On a generic class of two-node queueing systems

This paper analyzes a generic class of two-node queueing systems. A first queue is fed by an on-off Markov fluid source; the input of a second queue is a function of the state of the Markov fluid source as well, but now also of the first queue being empty or not. This model covers the classical two-node tandem queue and the two-class priority queue as special cases. Relying predominantly on probabilistic argumentation, the steady-state buffer content of both queues is determined (in terms of its Laplace transform). Interpreting the buffer content of the second queue in terms of busy periods of the first queue, the (exact) tail asymptotics of the distribution of the second queue are found. Two regimes can be distinguished: a first in which the state of the first queue (that is, being empty or not) hardly plays a role, and a second in which it explicitly does. This dichotomy can be understood by using large-deviations heuristics

Performance analysis of priority queueing systems in discrete time

The integration of different types of traffic in packet-based networks spawns the need for traffic differentiation. In this tutorial paper, we present some analytical techniques to tackle discrete-time queueing systems with priority scheduling. We investigate both preemptive (resume and repeat) and non-preemptive priority scheduling disciplines. Two classes of traffic are considered, high-priority and low-priority traffic, which both generate variable-length packets. A probability generating functions approach leads to performance measures such as moments of system contents and packet delays of both classes

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis