigt: Es geht. Inzwischen läuft mit dem Sommersemester 2020 das erste Online-Semester der Hochschulgeschichte. Auch das hätte Ende 2019 niemand für möglich gehalten, schon gar nicht so bald.
Das Referat für Presse- und Öffentlichkeitsarbeit musste wie alle Unibereiche lernen, mit den ungewöhnlichen Umständen umzugehen, die mal bedrohlich, mal lästig, mal ermüdend und mal eben einfach nur umständlich wirkten. Wir haben uns bemüht, so gut es ging, zu informieren – darüber was sich tat, was getan werden musste und konnte. Und was kommt. Doch wir wollten noch mehr wissen: Was sagen die Potsdamer Wissenschaftlerinnen und Wissenschaftler zur Corona- Pandemie, ihren Auswirkungen und Folgen, aber auch dazu, was sich dagegen tun lässt? Wie genau funktioniert eine Universität unter den besonderen Umständen? Wie wird gearbeitet, studiert, geforscht? Wie verlagert man ein ganzes Semester in den Online-Betrieb? Auf der Suche nach Antworten auf diese und viele weitere Fragen ist eine Vielzahl von Texten entstanden, die wir nach und nach auf der Webseite der UP veröffentlicht haben als „Beiträge aus der Universität Potsdam zur Corona-Pandemie“.* Eine gekürzte Auswahl dieser Texte haben wir für diese „Portal Spezial“ zusammengestellt. Nicht, weil wir über nichts anderes als den Corona-Virus mehr reden wollen, sondern weil wir dokumentieren wollen, dass die Universität Potsdam durch die Pandemie keineswegs in einen Dornröschenschlaf versetzt wurde. Vielmehr entstanden durch das Engagement vieler Forschender, Studierender und Beschäftigter zahlreiche Initiativen, Ideen, Projekte, Strukturen und Neuerungen, die zeigen: Die Universität Potsdam lässt sich nicht unterkriegen! Deshalb hoffen wir, dass die Lektüre des Heftes Ihnen trotz der weiterhin herausfordernden Umstände Freude und Mut macht. (Die Texte entstanden alle im März/April 2020, als viele Entwicklungen noch am Anfang standen und ihr Verlauf nicht absehbar war. Wir haben sie dennoch unverändert aufgenommen, um diese Phase und die Reaktion der Wissenschaft darauf zu dokumentieren.)