Cryptococcus neoformans (Cn) is the most common cause of fungal meningitis worldwide. In infected patients, growth of the fungus can occur within the phagolysosome of phagocytic cells, especially in non-activated macrophages of immunocompromised subjects. Since this environment is characteristically acidic, Cn must adapt to low pH to survive and efficiently cause disease. In the present work, we designed, tested, and experimentally validated a theoretical model of the sphingolipid biochemical pathway in Cn under acidic conditions. Simulations of metabolic fluxes and enzyme deletions or downregulation led to predictions that show good agreement with experimental results generated post hoc and reconcile intuitively puzzling results. This study demonstrates how biochemical modeling can yield testable predictions and aid our understanding of fungal pathogenesis through the design and computational simulation of hypothetical experiments.
Although the M/D/1/N queueing model is well solved from a computational point of view, there is no known analytical expression of the queue length distribution. In this paper, we derive closed-form formulae for the distribution of the number of customers in the system in the finite-capacity M/D/1 queue. We also give an explicit solution for the mean queue length and the average waiting time.
An analytical expression of the time-dependent probability distribution of M/D/1/N queues initialised in an arbitrary deterministic state is derived. We also obtain a simple analytical expression of the differential equation governing the transient average traffic which only involves probabilities of boundary states. As a by-product, a closed form solution of the departure rate from the system is also determined.
Although the M/D/1/N queueing model is well solved from a computational point of view, there is no known analytical expression of the queue length distribution. In this paper, we derive closed-form formulae for the distribution of the number of customers in the system in the finite-capacity M/D/1 queue. We also give an explicit solution for the mean queue length and the average waiting time.
International audienceFailure detection plays a central role in the engineering of distributed systems. Furthermore, many applications have timing constraints and require failure detectors that provide quality of service (QoS) with some quantitative timeliness guarantees. Therefore, they need failure detectors that are fast and accurate. We introduce the Two Windows Failure Detector (2W-FD), an algorithm that provides QoS and is able to react to sudden changes in network conditions, a property that currently existing algorithms do not satisfy. We ran tests on real traces and compared the 2W-FD to state-of-the-art algorithms. Our results show that our algorithm presents the best performance in terms of speed and accuracy in unstable scenarios
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