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Item Zeitschriftenaufsatz Open Access Approaching “the expert” in times of (digital) disruptions : towards a geography of expertise(2025) Brinks, Verena; Donner, FriedrichThe demand for “experts” and “expertise” has never been higher than in the present time, characterized by complexities, uncertainties and (digital) disruptions. At the same time, expertise has never been more contested and attacked, particularly due to social media. In this paper, we delve into the social-scientific literature on expert(ise) and argue for a strong differentiation between knowledge and expertise. We outline a geography of expertise, to be developed at the intersection of the three relational categories “authority,” “trust,” and “coalitions” and pay particular attention to digital media as the key driver for the re-configuration of expertise and expert roles.Item Zeitschriftenaufsatz Open Access Some remarks on spin-orbits of unit vectors(2024) Syed, TariqFor n ∈ N and a commutative ring R with 2 ∈ R×, the group SLn(R) acts on the set U mn(R) of unimodular vectors of length n and Spin2n(R) acts on the set of unit vectors U2n−1(R). We give an example of a ring for which the comparison map U mn(R)/SLn(R) → U2n−1(R)/Spin2n(R) fails to be bijective.Item Zeitschriftenaufsatz Open Access The SHADOWS calorimeter : a pointing calorimeter for future beam dump experiments(2024) Delogu, Claudia Caterina; Büscher, Volker; Degele, Reinhold; Geib, Karl; Ritter, Sebastian; Schönfelder, Steffen; Wanke, RainerThis contribution presents advancements in the design and testing of an electromagnetic calorimeter intended for the detection of feebly interacting particles in future beam dump experiments. The calorimeter is designed to accurately reconstruct particle decays into photons, focusing on achieving precise energy and direction measurements. We propose a plastic scintillator-based calorimeter capable of providing the necessary resolution for these measurements. The pointing capability has been validated through GEANT4 simulations, optimizing scintillator granularity for effective shower direction reconstruction. Additionally, we detail the prototyping efforts and the first results of test beam measurements conducted at DESY.Item Zeitschriftenaufsatz Open Access Intra-individual comparison of epicardial adipose tissue characteristics on coronary CT angiography between photon-counting detector and energy-integrating detector CT systems(2024) Kravchenko , Dmitrij; Vecsey-Nagy , Milan; Tremamunno, Giuseppe; Schoepf , U. Joseph; O’Doherty, Jim; Luetkens , Julian A.; Kuetting , Daniel; Isaak , Alexander; Hagar , Muhammad Taha; Emrich , Tilman; Varga-Szemes , AkosPurpose To explore the potential differences in epicardial adipose tissue (EAT) volume and attenuation measurements between photon-counting detector (PCD) and energy-integrating detector (EID)-CT systems. Methods Fifty patients (mean age 69 ± 8 years, 41 male [82 %]) were prospectively enrolled for a research coronary CT angiography (CCTA) on a PCD-CT within 30 days after clinical EID-based CCTA. EID-CT acquisitions were reconstructed using a Bv40 kernel at 0.6 mm slice thickness. The PCD-CT acquisition was reconstructed at a down-sampled resolution (0.6 mm, Bv40; [PCD-DS]) and at ultra-high resolutions (PCD-UHR) with a 0.2 mm slice thickness and Bv40, Bv48, and Bv64 kernels. EAT segmentation was performed semi-automatically at about 1 cm intervals and interpolated to cover the whole epicardium within a threshold of −190 to −30 HU. A subgroup analysis was performed based on quartile groups created from EID-CT data and PCD-UHRBv48 data. Differences were measured using repeated-measures ANOVA and the Friedman test. Correlations were tested using Pearson’s and Spearman’s rho, and agreement using Bland-Altman plots. Results EAT volumes significantly differed between some reconstructions (e.g. EID-CT: 138 ml [IQR 100, 188]; PCD-DS: 147 ml [110, 206]; P<0.001). Overall, correlations between PCD-UHR and EID-CT EAT volumes were excellent, e.g. PCD-UHRBv48: r: 0.976 (95 % CI: 0.958, 0.987); P<0.001; with good agreement (mean bias: −9.5 ml; limits of agreement [LoA]: −40.6, 21.6). On the other hand, correlations regarding EAT attenuation was moderate, e.g. PCD-UHRBV48: r: 0.655 (95 % CI: 0.461, 0.790); P<0.001; mean bias: 6.5 HU; LoA: −2.0, 15.0. Conclusion EAT attenuation and volume measurements demonstrated different absolute values between PCD-UHR, PCD-DS as well as EID-CT reconstructions, but showed similar tendencies on an intra-individual level. New protocols and threshold ranges need to be developed to allow comparison between PCD-CT and EID-CT data.Item Zeitschriftenaufsatz Open Access From GPUs to AI and quantum : three waves of acceleration in bioinformatics(2024) Schmidt, Bertil; Hildebrandt, AndreasThe enormous growth in the amount of data generated by the life sciences is continuously shifting the field from model-driven science towards data-driven science. The need for efficient processing has led to the adoption of massively parallel accelerators such as graphics processing units (GPUs). Consequently, the development of bioinformatics methods nowadays often heavily depends on the effective use of these powerful technologies. Furthermore, progress in computational techniques and architectures continues to be highly dynamic, involving novel deep neural network models and artificial intelligence (AI) accelerators, and potentially quantum processing units in the future. These are expected to be disruptive for the life sciences as a whole and for drug discovery in particular. Here, we identify three waves of acceleration and their applications in a bioinformatics context: (i) GPU computing, (ii) AI and (iii) next-generation quantum computers.Item Zeitschriftenaufsatz Open Access Diagnosis of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism : data from a practice-based longitudinal cohort(2024) Hobohm, Lukas; Paschke, Lena Marie; Farmakis, Ioannis T.; Barco, Stefano; Partovi, Sasan; Münzel, Thomas; Konstantinides, Stavros; Keller, Karsten; Below, MaikeBackground A large prospective multicenter cohort study with systematic follow-up recently reported a 2.3% 2-year cumulative incidence of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE). Objectives The present investigation aimed to determine the reported prevalence and incidence of CTEPH diagnosis after acute PE in real-world practice over a 12-year period. Methods This study was based on nationwide ambulatory billing claims and drug prescription data of all residents with public health insurance in Germany from 2010 to 2021. Results A total of 573 972 patients with acute PE (median age, 71 years; 57.4% women) were identified between 2010 and 2021. Prevalence of CTEPH among patients with history of PE increased during the period from 0.4% in 2010 to 0.9% in 2021. CTEPH was diagnosed in 2556 patients after acute PE, with most (17.6%) diagnoses reported within the first 3 months after the index PE event. The cumulative incidence rate after 3 months (first quarter) was calculated at 0.08% and after the first 2 years (eighth quarter) at 0.36%; it was 0.75% over the entire (90-month) follow-up period. Patients with CTEPH diagnosis during follow-up more often had right ventricular dysfunction at the index acute PE (14.9% vs 8.3%; P < .001). Conclusion The low CTEPH incidence rate after acute PE in the present analysis suggests low awareness of CTEPH. It further suggests a lack of systematic follow-up protocols for acute PE survivors in the real world. Improved implementation of existing recommendations on follow-up strategies after PE is warranted.Item Zeitschriftenaufsatz Open Access Self-similar co-ascent processes and Palm calculus(2024) Mönch , ChristianWe study certain renormalised first passage bridges of self-similar processes, generalising the “Brownian co-ascent process” discussed by Panzo (Sém. Prob. L, 2019) and introduced by Rosenbaum and Yor (Sém. Prob. XLVI, 2014). We provide a characterisation of co-ascent processes via Palm measures, namely that the co-ascent of a self-similar process is the process under the Palm distribution associated with its record measure. We use this representation to derive a distributional identity for -stable Lévy-subordinators with 𝛼 ∈ (0, 1).Item Zeitschriftenaufsatz Open Access Concurrent inflammation-related brain reorganization in multiple sclerosis and depression(2024) Galindo , Lara S. Molina; Gonzalez-Escamilla , Gabriel; Fleischer , Vinzenz; Grotegerd , Dominik; Meinert , Susanne; Ciolac , Dumitru; Person , Maren; Stein , Frederike; Brosch, Katharina; Nenadić, Igor; Alexander , Nina; Kircher , Tilo; Hahn, Tim; Winter, Yaroslav; Othman, Ahmed E.; Bittner, Stefan; Zipp, Frauke; Dannlowski , Udo; Groppa , SergiuBackground Neuroinflammation affects brain tissue integrity in multiple sclerosis (MS) and may have a role in major depressive disorder (MDD). Whether advanced magnetic resonance imaging characteristics of the gray-to-white matter border serve as proxy of neuroinflammatory activity in MDD and MS remain unknown. Methods We included 684 participants (132 MDD patients with recurrent depressive episodes (RDE), 70 MDD patients with a single depressive episode (SDE), 222 MS patients without depressive symptoms (nMS), 58 MS patients with depressive symptoms (dMS), and 202 healthy controls (HC)). 3 T-T1w MRI-derived gray-to-white matter contrast (GWc) was used to reconstruct and characterize connectivity alterations of GWc-covariance networks by means of modularity, clustering coefficient, and degree. A cross-validated support vector machine was used to test the ability of GWc to stratify groups according to their depression symptoms, measured with BDI, at the single-subject level in MS and MDD independently. Findings MS and MDD patients showed increased modularity (ANOVA partial-η2 = 0.3) and clustering (partial-η2 = 0.1) compared to HC. In the subgroups, a linear trend analysis attested a gradient of modularity increases in the form: HC, dMS, nMS, SDE, and RDE (ANOVA partial-η2 = 0.28, p < 0.001) while this trend was less evident for clustering coefficient. Reduced morphological integrity (GWc) was seen in patients with increased depressive symptoms (partial-η2 = 0.42, P < 0.001) and was associated with depression scores across patient groups (r = -0.2, P < 0.001). Depressive symptoms in MS were robustly classified (88 %). Conclusions Similar structural network alterations in MDD and MS exist, suggesting possible common inflammatory events like demyelination, neuroinflammation that are caught by GWc analyses. These alterations may vary depending on the severity of symptoms and in the case of MS may elucidate the occurrence of comorbid depression.Item Zeitschriftenaufsatz Open Access Application of RCS and signal-free RCS to tree-ring width and maximum latewood density data(2024) Homfeld, Inga K.; Büntgen, Ulf; Reinig, Frederick; Torbenson, Max Carl Arne; Esper, JanDendroclimatic research faces the challenge of selecting appropriate detrending methods for retaining low-frequency signals in temperature reconstructions. Among the numerous methods available to dendrochronologists, regional curve standardisation (RCS) and the signal-free approach in combination with RCS (SF-RCS) are increasingly used to preserve the full spectrum of temperature variance in tree-ring data. Here, we apply RCS and SF-RCS to tree-ring width (TRW) and maximum latewood density (MXD) datasets composed of only living and combined living and relict trees from northern Scandinavia. Whereas RCS and SF-RCS produce highly similar chronologies when applied to composite (living-plus-relict) datasets, particularly for MXD, both methods fail to establish chronologies coherent with regional temperature trends when applied to living-tree datasets. Additional tests including pruning of well-replicated living-tree datasets, to approximate the heterogenous age-structure of composite datasets, reveal improved results and coherent trends in MXD. While this demonstrates the applicability of joint detrending and pruning techniques to retain meaningful low-frequency variance in living-tree MXD chronologies, similar improvements were not achieved with TRW, likely because of the much stronger age-trend inherent to this widely used proxy. Further tests with other tree species and in alpine environments are needed to verify these findings. However, such assessments require an adjustment of tree-ring sampling protocols to increase replication to 50+ trees per site including old and young individuals to facilitate data pruning.Item Zeitschriftenaufsatz Open Access Dynamic interplay of cortisol and BDNF in males under acute and chronic psychosocial stress : a randomized controlled study(2024) Herhaus, Benedict; Heini, Martin; Bloch, Wilhelm; Petrowski, KatjaThe neurotrophic protein brain-derived neurotrophic factor (BDNF) plays a pivotal role in brain function and is affected by acute and chronic stress. We here investigate the patterns of BDNF and cortisol stress reactivity and recovery under the standardized stress protocol of the TSST and the effect of perceived chronic stress on the basal BDNF levels in healthy young men. Twenty-nine lean young men underwent the Trier Social Stress Test (TSST) and a resting condition. Serum BDNF and cortisol were measured before and repeatedly after both conditions. The perception of chronic stress was assessed by the Trier Inventory for Chronic Stress (TICS). After the TSST, there was a significant increase over time for BDNF and cortisol. Stronger increase in cortisol in response to stress was linked to an accelerated BDNF decline after stress. Basal resting levels of BDNF was significantly predicted by chronic stress perception. The increased BDNF level following psychosocial stress suggest a stress-induced neuroprotective mechanism. The presumed interplay between BDNF and the HPA-axis indicates an antagonistic relationship of cortisol on BDNF recovery post-stress. Chronically elevated high cortisol levels, as present in chronic stress, could thereby contribute to reduced neurogenesis, and an increased risk of neurodegenerative conditions in persons suffering from chronic stress.Item Zeitschriftenaufsatz Open Access An undergraduate classroom experiment illustrates an effect of observer bias on data collection in animal behaviour(2024) Keaney, Thomas A.; Jones, Theresa Melanie; Mulder, Raoul A. MulderBehavioural ecologists frequently collect data that involve the potential for subjective judgement, so it is important that researchers in the field develop awareness of potential issues around bias in data collection. We report the results of an undergraduate classroom experiment in which we estimated the potential for students' a priori expectations to bias their estimates of behaviour. Prior to conducting a set of behavioural observations on a video-recorded flock of foraging pigeons, we randomly primed half of the students to expect the pigeons to be hungry, while the other half were primed to expect the pigeons to be satiated. Students were blind to the treatment and subsequently estimated two variables expected to differ in their potential for subjectivity: the proportion of birds in the flock that were feeding (potentially subjective), and the feeding (peck) rates of two focal individuals (potentially objective). Surprisingly, we found no evidence that observer bias affected the estimate of the percentage of birds foraging. By contrast, we found a large effect of observer bias on feeding rate estimates, with students who expected a hungry state recording inflated feeding rate estimates relative to those that expected a satiated state. We furthermore found that students' expectations of foraging state did not always match their allocated primers: bias was predicted by ‘expected state’ but not by ‘allocated state’. Our experiment illustrates that bias associated with expectation can influence results. Furthermore, a variable we initially expected to be relatively objective proved to have a strong subjective element, inflating the effect of confirmation bias on estimation. We recommend blind data recording even when response variables are thought to be objective, as well as explicit teaching of university students about the potential for bias in data collection, and our experiment suggests a potentially useful way in which this can be undertaken.Item Zeitschriftenaufsatz Open Access Evolving patterns of intracranial hemorrhage in advanced therapies in patients with acute pulmonary embolism(2024) Christodoulou, Konstantinos C.; Mohr, Katharina; Uphaus, Timo; Jägersberg, Max; Valerio, Luca; Farmakis, Ioannis T.; Münzel, Thomas; Lurz, Philipp; Konstantinides, Stavros V.; Hobohm, Lukas; Keller, KarstenBackground Dissecting trends and contributing risk factors for intracranial hemorrhage (ICH) in patients treated for acute pulmonary embolism (PE) may allow for a better patient selection for existing and emerging treatment options. Methods The German nationwide inpatient sample was screened for patients admitted due to PE 2005–2020. Hospitalizations were stratified for the occurrence of ICH; risk factors for ICH and temporal trends were investigated. Results Overall, 816,653 hospitalizations due to acute PE in the period 2005–2020 were analyzed in the study. ICH was reported in 2516 (0.3 %) hospitalizations, and time trend analysis revealed a fluctuating but overall, largely unchanged annual incidence. There was an increase of ICH with age. Patients with ICH had a higher comorbidity burden (Charlson-Comorbidity-Index [CCI], 5.0 [4.0–7.0] vs. 4.0 [2.0–5.0]; P < 0.001), and higher CCI was associated with an OR of 1.26 (95%CI 1.24–1.27) for ICH. Further independent risk factors for ICH were age ≥ 70 years (OR 1.23 [1.12–1.34]), severe (versus low-risk) PE (OR 3.09 [2.84–3.35]), surgery (OR 1.59 [1.47–1.72]), acute kidney injury (OR 3.60 [3.09–4.18]), and ischemic stroke (OR 14.64 [12.61–17.00]). The identified risk factors for ICH varied among different reperfusion treatment groups. As expected, ICH had a substantial impact on case-fatality of PE (OR 6.16 [5.64–6.72]; P < 0.001). Conclusions Incidence of ICH in patients hospitalized for acute PE in Germany was overall low and depended on the patients' comorbidity burden. Identifying patients at risk for ICH allows tailored patient selection for the different reperfusion treatments and might prevent ICH.Item Zeitschriftenaufsatz Open Access The cytotoxic activities of the major diterpene extracted from Salvia multicaulis (Bardakosh) are mediated by the regulation of heat-shock response and fatty acid metabolism pathways in human leukemia cells(2024) Nabih, Heba K.; Yücer, Rümeysa; Mahmoud, Nuha; Dawood, Mona; Elbadawi, Mohamed; Shahhamzehei, Nasim; Atia, Mohamed A.M.; AbdelSadik, Ahmed; Hussien, Taha A.; Ibrahim, Mahmoud A.A.; Klauck, Sabine M.; Hegazy, Mohamed-Elamir R.; Efferth, ThomasBackground Leukemia is one of the most lethal cancers worldwide and represents the sixth-leading cause of cancer deaths. The results of leukemia treatment have not been as positive as desired, and recurrence is common. Purpose Thus, there is an urgent requirement for the development of new therapeutic drugs. Salvia multicaulis (Bardakosh) is a widespread species that contains multiple phytochemical components with anti-cancer activities. Methods We isolated and characterized the major diterpene candesalvone B methyl ester from S. multicaulis and investigated its action as a cytotoxic agent towards sensitive and drug-resistant leukemia cells by the resazurin reduction assay. Additionally, the targeted genes and the affected molecular mechanisms attributed to the potent cytotoxic activities were discovered by transcriptome-wide mRNA expression profiling. The targets predicted to be regulated by candesalvone B methyl ester in each cell line were confirmed by qRT-PCR, molecular docking, microscale thermophoresis, and western blotting. Moreover, cell cycle distribution and apoptosis were analyzed by flow cytometry. Results Candesalvone B methyl ester was cytotoxic with IC50 values of 20.95 ± 0.15 µM against CCRF-CEM cells and 4.13 ± 0.10 µM against multidrug-resistant CEM/ADR5000 leukemia cells. The pathway enrichment analysis disclosed that candesalvone B methyl ester could regulate the heat-shock response signaling pathway via targeting heat shock factor 1 (HSF1) in CCRF-CEM cells and ELOVL fatty acid elongase 5 (ELOVL5) controls the fatty acid metabolism pathway in CEM/ADR5000 cells. Microscale thermophoresis showed the binding of candesalvone B methyl ester with HSF1 and ELOVL5, confirming the results of molecular docking analysis. Down-regulation of both HSF1 and ELOVL5 by candesalvone B methyl ester as detected by both western blotting and RT-qPCR was related to the reversal of drug resistance in the leukemia cells. Furthermore, candesalvone B methyl ester increased the arrest in the sub-G1 phase of the cell cycle in a dose-dependent manner from 1.3 % to 32.3 % with concomitant induction of apoptosis up to 29.0 % in CCRF-CEM leukemic cells upon inhibition of HSF1. Conclusion Candesalvone B methyl ester isolated from S. multicaulis exerted cytotoxicity by affecting apoptosis, cell division, and modulation of expression levels of genes contributing to the heat stress signaling and fatty acid metabolism pathways that could relieve drug resistance of leukemia cells.Item Zeitschriftenaufsatz Open Access Careerism and working-class decline : the role of party selectorates in explaining trends in descriptive (mis-)representation(2024) Elsässer , LeaRecent decades have seen a growing underrepresentation of working-class legislators and the parallel rise of professionalized “career politicians”, especially in centre-left parties. While this changing class composition of parliaments has implications for representational inequality, we know little about its reasons. I focus on the candidate nomination processes in the German Social Democratic Party to understand the priorities and practices of party selectors. Drawing on interview data with key actors in the nomination processes for the 2021 federal election, I show that the representation of marginalized groups becomes more important, but class representation is excluded from party debates. Although many selectors share the view that the candidates’ narrowing class backgrounds impede the representation of lower-class constituents, they see the reasons for this development mainly in individual obstacles beyond their control. Thus, while the nomination procedures disadvantage working-class people, they do so in a more complex way than previous studies suggest.Item Zeitschriftenaufsatz Open Access Potential vs challenges of expanding the protein universe with genetic code expansion in eukaryotic cells(2024) Bhattacharjee, Rajanya; Lemke, Edward A.Following decades of innovation and perfecting, genetic code expansion has become a powerful tool for in vivo protein modification. Some of the major hurdles that had to be overcome include suboptimal performance of GCE-specific translational components in host systems, competing cellular processes, unspecific modification of the host proteome and limited availability of codons for reassignment. Although strategies have been developed to overcome these challenges, there is critical need for further advances. Here we discuss the current state-of-the-art in genetic code expansion technology and the issues that still need to be addressed to unleash the full potential of this method in eukaryotic cells.Item Zeitschriftenaufsatz Open Access Current goals of NSAID-ERD management : patient-centered approaches involving NSAID desensitization with and without biologics(2024) Bobolea, Irina; Hagermann, Jan; Sanak, Marek; Klimek, Ludger; Mullol, JoaquimThe classic approach of nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NSAID-ERD) includes pharmaceutical and surgical treatments, as well as avoidance of cyclooxygenase 1–inhibitor NSAIDs. The introduction of biologics in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps represents an alternative therapeutic approach to the classical aspirin therapy after desensitization (ATAD) in some regions, and with convincing results. However, their use is limited due to approval and/or high-cost restrictions. NSAID-ERD is a mainly type 2 and highly eosinophilic disease, and mAbs targeting IgE or IL-5, IL-4, and IL-13 have been shown to be effective for both severe asthma and severe chronic rhinosinusitis with nasal polyps. So far, dupilumab demonstrated greater efficacy in patients with NSAID-ERD than in aspirin-tolerant patients with regard to several clinical outcomes. Patients with NSAID-ERD respond very rapidly to omalizumab also, with reduction in the release of prostaglandin D2 and cysteinyl leukotrienes. Patients favored biologic treatment over ATAD in multiple retrospective analyses, which must be acknowledged when choosing one or the other option. Although this review will summarize ATAD in general, it will more prominently focus on when ATAD should be considered, even when type 2 biologics are available. In addition, there are conflicting studies as to whether patients on a type 2 biologic become desensitized to NSAIDs, because omalizumab proved to restore tolerance to aspirin in only two-third of patients. This goal of NSAID tolerance should be considered as part of disease control future approaches, representing one of many aspects in a patient-centered care approach.Item Zeitschriftenaufsatz Open Access Redox mechanisms in autoimmune thyroid eye disease(2024) Buonfiglio, Francesco; Ponto, Katharina A.; Pfeiffer, Norbert; Kahaly, George Jean; Gericke, AdrianThyroid eye disease (TED) is an autoimmune condition affecting the orbit and the eye with its adnexa, often occurring as an extrathyroidal complication of Graves' disease (GD). Orbital inflammatory infiltration and the stimulation of orbital fibroblasts, triggering de novo adipogenesis, an overproduction of hyaluronan, myofibroblast differentiation, and eventual tissue fibrosis are hallmarks of the disease. Notably, several redox signaling pathways have been shown to intensify inflammation and to promote adipogenesis, myofibroblast differentiation, and fibrogenesis by upregulating potent cytokines, such as interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β. While existing treatment options can manage symptoms and potentially halt disease progression, they come with drawbacks such as relapses, side effects, and chronic adverse effects on the optic nerve. Currently, several studies shed light on the pathogenetic contributions of emerging factors within immunological cascades and chronic oxidative stress. This review article provides an overview on the latest advancements in understanding the pathophysiology of TED, with a special focus of the interplay between oxidative stress, immunological mechanisms and environmental factors. Furthermore, cutting-edge therapeutic approaches targeting redox mechanisms will be presented and discussed.Item Zeitschriftenaufsatz Open Access On the robustness of hig-order upwind summation-by-parts methods for nonlinear conservation laws(2024) Ranocha, Hendrik; Winters, Andrew R.; Schlottke-Lakemper, Michael; Öffner, Philipp; Glaubitz, Jan; Gassner, GregorWe use the framework of upwind summation-by-parts (SBP) operators developed by Mattsson (2017, doi:10.1016/j.jcp.2017.01.042) and study different flux vector splittings in this context. To do so, we introduce discontinuous-Galerkin-like interface terms for multi-block upwind SBP methods applied to nonlinear conservation laws. We investigate the behavior of the upwind SBP methods for flux vector splittings of varying complexity on Cartesian as well as unstructured curvilinear multi-block meshes. Moreover, we analyze the local linear/energy stability of these methods following Gassner, Svärd, and Hindenlang (2022, doi:10.1007/s10915-021-01720-8). Finally, we investigate the robustness of upwind SBP methods for challenging examples of shock-free flows of the compressible Euler equations such as a Kelvin-Helmholtz instability and the inviscid Taylor-Green vortex.Item Zeitschriftenaufsatz Open Access The eight-legged confidant : narrativizing octopuses and non-human aging(2024) Gehrmann, RuthThis article follows an increased interest in the octopus in both popular science and fiction. Octopuses have long held fascination and are commonly tied to processes of aging: Even though their life expectancy tends to be lower than that of humans, they are often framed as “old”, not only by appearing as mythical creatures from an unknown past but also by appearing wise and intelligent. Whereas the octopus has been framed as Other, prominently by inspiring the aesthetics of alien life forms, recent examples have underlined the possibility of inter-species contact and communication. This article traces these moments of contact and investigates the role of aging in such fictional encounters. By focusing on two recent examples, Shelby Van Pelt's Remarkably Bright Creatures (2022) and Gina Chung's Sea Change (2023), it illustrates the ways that contemporary fiction narratively links the octopus to older age and discusses forms of non-human aging.Item Zeitschriftenaufsatz Open Access Enhancing cisplatin drug sensitivity through PARP3 inhibition : the influence on PDGF and G-coupled signal pathways in cancer(2024) Varol , Ayşegül; Klauck, Sabine M.; Dantzer , Françoise; Efferth, ThomasDrug resistance poses a significant challenge in cancer treatment despite the clinical efficacy of cisplatin. Identifying and targeting biomarkers open new ways to improve therapeutic outcomes. In this study, comprehensive bioinformatic analyses were employed, including a comparative analysis of multiple datasets, to evaluate overall survival and mutation hotspots in 27 base excision repair (BER) genes of more than 7,500 tumors across 23 cancer types. By using various parameters influencing patient survival, revealing that the overexpression of 15 distinct BER genes, particularly PARP3, NEIL3, and TDG, consistently correlated with poorer survival across multiple factors such as race, gender, and metastasis. Single nucleotide polymorphism (SNP) analyses within protein-coding regions highlighted the potential deleterious effects of mutations on protein structure and function. The investigation of mutation hotspots in BER proteins identified PARP3 due to its high mutation frequency. Moving from bioinformatics to wet lab experiments, cytotoxic experiments demonstrated that the absence of PARP3 by CRISPR/Cas9-mediated knockdown in MDA-MB-231 breast cancer cells increased drug activity towards cisplatin, carboplatin, and doxorubicin. Pathway analyses indicated the impact of PARP3 absence on the platelet-derived growth factor (PDGF) and G-coupled signal pathways on cisplatin exposure. PDGF, a critical regulator of various cellular functions, was downregulated in the absence of PARP3, suggesting a role in cancer progression. Moreover, the influence of PARP3 knockdown on G protein-coupled receptors (GPCRs) affects their function in the presence of cisplatin. In conclusion, the study demonstrated a synthetic lethal interaction between GPCRs, PDGF signaling pathways, and PARP3 gene silencing. PARP3 emerged as a promising target.