Bibliographische Beschreibung: Weuste, Malte Die Inhibition der Müllerzellschwellung unter hypotonen Bedingungen durch Heparine binding epidermal growth factor-like growth factor (HB-EGF) Universität Leipzig, Dissertation 62 S., 135 Lit., 30 Abb., 2 Tab. Referat: Die Einleitung der Arbeit beschreibt die Müllerzelle als vorherrschende Gliazelle der Säugetiernetzhaut. Müllerzellen eignen sich dadurch als Modell für andere Makrogliazellen des Zentralen Nervensystems. Sie sind an der Regulation des Wasser- und Ionenhaushaltes der Netzhaut beteiligt. Müllerzellen postischämischer sowie mit Bariumionen behandelter Netzhäute schwellen unter hypotonen Bedingungen an. In vielen Versuchen der vorliegenden Arbeit wurde daher ein postischämischer Zustand der Netzhaut durch Zugabe von Bariumionen zu gesunden Netzhäuten simuliert. Die Arbeit untersucht die Rolle des Wachstumsfaktors HB-EGF in der postischämischen Netzhaut der Ratte. Dazu wurde der HB-EGF-Gehalt in postischämischen und in Kontrollnetzhäuten mit Western Blots und immunohistochemischer Färbung dargestellt. Der Einfluss von HB-EGF auf die Müllerzellschwellung wurde an vitalen Müllerzellen in vitro untersucht. Hierzu wurden Müllerzellen in Netzhäuten der Ratte mit einem Vitalfarbstoff angefärbt und über einen Zeitraum von 5 Minuten mit hypotoner extrazellulärer Lösung perfundiert. Die Perfusionslösung diente dabei auch als Träger verschiedener Testsubstanzen. Das Schwellungsverhalten der Müllerzellsomata wurde in diesem Zeitraum mit einem konfokalen laser-scanning Mikroskop aufgezeichnet und mit der zum Mikroskop gehörenden Software ausgewertet. Die Versuche der vorliegenden Arbeit zeigten, dass der HB-EGF-Gehalt der synaptischen Schichten der Netzhaut nach einer Ischämie ansteigt. Es zeigte sich auch, dass HB-EGF eine Müllerzellschwellung im hypotonen Milieu hemmt. Durch Perfusion der Netzhäute mit verschiedenen Rezeptoragonisten und Rezeptorantagonisten sowie Enzyminhibitoren und Ionenkanalblockern konnte das Bild einer möglichen Signalkaskade der Schwellungsinhibition durch HB-EGF gezeichnet werden. An dieser Signalkaskade sind verschiedene Proteinkinasen, ein Anstieg des freien intrazellulären Kalziums, die neuronale Freisetzung von Glutamat, die Aktivierung von glialen Adenosinrezeptoren sowie die Öffnung unterschiedlicher Ionenkanäle beteiligt. Verschiedene Hypothesen zur Ätiologie und Pathogenese der glialen Zellschwellung und zu deren Inhibition werden diskutiert. Abschließend wird die Rolle der glialen Zellschwellung als Teil der Pathogenese von Erkrankungen, die mit einem Hirn- und Netzhautödemen einhergehen, dargestellt. In Zukunft könnten solche Erkrankungen einmal spezifisch mit Substanzen wie dem HB-EGF therapiert werden.

Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. A volume-regulated anion channel (VRAC) has been electrophysiologically characterized in innumerable mammalian cell types. VRAC is activated by cell swelling and mediates the volume regulatory efflux of Cl− and small organic solutes from cells. Two groups recently identified the mammalian leucine-rich repeat containing protein LRRC8A as an essential VRAC component. LRRC8A must be coexpressed with at least one of the other four members of this gene family, LRRC8B-E, to reconstitute VRAC activity in LRRC8−/− cells. LRRC8 genes likely arose with the origin of chordates. We identified LRRC8A and LRRC8C-E orthologs in the zebrafish genome and demonstrate that zebrafish embryo cells and differentiated adult cell types express a swelling-activated Cl− current indistinguishable from mammalian VRAC currents. Embryo cell VRAC currents are virtually eliminated by morpholino knockdown of the zebrafish LRRC8A ortholog lrrc8aa. VRAC activity is fully reconstituted in LRRC8−/− human cells by coexpression of zebrafish lrrc8aa and human LRRC8C cDNAs. lrrc8aa expression varies during zebrafish embryogenesis and lrrc8aa knockdown causes pericardial edema and defects in trunk elongation and somatogenesis. Our studies provide confirmation of the importance of LRRC8A in VRAC activity and establish the zebrafish as a model system for characterizing the molecular regulation and physiological roles of VRAC and LRRC8 proteins.

Persistent lip swelling can be a diagnostic challenge. We report an unusual case of lip edema in the setting of lip surgery 30 years before presentation and because of retained foreign material. This case highlights the importance of accurate historical information and aggressive diagnostic methods in assessing persistent lip swelling.

This dissertation studies the thermodynamic and structural properties of aqueous dispersions of ionic microgels ? soft colloidal particles composed of cross-linked polymer gels that swell in a good solvent. Starting from a coarse-grained model of microgel particles, we perform computer simulations and theoretical calculations using two complementary implementations of Poisson- Boltzmann (PB) theory. Within the framework of a cell model, the nonlinear PB equation is exactly solved and used to compute counterion distributions and osmotic pressures. By varying the free energy with respect to microgel size, we obtain exact statistical mechanical relations for the electrostatic component of the single-particle osmotic pressure. Explicit results are presented for equilibrium swelling ratios of charged microcapsules and of charged cylindrical and spherical microgels with fixed charge uniformly distributed over the surface or volume of the particle. Molecular dynamics simulations validate the theoretical findings. In the second method, within a one-component model framework, based on a linear-response approximation for effective electro- static interactions, we develop Monte Carlo (MC) simulations to compute the equilibrium swelling ratio, bulk osmotic pressure, radial distribution function, and static structure factor. Results presented in this dissertation demonstrate that swelling of ionic microgels increases with increasing microgel charge and decreases with increasing concentration of salt and microgels. In addition, results demonstrate that the microion distributions and osmotic pressure determine equilibrium swelling of microgels. Cell model predictions for bulk osmotic pressure agree well with data from MC simulations of the one-component model. The MC simulations also provide access to structural properties and to swelling behavior of microgels in highly concentrated suspensions. Taken together, results obtained in this work provide insight into factors of importance for practical use of microgels as drug delivery systems, in tissue engineering, and for other biomedical applications.

abstract: Droplet-structure interactions play a pivotal role in many engineering applications as droplet-based solutions are evolving. This work explores the physical understanding of these interactions through systematic research leading to improvements in thermal management via dropwise condensation (DWC), and breathable protective wearables against chemical aerosols for better thermoregulation. In DWC, the heat transfer rate can be further increased by increasing the nucleation and by optimally ‘refreshing’ the surface via droplet shedding. Softening of surfaces favor the former while having an adverse effect on the latter. This optimization problem is addressed by investigating how mechanical properties of a substrate impact relevant droplet-surface interactions and DWC heat transfer rate. The results obtained by combining droplet induced surface deformation with finite element model show that softening of the substrates below a shear modulus of 500 kPa results in a significant reduction in the condensation heat transfer rate. On the other hand, interactions between droplet and polymer leading to polymer swelling can be used to develop breathable wearables for use in chemically harsh environments. Chemical aerosols are hazardous and conventional protective measures include impermeable barriers which limit the thermoregulation. To solve this, a solution is proposed consisting of a superabsorbent polymer developed to selectively absorb these chemicals and closing the pores in the fabric. Starting from understanding and modeling the droplet induced swelling in elastomers, the extent and topological characteristic of swelling is shown to depend on the relative comparison of the polymer and aerosol geometries. Then, this modeling is extended to a customized polymer, through a simplified characterization paradigm. In that, a new method is proposed to measure the swelling parameters of the polymer-solvent pair and develop a validated model for swelling. Through this study, it is shown that for this polymer, the concentration-dependent diffusion coefficient can be measured through gravimetry and Poroelastic Relaxation Indentation, simplifying the characterization effort. Finally, this model is used to design composite fabric. Specifically, using model results, the SAP geometry, base fabric design, method of composition is optimized, and the effectiveness of the composite fabric highlighted in moderate-to-high concentrations over short durations. / Dissertation/Thesis / Doctoral Dissertation Mechanical Engineering 2019

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第20423号 / 農博第2208号 / 新制||農||1047(附属図書館) / 学位論文||H29||N5044(農学部図書室) / 京都大学大学院農学研究科食品生物科学専攻 / (主査)教授 安達 修二, 教授 金本 龍平, 教授 谷 史人 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(エネルギー科学) / 甲第21434号 / エネ博第376号 / 京都大学大学院エネルギー科学研究科エネルギー変換科学専攻 / (主査)教授 木村 晃彦, 教授 星出 敏彦, 教授 今谷 勝次 / 学位規則第4条第1項該当 / Doctor of Energy Science / Kyoto University / DGAM

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We work with two different mechanisms to generate geometric frustration on thin elastic sheets; isotropic differential growth and folding. We describe how controlled growth and prescribing folding patterns are useful tools for designing three-dimensional objects from information printed in two dimensions. The first mechanism is inspired by the possibility to control shapes by swelling polymer films, where we propose a solution for the problem of shape formation by asking the question, ``what 2D metric should be prescribed to achieve a given 3D shape?'', namely the reverse problem. We choose two different types of initial configurations of sheets, disk-like with one boundary and annular with two boundaries. We demonstrate our technique by choosing four examples of 3D axisymmetric shapes and finding the respective swelling factors to achieve the desired shape. Second, we present a mechanical model for a single curved fold that explains both the buckled shape of a closed fold and its mechanical stiffness. The buckling arises from the geometrical frustration between the prescribed crease angle and the bending energy of the sheet away from the crease. This frustration increases as the sheet's area increases. Stiff folds result in creases with constant space curvature while softer folds inherit the broken symmetry of the buckled shape. We extend the application of our numerical model to show the potential to study multiple fold structures.