Product forms for availability

This paper shows and illustrates that product form expressions for the steady state distribution, as known for queueing networks, can also be extended to a class of availability models. This class allows breakdown and repair rates from one component to depend on the status of other components. Common resource capacities and repair priorities, for example, are included. Conditions for the models to have a product form are stated explicitly. This product form is shown to be insensitive to the distributions of the underlying random variables, i.e. to depend only on their means. Further it is briefly indicated how queueing for repair can be incorporated. Novel product form examples are presented of a simple series/parallel configuration, a fault tolerant database system and a multi-stage interconnection network

Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.

Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate amino acids by mitochondrial aminoacyl-tRNA synthetases, with the exception of glutaminyl mt-tRNA (mt-tRNAGln). mt-tRNAGln is indirectly charged by a transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase complex. Defects involving the mitochondrial protein synthesis machinery cause a broad spectrum of disorders, with often fatal outcome. Here, we describe nine patients from five families with genetic defects in a GatCAB complex subunit, including QRSL1, GATB, and GATC, each showing a lethal metabolic cardiomyopathy syndrome. Functional studies reveal combined respiratory chain enzyme deficiencies and mitochondrial dysfunction. Aminoacylation of mt-tRNAGln and mitochondrial protein translation are deficient in patients' fibroblasts cultured in the absence of glutamine but restore in high glutamine. Lentiviral rescue experiments and modeling in S. cerevisiae homologs confirm pathogenicity. Our study completes a decade of investigations on mitochondrial aminoacylation disorders, starting with DARS2 and ending with the GatCAB complex

A Note on "Operating Characteristics of the (S-1, S) Inventory System with Partial Backorders and Constant Resupply Times"

No abstract available.

A Simple Approximation to the Renewal Function

This article presents a simple, easy to understand approximation to the renewal function; the approximation is easy to implement on a personal computer. The key idea is that, for small values of time, the renewal function is almost equal to the Cdf of the inter-renewal time, whereas for larger values of time an asymptotic expansion — depending upon only the first and second moment of the inter-renewal time — can be used. The relative error is typically smaller than a few percent for Weibull inter-renewal times. The simple approximation method works very well with one term if not too much accuracy is required (eg, in the block replacement problem) or if the inter-renewal (failure) distribution is not exactly known (eg, only the first two moments are known). Although the accuracy of the simple approximation can be improved by increasing the number of terms, we do not advocate this strategy, since then speed and simplicity are lost. If high accuracy is required it is better to use another approximating method (eg, power series expansion or cubic splines method)

Opportunity-based block replacement

In this paper we consider a block replacement model in which a component can be replaced preventively at maintenance opportunities only. Maintenance opportunities occur randomly and are modelled through a renewal process. In the first, theoretical part of the paper we derive an optimality equation and show that the optimal opportunity block replacement policy can be described as a so-called one-opportunity-look-ahead policy. In the second, computational part we present an exact optimisation algorithm in case of K2-distributed times between opportunities. This algorithm can also be used as an approximative method in case of other times between opportunity distributions. Together with another approximative method, based on the stationary forward recurrence time distribution, its performance is checked with simulation

Distinct Clinical Phenotypes Associated with a Mutation in the Mitochondrial Translation Elongation Factor EFTs

The 13 polypeptides encoded in mitochondrial DNA (mtDNA) are synthesized in the mitochondrial matrix on a dedicated protein-translation apparatus that resembles that found in prokaryotes. Here, we have investigated the genetic basis for a mitochondrial protein-synthesis defect associated with a combined oxidative phosphorylation enzyme deficiency in two patients, one of whom presented with encephalomyopathy and the other with hypertrophic cardiomyopathy. Sequencing of candidate genes revealed the same homozygous mutation (C997T) in both patients in TSFM, a gene coding for the mitochondrial translation elongation factor EFTs. EFTs functions as a guanine nucleotide exchange factor for EFTu, another translation elongation factor that brings aminoacylated transfer RNAs to the ribosomal A site as a ternary complex with guanosine triphosphate. The mutation predicts an Arg333Trp substitution at an evolutionarily conserved site in a subdomain of EFTs that interacts with EFTu. Molecular modeling showed that the substitution disrupts local subdomain structure and the dimerization interface. The steady-state levels of EFTs and EFTu in patient fibroblasts were reduced by 75% and 60%, respectively, and the amounts of assembled complexes I, IV, and V were reduced by 35%–91% compared with the amounts in controls. These phenotypes and the translation defect were rescued by retroviral expression of either EFTs or EFTu. These data clearly establish mutant EFTs as the cause of disease in these patients. The fact that the same mutation is associated with distinct clinical phenotypes suggests the presence of genetic modifiers of the mitochondrial translation apparatus