Optimality of the Fastest Available Server Policy

We give sufficient conditions under which a policy that assigns customers to the Fastest Available Server, labelled FAS, is optimal in queueing models with multiple independent Poisson arrival processes and heterogeneous parallel exponential servers. The criterion is to minimize the long-run average cost per unit time. We obtain results for loss models and for queueing systems with a finite-capacity or infinite-capacity buffer under a head-of-the-line priority scheme. The results depend on cost assumptions, so we analyze the robustness of the cost structure and present counter-examples to illustrate when FAS is not optimal

A commentary on current practice in mediating variable analyses in behavioural nutrition and physical activity

Objective : To critique current practice in, and provide recommendations for, mediating variable analyses (MVA) of nutrition and physical activity behaviour change. Strategy : Theory-based behavioural nutrition and physical activity interventions aim at changing mediating variables that are hypothesized to be responsible for changes in the outcome of interest. MVA are useful because they help to identify the most promising theoretical approaches, mediators and intervention components for behaviour change. However, the current literature suggests that MVA are often inappropriately conducted, poorly understood and inadequately presented. Main problems encountered in the published literature are explained and suggestions for overcoming weaknesses of current practice are proposed. Conclusion : The use of the most appropriate, currently available methods of MVA, and a correct, comprehensive presentation and interpretation of their findings, is of paramount importance for understanding how obesity can be treated and prevented

Vulvovaginal Trichosporonosis

Objective: Isolation of Trichosporon species from vaginal secretions is a rare event, and no data are available on its pathogenic role. A case series is presented to determine the pathogenic role of Trichosporon species in vulvovaginal infections. Methods: We performed a retrospective chart review of patients seen in the W.S.U. Vaginitis Clinic in order to identify patients from whom Trichosporon species were isolated. Results: Between 1986 and 2001, a total of 13 patients had a total of 18 positive vaginal cultures for Trichosporon species. All 18 vaginal isolates were T. inkin. In general, positive vaginal cultures were accompanied by low yeast colony counts. Four out of 18 positive T. inkin cultures were obtained from visits by asymptomatic patients. Of the remaining 14 positive T. inkin cultures from patients with symptoms, nine out of 14 cultures had other diagnoses (Candida albicans, six cases; bacterial vaginosis, two cases; Trichomonas, one case). Five positive T. inkin cultures were obtained from visits at which patients had symptoms and no associated diagnosis. In only one of the five episodes could we establish a clear pathogenic role for Trichosporon. In this case the patient was treated with boric acid and had resolution of symptoms and a negative culture at follow-up. In-vitro susceptibility tests revealed that T. inkin was resistant to flucytosine and susceptible to all topical and oral azoles. Conclusions: T. inkin is occasionally found in vulvovaginal cultures and is usually a non-pathogen. Transient colonization tended to occur in women, usually of African—American origin, with major perturbations in vaginal flora (bacterial vaginosis and trichomoniasis) and increased pH. Pathogenic consequences of Trichosporon colonization appear to be rare

Induction of Paralysis and Visual System Injury in Mice by T Cells Specific for Neuromyelitis Optica Autoantigen Aquaporin-4.

While it is recognized that aquaporin-4 (AQP4)-specific T cells and antibodies participate in the pathogenesis of neuromyelitis optica (NMO), a human central nervous system (CNS) autoimmune demyelinating disease, creation of an AQP4-targeted model with both clinical and histologic manifestations of CNS autoimmunity has proven challenging. Immunization of wild-type (WT) mice with AQP4 peptides elicited T cell proliferation, although those T cells could not transfer disease to naïve recipient mice. Recently, two novel AQP4 T cell epitopes, peptide (p) 135-153 and p201-220, were identified when studying immune responses to AQP4 in AQP4-deficient (AQP4-/-) mice, suggesting T cell reactivity to these epitopes is normally controlled by thymic negative selection. AQP4-/- Th17 polarized T cells primed to either p135-153 or p201-220 induced paralysis in recipient WT mice, that was associated with predominantly leptomeningeal inflammation of the spinal cord and optic nerves. Inflammation surrounding optic nerves and involvement of the inner retinal layers (IRL) were manifested by changes in serial optical coherence tomography (OCT). Here, we illustrate the approaches used to create this new in vivo model of AQP4-targeted CNS autoimmunity (ATCA), which can now be employed to study mechanisms that permit development of pathogenic AQP4-specific T cells and how they may cooperate with B cells in NMO pathogenesis

Proteome-Wide Effect of 17-β-Estradiol and Lipoxin A4 in an Endometriotic Epithelial Cell Line.

Endometriosis affects approximately 10% of women of reproductive age. This chronic, gynecological inflammatory disease results in a decreased quality of life for patients, with the main symptoms including chronic pelvic pain and infertility. The steroid hormone 17-β Estradiol (E2) plays a key role in the pathology. Our previous studies showed that the anti-inflammatory lipid Lipoxin A4 (LXA4) acts as an estrogen receptor-alpha agonist in endometrial epithelial cells, inhibiting certain E2-mediated effects. LXA4 also prevents the progression of endometriosis in a mouse model via anti-proliferative mechanisms and by impacting mediators downstream of ER signaling. The aim of the present study was therefore to examine global proteomic changes evoked by E2 and LXA4 in endometriotic epithelial cells. E2 impacted a greater number of proteins in endometriotic epithelial cells than LXA4. Interestingly, the combination of E2 and LXA4 resulted in a reduced number of regulated proteins, with LXA4 mediating a suppressive effect on E2-mediated signaling. These proteins are involved in diverse pathways of relevance to endometriosis pathology and metabolism, including mRNA translation, growth, proliferation, proteolysis, and immune responses. In summary, this study sheds light on novel pathways involved in endometriosis pathology and further understanding of signaling pathways activated by estrogenic molecules in endometriotic epithelial cells

Understanding Hadley Cell Expansion versus Contraction: Insights from Simplified Models and Implications for Recent Observations

This study seeks a deeper understanding of the causes of Hadley Cell (HC) expansion, as projected under global warming, and HC contraction, as observed under El Niño. Using an idealized general circulation model, the authors show that a thermal forcing applied to a narrow region around the equator produces “El Niño–like” HC contraction, while a forcing with wider meridional extent produces “global warming–like” HC expansion. These circulation responses are sensitive primarily to the thermal forcing’s meridional structure and are less sensitive to its vertical structure. If the thermal forcing is confined to the midlatitudes, the amount of HC expansion is more than three times that of a forcing of comparable amplitude that is spread over the tropics. This finding may be relevant to recently observed trends of rapid tropical widening. The shift of the HC edge is explained using a very simple model in which the transformed Eulerian mean (TEM) circulation acts to diffuse heat meridionally. In this context, the HC edge is defined as the downward maximum of residual vertical velocity in the upper troposphere ϖmax *; this corresponds well with the conventional Eulerian definition of the HC edge. In response to a positive thermal forcing, there is anomalous diabatic cooling, and hence anomalous TEM descent, on the poleward flank of the thermal forcing. This causes the HC edge (ϖmax *) to shift toward the descending anomaly, so that a narrow forcing causes HC contraction and a wide forcing causes HC expansion

Neutrino-induced deuteron disintegration experiment

Cross sections for the disintegration of the deuteron via neutral-current (NCD) and charged-current (CCD) interactions with reactor antineutrinos are measured to be 6.08 +/- 0.77 x 10^(-45) cm-sq and 9.83 +/- 2.04 x 10^(-45) cm-sq per neutrino, respectively, in excellent agreement with current calculations. Since the experimental NCD value depends upon the CCD value, if we use the theoretical value for the CCD reaction, we obtain the improved value of 5.98 +/- 0.54 x 10^(-45) for the NCD cross section. The neutral-current reaction allows a unique measurement of the isovector-axial vector coupling constant in the hadronic weak interaction (beta). In the standard model, this constant is predicted to be exactly 1, independent of the Weinberg angle. We measure a value of beta^2 = 1.01 +/- 0.16. Using the above improved value for the NCD cross section, beta^2 becomes 0.99 +/- 0.10.Comment: 22pages, 9 figure

Overexpression of stathmin in breast carcinomas points out to highly proliferative tumours

We recently discovered that stathmin was overexpressed in a subgroup of human breast carcinomas. Stathmin is a cytosolic phosphoprotein proposed to act as a relay integrating diverse cell signalling pathways, notably during the control of cell growth and differentiation. It may also be considered as one of the key regulators of cell division for its ability to destabilize microtubules in a phosphorylation-dependent manner. To assess the significance of stathmin overexpression in breast cancer, we evaluated the correlation of stathmin expression, quantified by reverse transcription polymerase chain reaction, with several disease parameters in a large series of human primary breast cancer (n = 133), obtained in strictly followed up women, whose clinico-pathological data were fully available. In agreement with our preliminary survey, stathmin was found overexpressed in a subgroup of tumours (22%). In addition, overexpression was correlated to the loss of steroid receptors (oestrogen, P = 0.0006; progesterone, P = 0.008), and to the Scarff–Bloom–Richardson histopathological grade III (P = 0.002), this latter being ascribable to the mitotic index component (P = 0.02). Furthermore studies at the DNA level indicated that stathmin is overexpressed irrespective of its genomic status. Our findings raise important questions concerning the causes and consequences of stathmin overexpression, and the reasons of its inability to counteract cell proliferation in the overexpression group. © 2000 Cancer Research Campaig

Merging microsatellite data: enhanced methodology and software to combine genotype data for linkage and association analysis

<p>Abstract</p> <p>Background</p> <p>Correctly merged data sets that have been independently genotyped can increase statistical power in linkage and association studies. However, alleles from microsatellite data sets genotyped with different experimental protocols or platforms cannot be accurately matched using base-pair size information alone. In a previous publication we introduced a statistical model for merging microsatellite data by matching allele frequencies between data sets. These methods are implemented in our software MicroMerge version 1 (v1). While MicroMerge v1 output can be analyzed by some genetic analysis programs, many programs can not analyze alignments that do not match alleles one-to-one between data sets. A consequence of such alignments is that codominant genotypes must often be analyzed as phenotypes. In this paper we describe several extensions that are implemented in MicroMerge version 2 (v2).</p> <p>Results</p> <p>Notably, MicroMerge v2 includes a new one-to-one alignment option that creates merged pedigree and locus files that can be handled by most genetic analysis software. Other features in MicroMerge v2 enhance the following aspects of control: 1) optimizing the algorithm for different merging scenarios, such as data sets with very different sample sizes or multiple data sets, 2) merging small data sets when a reliable set of allele frequencies are available, and 3) improving the quantity and 4) quality of merged data. We present results from simulated and real microsatellite genotype data sets, and conclude with an association analysis of three familial dyslipidemia (FD) study samples genotyped at different laboratories. Independent analysis of each FD data set did not yield consistent results, but analysis of the merged data sets identified strong association at locus D11S2002.</p> <p>Conclusion</p> <p>The MicroMerge v2 features will enable merging for a variety of genotype data sets, which in turn will facilitate meta-analyses for powering association analysis.</p