Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF-receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.

The consensus problem involves an asynchronous system of processes, some of which may be unreliable The problem ~9 for the reliable processes to agree on a binary value We show that every protocol for thus problem has the posslblhty of nontermmatlon, even with only one faulty process By way of contrast, solutions are known for the synchronous case, the "Byzantine Generals" problem

The string-to-string correction problem is to determine the distance between two strings as measured by the minimum cost sequence of “edit operations” needed to change the one string into the other. The edit operations investigated allow changing one symbol of a string into another single symbol, deleting one symbol from a string, or inserting a single symbol into a string. An algorithm is presented which solves this problem in time proportional to the product of the lengths of the two strings. Possible applications are to the problems of automatic spelling correction and determining the longest subsequence of characters common to two strings.

The computational power of networks of small resource-limited mobile agents is explored. Two new models of computation based on pairwise interactions of finite-state agents in populations of finite but unbounded size are defined. With a fairness condition on interactions, the concept of stable computation of a function or predicate is defined. Protocols are given that stably compute any predicate in the class definable by formulas of Presburger arithmetic, which includes Boolean combinations of threshold-k, majority, and equivalence modulo m. All stably computable predicates are shown to be in NL. Assuming uniform random sampling of interacting pairs yields the model of conjugating automata. Any counter machine with O(1) counters of capacity O(n) can be simulated with high probability by a conjugating automaton in a population of size n. All predicates computable with high probability in this model are shown to be in P; they can also be computed by a randomized logspace machine in exponential time. Several open problems and promising future directions are discussed.

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