The increasing rate of antibiotic resistance and slowing discovery of novel antibiotic treatments presents a growing threat to public health. Here, we consider a simple model of evolution in asexually reproducing populations which considers adaptation as a biased random walk on a fitness landscape. This model associates the global properties of the fitness landscape with the algebraic properties of a Markov chain transition matrix and allows us to derive general results on the non-commutativity and irreversibility of natural selection as well as antibiotic cycling strategies. Using this formalism, we analyze 15 empirical fitness landscapes of E. coli under selection by different β-lactam antibiotics and demonstrate that the emergence of resistance to a given antibiotic can be either hindered or promoted by different sequences of drug application. Specifically, we demonstrate that the majority, approximately 70%, of sequential drug treatments with 2-4 drugs promote resistance to the final antibiotic. Further, we derive optimal drug application sequences with which we can probabilistically 'steer' the population through genotype space to avoid the emergence of resistance. This suggests a new strategy in the war against antibiotic-resistant organisms: drug sequencing to shepherd evolution through genotype space to states from which resistance cannot emerge and by which to maximize the chance of successful therapy.

This paper discusses a template-based approach to aid in introducing the upper-division undergraduate (or first year graduate) to the rapidly emerging message passing parallel computing paradigm. Our template library facilitates an accelerated MPI programming learning environment that can realistically be included as one topic among many in an algorithms course. One template module is based on a backtracking solution to the satisfiablity problem (SAT), which the student first solves in the sequential setting. With the aid of a modified template, the student then develops a simple parallel SAT solver. The template includes such things as I/O functions, allowing the student to focus on the algorithm itself. The parallel part is partially provided by the template, with indicators given in places where the student needs to plug in missing MPI function calls. The students are excited about this hands-on-experience in the increasingly important world of message passing parallel computing, which might be missed if their curriculum does not include a course devoted to this topic.

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The fault tolerance has been defined as the fitness of a system to minimize the probability of appearance of faults and/or to minimize their effects. The design of a computer needs a constant watching of the fault tolerances components, as computer's reaction to failures that has to be forecasted.