Logarithmic asymptotics for unserved messages at a FIFO

We consider an infinite{buffered single server First In, First Out (FIFO) queue. Messages arrives at stochastic intervals and take random amounts of time to process. Logarithmic asymptotics are proved for the tail of the distribution of the number of messages awaiting service, under general large deviation and stability assumptions, and formulae presented for the asymptotic decay rate

Logarithmic asymptotics for unserved messages at a FIFO

We consider an infinite{buffered single server First In, First Out (FIFO) queue. Messages arrives at stochastic intervals and take random amounts of time to process. Logarithmic asymptotics are proved for the tail of the distribution of the number of messages awaiting service, under general large deviation and stability assumptions, and formulae presented for the asymptotic decay rate

Logarithmic asymptotics for the supremum of a stochastic process

Logarithmic asymptotics are proved for the tail of the supremum of a stochastic process, under the assumption that the process satisfies a restricted large deviation principle on regularly varying scales. The formula for the rate of decay of the tail of the supremum, in terms of the underlying rate function, agrees with that stated by Duffield and O’Connell [Math. Proc. Cambridge Philos. Soc. (1995) 118 363–374]. The rate function of the process is not assumed to be convex. A number of queueing examples are presented which include applications to Gaussian processes and Weibull sojourn sources

What the rodent prefrontal cortex can teach us about attention-deficit/hyperactivity disorder: The critical role of early developmental events on prefrontal function

The present review surveys a broad range of findings on the functions of the rodent prefrontal cortex (PFC) in the context of the known pathophysiology of attention-deficit/hyperactivity disorder (ADHD). An overview of clinical findings concludes that dysfunction of the right PFC plays a critical role in ADHD and that a number of early developmental factors conspire to increase the risk of the disorder. Rodent studies are described which go far in explaining how the core processes which are deficient in ADHD are mediated by the PFC and that the mesocortical dopamine (DA) system plays a central role in modulating these functions. These studies also demonstrate a surprising degree of cerebral lateralization of prefrontal function in the rat. Importantly, the PFC is highly vulnerable to a wide variety of early developmental insults, which parallel the known risk factors for ADHD. It is suggested that the regulation of physiological and behavioral arousal is a fundamental role of the PFC, upon which many “higher” prefrontal functions are dependent or at least influenced. These right hemispheric arousal systems, of which the mesocortical DA system is a component, are greatly affected by early adverse events, both peri- and post-natally. Abnormal development, particularly of the right PFC and its DAergic afferents, is suggested to contribute directly to the core deficits of ADHD through dysregulation of the right frontostriatal system

Carisbamate Blockade of T-Type Voltage-Gated Calcium Channels

Objectives Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca2+]i. Methods We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca2+]i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca2+ channels. Results In CA3 pyramidal neurons, kainic acid induced significant elevations in [Ca2+]i and long‐lasting neuronal hyperexcitability, both of which were reversed in a dose‐dependent manner by CRS. Similarly, CRS suppressed spontaneous rhythmic epileptiform activity in hippocampal slices exposed to zero‐Mg2+ or 4‐aminopyridine. Treatment with CRS also protected murine hippocampal HT‐22 cells against excitotoxic injury with glutamate, and this was accompanied by a reduction in [Ca2+]i. Neither kainic acid nor CRS alone altered the mitochondrial membrane potential (ΔΨ) in intact, acutely isolated mitochondria. In addition, CRS did not affect mitochondrial respiratory chain activity, Ca2+‐induced mitochondrial permeability transition, and Ca2+ release from the ER. However, CRS significantly decreased Ca2+ flux in human embryonic kidney tsA‐201 cells transfected with Cav3.1 (voltage‐dependent T‐type Ca2+) channels. Significance Our data indicate that the neuroprotective and antiseizure activity of CRS likely results in part from decreased [Ca2+]i accumulation through blockade of T‐type Ca2+ channels

High Frequency of Cytomegalovirus-Specific Cytotoxic T-Effector Cells in HLA-A*0201-Positive Subjects during Multiple Viral Coinfections

How the cellular immune response copes with diverse antigenic competition is poorly understood. Responses of virus-specific cytotoxic T lymphocytes (CTL) were examined longitudinally in an individual coinfected with human immunodeficiency virus type 1 (HIV-1), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). CTL responses to all 3 viruses were quantified by limiting dilution analysis and staining with HLA-A*0201 tetrameric complexes folded with HIV-1, EBV, and CMV peptides. A predominance of CMV-pp65-speciflc CTL was found, with a much lower frequency of CTL to HIV-1 Gag and Pol and to EBV-BMLF1 and LMP2. The high frequency of CMV-speciflc CTL, compared with HIV-1- and EBV-specific CTL, was confirmed in an additional 16 HLA-A*0201-positive virus-coinfected subjects. Therefore, the human immune system can mount CTL responses to multiple viral antigens simultaneously, albeit with different strength