963 research outputs found

    A reception study of machine translated subtitles for MOOCs

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    As access has grown to online courses in the form of MOOCs (Massive Open Online Courses), the language barrier has become an important issue for users worldwide. Machine translation (MT) appears to offer an alternative or complementary solution to existing forms of MOOC translation. Very little attention has been paid, however, to the use and utility of MT for MOOC content. The main goal of this research is to test the impact machine-translated subtitles have on Chinese viewers’ reception of MOOC content. We are interested in whether there is any difference between viewers’ reception of raw machine-translated subtitles as opposed to fully post-edited machine-translated (PEMT) subtitles and human-translated (HT) subtitles. Based on an eye-tracking experiment conducted at two Chinese universities and survey methods, we show that participants who were offered full PEMT subtitles scored better overall on our reception metrics than those who were offered raw MT subtitles. HT subtitles, on the other hand, did not necessarily lead to better reception as expected; in contrast, the participants who were offered HT subtitles performed the worst in some of our reception metrics

    Age dependence of serum beta-N-acetylhexosaminidase (NAG) activity

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    Serum Nacetyl-beta-Dglucosaminidase (NAG; EC 3.2.1.30) is a hexosaminidase and may be a predictor of vascular injury, e.g., in infant respiratory distress syndrome, pneumonia, bronchopulmonary dysplasia and necrotizing enterocolitis. To estimate the new diagnostic prospects we have modified our urinary NAG assay. In this sensitive colorimetric microassay, VRAGlcNAc was used as a substrate. In the present study the age dependence of serum NAG activity was investigated in newborn babies, infants (124 months), children (218 years) and adults (1980 years). Serum NAG activity was found to be agedependent; it is higher in early childhood (1159 U/l) but decreases to a constant value at the age of 12 years. After the age of 2 years it is similar to adults NAG (1030 U/l). In pediatrics agematched reference ranges must be taken into consideration

    Electrical performance and reliability characterization of a SiC MOSFET power module with embedded decoupling capacitors

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    Integration of decoupling capacitors in SiC MOSFET modules is an advanced solution to mitigate the effect of parasitic inductance induced by module assembly interconnects. In this paper, the switching transient behavior is reported for a 1.2kV SiC MOSFET module with embedded DC-link capacitors. It shows faster switching transition and less overshoot voltage compared to a module using an identical package but without capacitors. Active power cycling and passive temperature cycling are carried out for package reliability characterization and comparisons are made with commercial Si and SiC power modules. Scanning acoustic microscopy images and thermal structure functions are presented to quantify the effects of package degradation. The results demonstrate that the SiC modules with embedded capacitors have similar reliability performance to commercial modules and that the reliability is not adversely affected by the presence of the decoupling capacitors

    Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution

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    Pleiotropic regulatory mutations affect diverse cellular processes, posing a challenge to our understanding of genotype-phenotype relationships across multiple biological scales. Adaptive Laboratory Evolution (ALE) allows for such mutations to be found and characterized in the context of clear selection pressures. Here, several ALE-selected single-mutation variants in Escherichia coli's RNA polymerase (RNAP) are detailed using an integrated multi-scale experimental and computational approach. While these mutations increase cellular growth rates in steady environments, they reduce tolerance to stress and environmental fluctuations. We detail structural changes in the RNAP that rewire the transcriptional machinery to rebalance proteome and energy allocation towards growth and away from several hedging and stress functions. We find that while these mutations occur in diverse locations in the RNAP, they share a common adaptive mechanism. In turn, these findings highlight the resource allocation tradeoffs organisms face and suggest how the structure of the regulatory network enhances evolvability

    Onasemnogene abeparvovec preserves bulbar function in infants with presymptomatic spinal muscular atrophy: a post-hoc analysis of the SPR1NT trial

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    Bulbar function in spinal muscular atrophy has been defined as the ability to meet nutritional needs by mouth while maintaining airway protection and communicate verbally. The effects of disease-modifying treatment on bulbar function are not clear. A multidisciplinary team conducted post-hoc analyses of phase 3 SPR1NT trial data to evaluate bulbar function of infants at risk for spinal muscular atrophy who received one-time gene replacement therapy (onasemnogene abeparvovec) before symptom onset. Three endpoints represented adequate bulbar function in SPR1NT: (1) absence of physiologic swallowing impairment, (2) full oral nutrition, and (3) absence of adverse events indicating pulmonary instability. Communication was not assessed in SPR1NT. We descriptively assessed numbers/percentages of children who achieved each endpoint and all three collectively. SPR1NT included infants <6 postnatal weeks with two (n = 14) or three (n = 15) copies of the survival motor neuron 2 gene. At study end (18 [two-copy cohort] or 24 [three-copy cohort] months of age), 100% (29/29) of patients swallowed normally, achieved full oral nutrition, maintained pulmonary stability, and achieved the composite endpoint. When administered to infants before clinical symptom onset, onasemnogene abeparvovec allowed children at risk for spinal muscular atrophy to achieve milestones within published normal ranges of development and preserve bulbar function

    Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

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    Background Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. Methods A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Results Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Conclusions Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER

    Energy drink use, problem drinking and drinking motives in a diverse sample of Alaskan college students

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    Background. Recent research has identified the use of caffeinated energy drinks as a common, potentially risky behaviour among college students that is linked to alcohol misuse and consequences. Research also suggests that energy drink consumption is related to other risky behaviours such as tobacco use, marijuana use and risky sexual activity. Objective. This research sought to examine the associations between frequency of energy drink consumption and problematic alcohol use, alcohol-related consequences, symptoms of alcohol dependence and drinking motives in an ethnically diverse sample of college students in Alaska. We also sought to examine whether ethnic group moderated these associations in the present sample of White, Alaska Native/American Indian and other ethnic minority college students. Design. A paper-and-pencil self-report questionnaire was completed by a sample of 298 college students. Analysis of covariance (ANCOVA) was used to examine the effects of energy drink use, ethnic group and energy drink by ethnic group interactions on alcohol outcomes after controlling for variance attributed to gender, age and frequency of binge drinking. Results. Greater energy drink consumption was significantly associated with greater hazardous drinking, alcohol consequences, alcohol dependence symptoms, drinking for enhancement motives and drinking to cope. There were no main effects of ethnic group, and there were no significant energy drink by ethnic group interactions. Conclusion. These findings replicate those of other studies examining the associations between energy drink use and alcohol problems, but contrary to previous research we did not find ethnic minority status to be protective. It is possible that energy drink consumption may serve as a marker for other health risk behaviours among students of various ethnic groups

    Genome-wide signatures of complex introgression and adaptive evolution in the big cats.

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    The great cats of the genus Panthera comprise a recent radiation whose evolutionary history is poorly understood. Their rapid diversification poses challenges to resolving their phylogeny while offering opportunities to investigate the historical dynamics of adaptive divergence. We report the sequence, de novo assembly, and annotation of the jaguar (Panthera onca) genome, a novel genome sequence for the leopard (Panthera pardus), and comparative analyses encompassing all living Panthera species. Demographic reconstructions indicated that all of these species have experienced variable episodes of population decline during the Pleistocene, ultimately leading to small effective sizes in present-day genomes. We observed pervasive genealogical discordance across Panthera genomes, caused by both incomplete lineage sorting and complex patterns of historical interspecific hybridization. We identified multiple signatures of species-specific positive selection, affecting genes involved in craniofacial and limb development, protein metabolism, hypoxia, reproduction, pigmentation, and sensory perception. There was remarkable concordance in pathways enriched in genomic segments implicated in interspecies introgression and in positive selection, suggesting that these processes were connected. We tested this hypothesis by developing exome capture probes targeting ~19,000 Panthera genes and applying them to 30 wild-caught jaguars. We found at least two genes (DOCK3 and COL4A5, both related to optic nerve development) bearing significant signatures of interspecies introgression and within-species positive selection. These findings indicate that post-speciation admixture has contributed genetic material that facilitated the adaptive evolution of big cat lineages

    Comparison between nasopharyngeal swab and nasal wash, using culture and PCR, in the detection of potential respiratory pathogens

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    <p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carriage of potential pathogens is important as it is both the major source of transmission and the prerequisite of invasive disease. New methods for detecting carriage could improve comfort, accuracy and laboratory utility. The aims of this study were to compare the sensitivities of a nasopharyngeal swab (NPS) and a nasal wash (NW) in detecting potential respiratory pathogens in healthy adults using microbiological culture and PCR.</p> <p>Results</p> <p>Healthy volunteers attended for nasal washing and brushing of the posterior nasopharynx. Conventional and real-time PCR were used to detect pneumococcus and meningococcus. Statistical differences between the two nasal sampling methods were determined using a nonparametric Mann-Whitney U test; differences between culture and PCR methods were determined using the McNemar test.</p> <p>Nasal washing was more comfortable for volunteers than swabbing (n = 24). In detection by culture, the NW was significantly more likely to detect pathogens than the NPS (<it>p </it>< 0.00001). Overall, there was a low carriage rate of pathogens in this sample; no significant difference was seen in the detection of bacteria between culture and PCR methods.</p> <p>Conclusions</p> <p>Nasal washing and PCR may provide effective alternatives to nasopharyngeal swabbing and classical microbiology, respectively.</p

    Coastal saltmarsh managed realignment drives rapid breach inlet and external creek evolution, Freiston Shore (UK)

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    The creation of saltmarsh through the managed realignment of sea defences, implemented in NW Europe as a sustainable coastal defence option, represents a substantial hydrodynamic perturbation to the local coastal system. The impact of a significantly increased tidal prism on hydromorphological features was investigated at Freiston Shore, Lincolnshire UK. Local tidal conditions and inadequate drainage at this realignment trial contributed to significant channel erosion due to the establishment of water surface slopes and pooling between the newly realigned site and the adjacent intertidal zone. Very high spatial resolution aerial photography and blimp photography were used to monitor inlet evolution from breaching in August 2002 to March 2008, showing a highly non-linear response with breach channels increasing in width by up to 960% within 2.5. months. Airborne laser scanning/LiDAR and terrestrial laser scanning quantified breach channel volume increases, showing a similar pattern. Breach channel evolution did not follow established tidal prism-channel width/cross-sectional area relationships that are often used to guide realignment design. Pre- and post-breach rates of external creek morphology change between 1999 and 2006 were also quantified, with intertidal creeks attached to the breach channels increasing significantly after realignment in both width and depth. This study highlights the physical processes affected by managed realignment, and the importance of understanding the causes of complex water surface slopes at multiple scales. © 2013 Elsevier B.V
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