Teilungsanordnungen nach § 2048 BGB

Die Dissertation untersucht die offenen und umstrittenen Fragen im Zusammenhang mit letztwilligen Anordnungen nach § 2048 BGB. Die Arbeit zeigt zunächst die Möglichkeiten der Regelung von Teilungsanordnungen in letztwilligen Verfügungen von Todes wegen auf und grenzt die Teilungsanordnung zu anderen erbrechtlichen Regelungsmöglichkeiten wie Vorausvermächtnis, Auflage, Verwaltungsanordnung, Testamentsvollstreckung und Erbeinsetzung sowie zum „Erblasserappell“ ab. Im Rahmen der Befassung mit der Teilungsanordnung im eigentlichen Sinne gem. § 2048 S. 1 BGB werden die Regelungsvarianten und deren Rechtsfolgen betrachtet und Lösungen für im Gesetz nicht normierte Probleme in diesem Zusammenhang aufgezeigt. Nachfolgend wird die in der Literatur und Rechtsprechung kaum betrachtete Teilungsanordnung durch Bestimmung Dritter gem. § 2048 S. 2 und 3 BGB umfassend untersucht. Es wird gezeigt, dass diese Regelungsmöglichkeit dem ernannten Dritten bei der Auseinandersetzung weitreichende Flexibilität bietet, gleichzeitig aber auch die Rechte der Erben sichert. Es schliessen sich Ausführungen zu den steuerrechtlichen Auswirkungen von Anordnungen nach § 2048 BGB an sowie eine vergleichende Betrachtung von in der Literatur erörterten Formulierungsmustern für Anordnungen nach § 2048 BGB. Die Arbeit schließt mit einem eigenen umfassenden Formulierungsvorschlag und einer Zusammenfassung der Ergebnisse in Thesen

Development of a vernix caseosa substitute : a novel strategy to improve skin barrier function and repair

Vernix caseosa (VC) is the cheesy, white cream that covers the skin of the human fetus and the newborn. VC is a protective cream, which consists of water containing dead cells that are embedded in lipids. This natural cream is suggested to feature multiple biological functions such as facilitating the skin formation during pregnancy and hydrating the skin of the newborn. The aim of this thesis was the rational design of synthetic creams which mimic VC__s structure and its unique properties. Synthetic creams were made of highly hydrated synthetic particles embedded in wool wax and skin lipids. These creams were shown to mimic excellently the structure and composition of natural VC, while the water content and release properties could be controlled. The developed creams showed their great potential for disrupted and underdeveloped skin concerning several aspects: the skin barrier recovery rate was drastically reduced, crust formation was prevented and thickening of the epidermis was less frequently observed. These promising results give rise to future clinical studies in order to prove the benefits of the newly developed creams to treat healthy, dry and diseased human skin.STW, LACDR, CrodaPharmacolog

Apoptose induziert die proteolytische Prozessierung des IL-6 Rezeptors und trägt zum proinflammatorischen Trans-Signalling von Neutrophilen bei

Interleukin-6 (IL-6) trans-signalling has emerged as a prominent regulator of immune responses during both innate and acquired immunity. Regulation of IL-6 trans-signalling is reliant upon the release of soluble IL-6R (sIL-6R), which binds IL-6 to create an agonistic IL-6/sIL-6R complex capable of activating cell types that would normally not respond to IL-6 alone. Soluble IL-6R is generated by proteolytic cleavage of the membrane-anchored precursor (shedding) or from alternative spliced mRNA. Several inducers of IL-6R shedding such as bacterial pore forming toxins, bacterial metalloproteases, the phorbol ester PMA, cholesterol depleting agents and C-reactive protein have been identified in previous studies. IL-6R shedding induced by PMA and cholesterol depletion is dependent on the metalloprotease ADAM17 (A Disintegrin And Metalloprotease), and to a lesser extent on the related sheddase ADAM10. In this study apoptosis was identified as a natural stimulus of IL-6R shedding. Apoptosis, or programmed cell death, plays an important role in regulating growth, tissue homeostasis, development and immune responses. The induction of apoptosis is mediated by extrinsic and intrinsic pathways which require the cooperation of a series of molecules including signal molecules and receptors, enzymes and gene regulating proteins. Among them, the caspase-cascade signalling system is crucial for induction, transduction and amplification of intracellular apoptotic signals. This study demonstrates that intrinsic and extrinsic apoptotic stimulation of cells by DNA-damage, cytokine deprivation, UV irradiation and Fas ligation promotes shedding of the IL-6R from the cell surface thereby generating sIL-6R. Apoptosis-induced shedding of the IL-6R was caspase dependent but PKC, MAPK and ROS independent. Inhibition of ADAM17 during apoptosis by small pharmacological inhibitors or a dominant-negative ADAM17 variant resulted in prevention of IL-6R shedding. The sIL-6R generated during apoptosis was biological active and formed complexes with IL-6 thereby facilitating IL-6 trans-signalling in nonapoptotic cells. Neutrophils have a short life span and die rapidly via apoptosis in vivo and in vitro. In this study neutrophils were used as a cellular model. Induction of apoptosis by Fas-ligation or UV irradiation of primary human neutrophils promoted IL-6R shedding thereby resulting in a two-fold increase of sIL-6R release. Neutrophils represent the first cell population infiltrating inflamed areas and play a crucial role during inflammatory responses due to their extraordinary microbial capacity. Following phagocytosis of invaded microorganisms neutrophils undergo apoptosis as a mechanism to promote resolution of inflammation. The second cell population which migrates into the inflamed area consists mostly of mononuclear phagocytes (monocytes) which are responsible for the clearance of apoptotic neutrophils thus leading to resolution of the inflammatory reaction. Findings in this study indicate that apoptosis-induced shedding of the IL-6R from the neutrophils surface facilitates formation of an [IL-6/sIL-6R] complex which directs IL-6 trans-signalling presumably on endothelial cells to promote recruitment of mononuclear phagocytic cells involved in the nonphlogisic removal of apoptotic neutrophils. Using a mouse model of acute inflammation, it was demonstrated in this study that blocking IL-6R-mediated signal transduction by neutralizing antibodies or soluble gp130-Fc during acute inflammation resulted in a normal influx of neutrophils but a severely impaired influx of monocytes into the inflamed area. Therefore, IL-6R shedding and subsequent IL-6 trans-signalling represent important steps for the resolution of inflammatory responses by controlling the recruitment of mononuclear phagocytes. Thus, shedding of the IL-6R during neutrophil apoptosis may have profound effects on the outcome of the inflammatory response.Interleukin-6 (IL-6) vermitteltes Trans-signalling ist ein wichtiger regulatorischer Signalweg für die Steuerung der angeborenen und erworbenen Immunität. IL-6 Trans-signalling wird durch die Freisetzung vom löslichen Interleukin-6-Rezeptor (sIL-6R) moduliert; dieser bindet an IL-6, um einen IL-6/sIL-6R Komplex zu bilden. Der Komplex aus IL-6 und sIL-6R kann dann Zellen stimulieren, die lediglich gp130 exprimieren und normallerweise nicht in der Lage sind auf IL-6 zu reagieren, da ihnen die ligandenbindende Untereinheit (IL-6R) fehlt. Die lösliche Form des IL-6Rs kann entweder durch limitierte Proteolyse des membranständigen Rezeptors oder durch alternatives Spleißen der IL-6R mRNA generiert werden. In vorherigen Arbeiten konnte bereits gezeigt werden, dass die limitierte Proteolyse des IL-6Rs (Shedding) durch bakterielle porenformende Toxine, bakterielle Metalloproteasen, den Phorbolester PMA, Cholesterinentzug und C-reaktivem Protein induziert werden kann. Shedding des IL-6Rs durch Phorbolester und Cholesterinentzug wird hauptsächlich durch die Metalloprotease ADAM17 (A Disintegrin And Metalloprotease 17) und zum geringen Teil von der verwandten Protease ADAM10 vermittelt. Im Rahmen dieser Arbeit konnte gezeigt werden, dass apoptotische Zellen vermehrt den IL-6R spalten; demnach stellen apoptotische Prozesse einen physiologischen Stimulus für induzierte IL-6R Proteolyse dar. Apoptose wird auch als programmierter Zelltod bezeichnet und spielt in der Regulation von Zellwachstum, Gewebehomöostase und Immunreaktionen eine entscheidende Rolle. Apoptose kann abhängig von der Art des auslösenden Reizes auf verschiedene Wege eingeleitet werden; zum einen durch Aktivierung von Todesrezeptoren auf der Zellmembran und zum anderen durch mitochondrial vermittelte Signalwege. Hauptmerkmal beider Apoptosewege sind Caspasen (Cysteinproteasen), welche die morphologischen und biochemischen Merkmale der Apoptose durch Spaltung von zellulären Bestandteilen hervorrufen. Im Rahmen dieser Arbeit konnte gezeigt werden, dass sowohl todesrezeptoren- als auch mitochondrialvermittelte Apoptose zu vermehrter Proteolyse des IL-6Rs führt. Dabei wurde zelluläre Apoptose durch verschiedene Wege induziert, wie zum Beispiel durch toxische Substanzen, die zur Schädigung des genetischen Materials führen, UV-Bestrahlung, Aktivierung des Todesrezeptors CD95 (Fas) oder Entzug von Überlebensfaktoren. Das durch Apoptose induzierte IL-6R Shedding war Caspase-abhängig jedoch PKC-, MAPK- und ROS- unabhängig. Des Weiteren führte eine Inhibition von ADAM17 durch kleine pharmakologische Inhibitoren oder durch eine dominant-negative ADAM17 Variante während des programmierten Zelltodes zur kompletten Unterbindung von apoptosevermitteltem IL-6R Shedding. Der lösliche IL-6R, welcher während der Apoptose vermehrt gebildet wurde, war biologisch aktiv und konnte im Komplex mit IL-6 in nicht-apoptotischen gp130 exprimierenden Zellen Trans-signalling auslösen. Polymorphkernige Neutrophile sind kurzlebige Zellen mit einer Lebensdauer von 6-8 Stunden; danach sterben Neutrophile durch Apoptose. Im Rahmen dieser Arbeit wurden Neutrophile als zelluläres System verwendet. CD95 (Fas) Aktivierung und UV-Bestrahlung lösten in primären humanen Neutrophilen Apoptose aus, welche mit erhöhtem Shedding des IL-6Rs einherging. Bei Entzündungsprozessen stellen Neutrophile die erste Verteidigungslinie gegen Mikroorganismen dar. Neutrophile phagozytieren Mikroorganismen und töten diese durch vermehrte Produktion von Sauerstoffradikalen ab. Um die inflammatorische Reaktion zu beenden, müssen die aktivierten Neutrophilen eliminiert werden. Dies passiert durch die Einleitung von Apoptose in aktivierten Neutrophilen und anschließender Phagocytose durch mononukleäre Immunzellen (Monocyten), welche als zweite Zellpopulation in den Entzündungsort einwandern. Ergebnisse in dieser Arbeit zeigen, dass apoptotische Neutrophile verstärkt den IL-6R spalten. Dieser bildet einen Komplex mit IL-6. Der Komplex aus sIL-6R/IL-6 stimuliert daraufhin endotheliale Zellen, Mediatoren auszuschütten, die an der Rekrutierung von Monocyten beteiligt sind. Mit Hilfe eines murinen Krankheitsmodelles (Air-pouch-Modell) konnte gezeigt werden, dass Blockierung von sIL-6R-vermittelten Signalwegen durch neutralisierende Antikörper oder rekombinantem löslichen gp130-Fc zu einer stark verminderten Akkumulation von Monocyten in den Entzündungsherd führt. Demnach wird der sIL-6R von apoptotischen Neutrophilen freigesetzt und beeinflusst bei entzündlichen Prozessen die Einwanderung von Monocyten, welche für das Beenden der inflammatorischen Reaktion verantwortlich sind

Comparison of OCO-2 target observations to MUCCnet – is it possible to capture urban XCO2_{CO2} gradients from space?

In this paper, we compare Orbiting Carbon Observatory 2 (OCO-2) measurements of column-averaged dry-air mole fractions (DMF) of CO$_{2}$ (X$_{CO2}$) and its urban–rural differences against ground-based remote sensing data measured by the Munich Urban Carbon Column network (MUCCnet). Since April 2020, OCO-2 has regularly conducted target observations in Munich, Germany. Its target-mode data provide high-resolution X$_{CO2}$ within a 15 km × 20 km target field of view that is greatly suited for carbon emission studies from space in cities and agglomerated areas. OCO-2 detects urban X$_{CO2}$ with a root mean square different (RMSD) of less than 1 ppm when compared to the MUCCnet reference site. OCO-2 target X$_{CO2}$ is biased high against the ground-based measurements. The close proximity of MUCCnet\u27s five fully automated remote sensing sites enables us to compare spaceborne and ground-based X$_{CO2}$ in three urban areas of Munich separately (center, north, and west) by dividing the target field into three smaller comparison domains. Due to this more constrained collocation, we observe improved agreement between spaceborne and ground-based X$_{CO2}$ in all three comparison domains. For the first time, X$_{CO2}$ gradients within one OCO-2 target field of view are evaluated against ground-based measurements. We compare X$_{CO2}$ gradients in the OCO-2 target observations to gradients captured by collocated MUCCnet sites. Generally, OCO-2 detects elevated X$_{CO2}$ in the same regions as the ground-based monitoring network. More than 90 % of the observed spaceborne gradients have the same orientation as the X$_{CO2}$ gradients measured by MUCCnet. During our study, urban–rural enhancements are found to be in the range of 0.1 to 1 ppm. The low urban–rural gradients of typically well below 1 ppm in Munich during our study allow us to test OCO-2\u27s lower detection limits for intra-urban X$_{CO2}$ gradients. Urban X$_{CO2}$ gradients recorded by the OCO-2 instruments and MUCCnet are strongly correlated (R$^{2}$=0.68) with each other and have an RMSD of 0.32 ppm. A case study, which includes a comparison of one OCO-2 target overpass to WRF-GHG modeled X$_{CO2}$ , reveals a similar distribution of enhanced CO$_{2}$ column abundances in Munich. In this study, we address OCO-2\u27s capability to detect small-scale spatial X$_{CO2}$ differences within one target observation. Our results suggest OCO-2\u27s potential to assess anthropogenic emissions from space

LongProf-Handbuch: Longitudinale Professionalitätsentwicklung im Medizinstudium

Im Medizinstudium werden traditionell viele Fakten und klinische Kompetenzen vermittelt - wie sich Studierende persönlich zu Ärztinnen und Ärzten entwickeln und ihre professionelle Identität formen, ist jedoch selten expliziter Bestandteil und geschieht meist einfach „nebenbei“. Das Curriculum „LongProf“ am Universitätsklinikum Jena hat sich die professionelle Persönlichkeitsentwicklung im Medizinstudium zur Aufgabe gemacht. Besondere Schwerpunkte liegen auf der langfristigen Bindung zwischen Studierenden und begleitenden Lehrpersonen und der verständnisintensiven Lernqualität. Das vorliegende Handbuch beschreibt ein theoriebezogenes Rahmenkonzept für die Planung und Durchführung von Lehrveranstaltungen zur systematischen Professionalitätsentwicklung und zeigt Beispiele für die methodische Umsetzung. So ist ein Kompendium entstanden zur Inspiration für alle Lehrenden in der Medizindidaktik

Building indoor model in PALM-4U: indoor climate, energy demand, and the interaction between buildings and the urban microclimate

There is a strong interaction between the urban atmospheric canopy layer and the building energy balance. The urban atmospheric conditions affect the heat transfer through exterior walls, the long-wave heat transfer between the building surfaces and the surroundings, the short-wave solar heat gains, and the heat transport by ventilation. Considering also the internal heat gains and the heat capacity of the building structure, the energy demand for heating and cooling and the indoor thermal environment can be calculated based on the urban microclimatic conditions. According to the building energy concept, the energy demand results in an (anthropogenic) waste heat; this is directly transferred to the urban environment. Furthermore, the indoor temperature is re-coupled via the building envelope to the urban environment and affects indirectly the urban microclimate with a temporally lagged and damped temperature fluctuation. We developed a holistic building model for the combined calculation of indoor climate and energy demand based on an analytic solution of Fourier's equation and implemented this model into the PALM model.</p

Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance

Background: Anorectal malformations (ARM) are rare abnormalities that occur in approximately 1 in 3000 live births with around 40% of patients presenting with isolated forms. Multiple familial cases reported, suggest underlying genetic factors that remain largely unknown. The recurrence in relatives is considered rare, however transmission rates of ARM by affected parents have never been determined before. The inheritance pattern of ARM was investigated in our database of patients with isolated ARM. Results: Within our cohort of 327 patients with isolated ARM we identified eight adult patients from eight families who had in total 16 children with their healthy spouse. Of these ten had ARM, resulting in a recurrence risk of approximately one in two live births (10 of 16; 62%). From 226 families with 459 siblings we found two affected siblings in five families. Hence, the recurrence risk of ARM among siblings is approximately one in 92 live births (5 of 459; 1.0%). Conclusions: Comparing the observed recurrence risk in our cohort with the prevalence in the general population, we see a 1500-fold increase in recurrence risk for offspring and a 32-fold increase if a sibling is affected. The recurrence risk of approximately 62% indicates an autosomal dominant mode of inheritance. Reliable figures on recurrence of ARM are becoming increasingly important since improved surgical techniques are able to maintain sexual function resulting in more offspring of patients with ARM. These data allow more precise counseling of families with ARM and support the need for genetic studies

Database of Near-Wall Turbulent Flow Properties of a Jet Impinging on a Solid Surface under Different Inclination Angles

In the present paper, direct numerical simulation (DNS) and particle image velocimetry (PIV) have been applied complementarily in order to generate a database of near-wall turbulence properties of a highly turbulent jet impinging on a solid surface under different inclination angles. Thereby, the main focus is placed on an impingement angle of 45°, since it represents a good generic benchmark test case for a wide range of technical fluid flow applications. This specific configuration features very complex flow properties including the presence of a stagnation point, development of the shear boundary layer and strong streamline curvature. In particular, this database includes near-wall turbulence statistics along with mean and rms velocities, budget terms in the turbulent kinetic energy equation, anisotropy invariant maps, turbulent length/time scales and near-wall shear stresses. These properties are useful for the validation of near-wall modeling approaches in the context of Reynolds-averaged Navier–Stokes (RANS) and large-eddy simulations (LES). From this study, in which further impingement angles (0°, 90°) have been considered in the experiments only, it turns out that (1) the production of turbulent kinetic energy appears negative at the stagnation point for an impingement angle other than 0° and is balanced predominantly by pressure-related diffusion, (2) quasi-coherent thin streaks with large characteristic time scales appear at the stagnation region, while the organization of the flow is predominantly toroidal further downstream, and (3) near-wall shear stresses are low at the stagnation region and intense in regions where the direction of the flow changes suddenly