High-throughput interrogation of immune responses using the Human Immune Profiling Pipeline.

The current abundance of immunotherapy clinical trials presents an opportunity to learn about the underlying mechanisms and pharmacodynamic effects of novel drugs on the human immune system. Here, we present a protocol to study how these immune responses impact clinical outcomes using large-scale high-throughput immune profiling of clinical cohorts. We describe the Human Immune Profiling Pipeline, which comprises an end-to-end solution from flow cytometry results to computational approaches and unsupervised patient clustering based on lymphocyte landscape. For complete details on the use and execution of this protocol, please refer to Lyudovyk et al. (2022).1.

Effects of the direction and speed strategies on pedestrian dynamics.

In this work, we propose a velocity-based model for pedestrian movements containing two sub-models to study how the direction and speed selection strategies affect pedestrian dynamics. Affected by others in the view, pedestrians deviate their moving direction from the desired one to resolve space and velocity conflicts, the sensitivity to which is adjusted by two proportional parameters. After determining the moving direction, they choose a reasonable speed to avoid immediate collisions. The tolerance of personal-space violations is considered given that people accept physical contacts in some contexts and may squeeze despite the lack of space instead of matching the speed of the one in front. Simulation results demonstrate that the direction and speed selection strategies affect pedestrian dynamics in several aspects, including the time and metabolic energy cost, density-velocity relations, and crowd stability. Intriguingly, the discrepant empirical fundamental diagrams of pedestrians can be reproduced and explained in a natural way.

Experimental Study on Panic during Simulated Fire Evacuation Using Psycho- and Physiological Metrics.

Under circumstances of fire, panic usually brings uncertainty and unpredictability to evacuation. Therefore, a deep understanding of panic is desired. This study aims to dig into the underlying mechanism of fire evacuation panic by measuring and analysing psycho- and physiological indicators. In the experiment, participants watched a simulated train station within which three sets of stimuli were triggered separately. Eye movement and brain haemodynamic responses were collected during the watch, while questionnaires and interviews of emotions were conducted after. The analysed physiological indicators include the amplitude of pupil dilation, the time ratios of fixation and saccade, the binned entropy of gaze location, and the brain activation coefficients. The results of this research indicate that fire evacuation panic can be broken down into two elements. (1) Unawareness of situation: less knowledge of the situation leads to a higher level of panic; (2) Intensity of visual stimulation: the panic level is escalated with increased severity of fire that is perceived.

STAT5 interferes with PD-1 transcriptional activation and affects CD8+ T-cell sensitivity to PD-1-dependent immunoregulation.

Programmed cell death-1 (PD-1) is a co-inhibitory receptor that dampens immune responses upon interaction with PD-L1 and PD-L2. Although PD-1 expression on T cells is known to be activation-dependent, how cytokines modify its regulation is not fully resolved. Using polyclonal T-cell activation to study cytokine-dependent PD-1 regulation, we found that IL-2 inhibited transcriptional up-regulation of PD-1 despite the promotion of T-cell activation. The IL-2-mediated reduction in PD-1 expression augmented CD8+ T-cell activities against PD-L1-expressing target cells. To study the mechanism of PD-1 reduction, we focused on STAT5 activation in the IL-2 signaling pathway. Bioinformatic analysis suggested a novel conserved PD-1 promoter domain where NFAT and STAT5 can potentially compete with each other for binding. NFAT1 interaction with this domain revealed substantial potency in PD-1 transcription compared to STAT5A, and STAT5A overexpression could quench NFAT1-dependent PD-1 up-regulation in a sequence-specific manner. Chromatin immunoprecipitation analysis of activated T cells showed that IL-2 treatment significantly diminished the binding of NFAT1 and NFAT2 in the hypothesized competition site, while STAT5 binding to the same region was increased. These results raise the possibility that the competition of transcriptional factors might be involved in the fine-tuning of PD-1 expression by cytokines such as IL-2.