Microtargeting via Facebook and its impacts on federal state elections in Hamburg

The case of Cambridge Analytica in 2018 showed how the digital age and the resulting new possibilities for commercial marketing affect political campaigning. Despite concerns, today we observe that Facebook ad services are growing and political microtargeting has arrived in Europe. Since research in this context is still rare, this thesis aimed to analyze how advertising on a specific social media channel could impact a regional German election. Using Critical Discourse Analysis (CDA), political advertisements on Facebook during a two-month period before the federal state election in Hamburg in 2020 were studied. Content and discourse analysis were in line with Roemmele's and Gibson’s (2020) argument that the "subversive" form of microtargeting is very apparent and undermining the potential positive consequences of targeting political advertisements (p. 595). While inducing negative emotions such as fear and feelings of physical and social insecurity, targeted advertisements showed sexist and ageist attitudes, as well as they encouraged local identity and xenophobia. Essentially, the thesis argues that microtargeting encourages digital inequality, contributes to a voting culture which is emotionally and ideologically motivated, and may accelerate the polarization in society. Above all, the large share of discourse aiming to convince voters rather than to inform them, leads to the assumption, that microtargeting is a tool that serves to win potential voters at lowest possible information levels.O caso da Cambridge Analytica em 2018 mostrou como a era digital e as novas possibilidades resultantes do marketing comercial afectam as campanhas políticas. Apesar das preocupações, observamos hoje que os serviços de publicidade no Facebook estão a crescer e que o microtargeting político chegou à Europa. Uma vez que a investigação neste contexto ainda é escassa, esta tese visa analisar como a publicidade num canal específico dos meios de comunicação social poderia ter impacto numa eleição regional alemã. Utilizando a Análise do Discurso Crítico (CDA), foram estudados anúncios políticos no Facebook durante um período de dois meses antes das eleições estaduais federais em Hamburgo, em 2020. A análise do conteúdo e do discurso estava de acordo com o argumento de Roemmele e Gibson (2020) de que a forma "subversiva" de microtargeting é muito aparente e mina as potenciais consequências positivas de visar anúncios políticos (p. 595). Embora induzindo emoções negativas como o medo e sentimentos de insegurança física e social, as propagandas direccionadas mostraram atitudes sexistas e anti-idade, assim como encorajaram a identidade local e a xenofobia. Essencialmente, a tese argumenta que o microtargeting encoraja a desigualdade digital, contribui para uma cultura de voto que é emocional e ideologicamente motivada e pode acelerar a polarização da sociedade. Acima de tudo, a grande parte do discurso que visa convencer os eleitores em vez de os informar, leva à suposição de que o microtargeting é uma ferramenta que serve para ganhar potenciais eleitores aos níveis de informação mais baixos possíveis

A Reproducible Bioprinted 3D Tumor Model Serves as a Preselection Tool for CAR T Cell Therapy Optimization

Chimeric antigen receptor (CAR) T cell performance against solid tumors in mouse models and clinical trials is often less effective than predicted by CAR construct selection in two-dimensional (2D) cocultures. Three-dimensional (3D) solid tumor architecture is likely to be crucial for CAR T cell efficacy. We used a three-dimensional (3D) bioprinting approach for large-scale generation of highly reproducible 3D human tumor models for the test case, neuroblastoma, and compared these to 2D cocultures for evaluation of CAR T cells targeting the L1 cell adhesion molecule, L1CAM. CAR T cells infiltrated the model, and both CAR T and tumor cells were viable for long-term experiments and could be isolated as single-cell suspensions for whole-cell assays quantifying CAR T cell activation, effector function and tumor cell cytotoxicity. L1CAM-specific CAR T cell activation by neuroblastoma cells was stronger in the 3D model than in 2D cocultures, but neuroblastoma cell lysis was lower. The bioprinted 3D neuroblastoma model is highly reproducible and allows detection and quantification of CAR T cell tumor infiltration, representing a superior in vitro analysis tool for preclinical CAR T cell characterization likely to better select CAR T cells for in vivo performance than 2D cocultures

Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH.

Nonalcoholic steatohepatitis (NASH) is a manifestation of systemic metabolic disease related to obesity, and causes liver disease and cancer1,2. The accumulation of metabolites leads to cell stress and inflammation in the liver3, but mechanistic understandings of liver damage in NASH are incomplete. Here, using a preclinical mouse model that displays key features of human NASH (hereafter, NASH mice), we found an indispensable role for T cells in liver immunopathology. We detected the hepatic accumulation of CD8 T cells with phenotypes that combined tissue residency (CXCR6) with effector (granzyme) and exhaustion (PD1) characteristics. Liver CXCR6+ CD8 T cells were characterized by low activity of the FOXO1 transcription factor, and were abundant in NASH mice and in patients with NASH. Mechanistically, IL-15 induced FOXO1 downregulation and CXCR6 upregulation, which together rendered liver-resident CXCR6+ CD8 T cells susceptible to metabolic stimuli (including acetate and extracellular ATP) and collectively triggered auto-aggression. CXCR6+ CD8 T cells from the livers of NASH mice or of patients with NASH had similar transcriptional signatures, and showed auto-aggressive killing of cells in an MHC-class-I-independent fashion after signalling through P2X7 purinergic receptors. This killing by auto-aggressive CD8 T cells fundamentally differed from that by antigen-specific cells, which mechanistically distinguishes auto-aggressive and protective T cell immunity