119 research outputs found

    Response Time Approximations in Fork-Join Queues

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    Fork-join queueing networks model a network of parallel servers in which an arriving job splits into a number of subtasks that are serviced in parallel. Fork-join queues can be used to model disk arrays. A response time approximation of the fork-join queue is presented that attempts to comply with the additional constraints of modelling a disk array. This approximation is compared with existing analytical approximations of the fork-join queueing network

    Validation of Large Zoned RAID Systems

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    Building on our prior work we present an improved model for for large partial stripe following full stripe writes in RAID 5. This was necessary because we observed that our previous model tended to underestimate measured results. To date, we have only validated these models against RAID systems with at most four disks. Here we validate our improved model, and also our existing models for other read and write configurations, against measurements taken from an eight disk RAID array

    Standard and inverse site percolation of straight rigid rods on triangular lattices: Isotropic and nematic deposition/removal

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    Numerical simulations and finite-size scaling analysis have been carried out to study standard and inverse percolation of straight rigid rods on triangular lattices. In the case of standard (inverse) percolation, the lattice is initially empty(occupied) and linear kk-mers (kk linear consecutive sites) are randomly and sequentially deposited on(removed from) the lattice, considering an isotropic and nematic scheme. The study is conducted by following the behavior of four critical concentrations with the size kk, determined for a wide range of kk : (i)(i)[(ii)(ii)] standard isotropic[nematic] percolation threshold θc,k\theta_{c,k}[ϑc,k\vartheta_{c,k}], and (iii)(iii)[(iv)(iv)] inverse isotropic[nematic] percolation threshold θc,ki\theta^i_{c,k}[ϑc,ki\vartheta^i_{c,k}]. The obtained results indicate that: (1)(1) θc,k\theta_{c,k}[θc,ki\theta^i_{c,k}] exhibits a non-monotonous dependence with kk. It decreases[increases], goes through a minimum[maximum] around k=11k = 11, then increases and asymptotically converges towards a definite value for large kk θc,k=0.500(2)\theta_{c,k \rightarrow \infty}=0.500(2)[θc,ki=0.500(1)\theta^i_{c,k \rightarrow \infty}=0.500(1)]; (2)(2) ϑc,k\vartheta_{c,k}[ϑc,ki\vartheta^i_{c,k}] rapidly increases[decreases] and asymptotically converges towards a definite value for infinitely long kk-mers ϑc,k=0.5334(6)\vartheta_{c,k \rightarrow \infty}=0.5334(6)[ϑc,ki=0.4666(6)\vartheta^i_{c,k \rightarrow \infty}=0.4666(6)]; (3)(3) for both models, the curves of standard and inverse percolation thresholds are symmetric with respect to θ=0.5\theta = 0.5. Thus, a complementary property is found θc,k+θc,ki=1\theta_{c,k} + \theta^i_{c,k} = 1 (and ϑc,k+ϑc,ki=1\vartheta_{c,k} + \vartheta^i_{c,k} = 1), which has not been observed in other regular lattices. This condition is analytically validated by using exact enumeration of configurations for small systems; and (4)(4) in all cases, the model presents percolation transition for the whole range of kk

    Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer--comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial.

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    Defining risk categories in breast cancer is of considerable clinical significance. We have developed a novel risk classification algorithm and compared its prognostic utility to the Web-based tool Adjuvant! and to the St Gallen risk classification. After a median follow-up of 10 years, we retrospectively analyzed 410 consecutive node-negative breast cancer patients who had not received adjuvant systemic therapy. High risk was defined by any of the following criteria: (i) age <35 years, (ii) grade 3, (iii) human epithelial growth factor receptor-2 positivity, (iv) vascular invasion, (v) progesterone receptor negativity, (vi) grade 2 tumors >2 cm. All patients were also characterized using Adjuvant! and the St Gallen 2007 risk categories. We analyzed disease-free survival (DFS) and overall survival (OS). The Node-Negative-Breast Cancer-3 (NNBC-3) algorithm enlarged the low-risk group to 37% as compared with Adjuvant! (17%) and St Gallen (18%), respectively. In multivariate analysis, both Adjuvant! [P = 0.027, hazard ratio (HR) 3.81, 96% confidence interval (CI) 1.16-12.47] and the NNBC-3 risk classification (P = 0.049, HR 1.95, 95% CI 1.00-3.81) significantly predicted OS, but only the NNBC-3 algorithm retained its prognostic significance in multivariate analysis for DFS (P < 0.0005). The novel NNBC-3 risk algorithm is the only clinicopathological risk classification algorithm significantly predicting DFS as well as OS

    Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer—comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial

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    Background: Defining risk categories in breast cancer is of considerable clinical significance. We have developed a novel risk classification algorithm and compared its prognostic utility to the Web-based tool Adjuvant! and to the St Gallen risk classification. Patients and methods: After a median follow-up of 10 years, we retrospectively analyzed 410 consecutive node-negative breast cancer patients who had not received adjuvant systemic therapy. High risk was defined by any of the following criteria: (i) age 2 cm. All patients were also characterized using Adjuvant! and the St Gallen 2007 risk categories. We analyzed disease-free survival (DFS) and overall survival (OS). Results: The Node-Negative-Breast Cancer-3 (NNBC-3) algorithm enlarged the low-risk group to 37% as compared with Adjuvant! (17%) and St Gallen (18%), respectively. In multivariate analysis, both Adjuvant! [P = 0.027, hazard ratio (HR) 3.81, 96% confidence interval (CI) 1.16-12.47] and the NNBC-3 risk classification (P = 0.049, HR 1.95, 95% CI 1.00-3.81) significantly predicted OS, but only the NNBC-3 algorithm retained its prognostic significance in multivariate analysis for DFS (P < 0.0005). Conclusion: The novel NNBC-3 risk algorithm is the only clinicopathological risk classification algorithm significantly predicting DFS as well as O

    Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

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    In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

    High-dose clevudine impairs mitochondrial function and glucose-stimulated insulin secretion in INS-1E cells

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    <p>Abstract</p> <p>Background</p> <p>Clevudine is a nucleoside analog reverse transcriptase inhibitor that exhibits potent antiviral activity against hepatitis B virus (HBV) without serious side effects. However, mitochondrial myopathy has been observed in patients with chronic HBV infection taking clevudine. Moreover, the development of diabetes was recently reported in patients receiving long-term treatment with clevudine. In this study, we investigated the effects of clevudine on mitochondrial function and insulin release in a rat clonal β-cell line, INS-1E.</p> <p>Methods</p> <p>The mitochondrial DNA (mtDNA) copy number and the mRNA levels were measured by using quantitative PCR. MTT analysis, ATP/lactate measurements, and insulin assay were performed.</p> <p>Results</p> <p>Both INS-1E cells and HepG2 cells, which originated from human hepatoma, showed dose-dependent decreases in mtDNA copy number and cytochrome c oxidase-1 (Cox-1) mRNA level following culture with clevudine (10 μM-1 mM) for 4 weeks. INS-1E cells treated with clevudine had reduced total mitochondrial activities, lower cytosolic ATP contents, enhanced lactate production, and more lipid accumulation. Insulin release in response to glucose application was markedly decreased in clevudine-treated INS-1E cells, which might be a consequence of mitochondrial dysfunction.</p> <p>Conclusions</p> <p>Our data suggest that high-dose treatment with clevudine induces mitochondrial defects associated with mtDNA depletion and impairs glucose-stimulated insulin secretion in insulin-releasing cells. These findings partly explain the development of diabetes in patients receiving clevudine who might have a high susceptibility to mitochondrial toxicity.</p

    Perceptual Other-Race Training Reduces Implicit Racial Bias

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    Background: Implicit racial bias denotes socio-cognitive attitudes towards other-race groups that are exempt from conscious awareness. In parallel, other-race faces are more difficult to differentiate relative to own-race faces – the ‘‘Other-Race Effect.’ ’ To examine the relationship between these two biases, we trained Caucasian subjects to better individuate other-race faces and measured implicit racial bias for those faces both before and after training. Methodology/Principal Findings: Two groups of Caucasian subjects were exposed equally to the same African American faces in a training protocol run over 5 sessions. In the individuation condition, subjects learned to discriminate between African American faces. In the categorization condition, subjects learned to categorize faces as African American or not. For both conditions, both pre- and post-training we measured the Other-Race Effect using old-new recognition and implicit racial biases using a novel implicit social measure – the ‘‘Affective Lexical Priming Score’ ’ (ALPS). Subjects in the individuation condition, but not in the categorization condition, showed improved discrimination of African American faces with training. Concomitantly, subjects in the individuation condition, but not the categorization condition, showed a reduction in their ALPS. Critically, for the individuation condition only, the degree to which an individual subject’s ALPS decreased was significantly correlated with the degree of improvement that subject showed in their ability to differentiate African American faces

    Evolutionary Mirages: Selection on Binding Site Composition Creates the Illusion of Conserved Grammars in Drosophila Enhancers

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    The clustering of transcription factor binding sites in developmental enhancers and the apparent preferential conservation of clustered sites have been widely interpreted as proof that spatially constrained physical interactions between transcription factors are required for regulatory function. However, we show here that selection on the composition of enhancers alone, and not their internal structure, leads to the accumulation of clustered sites with evolutionary dynamics that suggest they are preferentially conserved. We simulated the evolution of idealized enhancers from Drosophila melanogaster constrained to contain only a minimum number of binding sites for one or more factors. Under this constraint, mutations that destroy an existing binding site are tolerated only if a compensating site has emerged elsewhere in the enhancer. Overlapping sites, such as those frequently observed for the activator Bicoid and repressor Krüppel, had significantly longer evolutionary half-lives than isolated sites for the same factors. This leads to a substantially higher density of overlapping sites than expected by chance and the appearance that such sites are preferentially conserved. Because D. melanogaster (like many other species) has a bias for deletions over insertions, sites tended to become closer together over time, leading to an overall clustering of sites in the absence of any selection for clustered sites. Since this effect is strongest for the oldest sites, clustered sites also incorrectly appear to be preferentially conserved. Following speciation, sites tend to be closer together in all descendent species than in their common ancestors, violating the common assumption that shared features of species' genomes reflect their ancestral state. Finally, we show that selection on binding site composition alone recapitulates the observed number of overlapping and closely neighboring sites in real D. melanogaster enhancers. Thus, this study calls into question the common practice of inferring “cis-regulatory grammars” from the organization and evolutionary dynamics of developmental enhancers

    Attentional Prioritization of Infant Faces Is Limited to Own-Race Infants

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    Background: Recent evidence indicates that infant faces capture attention automatically, presumably to elicit caregiving behavior from adults and leading to greater probability of progeny survival. Elsewhere, evidence demonstrates that people show deficiencies in the processing of other-race relative to own-race faces. We ask whether this other-race effect impacts on attentional attraction to infant faces. Using a dot-probe task to reveal the spatial allocation of attention, we investigate whether other-race infants capture attention. Principal Findings: South Asian and White participants (young adults aged 18–23 years) responded to a probe shape appearing in a location previously occupied by either an infant face or an adult face; across trials, the race (South Asian/ White) of the faces was manipulated. Results indicated that participants were faster to respond to probes that appeared in the same location as infant faces than adult faces, but only on own-race trials. Conclusions/Significance: Own-race infant faces attract attention, but other-race infant faces do not. Sensitivity to facespecific care-seeking cues in other-race kindenschema may be constrained by interracial contact and experience
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