778 research outputs found

    Diversified spatial keyword search on road networks

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    With the increasing pervasiveness of the geo-positioning technologies, there is an enormous amount of spatio-textual objects available in many applications such as location based services and social networks. Consequently, various types of spatial keyword searches which explore both locations and textual descriptions of the objects have been intensively studied by the research communities and commercial organizations. In many important applications (e.g., location based services), the closeness of two spatial objects is measured by the road network distance. Moreover, the result diversification is becoming a common practice to enhance the quality of the search results. Motived by the above facts, in this paper we study the problem of diversified spatial keyword search on road networks which considers both the relevance and the spatial diversity of the results. An efficient signature-based inverted indexing technique is proposed to facilitate the spatial keyword query processing on road networks. Then we develop an efficient diversified spatial keyword search algorithm by taking advantage of spatial keyword pruning and diversity pruning techniques. Comprehensive experiments on real and synthetic data clearly demonstrate the efficiency of our methods

    Stress induced polarization of immune-neuroendocrine phenotypes in Gallus gallus

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    Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals’ interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-γ and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.Fil: Nazar, Franco Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Estevez, Inma. Centro de Investigación. Neiker - Tecnalia; EspañaFil: Correa, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Marin, Raul Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

    Overlapping committee membership and cost of equity capital

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    This study examines the association between overlapping committee membership and the cost of equity capital among listed companies in Australia. Overlapping committee membership occurs when a director serves on multiple supervisory committees concurrently. To the extent overlapping committee membership reduces information asymmetry, improves financial reporting quality, and consequently reduces the overall risk of the firms, we expect a negative relationship between overlapping membership and the cost of equity capital. Consistent with our argument, we find a positive impact of overlapping committee membership and provide evidence that firms with overlapping committee membership have a lower cost of equity capital. Furthermore, our results indicate that the positive impact of overlapping committee membership on the cost of equity capital is more evident when overlapping committee members are non-busy directors.fals

    Perspective of Saudi undergraduate pharmacy students on pharmacovigilance and adverse drug reaction reporting: A National Survey

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    Introduction: The purpose of this study was to evaluate Saudi undergraduate pharmacy students’ knowledge, attitude, and readiness towards pharmacovigilance and reporting of adverse drug reactions (ADRs). Methods: A cross-sectional survey was conducted between January 15, 2016 and February 18, 2016 using a structured, validated and pilot-tested questionnaire among senior (year 4, 5, and 6) undergraduate pharmacy students enrolled at a governmental or private university/college. Students completed an online 27-item questionnaire developed using Google Forms™. The questionnaire consisted of four sections: demographics; knowledge about pharmacovigilance and ADR reporting; attitudes towards ADR reporting; and pharmacy students’ readiness towards ADR reporting. Results: Two hundred and fifty-nine students completed the questionnaire. Most of the participants were females (n=174; 67.2%) and were year 4 (n=128; 49.4%) students. Out of a total possible score of seven, the mean knowledge score (SD) was 4.15 (1.1). Multiple linear regression showed that after adjusting for gender and program of study (BPharm/PharmD), year of the study was found to be an independent predictor (p=0.03) of the total knowledge score. More than half of the respondents (n=166; 64.1%) acknowledged that they do not know how to report ADRs to the relevant authorities in Saudi Arabia. The majority (n=213; 82.2%) of respondents believed that information on how to report ADRs should be taught to senior pharmacy students

    Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases.

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    Developmental and/or epileptic encephalopathies (DEEs) are a group of devastating genetic disorders, resulting in early-onset, therapy-resistant seizures and developmental delay. Here we report on 22 individuals from 15 families presenting with a severe form of intractable epilepsy, severe developmental delay, progressive microcephaly, visual disturbance and similar minor dysmorphisms. Whole exome sequencing identified a recurrent, homozygous variant (chr2:64083454A > G) in the essential UDP-glucose pyrophosphorylase (UGP2) gene in all probands. This rare variant results in a tolerable Met12Val missense change of the longer UGP2 protein isoform but causes a disruption of the start codon of the shorter isoform, which is predominant in brain. We show that the absence of the shorter isoform leads to a reduction of functional UGP2 enzyme in neural stem cells, leading to altered glycogen metabolism, upregulated unfolded protein response and premature neuronal differentiation, as modeled during pluripotent stem cell differentiation in vitro. In contrast, the complete lack of all UGP2 isoforms leads to differentiation defects in multiple lineages in human cells. Reduced expression of Ugp2a/Ugp2b in vivo in zebrafish mimics visual disturbance and mutant animals show a behavioral phenotype. Our study identifies a recurrent start codon mutation in UGP2 as a cause of a novel autosomal recessive DEE syndrome. Importantly, it also shows that isoform-specific start-loss mutations causing expression loss of a tissue-relevant isoform of an essential protein can cause a genetic disease, even when an organism-wide protein absence is incompatible with life. We provide additional examples where a similar disease mechanism applies

    Anti-cancer drug validation: the contribution of tissue engineered models

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    Abstract Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current Bstate of art^ on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their studyThis article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This article was also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.info:eu-repo/semantics/publishedVersio

    Energy allocation and behaviour in the growing broiler chicken

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    Broiler chickens are increasingly at the forefront of global meat production but the consequences of fast growth and selection for an increase in body mass on bird health are an ongoing concern for industry and consumers. To better understand the implications of selection we evaluated energetics and behaviour over the 6-week hatch-to-slaughter developmental period in a commercial broiler. The effect of posture on resting metabolic rate becomes increasingly significant as broilers grow, as standing became more energetically expensive than sitting. The proportion of overall metabolic rate accounted for by locomotor behaviour decreased over development, corresponding to declining activity levels, mean and peak walking speeds. These data are consistent with the inference that broilers allocate energy to activity within a constrained metabolic budget and that there is a reducing metabolic scope for exercise throughout their development. Comparison with similarly sized galliforms reveals that locomotion is relatively energetically expensive in broilers

    Whole‐brain steady‐state CEST at 3 T using MR Multitasking

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    PurposeTo perform fast 3D steady-state CEST (ss-CEST) imaging using MR Multitasking.MethodsA continuous acquisition sequence with repetitive ss-CEST modules was developed. Each ss-CEST module contains a single-lobe Gaussian saturation pulse, followed by a spoiler gradient and eight FLASH readouts (one "training line" + seven "imaging lines"). Three-dimensional Cartesian encoding was used for k-space acquisition. Reconstructed CEST images were quantified with four-pool Lorentzian fitting.ResultsSteady-state CEST with whole-brain coverage was performed in 5.6 s per saturation frequency offset at the spatial resolution of 1.7 × 1.7 × 3.0 mm3 . The total scan time was 5.5 min for 55 different frequency offsets. Quantitative CEST maps from multipool fitting showed consistent image quality across the volume.ConclusionThree-dimensional ss-CEST with whole-brain coverage can be done at 3 T within 5.5 min using MR Multitasking

    2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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    Repair and Reconstruction of a Resected Tumor Defect Using a Composite of Tissue Flap–Nanotherapeutic–Silk Fibroin and Chitosan Scaffold

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    A multifaceted strategy using a composite of anti-cancer nanotherapeutic and natural biomaterials silk fibroin (SF) and chitosan (CS) blend scaffolds was investigated for the treatment of a tissue defect post-tumor resection by providing local release of the therapeutic and filling of the defect site with the regenerative bioscaffolds. The scaffold-emodin nanoparticle composites were fabricated and characterized for drug entrapment and release, mechanical strength, and efficacy against GILM2 breast cancer cells in vitro and in vivo in a rat tumor model. Emodin nanoparticles were embedded in SF and SFCS scaffolds and the amount of emodin entrapment was a function of the scaffold composition and emodin loading concentration. In vitro, there was a burst release of emodin from all scaffolds during the first 2 days though it was detected even after 24 days. Increase in emodin concentration in the scaffolds decreased the overall elastic modulus and ultimate tensile strength of the scaffolds. After 6 weeks of in vivo implantation, the cell density (p < 0.05) and percent degradation (p < 0.01) within the remodeled no emodin SFCS scaffold was significantly higher than the emodin loaded SFCS scaffolds, although there was no significant difference in the amount of collagen deposition in the regenerated SFCS scaffold. The presence and release of emodin from the SFCS scaffolds inhibited the integration of SFCS into the adjacent tumor due to the formation of an interfacial barrier of connective tissue that was lacking in emodin-free SFCS scaffolds. While no significant difference in tumor size was observed between the in vivo tested groups, tumors treated with emodin loaded SFCS scaffolds had decreased presence and size and similar regeneration of new tissue as compared to no emodin SFCS scaffolds
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