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Hoerner, S.

Publications and source records attributed to Hoerner, S..

2 recordsLinked to original sources

Behavior of downstream swimming brown trout in accelerating and high flow velocity - Movement matters

Studies on active and sedated fish passing through turbines and pumps show different mortality and injury rates for both cases. Consequently, fish behavior appears to play a substantial role in these outcomes. However, direct behavioral observations in hydraulic machines using quantitative parameters to draw conclusions about the underlying mechanisms are hardly possible and remain understudied. In this study, we examined the behavior of adult brown trout (Salmo trutta) in an experimental flume under hydraulic conditions characterized by strong flow acceleration and high velocities typical of turbine and pump intakes. Fish movement behavior was analyzed based on a quantitative approach to enable the analysis of swimming behavior even in flow velocities exceeding the sprint swimming speed of fish. The application of Hidden Markov Models (HMM) to analyze activity states and movement modes of fish from video tracking data demonstrated significant effects of the spatial velocity gradient (SVG) and flow velocity on fish behavior. Notably, SVG emerged as the primary trigger for avoidance reactions when exceeding a threshold of [Formula]. Fish exhibited distinct movement patterns under dark and daylight conditions, with more avoidance reactions in darkness. Whereas a considerable proportion of fish in daylight increased their swimming activity in the zone were flow velocity exceeded sprint swimming speed, in dark conditions no activity peak occurred in the same zone. The results illustrate how hydraulic conditions and lighting influence fish behavior. Integrating the behavioral rules identified in this study into numerical mortality-risk models could substantially improve their predictive accuracy. Thus, the findings allow for the development of less fish harming engineering solutions for hydropower facilities and pumping stations.

animal behavior and cognition↗

Bivalent bispecific CD28 antibodies reinforce T-cell responsiveness and revert anergy/quiescence in patients treated with bispecific CD3 antibodies

Bispecific T-cell engagers stimulating CD3 (TCEs) rapidly gain momentum in oncological therapy. We report that single-agent TCE-treatment of cancer patients induces T cell hyporesponsiveness including abolished proliferative and lytic capacity. Single-cell RNA-sequencing identified transcriptional features of anergy/quiescence like upregulation of CBLB and BACH2, and suppression of AP 1-dependent activation programs due to isolated provision of T cell signal-1. To restore T cell functionality, we engineered bispecific costimulators (BiCos) which deliver signal-2 via highly efficient bivalent CD28-binding yet maintain strictly target-restricted activity after binding antigens expressed not only by tumor cells but also the extracellular matrix. Preclinical analyses documented that BiCos potentiate efficacy of single-agent TCE treatment with activity exceeding that of univalent Knob-into-Hole CD28-costimulators and revert T cell hyporesponsiveness. In humanized mice, BiCos induced elimination of established tumors in combination with very low doses of TCE. Finally, BiCos reversed molecular hallmark features of quiescence such as high expression of BACH2 and KLF2 in T cells of TCE-treated patients resulting in complete restoration of cellular function, thereby reinstating durable antitumor immunity.

immunology↗