5,769 research outputs found

    On redundancy in simple temporal networks

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    © 2016 The Authors and IOS Press. The Simple Temporal Problem (STP) has been widely used in various applications to schedule tasks. For dynamical systems, scheduling needs to be efficient and flexible to handle uncertainty and perturbation. To this end, modern approaches usually encode the temporal information as an STP instance. This representation contains redundant information, which can not only take a significant amount of storage space, but also make scheduling inefficient due to the non-concise representation. In this paper, we investigate the problem of simplifying an STP instance by removing redundant information. We show that such a simplification can result in a unique minimal representation without loss of temporal information, and present an efficient algorithm to achieve this task. Evaluation on a large benchmark dataset of STP exhibits a significant reduction in redundant information for the involved instances

    Accretion disc winds in tidal disruption events: Ultraviolet spectral lines as orientation indicators

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    ABSTRACT Some tidal disruption events (TDEs) exhibit blueshifted broad absorption lines (BALs) in their rest-frame ultraviolet (UV) spectra, while others display broad emission lines (BELs). Similar phenomenology is observed in quasars and accreting white dwarfs, where it can be interpreted as an orientation effect associated with line formation in an accretion disc wind. We propose and explore a similar unification scheme for TDEs. We present synthetic UV spectra for disc and wind-hosting TDEs, produced by a state-of-the-art Monte Carlo ionization and radiative transfer code. Our models cover a wide range of disc wind geometries and kinematics. Such winds naturally reproduce both BALs and BELs. In general, sightlines looking into the wind cone preferentially produce BALs, while other orientations preferentially produce BELs. We also study the effect of wind clumping and CNO-processed abundances on the observed spectra. Clumpy winds tend to produce stronger UV emission and absorption lines, because clumping increases both the emission measure and the abundances of the relevant ionic species, the latter by reducing the ionization state of the outflow. The main effect of adopting CNO-processed abundances is a weakening of C iv 1550 Å  and an enhancement of N v 1240 Å  in the spectra. We conclude that line formation in an accretion disc wind is a promising mechanism for explaining the diverse UV spectra of TDEs. If this is correct, the relative number of BAL and BEL TDEs can be used to estimate the covering factor of the outflow. The models in this work are publicly available online and upon request.</jats:p

    Minor differences in haplotype frequency estimates can produce very large differences in heterogeneity test statistics

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    <p>Abstract</p> <p>Background</p> <p>Tests for association between a haplotype and disease are commonly performed using a likelihood ratio test for heterogeneity between case and control haplotype frequencies. Using data from a study of association between heroin dependence and the DRD2 gene, we obtained estimated haplotype frequencies and the associated likelihood ratio statistic using two different computer programs, MLOCUS and GENECOUNTING. We also carried out permutation testing to assess the empirical significance of the results obtained.</p> <p>Results</p> <p>Both programs yielded similar, though not identical, estimates for the haplotype frequencies. MLOCUS produced a p value of 1.8*10<sup>-15 </sup>and GENECOUNTING produced a p value of 5.4*10<sup>-4</sup>. Permutation testing produced a p value 2.8*10<sup>-4</sup>.</p> <p>Conclusion</p> <p>The fact that very large differences occur between the likelihood ratio statistics from the two programs may reflect the fact that the haplotype frequencies for the combined group are not constrained to be equal to the weighted averages of the frequencies for the cases and controls, as they would be if they were directly observed rather than being estimated. Minor differences in haplotype frequency estimates can result in very large differences in the likelihood ratio statistic and associated <it>p </it>value.</p

    How a turn to critical race theory can contribute to our understanding of 'race', racism and anti-racism in sport

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    As long as racism has been associated with sport there have been consistent, if not coordinated or coherent, struggles to confront its various forms. Critical race theory (CRT) is a framework established to challenge these racialized inequalities and racism in society and has some utility for anti-racism in sport. CRT's focus on social justice and transformation are two areas of convergence between critical race theorists and anti-racists. Of the many nuanced and pernicious forms of racism, one of the most obvious and commonly reported forms of racism in sport, racial abuse, has been described as a kind of dehumanizing process by Gardiner (2003), as those who are its target are simultaneously (re)constructed and objectified according to everyday myth and fantasy. However, this is one of the many forms of everyday racist experiences. Various forms of racism can be experienced in boardrooms, on television, in print, in the stands, on the sidelines and on the pitch. Many times racism is trivialized and put down as part of the game (Long et al., 2000), yet its impact is rarely the source of further exploration. This article will explore the conceptualization of 'race' and racism for a more effective anti-racism. Critical race theory will also be used to explore the ideas that underpin considerations of the severity of racist behaviour and the implications for anti-racism. © The Author(s) 2010

    Inhibition of CK2α Down-Regulates Hedgehog/Gli Signaling Leading to a Reduction of a Stem-Like Side Population in Human Lung Cancer Cells

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    Protein kinase CK2 is frequently elevated in a variety of human cancers. The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance, and its aberrant activation has been indicated in several types of cancer, including lung cancer. In this study, we show that CK2 is positively involved in Hh/Gli signaling in lung cancer cell lines A549 and H1299. First, we found a correlation between CK2α and Gli1 mRNA levels in 100 primary lung cancer tissues. Down-regulation of Gli1 expression and transcriptional activity were demonstrated after the silencing of CK2α in lung cancer cells. In addition, CK2α siRNA down-regulated the expression of Hh target genes. Furthermore, two small-molecule CK2α inhibitors led to a dose-dependent inhibition of Gli1 expression and transcriptional activity in lung cancer cells. Reversely, forced over-expression of CK2α resulted in an increase both in Gli1 expression and transcriptional activity in A549 cells. Finally, the inhibition of Hh/Gli by CK2α siRNA led to a reduction of a cancer stem cell-like side population that shows higher ABCG2 expression level. Thus, we report that the inhibition of CK2α down-regulates Hh/Gli signaling and subsequently reduces stem-like side population in human lung cancer cells

    Investigating CXCR4 expression of tumor cells and the vascular compartment: A multimodal approach

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    The C-X-C chemokine receptor 4 (CXCR4) is G protein-coupled receptor that upon binding to its cognate ligand, can lead to tumor progression. Several CXCR4-targeted therapies are currently under investigation, and with it comes the need for imaging agents capable of accurate depiction of CXCR4 for therapeutic stratification and monitoring. PET agents enjoy the most success, but more cost-effective and radiation-free approaches such as ultrasound (US) imaging could represent an attractive alternative. In this work, we developed a targeted microbubble (MB) for imaging of vascular CXCR4 expression in cancer. A CXCR4-targeted MB was developed through incorporation of the T140 peptide into the MB shell. Binding properties of the T140-MB and control, non-targeted MB (NT-MB) were evaluated in MDA-MB-231 cells where CXCR4 expression was knocked-down (via shRNA) through optical imaging, and in the lymphoma tumor models U2932 and SuDHL8 (high and low CXCR4 expression, respectively) by US imaging. PET imaging of [18F]MCFB, a tumor-penetrating CXCR4-targeted small molecule, was used to provide whole-tumor CXCR4 readouts. CXCR4 expression and microvessel density were performed by immunohistochemistry analysis and western blot. T140-MB were formed with similar properties to NT-MB and accumulated sensitively and specifically in cells according to their CXCR4 expression. In NOD SCID mice, T140-MB persisted longer in tumors than NT-MB, indicative of target interaction, but showed no difference between U2932 and SuDHL8. In contrast, PET imaging with [18F]MCFB showed a marked difference in tumor uptake at 40–60 min post-injection between the two tumor models (p<0.05). Ex vivo analysis revealed that the large differences in CXCR4 expression between the two models are not reflected in the vascular compartment, where the MB are restricted; in fact, microvessel density and CXCR4 expression in the vasculature was comparable between U2932 and SuDHL8 tumors. In conclusion, we successfully developed a T140-MB that can be used for imaging CXCR4 expression in the tumor vasculature

    Evaluation of [18F]AlF-EMP-105 for molecular imaging of 2 C-Met

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    C-Met is a receptor tyrosine kinase that is overexpressed in a range of different cancer types, and has been identified as a potential biomarker for cancer imaging and therapy. Previously, a 68Ga-labelled peptide, [68Ga]Ga-EMP-100, has shown promise for imaging c-Met in renal cell carcinoma in humans. Herein, we report the synthesis and preliminary biological evaluation of an [18F]AlF-labelled analogue, [18F]AlF-EMP-105, for c-Met imaging by positron emission tomography. EMP-105 was radiolabelled using the aluminium-[18F]fluoride method with 46 ± 2% RCY and >95% RCP in 35–40 min. In vitro evaluation showed that [18F]AlF-EMP-105 has a high specificity for c-Met-expressing cells. Radioactive metabolite analysis at 5 and 30 min post-injection revealed that [18F]AlF-EMP-105 has good blood stability, but undergoes transformation—transchelation, defluorination or demetallation—in the liver and kidneys. PET imaging in non-tumour-bearing mice showed high radioactive accumulation in the kidneys, bladder and urine, demonstrating that the tracer is cleared predominantly as [18F]fluoride by the renal system. With its high specificity for c-Met expressing cells, [18F]AlF-EMP-105 shows promise as a potential diagnostic tool for imaging cancer
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