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Phosphatidylcholine synthesis and remodeling in brain endothelial cells
Get PDFMammalian cells synthesize hundreds of different variants of their prominent membrane lipid phosphatidylcholine (PC), all differing in the side chain composition. This batch is constantly remodeled by the Lands cycle, a metabolic pathway replacing one chain at a time. Using the alkyne lipid lyso-phosphatidylpropargylcholine (LpPC), a precursor and intermediate in PC synthesis and remodeling, we study both processes in brain endothelial bEND3 cells. A novel method for multiplexed sample analysis by mass spectrometry is developed that offers high throughput and molecular species resolution of the propargyl-labeled PC lipids. Their time-resolved profiles and kinetic parameters of metabolism demonstrate the plasticity of the PC pool and the acute handling of lipid influx in endothelial cells differs from that in hepatocytes. Side chain remodeling as a form of lipid cycling adapts the PC pool to the cell's need and maintains lipid homeostasis. We estimate that endothelial cells possess the theoretical capacity to remodel up to 99% of their PC pool within 3.5 h using the Lands cycle. However, PC species are not subjected stochastically to this remodeling pathway as different species containing duplets of saturated, omega-3, and omega-6 side chains show different decay kinetics. Our findings emphasize the essential function of Lands cycling for monitoring and adapting the side chain composition of PC in endothelial cells
Modulare Synthese Carbonsäure-terminierter Phenylen-Ethinylen-Stäbchen zur präorganisierten Parkettierung von HOPG-Oberflächen
Get PDFIm Rahmen der vorliegenden Arbeit wurden verschiedene säurefunktionalisierte Phenylen-Ethinylen-Stäbchen mit unterschiedlichen dendritischen Seitenbausteinen synthetisiert, welche auf hochorientiertem pyrolytischem Graphit (HOPG) selbstassemblierte Monolagen (SAM) bildeten. Die Unterteilung der Stäbchen in drei Fragmente (Mittelbaustein, dendritischer Baustein und säurefunktionalsierter Seitenbaustein) ermöglichte einen schnellen synthetischen Zugang. Anschließend wurden die Stäbchen mittels Rastertunnelmikroskopie (STM) auf ihr Interdigitationsverhalten sowie auf einen Isomorphismus zwischen zwei Bindungsmotiven (Butadiinylene und Carbonsäuredimere) untersucht.
Im ersten Teil wurden drei Stäbchen synthetisiert, die den 3,5-Dihexadecyloxybenzyl-Rest, den 3,4,5-Trihexadecyloxybenzyl-Rest, oder den asymmetrischen 3,4‑Bis(hexadecyl-oxy)‑5‑methoxybenzyl-Rest trugen um intermolekular interdigitierende Blöcke von vier bzw. sechs Alkoxyketten, sog. Quadrupletts und Sextupletts zu erzeugen. Hierbei wurde vor allem der Einfluss der dendritischen Bausteine auf die Monolagen untersucht. Die STM-Untersuchungen zeigten, dass der asymmetrische 3,4‑Bis(hexadecyloxy)‑5‑methoxybenzyl-Rest als einziges zuverlässig Multiplettstrukturen in der Monolage ausbildete. Mittels zweier Testsysteme sollte das Verhalten auf weitere asymmetrische Vertreter, wie den 3,4‑Bis(hexa-decyloxy)-5‑hexyloxybenzyl-Rest ausgeweitet werden, um die vielversprechenden Assemblierungseigenschaften später in größeren Strukturen anzuwenden. Die Untersuchungen mittels STM zeigten, dass beide asymmetrischen Vertreter ähnliche Muster bildeten.
Im zweiten Teil wurden zwei verschiedene butadiinylenverbrückte Carbonsäure-terminierte Oligomere zur weitergehenden Untersuchung des Isomorphismus von Butadiinylenen und Carbonsäuredimeren synthetisiert und bis zum Octamer monodispers isoliert. Weiterhin konnten diese der Klasse der semiflexiblen Polymeren zugeordnet werden. Als dendritische Bausteine wurden der 3,4,5-Trihexadecyloxybenzyl-Rest sowie der 3,4‑Bis(hexadecyloxy)-5‑hexyloxybenzyl-Rest verwendet. STM-Untersuchungen ausgewählter Oligomere konnten den Isomorphismus von Butadiinylenen und Carbonsäuredimeren verifizieren. Abschließend wurden ein Isophthalsäure-Derivat und dessen butadiinylenverbrücktes Dimer zur Bestätigung des Isomorphismus in kleinen Systemen synthetisiert, dabei trugen sie den 3,4,5-Tributyloxybenzyl-Rest. Der Isomorphismus konnte mittels STM verifiziert werden
Policy-Driven Structural Change – Governance in the Transition from Coal to Bioeconomy
Get PDFWith the Agenda 2030, the international community has committed to ambitious goals for sustainable development. A core component of the envisioned transformation is to reduce dependence on fossil resources in sectors such as energy and agriculture. The overarching objective of a sustainable economy is widely agreed upon. Perceptions of sustainability and the measures considered necessary, however, differ. Previous experiences with the energy transition have shown that the stakeholders involved act based on their subjective perceptions and interests, which influences decision-making. This leads to a complex decision-making process that is determined by the dynamic interaction of the stakeholders involved and must take into account economic, social, and environmental considerations – and thus often conflicting objectives.
As part of this policy-driven transformation process and efforts towards climate protection, Germany currently faces the challenge of transforming the Rhenish lignite mining region. Following the far-reaching energy policy decision in the form of the coal phase-out, this regional structural change affects large parts of society and requires comprehensive governance. The aim of the envisioned transformation is to establish a sustainable bioeconomy. Identifying regional transformation pathways that are feasible, desirable, and acceptable, while considering the perspectives of individual stakeholders, constitutes a complex task.
This thesis integrates the perceptions of stakeholders and regional transformation pathways in a decision support system based on the operationalization of Amartya Sen's work on collective decision-making and methods of multi-criteria decision aid. The developed decision support system is applied to the Rhenish lignite mining region, as the region is particularly affected by the phase-out of coal and is to be developed as a model region for a sustainable bioeconomy. This work thus contributes to a better understanding of transformation dynamics and supports governance by deriving policy recommendations.Mit der Agenda 2030 hat sich die Weltgemeinschaft ambitionierte Ziele für eine nachhaltige Entwicklung gesetzt. Ein wesentlicher Teil des angestrebten Wandels besteht darin, die Abhängigkeit von fossilen Ressourcen in Sektoren wie Energie und Landwirtschaft zu verringern. Das übergeordnete Ziel einer nachhaltigen Wirtschaftsweise ist dabei grundsätzlich konsensfähig. Die Vorstellungen darüber, was unter Nachhaltigkeit zu verstehen ist und welche Maßnahmen erforderlich sind, unterscheiden sich jedoch. Frühere Erfahrungen im Zusammenhang mit der Energiewende haben gezeigt, dass beteiligte Stakeholder nach ihren subjektiven Wahrnehmungen und Interessen handeln, was die Entscheidungsfindung beeinflusst. Daraus ergibt sich ein komplexer Entscheidungsprozess, der durch die dynamische Interaktion der Beteiligten bestimmt wird und wirtschaftliche, soziale und ökologische Erwägungen – und damit oft widersprüchliche Ziele – berücksichtigen muss.
Im Rahmen dieses politisch motivierten Transformationsprozesses und der Bemühungen zum Klimaschutz steht Deutschland derzeit vor der Herausforderung der Transformation des Rheinischen Braunkohlereviers. Folgend auf die grundlegende energiepolitische Weichenstellung durch das Kohleausstiegsgesetz betrifft dieser regionale Strukturwandel weite Teile der Gesellschaft und erfordert ein hohes Maß an politischer Steuerung. Ziel der angestrebten Transformation ist eine nachhaltige Bioökonomie. Die Identifizierung regionaler Transformationspfade, die unter Berücksichtigung der Perspektiven der einzelnen Stakeholder realisierbar, wünschenswert und akzeptabel sind, stellt dabei eine komplexe Aufgabe dar.
In dieser Arbeit werden die Wahrnehmungen der Stakeholder und regionale Transformationspfade in einem System zur Entscheidungsunterstützung zusammengeführt, das auf der Operationalisierung von Amartya Sens Werken zur kollektiven Entscheidungsfindung und den Methoden der multikriteriellen Entscheidungsunterstützung basiert. Die Anwendung des entwickelten Systems zur Entscheidungsunterstützung erfolgt im Rheinischen Braunkohlerevier, da die Region besonders vom Kohleausstieg betroffen ist und als Modellregion für eine nachhaltige Bioökonomie entwickelt werden soll. Die Arbeit trägt damit zu einem besseren Verständnis von Transformationsdynamiken bei und unterstützt politische Steuerung durch die Ableitung von Politikempfehlungen
Sialylation as a checkpoint for inflammatory and complement-related retinal diseases
Get PDFSialylation is a modification process involving the addition of sialic acid residues to the termini of glycoproteins and glycolipids in mammalian cells. Sialylation serves as a crucial checkpoint inhibitor of the complement and immune systems, particularly within the central nervous system (CNS), including the retina. Complement factor H (FH), complement factor properdin (FP), and sialic acid-binding immunoglobulin-like lectin (SIGLEC) receptors of retinal mononuclear phagocytes are key players in regulating the complement and innate immune systems in the retina by recognizing sialic acid (Sia) residues. Intact retinal sialylation prevents any long-lasting and excessive complement or immune activation in the retina. However, sialylated glycolipids are reduced in the CNS with aging, potentially contributing to chronic inflammatory processes in the retina. Particularly, genetically induced hyposialylation in mice leads to age-related, complement factor C3-mediated retinal inflammation and bipolar cell loss. Notably, most of the gene transcript pathways enriched in the mouse retina, following genetically induced hyposialylation, are also involved in age-related macular degeneration (AMD). Interestingly, intravitreal application of polysialic acid (polySia) controlled the innate immune responses in the mouse retina by blocking mononuclear phagocyte reactivity, inhibiting complement activation, and protecting against vascular damage in two different humanized SIGLEC-11 animal models. Accordingly, a polySia polymer conjugate has entered clinical phase II/III testing in patients with geographic atrophy secondary to AMD. Thus, hyposialylation or dysfunctional sialylation should be considered as an age-related contributor to inflammatory retinal diseases, such as AMD. Consequently, sialic acid-based biologics could provide novel therapies for complement-related retinal diseases
Postoperative Infusionstherapie kristalloid versus kolloidal auf der kinderkardiochirurgischen Intensivstation
Get PDFDie perioperative Flüssigkeitstherapie mit kristalloiden und kolloidalen Lösungen besitzt insb. bei der Behandlung pädiatrischer Patienten eine hohe klinische Relevanz, wobei die verfügbare Evidenzlage bislang unzureichend ist.
Die vorliegende Arbeit untersucht retrospektiv die klinische Praxis der Infusionstherapie auf der kinderkardiochirurgischen Intensivstation des Universitätsklinikums Bonn. Insgesamt wurden die Daten von 312 Patienten statistisch ausgewertet. Analysiert wurden u.a. die Art der verwendeten Infusionslösungen sowie deren Einfluss auf die Hospitalisierungs- und Beatmungszeit, Drainageverluste (Outcome-Parameter) und weitere klinische Parameter.
Die Haupthypothese, dass die kolloidale Flüssigkeitssubstitution den kristalloiden Lösungen hinsichtlich der Outcome-Parameter überlegen wäre, konnte durch unsere Untersuchungen nicht bestätigt werden. Vielmehr zeigten sich im kolloidalen Kollektiv tendenziell längere Aufenthalts- und Beatmungszeiten sowie höhere Drainageverluste. Hinweise auf einen positiven Therapieeffekt der Kolloide, wie die Reduktion der kumulativen Kristalloidmenge oder des Katecholamin-Bedarfs, ließen sich nicht ableiten. Durch die kolloidale Substitution einer postoperativen Hypalbuminämie war außerdem kein gesicherter Nutzen für den postoperativen Serum Albumin-Anstieg und das Patienten-Outcome zu verzeichnen.
Die Ergebnisse sprechen dafür die kolloidale Flüssigkeitstherapie bei Kindern kritisch zu hinterfragen. Zur Etablierung evidenzbasierter Behandlungsleitlinien sind prospektiv randomisierte Studien erforderlich
From classrooms to real-world contexts : enhancing vaccine education through open schooling
Get PDFThe topic of vaccination has been a highly debated issue for many years, whether related to measles, HPV, or the recent COVID-19 pandemic. It necessitates deeper exploration, particularly in school biology classes where it is often superficially covered, with ethical considerations rarely addressed. To enable students to engage in an in-depth examination of this complex socio-scientific issue and to enhance their argumentation and decision-making skills, a vaccine educational project was implemented based on the concept of open schooling, where schools collaborate with various societal institutions. Over a three-day interdisciplinary program, secondary school students worked with scientists from diverse fields, including immunobiology, medicine, and ethics, across different career levels, providing varied perspectives. Students actively engaged in real-world learning contexts with authentic problems, fostering individual reflection. A qualitative study, which involved observations and interviews with students, scientists, and teachers, highlighted key success factors in developing student interest and engagement in the topic of vaccination: learner-centered design, interaction with experts, exposure to diverse professional environments, active science learning, and the integration of ethical aspects. This approach promoted not only student engagement with the complex subject matter but also critical thinking and argumentation, contributing to informed decision-making and public health awareness
Amtliche Bekanntmachungen, 55. Jahrgang, Nr. 84
No full textÄnderung und zugleich Neubekanntmachung der Ordnung für die Wahl zum Fakultätsrat der Mathematisch-Naturwissenschaftlichen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn vom 4. November 202
Algorithms for Consistent Dynamic Labeling of Maps With a Time-Slider Interface
Get PDFUser interfaces for inspecting spatio-temporal events often allow their users to filter the events by specifying a time window with a time slider. We consider the case that filtered events are visualized on a map using textual or iconic labels. However, to ensure a clear visualization, not all filtered events are annotated with a label. We present algorithms for setting up a data structure that encodes for every possible time window the set of displayed labels. Our algorithms ensure that the displayed labels never overlap and guarantee the stability of the labeling during certain basic interactions with the time slider. Assuming that the labels have different priorities (weights), we aim to maximize the weight of the displayed labels integrated over all possible time windows. As basic interactions, we consider moving the entire time window, symmetrically scaling it, and dragging one of its endpoints. We consider two stability requirements: (1) during a basic interaction, a label should appear and disappear at most once; (2) if a label is displayed for a time window Q, then it is also displayed for all the time windows contained in Q and that contain its timestamp. We prove that finding an optimal solution is NP-hard and propose efficient constant-factor approximation algorithms for unit-square and unit-disk labels, as well as a fast greedy heuristic for arbitrarily shaped labels. In experiments on real-world data, we compare the non-exact algorithms with an exact approach through integer linear programming
In Vivo Antibiotic Elution and Inflammatory Response During Two-Stage Total Knee Arthroplasty Revision : A Microdialysis Pilot Study
Get PDFIntroduction: Two-stage revision with an antibiotic-loaded, temporary static cement spacer is a common treatment for periprosthetic joint infection (PJI) of the knee. However, limited data exists on in vivo antibiotic elution kinetics after spacer implantation. This pilot study uses the technique of microdialysis (MD) to collect intra-articular knee samples. The aim was to evaluate MD as an intra-articular sampling method to detect spacer-eluted antibiotics within 72 h after surgery and to determine whether they show specific elution kinetics.
Methods: Ten patients (six male, four female; age median 71.5 years) undergoing two-stage revision for knee PJI were included. A MD catheter was inserted into the joint during explantation of the infected inlying implant and implantation of a custom-made static spacer coated with COPAL cement (0.5 g gentamicin (G) and 2 g vancomycin (V)). Over 72 h postoperatively, samples were collected and analyzed for spacer-eluted antibiotics, intravenously administered antibiotics (e.g., cefazolin and cefuroxime), metabolic markers (glucose and lactate), and Interleukin-6 (IL-6). Local and systemic levels were compared.
Results: All catheters were positioned successfully and well tolerated for 72 h. Antibiotic concentrations in MD samples peaked within the first 24 h (G: median 9.55 µg/mL ; V: 37.57 µg/mL [95% CI: 3.26–81.6]) and decreased significantly over 72 h (for both p p p
Conclusions: Monitoring antibiotics eluted by a static spacer with intra-articular MD for 72 h is feasible. Gentamicin and vancomycin levels remained above the minimal inhibitory concentration. Differentiating infection from surgical response using metabolic and immunological markers remains challenging. Prolonged in vivo studies with MD are required to evaluate extended antibiotic release in two-stage exchanges
Learning Image-Based VR Facial Animation and Face Reenactment
No full textThe field of facial animation deals with the manipulation of facial representations, such as images or meshes, primary with the objective of generating a natural and consistent animation sequence. This thesis focuses on images and presents methods for Virtual Reality (VR) facial animation and face reenactment. Facial animation in virtual reality environments (VR facial animation) is essential for applications that necessitate clear visibility of the user’s face and the ability to convey emotional signals and expressions. The primary challenge is to reconstruct the complete face of an individual utilizing a head-mounted display (HMD). In our case, all information relevant for the animation is obtained from one mouth camera mounted below the HMD and two eye cameras inside the HMD. The principal use case for our methods is to animate the face of an operator who controls our robotic avatar system at the ANA Avatar XPRIZE competition.
For the semifinals, we initially propose a real-time capable pipeline with very fast adaptation for specific operators. The method can be trained on talking-head datasets and generalizes to unseen operators, while requiring only a quick enrollment step, during which two short videos are captured. The first video is a sequence of source images from the operator without the VR headset which contain all the important operator-specific appearance information. During inference, we then use the operator keypoint information extracted from a mouth camera and two eye cameras to estimate the target expression, to which we map the appearance of a source still image. In order to enhance the mouth expression accuracy, we dynamically select an auxiliary expression frame from the captured sequence. This selection is done by learning to transform the current mouth keypoints into the source image space, where the alignment can be determined accurately.
Based on this method, we propose an extension that was used in the ANA Avatar XPRIZE finals. We significantly improve the temporal consistency and animation accuracy. In addition, we are able to represent a much broader range of facial expressions by resolving kepoint ambiguities occurring in our method used in the semifinals. Purely keypoint-driven animation approaches struggle with the complexity of facial movements. We present a hybrid method that uses both keypoints and direct visual guidance from a mouth camera. Instead of using only one source image, multiple source images are selected with the intention to cover different facial expressions. We employ an attention mechanism to determine the importance of each source image. To resolve keypoint ambiguities and animate a broader range of mouth expressions, we propose to inject visual mouth camera information into the latent space. We enable training on large-scale talking-head datasets by simulating the mouth camera input with its perspective differences and facial deformations.
We then approach the task of face reenactment, which involves transferring the head motion and facial expressions from a facial driving video to the appearance of a source image, which may be of a different person (cross-reenactment). Most existing methods are CNN-based and estimate optical flow from the source image to the current driving frame. After deforming the source image into the driving frame, it is inpainted and refined to produce the output animation. We propose a transformer-based encoder for computing a set-latent representation of the source image(s). We then predict the output color of a query pixel using a transformer-based decoder, which is conditioned with keypoints and a facial expression vector extracted from the driving frame. Latent representations of the source person are learned in a self-supervised manner that factorize their appearance, head pose, and facial expressions. Thus, they are perfectly suited for cross-reenactment. In contrast to most related work, our method naturally extends to multiple source images and can thus adapt to person-specific facial dynamics. We also propose data augmentation and regularization schemes that are necessary to prevent overfitting and support generalizability of the learned representations. We evaluate our approach in a randomized user study. The results indicate superior performance compared to previous state-of-the-art methods in terms of motion transfer quality and temporal consistency. Finally, we demonstrate in a separate experiment that the method can be adapted for the VR facial animation task, while simultaneously reducing the preprocessing time significantly in comparison to our previous approaches