Fumarate-containing pharmaceuticals are potent therapeutic agents that influence multiple cellular pathways. Despite proven clinical efficacy, there is a significant lack of data that directly defines the molecular mechanisms of action of related, yet distinct fumarate compounds. We systematically compared the impact of dimethyl fumarate (DMF), monomethyl fumarate (MMF) and a mixture of monoethyl fumarate salts (Ca(++), Mg(++), Zn(++); MEF) on defined cellular responses. We demonstrate that DMF inhibited NF-κB-driven cytokine production and nuclear translocation of p65 and p52 in an Nrf2-independent manner. Equivalent doses of MMF and MEF did not affect NF-κB signaling. These results highlight a key difference in the biological impact of related, yet distinct fumarate compounds.

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The paper begins with a review of the rational for development of personal rapid transit, the reasons it has taken so long to develop, and the process needed to develop it. Next I show how the PRT concept can be derived from a system-significant equation for life-cycle cost per passenger-mile as the system that minimizes this quantity. In the bulk of the paper I discuss the state-of-the-art of a series of technical issues that had to be resolved during the development of an optimum PRT design. These include capacity, switching, the issue of hanging vs. supported vehicles, guideways, vehicles, control, station operations, system operations, reliability, availability, dependability, safety, the calculation of curved guideways, operational simulation, power and energy. The paper concludes with a listing of the implications for a city that deploys an optimized PRT system.

The problem of precise longitudinal control of vehicles so that they follow predetermined timevarying speeds and positions has been solved. To control vehicles to the required close headway of at least 0.5 sec, the control philosophy is different from but no less rigorous than that of railroad practice. The preferred control strategy is one that could be called an "asynchronous point follower." Such a strategy requires no clock synchronization, is flexible in all unusual conditions, permits the maximum possible throughput, requires a minimum of maneuvering and uses a minimum of software. Since wayside zone controllers have in their memory exactly the same maneuver equations as the on-board computers, accurate safety monitoring is practical. The paper discusses the functions of vehicle control; the control of station, merge, and diverge zones; and central control.