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Beyond the Music - Fan Communities, Transformative Labour, and the Global Ascendancy of K-Pop
No full textThe fifth volume section – DIGITALIZING – listens in as sound, voice, and music travel from ‘real life’ to online spaces and virtual interactions.
In their contribution, Şelale Hannah Erduran and Elena Möhler trace the paths of K-pop's global spread. They pay particular attention to fan community dynamics, to the role of language and physical props in fannish identity formation, and to the material as well as participatory dimensions of fandom. Finally, the analysis highlights the various forms of labour performed by fan communities, which go far beyond the mere act of (purchasing and) listening to music
Series Foreword: JMU Cultural Studies - Strategies for Struggling with the Obvious
No full textSeries editors Zeno Ackermann and MaryAnn Snyder-Körber outline the aims of the publication series: to continue the project of “bringing light into the darkness of the obvious,” as Stuart Hall once proposed, but also to test the analytical approaches of the cultural studies tradition and retool them for the challenges of the contemporary world
Delta- and Kalman-filter designs for multi-sensor pose estimation on spherical mobile mapping systems
No full textSpherical mobile mapping systems are not thoroughly studied in terms of inertial pose estimation filtering. The underlying inherent rolling motion introduces high angular velocities and aggressive system dynamics around all principal axes. This motion profile also needs different modeling compared to state-of-the-art competitors, which heavily focus on more rotationally-restricted systems such as UAV, handheld, or cars. In this work we compare our previously proposed “Delta-filter”, which was heavily motivated by the sensors inability to provide covariance estimations, with a Kalman-filter design using a covariance model. Both filters fuse two 6-DoF pose estimators with a motion model in real-time, however the designs are theoretically suitable for an arbitrary number of estimators. We evaluate the trajectories against ground truth pose measurement from an OptiTrack™ motion capturing system. Furthermore, as our spherical systems are equipped with laser-scanners, we evaluate the resulting point clouds against ground truth maps available from a Riegl VZ400 terrestrial laser-scanner (TLS). Our source code and datasets can be found on github (Arzberger, 2023)
CNN-based pose estimation of a noncooperative spacecraft With symmetries from LiDAR point clouds
No full textLight detection and ranging (LiDAR) sensors provide accurate 3-D point clouds for noncooperative spacecraft pose estimation. Several robust methods, such as iterative closest point, exist to perform a local refinement of the pose starting from an initial estimate. However, finding the initial pose of the spacecraft is a global optimization problem, which is challenging to solve in real time. This is especially true on space hardware with limited computing power. In addition, many spacecrafts have a shape with multiple symmetries, making an unambiguous initial pose estimation impossible. This work introduces a convolutional-neural-network-based pose estimation method, accounting for potential symmetries of the target satellite. The point clouds are projected to a 2-D depth image before being processed by the network. To generate a sufficient amount of training data, a LiDAR simulator integrating multiple effects such as reflections or laser beam divergence is developed. While being trained solely on synthetic point clouds, the pose estimation method shows to be precise, efficient, and reliable when evaluated on real point clouds taken at a hardware-in-the-loop rendezvous test facility. A runtime evaluation on potential space computing hardware is also performed to demonstrate the applicability of the method to real-time onboard pose estimation
Advances in CD19-targeting CAR-T cell therapies for multiple myeloma
No full textIntroduction: Emerging evidence suggests that, while CD19 is primarily expressed on immature B-cell precursors, it is also present on drug-resistant plasma cells that have been postulated to function as multiple myeloma (MM) stem cells, driving the progression of relapsing disease. Targeting CD19 with chimeric antigen receptor (CAR) T cells offers a promising strategy for addressing this residual disease burden, potentially leading to more durable treatments and enhanced relapse prevention.
Areas covered: This review examines the molecular basis of CD19-targeted CAR-T therapy in MM, highlighting its potential, key challenges, and efficacy and safety in early clinical trials for relapsed/refractory and newly diagnosed MM.
Expert opinion: CD19 expression in MM correlates with poor prognosis and may be significantly underestimated, particularly following debulking therapy, as demonstrated by advanced visualization technologies like single molecule-sensitive direct stochastic optical reconstruction microscopy (dSTORM). Early-phase trials using CD19-directed CAR-T as post-transplant consolidation show promise in prolonging progression-free survival. Multi-target approaches, e.g. the bispecific BCMA×CD19 CAR-T product GC012F, are advancing through clinical development with encouraging safety and efficacy data. However, randomized controlled trials will be necessary to confirm the role and positioning of CD19-directed CAR-T cells within the current MM treatment landscape
Machtvolle Verwicklungen ent-wickeln: Prinzipien rassismuskritischer Organisationsentwicklung in Bildungseinrichtungen
No full textBildungseinrichtungen sind lernende Organisationen, die die Aufgabe haben, eigenen rassialisierenden Verwicklungen zu begegnen. Eine Adressierung dieser Verwicklungen kann mithilfe von Ent-wicklungsprozessen geschehen. Zur Implementierung organisationaler Ent-wicklungsprozesse werden aus rassismuskritischen Analyseperspektiven vier Prinzipien abgeleitet: (1) Wissensbestände ent-rassialisieren, (2) Positionsreflexivität üben, (3) Intersektionales Bewusstsein etablieren und (4) Postkommunitäre Solidarität leben. Die Prinzipien können als Orientierungsgrundsätze aufgegriffen werden, die es (non-)formalen Bildungseinrichtungen ermöglichen können, sich mit der eigenen Involviertheit in rassialisierenden Machtdynamiken auseinanderzusetzen und diesen reflexiv zu begegnen.Educational organisations are learning organisations with the responsibility of confronting their own racist entanglements. Dismantling these problems can be facilitated through development processes. Based on a racism-critical perspective, four key principles can be identified for the implementation of organisational development processes: (1) deconstructing knowledge resources, (2) cultivating a reflexive positionality, (3) establishing an intersectional consciousness and (4) fostering a post-communitarian solidarity. These principles serve as an orientation framework that enables educational organisations to critically engage with and reflexively address their own entanglement in racist power dynamics
Parental involvement in the inclusive transition to school: preschool teachers’ transition practices in a German context
No full textParental involvement (PI) in the transition from preschool to primary school is an important prerequisite for children with disabilities to start school successfully. Therefore, the present study looks at PI practices that are conducted to support successful inclusive transition processes in Germany. The focus is on practices that take place in the institutional context of early childhood facilities. The data base consists of qualitative guideline-based interviews with n = 22 preschool teachers. The data analysis comprises two steps: 1) a qualitative content analysis and 2) a systematic comparison of teachers and their transition practices according to specific teacher characteristics, such as professional experience. The results show that communication formats between teachers and parents regarding a child’s development or general issues such as the course of the last preschool year are most widely established to involve parents in the transition process. Some teachers also claim to inform parents about additional support for their child and involve parents in preschool or school visits. Moreover, findings indicate that parental involvement hardly differs systematically between teachers with different backgrounds (e.g., different levels of professional experience)
Micronuclei as genotoxicity endpoint applied in the co-culture of two mammalian cell lines
No full textThere has been a shift from traditional animal models towards alternative methods. While 2D cell culture has a decade long tradition, more advances methods like 3D cultures, organoids, and co-culture techniques, which better mimic in vivo conditions, are not yet well established in every research area. Genotoxicity assessment is an integral part of toxicological testing or regulatory approval of pharmaceuticals and chemicals. The micronucleus assay is now a standard method in this context. In this systematic literature review, we aim to describe the state of the art of the application of co-cultures of two mammalian cell lines for micronucleus assessment. We summarized the cell types used, methods for co-culture, disease models and agents, as well as the application of additional genotoxicity endpoints and viability tests. Airway system cells were the most frequent, followed by macrophage-like cells, liver cells, and various others. Co-culture techniques involve either direct physical contact or separation by porous membranes. Within a limited number of investigations using other genotoxicity assays like the comet and γH2AX assays in parallel, the micronucleus assay performed well. Overall, the micronucleus test demonstrating its suitability in disease models and for a more complex substance testing beyond simple 2D cultures, encouraging a more widespread use in co-culture systems in the future
Pain classification and characterization in Pakinson disease
No full textSchmerzen gehören zu den häufigsten und beeinträchtigendsten NMS des M. Parkinson. Die Datenlage zur Charakterisierung, Diagnostik sowie Therapie von Parkinson-assoziierten Schmerzen ist dabei spärlich und teilweise widersprüchlich. Ziel unserer Studie war es, Schmerzen bei Patienten mit M. Parkinson zunächst nach ihrem zugrundeliegenden Schmerztyp anhand für Patienten mit M. Parkinson validierter diagnostischer Kriterien zu klassifizieren und anschließend ausführlich zu charakterisieren. In dieser prospektiven Querschnittsstudie wurde eine Kohorte von n=168 Patienten mit M. Parkinson monozentrisch rekrutiert. Daten von 150 Patienten, die Fragebögen bezüglich der Parkinson-Erkrankung, Schmerzen sowie Depression ausfüllten, wurden analysiert. Schmerzen traten bei Patienten mit M. Parkinson häufig (117/150, 78%) auf, wovon wiederum die meisten Patienten (90/117, 77%) mit Parkinson-assoziierte Schmerzen klassifiziert werden konnten. In der Patientenkohorte waren Parkinson-assoziierte Schmerzen am häufigsten als nozizeptiv (67/90, 74%) einzuorden. Diese waren überwiegend in den unteren Extremitäten lokalisiert, wovon die Füße (51/90, 57%) am häufigsten betroffen waren. Parkinson-assoziierte Schmerzen manifestierten sich zudem überwiegend als Schmerzattacken (64/90, 71%), traten in einer mittleren bis starken Schmerzintensität (mediane Schmerzintensität von ≥5 NRS-Punkten) überwiegend in der Nacht (56/90, 62%) auf und wurden als „Krämpfe“ (32/90, 36%) oder als „Stechen“ (31/90, 34%) empfunden. Die Mehrheit der Patienten mit Parkinson-assoziierten Schmerzen, die eine Schmerzbeeinflussung durch externe Faktoren angaben, erfuhren durch körperliche Betätigung (26/53, 49%) einen schmerzlindernden Effekt. Medikamentös wurden weniger als die Hälfte der Patienten mit Analgetika behandelt (38/90, 42%). Hierbei waren die am häufigsten eingesetzten Analgetika NSAR (31/38, 82%), Opioide dagegen waren die wirksamsten Schmerzmittel (mediane Schmerzreduktion von 70%). In der hier vorliegenden Studie konnte gezeigt werden, dass sich Parkinson-assoziierte Schmerzen am häufigsten als nozizeptive, nächtliche Fußschmerzen manifestierten. Aufgrund der Häufigkeit und Schwere dieser Schmerzen empfiehlt es sich mithilfe einer detaillierten Schmerzanamnese sowie für Patienten mit M. Parkinson validierter Fragebögen, insbesondere des PD-PCS und KPDPS, nach diesen zu fahnden. Weitere Studien, die einen für den jeweils zugrundeliegenden Schmerztyp geeigneten Therapiealgorithmus empfehlen, sollten auf Basis der unter anderem hier vorliegenden Daten folgen.Pain in Parkinson´s disease is one of the most common and debilitating non motor symptoms. Despite its clinical relevance data on the characterization, classification, diagnosis and management of pain remain scarce and contradictory. The aim of this study was to first classify Parkinson´s disease related pain by applying validated criteria and then to comprehensively characterize Parkinson´s disease related pain. In this prospective cross-sectional study n=168 patients were recruited, data from 150 patients were analyzed. Pain was frequent (117/150, 78%) and often classified as pain related to Parkinson´s disease (90/117, 77%). Parkinson´s disease related pain was primarily nociceptive (67/90, 74%) and predominantly localized in the lower extremities, particularly in the feet (51/90, 57%). Pain presented as episodic pain (64/90, 71%), was mostly reported to have a moderate to severe intensity (median pain intensity ≥5 NRS points) and occured during the night time (56/90, 62%). The most commonly reported pain qualities were cramping (32/90, 36%) and stabbing sensations (31/90, 34%). Parkinson´s disease related pain was alleviated by physical activity (26/53, 49%). Despite the high burden of pain, less than half of the patients with Parkinson´s disease related pain recieved analgesic treatment (38/90, 42%). The most frequently prescribed analgesics were nonsteroidal anti-inflammatory drugs (31/38, 82%), whereas opioids were reported the most effective (median pain intensity reduction of 70%). These findings highlight that Parkinson´s disease related pain is frequent, nociceptive and primarily manifests as nocturnal podalgia. Given its high prevalence and severity pain should be assessed using a comprehensive pain history and validated pain questionaires (e.g. PD-PCS and KPDPS). Further research recommending analgesic management strategies tailored for the specific, underlying pain type is warranted
Influence of the HGF/c-MET signaling pathway on glucose metabolism and PD-L1 expression in HPV-positive and -negative head and neck carcinoma cells
No full textIm Rahmen dieser Arbeit wurde der Einfluss des HGF/c-Met-Signalweges auf die HPV-negativen HNSCC-Zelllinien Detroit 562, FaDu und SCC-9 sowie die HPV-positive HNSCC-Zelllinie SCC-154 untersucht. Die Rolle der HGF/c-Met-Achse als wichtiger Bestandteil der Tumorgenese, nicht nur von Kopf-Hals-Karzinomen, sondern einer Viel-zahl verschiedener Tumorentitäten wurde bereits über eine Vielzahl von Studien im Lau-fe der Jahre dokumentiert. Ziel dieser Arbeit war es der zunehmenden Bedeutung des HPV-Status von HNSCC Rechnung zu tragen und zu untersuchen wie sich dieser auf die Einflussnahme des HGF/c-Met-Signalweges auf die Tumorzellen auswirkt. Die Be-trachtung des Glukosemetabolismus und der Expression des Immuncheckpoint-Proteins PD-L1 sollte darüber hinaus Erkenntnisse über die Wechselwirkungen zwi-schen Tumorzellen und TME geben, die in den letzten Jahren zunehmend in den Fokus der Tumorforschung gerückt sind. Die Interaktion von PD-L1 auf der Oberfläche von Tumorzellen mit dem PD-1-Rezeptor tumorinfiltrierender T-Zellen spielt eine entschei-dende Rolle in der Immunevasion. Aufgrund dieses Mechanismus konnten sich in den letzten Jahren gegen PD-1 und PD-L1 gerichtete Immuntherapien als Standard bei Pati-enten mit erhöhter Expression etablieren. Die aerobe Glykolyse von Tumoren dient nicht nur der Deckung des erhöhten Energiebedarfs, sondern bildet über die Bereitstel-lung glykolytischer Intermediate und Endprodukte eine wichtige Schnittstelle zum TME und inhibiert zusätzlich die T-Zell-Funktion über die Azidifizierung des Tumorstromas. Mittels Durchflusszytometrie konnte gezeigt werden, dass die HGF-Stimulation sowohl in der HPV-negativen Zelllinie Detroit 562 als auch in der HPV-positiven Zelllinie SCC-154 eine verstärkte Expression von PD-L1 auf der Zelloberfläche der Tumorzellen be-wirkte. Durch den gegen den HGF-Rezeptor c-Met gerichteten TKI Foretinib konnte diese Expressionsinduktion aufgehoben werden. Die Messung des glykolytischen Pro-tonenausstroms demonstrierte eine verstärkte Glykolyseaktivität aller untersuchten Zelllinien infolge einer HGF-Stimulation. Wie auch bei der Untersuchung der PD-L1-Expression ließ sich dieser Effekt mithilfe einer c-Met-Inhibition aufheben. Eines der Schlüsselenzyme der aeroben Glykolyse ist die HK-II. Mittels Western Blot konnte für alle vier Zelllinien eine verstärkte Expression nach HGF-Stimulation sowie eine Inhibition des Effektes mit Foretinib nachgewiesen werden. In der Vergangenheit konnte in ver-schiedenen Studien eine Assoziation zwischen der Überexpression von HK-II und ei-nem verringerten Gesamtüberleben, einem verkürzten progressionsfreien Überleben, gehäufter Metastasierung und Therapieresistenz gezeigt werden. Ein weiteres glykolyt-isches Schlüsselenzym, PKM2 hingegen zeigte keine verstärkte Expression und Akti-vierung als Reaktion auf eine Stimulation mit HGF. Besonders interessant erscheint bei der Betrachtung der Ergebnisse die Tatsache, dass die HPV-negative Zelllinie Detroit 562 und die HPV-positive Zelllinie SCC-154 zumeist die ausgeprägtesten Reaktionen infolge der HGF-Stimulation zeigten. Im Falle von Detroit 562 könnte die nachgewiesene MET-Amplifikation mit verstärkter mRNA Expression sowie deren Ursprung aus Pleu-rametastasen eines Kopf-Hals-Karzinom ursächlich für die Ausprägung sein. Für Tu-moren in fortgeschrittenen Stadien und Metastasen konnten in multiplen Studien höhere c-Met-Expressionslevel belegt werden, sodass dies eine stärkere Reaktion auf eine HGF-Stimulation erklären könnte. Für SCC-154 ist ein Zusammenhang mit der Interak-tion viraler Onkoproteine, insbesondere mit dem Tumorsuppressor p53 und eine daraus resultierend Hochregulation HIF-1-vermittelter Prozesse möglich. Diese sind maßgeb-lich an der Regulation der aeroben Glykolyse beteiligt. Darüber hinaus wurde in der Vergangenheit auch eine direkte Hochregulation der PD-1/PD-L1-Achse sowie glykolyt-ischer Schlüsselenzyme durch virale Onkoproteine beschrieben. Insgesamt tragen die Erkenntnisse dieser Arbeit zum besseren Verständnis des HGF/c-Met-Signalweges und dessen Bedeutung in Kopf-Hals-Karzinomen, auch in Abhängigkeit des HPV-Status bei. Aufgrund der vielfältigen Verflechtungen bietet ein gezielter Eingriff in den HGF/c-Met-Signalweg ein erhebliches therapeutisches Potenzial, das es weiter und eingehen-der zu untersuchen gilt.In this study, the influence of the HGF/c-Met signaling pathway on the HPV-negative HNSCC cell lines Detroit 562, FaDu, and SCC-9, as well as the HPV-positive HNSCC cell line SCC-154, was investigated. The role of the HGF/c-Met axis as a key component of tumorigenesis—not only in head and neck cancers but across a wide variety of tumor entities—has been well documented in numerous studies over the years. The aim of this work was to address the growing importance of HPV status in HNSCC and to examine how it affects the impact of the HGF/c-Met signaling pathway on tumor cells.
By analyzing glucose metabolism and the expression of the immune checkpoint protein PD-L1, this study further sought to gain insight into the interactions between tumor cells and the tumor microenvironment (TME), which have increasingly come into the focus of cancer research in recent years. The interaction between PD-L1 on the surface of tumor cells and the PD-1 receptor of tumor-infiltrating T cells plays a critical role in immune evasion. Due to this mechanism, immunotherapies targeting PD-1 and PD-L1 have become standard treatments for patients with elevated expression levels in recent years.
Tumor aerobic glycolysis not only serves to meet the increased energy demand but also provides glycolytic intermediates and end products that form a crucial interface with the TME and inhibit T-cell function by acidifying the tumor stroma. Using flow cytometry, it was shown that HGF stimulation led to increased PD-L1 surface expression on tumor cells in both the HPV-negative Detroit 562 and the HPV-positive SCC-154 cell lines. This induction was reversed by the tyrosine kinase inhibitor (TKI) Foretinib, which targets the HGF receptor c-Met.
Measurements of glycolytic proton efflux demonstrated increased glycolytic activity in all tested cell lines following HGF stimulation. Similar to PD-L1 expression, this effect could be abrogated by c-Met inhibition. One of the key enzymes of aerobic glycolysis, hexokinase II (HK-II), showed increased expression in all four cell lines after HGF stimulation, which was again reversible by Foretinib, as demonstrated via Western blotting. Previous studies have shown that HK-II overexpression is associated with reduced overall survival, shortened progression-free survival, increased metastasis, and therapy resistance.
Another key glycolytic enzyme, pyruvate kinase M2 (PKM2), on the other hand, did not show increased expression or activation in response to HGF stimulation. Notably, the HPV-negative Detroit 562 and the HPV-positive SCC-154 cell lines displayed the most pronounced responses to HGF stimulation. For Detroit 562, this may be due to a documented MET amplification with elevated mRNA expression, as well as its origin from pleural metastases of a head and neck carcinoma. Elevated c-Met expression levels in advanced-stage tumors and metastases have been demonstrated in multiple studies, possibly explaining the stronger response to HGF.
In the case of SCC-154, a link to the interaction of viral oncoproteins—particularly with the tumor suppressor p53—and the resulting upregulation of HIF-1-mediated processes is conceivable. These processes are critically involved in regulating aerobic glycolysis. Additionally, a direct upregulation of the PD-1/PD-L1 axis and glycolytic key enzymes by viral oncoproteins has been previously reported.
Overall, the findings of this study contribute to a deeper understanding of the HGF/c-Met signaling pathway and its significance in head and neck squamous cell carcinomas, including in relation to HPV status. Given the complex interconnections involved, targeted intervention in the HGF/c-Met pathway offers considerable therapeutic potential that warrants further in-depth investigation