Civil Rights Then & Now

Lucy Partlow-Loyall, a senior majoring in Social Work, will be presenting on civil rights in a historical context and what people can do to protect civil rights today

The World According To GARP

This technical report consists of two papers describing the GARP concurrent programming system. Garp: Graph Abstractions for Concurrent Programming investigates construction of dynamic process topologies in parallel processing languages. It proposes the use of a graph-grammar based formalism to control the complexities arising from trying to program such dynamic networks. Garp: A Graphical Language for Concurrent Programming describes the GARP system, a programming environment that implements this graph-grammar approach, and gives solutions to example problems in which the topologies of concurrent systems dynamically change

Authoring Multi-Actor Behaviors in Crowds With Diverse Personalities

Multi-actor simulation is critical to cinematic content creation, disaster and security simulation, and interactive entertainment. A key challenge is providing an appropriate interface for authoring high-fidelity virtual actors with featurerich control mechanisms capable of complex interactions with the environment and other actors. In this chapter, we present work that addresses the problem of behavior authoring at three levels: Individual and group interactions are conducted in an event-centric manner using parameterized behavior trees, social crowd dynamics are captured using the OCEAN personality model, and a centralized automated planner is used to enforce global narrative constraints on the scale of the entire simulation. We demonstrate the benefits and limitations of each of these approaches and propose the need for a single unifying construct capable of authoring functional, purposeful, autonomous actors which conform to a global narrative in an interactive simulation

Preclinical evaluation of cancer immune therapy using patient-derived tumor antigen-specific T cells in a novel xenograft platform.

Objectives: With a rapidly growing list of candidate immune-based cancer therapeutics, there is a critical need to generate highly reliable animal models to preclinically evaluate the efficacy of emerging immune-based therapies, facilitating successful clinical translation. Our aim was to design and validate a novel Methods: Tumor xenografts are established rapidly in the greater omentum of globally immunodeficient NOD- Results: The tumors progress rapidly and disseminate in the mice unless patient-derived tumor-specific T cells are introduced. An initial T cell-mediated tumor arrest is later followed by a tumor escape, which correlates with the upregulation of the checkpoint molecules programmed cell death-1 (PD-1) and lymphocyte-activation gene 3 (LAG3) on T cells. Treatment with immune-based therapies that target these checkpoints, such as anti-PD-1 antibody (nivolumab) or interleukin-12 (IL-12), prevented or delayed the tumor escape. Furthermore, IL-12 treatment suppressed PD-1 and LAG3 upregulation on T cells. Conclusion: Together, these results validate the X-mouse model and establish its potential to preclinically evaluate the therapeutic efficacy of immune-based therapies

Novel phosphatidylserine-binding molecule enhances antitumor T-cell responses by targeting immunosuppressive exosomes in human tumor microenvironments.

BACKGROUND: The human tumor microenvironment (TME) is a complex and dynamic milieu of diverse acellular and cellular components, creating an immunosuppressive environment, which contributes to tumor progression. We have previously shown that phosphatidylserine (PS) expressed on the surface of exosomes isolated from human TMEs is causally linked to T-cell immunosuppression, representing a potential immunotherapeutic target. In this study, we investigated the effect of ExoBlock, a novel PS-binding molecule, on T-cell responses in the TME. METHODS: We designed and synthesized a new compound, (ZnDPA) RESULTS: ExoBlock was able to bind PS with high avidity and was found to consistently and significantly block the immunosuppressive activity of human ovarian tumor and melanoma-associated exosomes in vitro. ExoBlock was also able to significantly enhance T cell-mediated tumor suppression in vivo in both the X-mouse and the OTX model. In the X-mouse model, ExoBlock suppressed tumor recurrence in a T cell-dependent manner. In the OTX model, ExoBlock treatment resulted in an increase in the number as well as function of CD4 and CD8 T cells in the TME, which was associated with a reduction in tumor burden and metastasis, as well as in the number of circulating PS+ exosomes in tumor-bearing mice. CONCLUSION: Our results establish that targeting exosomal PS in TMEs with ExoBlock represents a promising strategy to enhance antitumor T-cell responses