3633 research outputs found
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CAR T cells re-directed by a rationally designed human peptide tag demonstrate efficacy in preclinical models
Get PDFCurrently, only a few chimeric antigen receptor (CAR) T cell therapies have been approved by the Food and Drug Administration and European Medicines Agency for the treatment of B-cell malignancies. To enable broader application of the CAR T cell technology in other indications, improved control and flexible targeting of multiple tumor antigens are required. Here, we developed a novel adapter CAR (AdCAR) T cell platform for flexible targeting of multiple tumor antigens. This platform is based on a short peptide tag derived from an interdomain region of fibroblast growth factor receptor 2 (FGFR2), commonly mutated in cancer. To select AdCARs specific for mutated FGFR2-derived peptide tags, a multistep pooled screening approach in primary T cells was employed, incorporating MACS separation and next-generation sequencing. The resulting AdCAR was highly specific for the FGFR2-derived peptide tag. Using different in vitro and in vivo model systems, the activity of AdCAR T cells was shown to be strictly dependent on the presence of the adapter and corresponding target antigen. Moreover, AdCAR T cells could be redirected to different target antigens by the addition of respective adapter molecules (AM). Finally, in situ expression of functional AM in primary T cells under control of a drug-inducible promoter system was demonstrated, highlighting the potential for controlling the activity of AdCAR T cells by cellular micropharmacies
The influence of economics education in school on future entrepreneurial behavior
No full textWhereas much research has focused on the predictors of entrepreneurial behavior during adulthood, we know little about how preadulthood experiences influence entrepreneurial behavior later in life. Grounded in imprinting theory, this study examines whether introducing economics classes in school enhances students’ entrepreneurial behavior in adulthood. Using a difference-in-differences approach exploiting curriculum reforms in Germany, we find that participating in economics classes increases students’ later entrepreneurial activities by four percentage points. We also investigate the underlying mechanism and find that the impact on entrepreneurial behavior is driven by individual-centered rather than market-centered economics curricula
Why do few women choose IT-related programmes? A study of gender-specific perceptions and preferences in the context of business informatics
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Digital transformation is a key factor in the competitiveness of modern businesses. However, the shortage of IT specialists poses a significant challenge. The significant underrepresentation of women in IT-related programmes in higher education further increases the skills shortage and reduces diversity and creativity. Against this background, this study aims to investigate the gender-specific factors influencing the decision to pursue IT-related degrees in the context of business informatics (B-Inf) in Germany to understand why few young women choose this field of study.
Design/methodology/approach
A quantitative survey was conducted with 186 undergraduate students in Germany. The survey examined the perceptions and priorities of both male and female students when choosing their field of study.
Findings
The results reveal that women place greater emphasis on job security and societal impact when selecting their field of study, whereas men tend to prioritise interest in technology, personal development and enjoyment of IT-related work.
Originality/value
Although previous research has focused on computer science programmes, little attention has been paid specifically to B-Inf programmes, which are a distinct discipline combining computer science and business administration. This study contributes new insights into the gender-specific preferences influencing the choice of B-Inf degrees, offering practical implications for increasing female participation and addressing the IT skills gap
Targeting CD276 with Adapter-CAR T-cells provides a novel therapeutic strategy in small cell lung cancer and prevents CD276-dependent fratricide
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Background
Survival rates in Small Cell Lung Cancer (SCLC) remain dismal, posing a huge medical need for novel therapies. T-cells, engineered to express chimeric antigen receptors (CAR-T) have demonstrated clinical activity against a variety of haematological malignancies. Yet, efficacy against solid tumour entities remains limited.
Methods
In this study, we investigated the expression of CD276 (B7-H3), an immune checkpoint molecule and promising target antigen for CAR-T therapy in SCLC, at the RNA and protein level. We further developed novel Fab-based adapter molecules (AM) targeting CD276 and optimized our previously established modular Adapter CAR-T (AdCAR-T) platform as well as AM dosing schemes.
Results
CD276 is broadly expressed across SCLC subtypes, representing a promising target for CAR-T therapy. We describe that T-cell activation and CAR-signalling induces CD276-expression on CAR-T, resulting in CD276-dependent fratricide, limiting anti-CD276-CAR-T expansion and activity. The AdCAR-T platform allows CAR-T expansion in absence of CD276 targeting. Novel CD276 targeted AMs demonstrate potent in vitro and in vivo activity against SCLC. Intermittent AM-dosing allows functional persistence of AdCAR-T in vivo in contrast to CD276-targeted conventional CAR-T. AdCAR-T in vivo expansion and activity is further promoted by introducing activation-induced, AM remote controlled, IL-18 secretion into the AdCAR-T design.
Conclusion
We identified CD276 as a promising target antigen, uniformly expressed in SCLC and demonstrate the therapeutic potential of novel anti-CD276 Fab-based AM in combination with optimized, IL-18 armoured AdCAR-T
Projektorientierte Hochschullehre im Labor „Financial and Actuarial Data Science“ am Beispiel eines „Robo Advisor“- Projekts
No full textEgal ob es um frühere Studieninhalte geht, um unsere Aktuarausbildung oder aber um Weiterbildungen: Alle von uns haben sicher schon mal die Erfahrung gemacht, dass es schwerfallen kann, das gelernte im Alltag konkret umzusetzen. Unabhängig davon, wie interessant das Thema und die Lehrveranstaltung im Moment des Besuchs auch waren. Monate später trifft man in einem anderen Kontext wieder auf die Lerninhalte, und es drängt sich der Gedanke auf „das habe ich schon mal gehört“, ohne aber jemals selbst einen praxisrelevanten Anwendungsbezug hergestellt zu haben. Aus Sicht der Lehre stellt sich die Frage, wie diese gestaltet werden kann, sodass nicht überwiegend solches „träges Wissen“ (vgl. z. B. (Seibert, et al., 2019)) entsteht, sondern vielmehr konkret anwendbares Wissen, das direkt zur Problemlösung eingesetzt werden kann und eingesetzt wird
Does socially non-compliant corporate behavior lead to underperformance? Event analysis related to the Russia–Ukraine conflict and the CELI list
Get PDFFollowing the escalation of Russia’s invasion of Ukraine in February 2022, the conflict prompted extensive economic sanctions against the Russian Federation. This study examines the stock performance of companies across various countries and continents that either continued business operations in Russia or chose to withdraw. Using signaling theory in the context of military conflict, we apply multiple event study methodologies. Companies are categorized based on their engagement in Russia, using the CELI list as an ESG-equivalent signal to construct distinct portfolios. These are tested against several EU sanctions packages, accounting for different estimation windows. Results show that European companies that exited Russia outperformed those that remained, suggesting that markets reward compliance-oriented behavior. However, industrial and geographical factors also influence the results. Our findings emphasize the importance of strategic decision-making under geopolitical risk and encourage investors to consider conflict risk. Furthermore, we recommend regulators incorporate socially responsible investing into policy frameworks to promote ethical conduct
Opportunities and challenges of artificial intelligence in hiring from a recruiter’s perspective
No full textArtificial Intelligence (AI) provides unprecedented possibilities to accelerate and improve the hiring process. However, the willingness of recruiters to use–and in turn–profit from AI is crucial. Perceptions of human resource (HR) experts on AI-based hiring has been explored further in an empirical study, which is partly shown in this paper. As the existing body of research is still small, an inductive approach was chosen. We conducted seven semi-structured expert interviews with recruiters from the German manufacturing industry. Based on the findings, we developed a conceptual model with testable hypotheses and practical implications. Noticeably, the recruiters both praised and criticised AI for providing a fact-based assessment of candidates. AI’s increased efficiency was recognised as a major opportunity or even necessity. The most promising approach seems to be a tandem of human and algorithmic decision-making, each offsetting the shortcomings of the other
A coalition framework for increasing market participation of electrolysers and renewable energy sources
No full textThe generation of electricity from renewable energy sources is highly volatile and intermittent. The excess energy generated by renewable energy sources can be used to generate green hydrogen using electrolysers, thus generating energy demand for the excess energy and maximizing the utilization of renewable energy sources. The paper presents a decentralized framework through which electrolysers and renewable energy sources form a coalition to balance the energy production and demand, maximize the overall revenue and encourage early adopters of electrolyser technology without the need of public subsidies. This guarantees a reasonable distribution of revenue for all participants in the coalition regardless of their entry time into the market. This approach will naturally evolve into a market model in which the most efficient electrolysers will succeed as soon as the investment cost settles and the supply chains develop. Thus, potential electrolyser technology adopters are motivated to participate in a peer-to-peer electricity trading market for the production of hydrogen and drive forward the hydrogen economy
Mid- and near-infrared spectroscopies for quantitative tracking of isocyanate content: streamlined development of monitoring tools for reactive extrusion synthesis of specialty polyurethanes
Get PDFRobust in-situ monitoring can expedite the development and tuning of reactive extrusion (REX) processes, especially for the synthesis of polymers requiring insight into the reaction course, such as specialty polyurethanes (PUs). In order to advance the feasibility of such analysis, our research concentrated on a spectroscopic protocol that combines at-line mid-infrared (MIR) and on-line near-infrared (NIR) measurements in a laboratory extruder, assessing both their qualitative and quantitative capabilities. To mimic the depletion of the reactive species during polymerisation, a series of premixes were formulated and characterised under non-reactive conditions using a benchmark pair of a polyol and a diisocyanate. By this means, we identified suitable spectral features for quantifying isocyanate content via multivariate regression models. This approach achieved good calibration metrics for both MIR and NIR models and enabled a robust assessment of their predictive performance through cross-validation, using only a moderate number of spectral datasets. Our work is therefore the first step towards establishing a method for in-process NIR analysis with streamlined at-line MIR verification. It provides a shortcut for designing monitored REX syntheses of PUs and other material systems amenable to quantitative calibration based on spectroscopic data from raw reagents