David B. O’Sullivan

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A "switch" from oxidative phosphorylation (OXPHOS) to aerobic glycolysis is a hallmark of T cell activation and is thought to be required to meet the metabolic demands of proliferation. However, why proliferating cells adopt this less efficient metabolism, especially in an oxygen-replete environment, remains incompletely understood. We show here that(More)
Failure of T cells to protect against cancer is thought to result from lack of antigen recognition, chronic activation, and/or suppression by other cells. Using a mouse sarcoma model, we show that glucose consumption by tumors metabolically restricts T cells, leading to their dampened mTOR activity, glycolytic capacity, and IFN-γ production, thereby(More)
Lymphocytes must adapt to a wide array of environmental stressors as part of their normal development, during which they undergo a dramatic metabolic remodeling process. Research in this area has yielded surprising findings on the roles of diverse metabolic pathways and metabolites, which have been found to regulate lymphocyte signaling and influence(More)
Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned(More)
Agent-based models (ABM) are an increasingly popular tool in the social sciences. This trend seems likely to continue, so that they will become widely used in geography and urban and regional planning. We present an overview of examples of these models in the life sciences, economics, planning, sociology, and archaeology. We conclude that agent-based models(More)
Transplantation of embryonic dopaminergic neurones has shown promise for the treatment of Parkinson’s disease (PD), but this approach is limited by the poor survival of the transplanted cells. Exogenous dopaminergic neurotrophic factors such as growth/differentiation factor 5 (GDF5) have been found to enhance the survival of transplanted dopaminergic(More)
Innovation provides the means for enterprises to survive and grow. Due to the distributed and heterogeneous characteristics, it’s difficult to manage innovation across the extended enterprise. A novel vision for Semantic Innovation Management (SIM) is introduced. The system architecture combines ontology, inference and mediation technologies used to create(More)
Microtubule-stabilizing agents are an important class of anticancer compounds. Peloruside A and laulimalide bind to a different site on the microtubule to taxoid site drugs such as paclitaxel (Taxol®), docetaxel (Taxotere®), ixabepilone (Ixempra®), the epothilones, and discodermolide. The purpose of this study was to examine the synergistic interactions of(More)
Pedestrian movement models have been developed since the 1970s. A review of the literature shows that such models have been developed to explain and predict macro, meso and micro movement patterns. However, recent developments in modelling techniques, and especially advances in agent-based simulation, open up the possibility of developing integrative and(More)