1,689 research outputs found

    A paradox of syntactic priming: why response tendencies show priming for passives, and response latencies show priming for actives

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    Speakers tend to repeat syntactic structures across sentences, a phenomenon called syntactic priming. Although it has been suggested that repeating syntactic structures should result in speeded responses, previous research has focused on effects in response tendencies. We investigated syntactic priming effects simultaneously in response tendencies and response latencies for active and passive transitive sentences in a picture description task. In Experiment 1, there were priming effects in response tendencies for passives and in response latencies for actives. However, when participants' pre-existing preference for actives was altered in Experiment 2, syntactic priming occurred for both actives and passives in response tendencies as well as in response latencies. This is the first investigation of the effects of structure frequency on both response tendencies and latencies in syntactic priming. We discuss the implications of these data for current theories of syntactic processing

    Food allergy management from the perspective of patients or caregivers, and allergists: a qualitative study

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    <p>Abstract</p> <p>Background</p> <p>Research has shown that the long term management of food allergy is suboptimal. Our study aims to provide direction for improvement, by evaluating food allergy management from the perspective of, food allergic patients or their caregivers, and allergists in selected outpatient settings in Ontario.</p> <p>Methods</p> <p>This two-part study included an anonymous questionnaire completed by patients or their caregivers in allergy clinics, and a qualitative interview with allergists. In Part A, food allergic patients or their caregivers were surveyed about information they received on food allergy, their level of confidence with self-management, and their learning needs. In Part B, allergists were interviewed about teaching priorities and the challenges and strategies that currently exist in food allergy management. The questionnaire was developed and piloted at the Hamilton Health Sciences Corporation-McMaster University Medical Center Site. Using convenience sampling, participants were recruited from 6 allergy clinics in 5 Ontario cities. Patients of any age with food allergy who were evaluated by an allergist were considered for inclusion. Quantitative data was analyzed using descriptive statistics and frequency analysis. Audio recorded interviews with allergists were transcribed verbatim and analyzed using content analysis of grounded theory methodology.</p> <p>Results</p> <p>Ninety-two food allergic families in the care of 6 allergists in Toronto, Hamilton, London, Kitchener, and Kingston participated in the study. Key areas requiring improvement in food allergy management were identified: 33% of families were not shown how to use an epinephrine auto-injector with a trainer, only 57% were asked to demonstrate an auto-injector, despite being on average at their 5th visit, and only about 30% felt very confident about when and how to give an auto-injector. Fifty percent of families did not receive sufficient information on medical identification and 21% did not receive information about support groups. Interviews with allergists revealed limitations in time and nursing resources.</p> <p>Conclusions</p> <p>Our study highlights the educational gaps and overall experiences of food allergic families in Ontario, and the challenges faced by the allergists managing them.</p

    The Thermal Design, Characterization, and Performance of the SPIDER Long-Duration Balloon Cryostat

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    We describe the SPIDER flight cryostat, which is designed to cool six millimeter-wavelength telescopes during an Antarctic long-duration balloon flight. The cryostat, one of the largest to have flown on a stratospheric payload, uses liquid helium-4 to deliver cooling power to stages at 4.2 and 1.6 K. Stainless steel capillaries facilitate a high flow impedance connection between the main liquid helium tank and a smaller superfluid tank, allowing the latter to operate at 1.6 K as long as there is liquid in the 4.2 K main tank. Each telescope houses a closed cycle helium-3 adsorption refrigerator that further cools the focal planes down to 300 mK. Liquid helium vapor from the main tank is routed through heat exchangers that cool radiation shields, providing negative thermal feedback. The system performed successfully during a 17 day flight in the 2014-2015 Antarctic summer. The cryostat had a total hold time of 16.8 days, with 15.9 days occurring during flight.Comment: 15 pgs, 17 fig

    Methylating mushrooms

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    Peptide N-methylation is an important strategy used by medicinal chemists to improve cell permeability, oral bioavailability, and target affinity of peptide-based inhibitors. Correspondingly, N-methyl amides appear extensively in bioactive natural products. In the case of the immunosuppressant cyclosporine, for example, specific N-methylation of seven out of ten backbone amide nitrogens in the cyclic decapeptide is thought to allow a conformational ‘shapeshifting’ that hides polar N–H moieties and facilitates passive diffusion across cell membranes. Until now, N-methylation has primarily been the mark of peptide natural products from complex nonribosomal peptide synthetase (NRPS) assembly lines, and has not previously been found among their cousins, the ribosomally synthesized and post-translationally modified peptide (RiPP) natural products. In this issue, van der Velden et al. uncover the biosynthetic origins of the omphalotins, peptide natural products from the bioluminescent fungus O. olearius (Fig. 1a), and bring peptide backbone N-methylation into the realm of peptide post-translational modifications

    Aging affects attunement in perceiving length by dynamic touch

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    Earlier studies have revealed age-dependent differences in perception by dynamic touch. In the present study, we examined whether the capacity to learn deteriorates with aging. Adopting an ecological approach to learning, the authors examined the process of attunement—that is, the changes in what informational variable is exploited. Young and elderly adults were trained to perceive the lengths of unseen, handheld rods. It was found that the capacity to attune declines with aging: Contrary to the young adults, the elderly proved unsuccessful in learning to detect the specifying informational variables. The fact that aging affects the capacity to attune sets a new line of research in the study of perception and perceptual-motor skills of elderly. The authors discuss the implications of their findings for the ongoing discussions on the ecological approach to learning

    Clinical and pathological features of BRCA1 associated carcinomas in a hospital-based sample of Dutch breast cancer patients

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    Thus far, studies investigating the differences in tumour characteristics between breast cancer in BRCA1-carriers and other patients, have focused on highly selected groups of patients, potentially limiting the conclusions that can be drawn. Previously, we had identified 10 patients with BRCA1 germline mutations in a hospital-based series of 642 breast cancer patients not selected for age or family history. The aim of this analysis is to investigate the clinical and pathological features of these BRCA1 associated carcinomas as compared to other breast cancers in this representative sample. Tumours from patients with BRCA1 germline mutations (n= 10) were compared to an age-matched sample of other patients (n= 50) from the same cohort. The following characteristics were considered: axillary nodal status and tumour size, histologic parameters (tumour type, histologic grade, mitotic rate, tubule formation, nuclear grade, CIS and lymphangio invasion) and expression of several proteins (oestrogen and progesterone receptors, cyclin D1, p53, HER2/neu, E-cadherin). In BRCA1associated tumours receptors for oestrogen and progesterone were expressed less frequently (respectively P= 0.001 and P= 0.002) than in controls, which is in line with findings from other studies. Other differences were also in accordance with findings from other studies, although not statistically significant. We conclude that the features of BRCA1 associated tumours detected in a hospital-based series of breast cancer patients not selected for family history of age at diagnosis are similar to tumours in cases selected for family history or age at diagnosis. © 2001 Cancer Research Campaign  http://www.bjcancer.co

    De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

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    Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

    DNA Methylation Analysis of Chromosome 21 Gene Promoters at Single Base Pair and Single Allele Resolution

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    Differential DNA methylation is an essential epigenetic signal for gene regulation, development, and disease processes. We mapped DNA methylation patterns of 190 gene promoter regions on chromosome 21 using bisulfite conversion and subclone sequencing in five human cell types. A total of 28,626 subclones were sequenced at high accuracy using (long-read) Sanger sequencing resulting in the measurement of the DNA methylation state of 580427 CpG sites. Our results show that average DNA methylation levels are distributed bimodally with enrichment of highly methylated and unmethylated sequences, both for amplicons and individual subclones, which represent single alleles from individual cells. Within CpG-rich sequences, DNA methylation was found to be anti-correlated with CpG dinucleotide density and GC content, and methylated CpGs are more likely to be flanked by AT-rich sequences. We observed over-representation of CpG sites in distances of 9, 18, and 27 bps in highly methylated amplicons. However, DNA sequence alone is not sufficient to predict an amplicon's DNA methylation status, since 43% of all amplicons are differentially methylated between the cell types studied here. DNA methylation in promoter regions is strongly correlated with the absence of gene expression and low levels of activating epigenetic marks like H3K4 methylation and H3K9 and K14 acetylation. Utilizing the single base pair and single allele resolution of our data, we found that i) amplicons from different parts of a CpG island frequently differ in their DNA methylation level, ii) methylation levels of individual cells in one tissue are very similar, and iii) methylation patterns follow a relaxed site-specific distribution. Furthermore, iv) we identified three cases of allele-specific DNA methylation on chromosome 21. Our data shed new light on the nature of methylation patterns in human cells, the sequence dependence of DNA methylation, and its function as epigenetic signal in gene regulation. Further, we illustrate genotype–epigenotype interactions by showing novel examples of allele-specific methylation
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