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Simulation of S Tracer Diffusion Processes at the Ag(100) and Au(100) Surfaces in the Presence of Br Coadsorbates Based on DFT
Get PDFSurface diffusion governs adsorbate self-assembly, catalysis, and metal deposition. Experiments using electrochemical video-STM have shown that S tracer diffusion in halide adlayers on coinage metals displays potential-dependent activation energies, attributed to the interaction of the adsorbates' dipole moments with the double layer field. Unexpectedly, in the disordered Br phase on Ag(100), S adatom hopping accelerates with increasing potential and Br coverage. This work investigates S/Br/Ag(100) in vacuum using periodic density functional theory (DFT) simulations. Br–Br and S–Br interactions are dominated by dipole–dipole forces, with additional elastic and oscillatory contributions. A simple polarizability model reproduces adatom depolarization. Monte Carlo simulations based on DFT interactions reproduce the experimentally observed rise in S nearest-neighbor hopping only partially; many-body effects increase the rate, yet it still falls far short of experimental values. A complementary S–Ag vacancy ingress–egress mechanism is proposed to account for longer jumps. For the ordered c(2×2)-Br phase on Ag(100), DFT suggests Ag-vacancy-assisted subsurface S diffusion paths, but estimated subsurface occupation probabilities are too low to match experiment. A related study of S in the c(√2×2√2)R45° Br adlayer on Au(100) finds strong binding between S and adlayer vacancies, yet a Br-vacancy-mediated diffusion path is identified whose energy barrier remains too low to explain observed mobility. Overall, discrepancies between theory and experiment indicate that realistic modeling must include electrolyte effects absent from vacuum DFT
How Are Taxes Moving Stock Markets and Social Media?: Essays on Reactions to Major Tax Reforms and Corporate Tax Avoidance
No full textThis cumulative dissertation consists of three separate essays contributing to the literature on major tax reforms and corporate tax avoidance. The focus lies on the analysis of stock market and social media reactions. The first essay provides a comprehensive literature review on the growing strand of tax-related event studies that examine investor responses to corporate tax avoidance and major tax reforms. Overall, the review emphasizes the value relevance of corporate taxes as it shows that stock market investors incorporate tax-related information into stock prices. Moreover, it illustrates that investors evaluate costs and benefits of tax events in a highly differentiated manner. In addition to structuring and summarizing the tax event studies, the review also discusses methodological issues and trends. The second essay is an event study that examines the stock market reaction to a tax reform announcement in the United Kingdom during the COVID-19 pandemic. The results show that governments face tradeoffs in stabilizing the economy in the recovery phase of a crisis. While struggling firms benefit from assured government support, innovative and diversified firms suffer from an announced tax hike, which jeopardizes future growth. However, the situation changes when excessive public debt lead to macro-financial risk. In this case, restoring fiscal stability becomes most important for investors. The third essay uses a major tax avoidance scandal, namely the LuxLeaks, to analyze how corporate tax avoidance is perceived on social media. The results are ambiguous and no strong social media (and news media) reaction regarding companies involved in the scandal is found. Therefore, the LuxLeaks scandal does not seem to cause social media (and news media) tension for LuxLeaks companies. This finding is somewhat surprising, but it confirms results of previous literature, according to which reputational costs of corporate tax avoidance are rather low
Fecal lipid markers in tandem with ancient sedimentary DNA as a tool for tracing past livestock farming from soils and sediments
Get PDFReconstructing past environments can be challenging when archaeological materials are missing. The study of organic molecules, which remain as traces in the environment over millennia, represents one way to overcome this drawback. Fecal lipid markers (steroids and bile acids) and ancient sedimentary DNA offer a complementary and cross-validating analytical tool to broaden the range of methods used in environmental archaeology. However, little is known about the benefits of combining these two approaches. We present a brief overview of the current state of knowledge on fecal lipid markers and ancient sedimentary DNA. We identify scientific and methodological gaps and suggest their potential relevance for a better understanding of dynamic, human-animal relationships of the past. With this review, we aim to facilitate new research avenues, both in established disciplines and in conjunction with analytical approaches that have rarely been combined to date
Performance Responses and Fillet Quality of Rainbow Trout (Oncorhynchus mykiss) to Increasing Addition Levels of Dietary Supplementation of Guanidinoacetic Acid
Get PDFGuanidinoacetic acid (GAA) plays an important role in cellular energy use and protein synthesis. The objectives of this study were to determine the optimal level of dietary GAA regarding the growth performance and fillet characteristics of rainbow trout (Oncorhynchus mykiss). A total of 300 trout (initial weight, 66.84 ± 7.82 g) were fed isonitrogenous (34%) and isocaloric (20.6 MJ kg-1) diets with increasing levels of GAA (0.00, 0.06, 0.12, 0.18%) for 90 days. The results showed that trout fed GAA (either 0.06, 0.12, or 0.18%) yielded better (p 0.05) were observed for BW, BWG, nor FCR among trout fed GAA. Nonetheless, trout fed a diet with a 0.12% GAA inclusion had the highest (p 0.05) for cook loss, shear force, nor colour. Trout fed 0.06% GAA inclusion tended (p = 0.08) to have a higher WHC. Moreover, trout fed 0.12 and 0.18% GAA had lower (p < 0.05) pH values than trout fed the control diet and 0.06% GAA. Our findings give insights for the growth promotion and fillet quality of trout fed diets supplemented with GAA, especially at the level of 0.12%
Direct and indirect effects of degree of interdisciplinarity on firms' innovation performance: The moderating role of firms' capabilities
Get PDFCombinations of heterogeneous knowledge from different scientific domains may drive highly innovative outcomes. Our study investigates whether firms can benefit from interdisciplinary research and development (R&D) activities by also reflecting on the potential negative consequences of increasing complexity of outcome validation activities at later stages of innovation processes. We explore which resources and organizational capabilities may influence the efficacy of interdisciplinary R&D activities. We examine whether the available financial slack, collaborations with universities, and a high betweenness centrality in scientific networks may promote the flexibility, scope, and efficiency of knowledge integration, and thus moderate the direct and mediated relationships between the degree of interdisciplinarity (DoI) of a firm's R&D activities and innovation performance. To test our hypotheses, we performed an analysis of medical technology firms that are highly dependent on interdisciplinary R&D. We collected a panel dataset of R&D activities and successful market launches of new products from 79 large medical technology firms between 1997 and 2021. The measurement of a firm's DoI is based on a novel approach involving neural networks in a bibliographic data graph. Our results suggest that firms can improve their innovation performance if they conduct interdisciplinary R&D activities. However, higher levels of DoI also increase the complexity of the required outcome validation, which reduces a firm's innovation performance. We also found that high levels of financial slack help to overcome barriers of implementing interdisciplinary R&D activities. Collaborations with universities, and good access to knowledge in scientific networks, further foster interdisciplinary knowledge application in new product development
Anti-TNF therapy impairs both short- and long-term IgG responses after repeated vaccination
Get PDFBackground Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti-tumor necrosis factor (TNF) treatment leads to impaired vaccine-induced immune responses and protection against breakthrough infections. However, the effects of TNF blockade on short- and long-term immune responses after repeated vaccination remain unclear. Vaccination studies have shown that initial short-term IgG antibodies (Abs) carry highly galactosylated and sialylated Fc glycans, whilst long-term IgG Abs have low levels of galactosylation and sialylation and are most likely generated by long-lived plasma cells (PCs) derived primarily from the germinal center (GC) response. Thus, IgG Fc glycosylation patterns may be applicable to distinguish short- and long-term vaccine responses after repeated vaccination under the influence of anti-TNF treatment. Methods We used COVID-19 vaccination as a model to investigate vaccine-induced IgG subclass levels and Fc glycosylation patterns, B cell subsets, and effector functions of short- and long-term Ab responses after up to three vaccinations in patients on anti-TNF or other immunosuppressive treatments and in healthy individuals. Using TriNetX, a global healthcare database, we determined the risk of SARS-CoV-2 breakthrough infections in vaccinated patients treated with anti-TNF or other immunosuppressive drugs. Results Anti-TNF treatment reduced the long-term abundance of all anti-S IgG subclasses with low levels of galactosylation and sialylation. Re-activation of potential memory B cells initially [...] Conclusions The data suggest that anti-TNF treatment reduces both GC-dependent long-lived PCs and GC-dependent memory B cell-derived short-lived PCs, hence both the long- and short-term IgG subclass responses, respectively, after repeated vaccination. We propose that anti-TNF therapy, especially in the elderly, reduces the benefit of booster vaccination
Ermittlung der Akzeptanz und Praktikabilität von metallfreien Hilfsmitteln zur Zahnzwischenraumreinigung durch Befragung von zahnmedizinischem Fachpersonal
Get PDFDie Motivation und Anleitung zur häuslichen Mundhygiene durch zahnmedizinisches Fachpersonal ist ein zentraler Bestandteil der Prophylaxe. Studien zeigten, dass gummierte Interdentalraumpicks (IRP) von Patientinnen und Patienten besser akzeptiert werden als klassische Interdentalbürsten (IRB). Eine Umfrage unter zahnmedizinischem Fachpersonal (2018 & 2021) untersuchte (1) das Empfehlungsverhalten und (2) die Einschätzung der Benutzerfreundlichkeit von IRPs. Befragt wurden Teilnehmer/-innen an drei Fortbildungsstandorten, die sechs metallfreie Hilfsmittel testeten (fingerförmige und noppenförmige IRPs, Zahnholz). Die Ergebnisse zeigten: Nur 32 % der Befragten mit Fortbildung und 47 % ohne berücksichtigten Patientenwünsche bei Empfehlungen. 77 % (2021: 73 %) nannten persönliche Erfahrungen als Hauptgrundlage. Obwohl die Mehrheit (70–80 %) Zahnseide bevorzugte, wurden IRBs in 90–100 % der Fälle empfohlen – IRPs von 25 %. Finger- und noppenförmige IRPs wurden im Vergleich zu Zahnhölzern als deutlich benutzerfreundlicher bewertet (p<0,001). Entscheidender Faktor war die einfache Handhabung (Odds Ratio 22,7; p<0,001). Empfehlungen basierten häufig auf eigenen Erfahrungen, während wissenschaftliche Erkenntnisse oder individuelle Patientenfaktoren oft vernachlässigt wurden. Fazit: Auch zahnmedizinische Fachangestellte ohne zertifizierte Fortbildung können nach Anleitung erfolgreich zur Interdentalpflege instruieren – ein Beitrag zur Verbesserung der Versorgung und zur Stärkung des Berufsbilds
Workflow for E3 Ligase Ligand Validation for PROTAC Development
Get PDFProteolysis targeting chimeras (PROTACs) have gained considerable attention as a new modality in drug discovery. The development of PROTACs has been mainly focused on using CRBN (Cereblon) and VHL (Von Hippel-Lindau ligase) E3 ligase ligands. However, the considerable size of the human E3 ligase family, newly developed E3 ligase ligands, and the favorable druggability of some E3 ligase families hold the promise that novel degraders with unique pharmacological properties will be designed in the future using this large E3 ligase space. Here, we developed a workflow aiming to improve and streamline the evaluation of E3 ligase ligand efficiency for PROTAC development and the assessment of the corresponding "degradable" target space using broad-spectrum kinase inhibitors and the well-established VHL ligand VH032 as a validation system. Our study revealed VH032 linker attachment points that are highly efficient for kinase degradation as well as some of the pitfalls when using protein degradation as a readout. For instance, cytotoxicity was identified as a major mechanism leading to PROTAC- and VHL-independent kinase degradation. The combination of E3 ligase ligand negative controls, competition by kinase parent compounds, and neddylation and proteasome inhibitors was essential to distinguish between VHL-dependent and -independent kinase degradation events. We share here the findings and limitations of our study and hope that this study will provide guidance for future evaluations of new E3 ligase ligand systems for degrader development
High-throughput numerical modeling of the tunable synaptic behavior in 2D MoS2 memristive devices
Get PDFMemristive devices based on two-dimensional (2D) materials have emerged as potential synaptic candidates for next-generation neuromorphic computing hardware. Here, we introduce a numerical modeling framework that facilitates efficient exploration of the large parameter space for 2D memristive synaptic devices. High-throughput charge-transport simulations are performed to investigate the voltage pulse characteristics for lateral 2D memristors and synaptic device metrics are studied for different weight-update schemes. We show that the same switching mechanism can lead to fundamentally different pulse characteristics influencing not only the device metrics but also the weight-update direction. A thorough analysis of the parameter space allows simultaneous optimization of the linearity, symmetry, and drift in the synaptic behavior that are related through tradeoffs. The presented modeling framework can serve as a tool for designing 2D memristive devices in practical neuromorphic circuits by providing guidelines for materials properties, device functionality, and system performance for target applications
Dual Topoisomerase Inhibitor Is Highly Potent and Improves Antitumor Response to Radiotherapy in Cervical Carcinoma
Get PDFDespite advances in vaccination and early detection, the total number of cases and deaths from cervical cancer has risen steadily in recent decades, making it the fourth most common type of cancer in women worldwide. Low-income countries in particular struggle with limited resources and treatment limitations for cervical cancer. Thus, effective medicines that are simple to manufacture are needed. The newly developed dual topoisomerase inhibitor P8-D6, with its outstanding ability to induce apoptosis, could be a promising option. In this study, the efficacy of P8-D6 in combination with radiochemotherapy against cervical carcinoma was investigated in established cell lines and in a translational approach in ex vivo patient cells by measuring the cytotoxicity, cell viability and caspase activity in vitro in 2D and 3D cell cultures. Treatment with P8-D6 resulted in significantly greater cytotoxicity and apoptosis induction compared to standard therapeutic cisplatin in both 2D and 3D cell cultures. Specifically, a considerably stronger anti-proliferative effect was observed. The treatment also led to morphological changes and a loss of membrane integrity in the 3D spheroids. Radiotherapy also benefited greatly from P8-D6 treatment. In fact, P8-D6 was a more potent radiosensitizer than cisplatin. Simple synthesis, favorable physicochemical properties and high potency make P8-D6 a promising cervical cancer drug candidate