Quantitative exponential bounds for the renewal theorem with spread-out distributions

We establish explicit exponential convergence estimates for the renewal theorem, in terms of a uniform component of the inter arrival distribution, of its Laplace transform which is assumed finite on a positive interval, and of the Laplace transform of some related random variable. Our proof is based on a coupling construction relying on discrete-time Markovian structures that underly the renewal processes and on Lyapunov-Doeblin type arguments.Comment: Accepted for publication in Markov Processes and Related Field

Allosteric control of cyclic di-GMP signaling

Cyclic di-guanosine monophosphate is a bacterial second messenger that has been implicated in biofilm formation, antibiotic resistance, and persistence of pathogenic bacteria in their animal host. Although the enzymes responsible for the regulation of cellular levels of c-di-GMP, diguanylate cyclases (DGC) and phosphodiesterases, have been identified recently, little information is available on the molecular mechanisms involved in controlling the activity of these key enzymes or on the specific interactions of c-di-GMP with effector proteins. By using a combination of genetic, biochemical, and modeling techniques we demonstrate that an allosteric binding site for c-di-GMP (I-site) is responsible for non-competitive product inhibition of DGCs. The I-site was mapped in both multi- and single domain DGC proteins and is fully contained within the GGDEF domain itself. In vivo selection experiments and kinetic analysis of the evolved I-site mutants led to the definition of an RXXD motif as the core c-di-GMP binding site. Based on these results and based on the observation that the I-site is conserved in a majority of known and potential DGC proteins, we propose that product inhibition of DGCs is of fundamental importance for c-di-GMP signaling and cellular homeostasis. The definition of the I-site binding pocket provides an entry point into unraveling the molecular mechanisms of ligand-protein interactions involved in c-di-GMP signaling and makes DGCs a valuable target for drug design to develop new strategies against biofilm-related diseases

Misfolding and aggregation of nascent proteins: a novel mode of toxic cadmium action in vivo.

Cadmium is a highly poisonous metal and a human carcinogen, but the molecular mechanisms underlying its cellular toxicity are not fully understood. Recent findings in yeast cells indicate that cadmium exerts its deleterious effects by inducing widespread misfolding and aggregation of nascent proteins. Here, we discuss this novel mode of toxic heavy metal action and propose a mechanism by which molecular chaperones may reduce the damaging effects of heavy metal ions on protein structures

Dynamic sorted neighborhood indexing for real-time entity resolution

Real-time Entity Resolution (ER) is the process of matching query records in subsecond time with records in a database that represent the same real-world entity. Indexing techniques are generally used to efficiently extract a set of candidate records from the database that are similar to a query record, and that are to be compared with the query record in more detail. The sorted neighborhood indexing method, which sorts a database and compares records within a sliding window, has been successfully used for ER of large static databases. However, because it is based on static sorted arrays and is designed for batch ER that resolves all records in a database rather than resolving those relating to a single query record, this technique is not suitable for real-time ER on dynamic databases that are constantly updated. We propose a tree-based technique that facilitates dynamic indexing based on the sorted neighborhood method, which can be used for real-time ER, and investigate both static and adaptive window approaches. We propose an approach to reduce query matching times by precalculating the similarities between attribute values stored in neighboring tree nodes. We also propose a multitree solution where different sorting keys are used to reduce the effects of errors and variations in attribute values on matching quality by building several distinct index trees. We experimentally evaluate our proposed techniques on large real datasets, as well as on synthetic data with different data quality characteristics. Our results show that as the index grows, no appreciable increase occurs in both record insertion and query times, and that using multiple trees gives noticeable improvements on matching quality with only a small increase in query time. Compared to earlier indexing techniques for real-time ER, our approach achieves significantly reduced indexing and query matching times while maintaining high matching accuracy

Symmetry of two terminal, non-linear electric conduction

The well-established symmetry relations for linear transport phenomena can not, in general, be applied in the non-linear regime. Here we propose a set of symmetry relations with respect to bias voltage and magnetic field for the non-linear conductance of two-terminal electric conductors. We experimentally confirm these relations using phase-coherent, semiconductor quantum dots.Comment: 4 pages, 4 figure