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A spatially adaptive Monte Carlo method is introduced directly from the underlying microscopic mechanisms, which satisfies detailed balance, gives the correct noise, and describes accurately dynamic and equilibrium states for adsorption-desorption (grand canonical ensemble) processes. It enables simulations of large scales while capturing sharp gradients(More)
Infections caused by antibiotic-resistant bacteria are a rising public health threat and make the identification of new antibiotics a priority. From a cell-based screen for bactericidal compounds against Mycobacterium tuberculosis under nutrient-deprivation conditions we identified auranofin, an orally bioavailable FDA-approved antirheumatic drug, as having(More)
Growing evidence suggests that the presence of a subpopulation of hypoxic non-replicating, phenotypically drug-tolerant mycobacteria is responsible for the prolonged duration of tuberculosis treatment. The discovery of new antitubercular agents active against this subpopulation may help in developing new strategies to shorten the time of tuberculosis(More)
For N possible customers or agents and N price-wise identical (one customer a day) restaurants (or any other type of service providers), we study the collective dynamical states of choices. Each evening the choice problem of any agent is to go to a restaurant. The agent makes this choice based on two things (a) his/her own past experiences and (b) the past(More)
Most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4000 commercially available compounds with previously demonstrated blood-stage(More)
Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of(More)
Candidate antibacterials are usually identified on the basis of their in vitro activity. However, the apparent inhibitory activity of new leads can be misleading because most culture media do not reproduce an environment relevant to infection in vivo. In this study, while screening for novel anti-tuberculars, we uncovered how carbon metabolism can affect(More)
The quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations(More)
Interpretation theory formalizes the conservative approximation of the semantics of hardware and software computer systems. Abstract Interpretation approximates semantics according to some property of choice, this is formalized by choosing an appropriate abstract domain to use as abstraction of the semantics. A great variety of abstract domains can be(More)
Renewed global efforts toward malaria eradication have highlighted the need for novel antimalarial agents with activity against multiple stages of the parasite life cycle. We have previously reported the discovery of a novel class of antimalarial compounds in the imidazolopiperazine series that have activity in the prevention and treatment of blood stage(More)