Repair systems with exchangeable items and the longest queue mechanism

We consider a repair facility consisting of one repairman and two arrival streams of failed items, from bases 1 and 2. The arrival processes are independent Poisson processes, and the repair times are independent and identically exponentially distributed. The item types are exchangeable, and a failed item from base 1 could just as well be returned to base 2, and vice versa. The rule according to which backorders are satisfied by repaired items is the longest queue rule: at the completion of a service (repair), the repaired item is delivered to the base that has the largest number of failed items. We point out a direct relation between our model and the classical longer queue model. We obtain simple expressions for several probabilities of interest, and show how all two-dimensional queue length probabilities may be obtained. Finally, we derive the sojourn time distributions

Phosphatidylinositol kinase is reduced in Alzheimer's disease

Abstract: Phosphatidylinositol (PI) kinase and PI phosphate (PIP) kinase activities were measured in postmortem samples of brain tissue from patients with Alzheimer's disease and nondemented control subjects. A membrane‐free cytosolic fraction from four neocortical locations, with exogenous inositol lipids as the substrate, was used. Tissue from patients with Alzheimer's disease was characterized by reduced PIP formation; the reduction was 50% in prefrontal cortex, temporal cortex, and parietal cortex and 40% in precentral gyrus. In contrast, no alterations were found in PI bisphosphate formation in these four neocortical locations. The specific changes in PI kinase but not PIP kinase activity suggest that the findings may have functional relevance to the involvement of brain membrane processes in Alzheimer's disease

Activation of adenosine A2B receptors enhances ciliary beat frequency in mouse lateral ventricle ependymal cells

<p>Abstract</p> <p>Background</p> <p>Ependymal cells form a protective monolayer between the brain parenchyma and cerebrospinal fluid (CSF). They possess motile cilia important for directing the flow of CSF through the ventricular system. While ciliary beat frequency in airway epithelia has been extensively studied, fewer reports have looked at the mechanisms involved in regulating ciliary beat frequency in ependyma. Prior studies have demonstrated that ependymal cells express at least one purinergic receptor (P2X₇). An understanding of the full range of purinergic receptors expressed by ependymal cells, however, is not yet complete. The objective of this study was to identify purinergic receptors which may be involved in regulating ciliary beat frequency in lateral ventricle ependymal cells.</p> <p>Methods</p> <p>High-speed video analysis of ciliary movement in the presence and absence of purinergic agents was performed using differential interference contrast microscopy in slices of mouse brain (total number of animals = 67). Receptor identification by this pharmacological approach was corroborated by immunocytochemistry, calcium imaging experiments, and the use of two separate lines of knockout mice.</p> <p>Results</p> <p>Ciliary beat frequency was enhanced by application of a commonly used P2X₇agonist. Subsequent experiments, however, demonstrated that this enhancement was observed in both P2X₇^+/+and P2X₇^-/-mice and was reduced by pre-incubation with an ecto-5'-nucleotidase inhibitor. This suggested that enhancement was primarily due to a metabolic breakdown product acting on another purinergic receptor subtype. Further studies revealed that ciliary beat frequency enhancement was also induced by adenosine receptor agonists, and pharmacological studies revealed that ciliary beat frequency enhancement was primarily due to A_2Breceptor activation. A_2Bexpression by ependymal cells was subsequently confirmed using A_2B^-/-/β-galactosidase reporter gene knock-in mice.</p> <p>Conclusion</p> <p>This study demonstrates that A_2Breceptor activation enhances ciliary beat frequency in lateral ventricle ependymal cells. Ependymal cell ciliary beat frequency regulation may play an important role in cerebral fluid balance and cerebrospinal fluid dynamics.</p

Measurement error in the estimation of intake from herbage patches by non-fistulated heifers on apparently uniform swards

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Chew-Bites, Jaw Movement Allocation and Bite Rate in Grazing Cattle as Identified by Acoustic Monitoring

Bite rate derives from the time budget of the biting and chewing processes of intake, which are both performed by jaw movements. A new type of jaw movement was revealed by acoustic monitoring in cattle - the chew-bite -which chews herbage already in the mouth and harvests fresh herbage with the same jaw movement (Laca et al., 1992). Chew-biting should enable the animal to reduce the total number of jaw movements performed per bite without reducing the number of chews per bite. We examined the variation among individuals in the allocation of jaw movements between the three types, and its relation to bite rate

The Importance of Patch Size in Estimating Steady-State Bite Rate in Grazing Cattle

Since the pioneering work of Black and Kenney (1984), various intake studies have been conducted at the spatial scale of a single feeding station ( patch ) to elucidate the processes that determine instantaneous intake rate (e.g. Laca et al., 1994). While these are well-suited for patch depletion studies, it is less clear how well they represent non-patchy and relatively homogeneous environments (Ungar & Griffiths, 2002). Clearly, grazing should be restricted to the upper grazing horizon (i.e. layer of bites), but sample duration may be insufficient to characterize steady-state behaviour, especially when grazing commences on an empty mouth. We examined the impact of feeding station size on bite rate and jaw movement allocation between bites and chews

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion.

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance