A first principles dynamic model of the physical, chemical, and electrochemical processes at work in a proton exchange membrane fuel cell has been developed. The model solves the dynamic equations that govern the physics, chemistry and electrochemistry for time scales greater than about 10 ms. The dynamic equations are solved for a typical but simplified quasi-three dimensional geometric representation of a single cell repeat unit of a fuel cell stack. The current approach captures spatial and temporal variations in the important physics of heat transfer and water transport in a manner that is simple enough to make the model amenable to PEMFC system simulations and controls development. Comparisons of model results to experimental data indicate that the model can well predict steady state voltage-current relationships as well as the oxygen, water, and nitrogen spatial distribution within the fuel cell. In addition, the model gives dynamic insight into the distribution of current, water flux, species mole fractions, and temperatures within the fuel cell. Finally, a control system test is demonstrated using the simplified dynamic model. © 2006 Elsevier B.V. All rights reserved.

The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells. CEMIP depletion in tumour cells impaired brain metastasis, disrupting invasion and tumour cell association with the brain vasculature, phenotypes rescued by pre-conditioning the brain microenvironment with CEMIP⁺ exosomes. Moreover, uptake of CEMIP⁺ exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating the pro-inflammatory cytokines encoded by Ptgs2, Tnf and Ccl/Cxcl, known to promote brain vascular remodelling and metastasis. CEMIP was elevated in tumour tissues and exosomes from patients with brain metastasis and predicted brain metastasis progression and patient survival. Collectively, our findings suggest that targeting exosomal CEMIP could constitute a future avenue for the prevention and treatment of brain metastasis.