151 research outputs found

    Form removal aspects on the waviness parameters for steel sheet in automotive applications : fourier filtering versus polynomial regression

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    Premium car makers attach great importance to the visual appearance of the painted car skin as an indication of product quality. The “orange peel” phenomenon constitutes a major problem here. It is not only depending on the paint’s chemical composition and application method, but also on possible waviness components in the sheet substrate. Therefore one is searching hard for a valuable waviness parameter to quantify the substrate’s fitness for purpose. A technically emerging problem is how to remove the form from the measured signal, which is indeed not significant to the orange peel phenomenon. This paper will compare two commonly used approaches: i.e. Fourier filtering versus polynomial regression and will reveal and quantify some common aspects in terms of wavelengths

    A Strong Decline in the Incidence of Childhood Otitis Media During the COVID-19 Pandemic in the Netherlands

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    Introduction: Recent reports have highlighted the impact of the COVID-19 pandemic on the incidence of infectious disease illnesses and antibiotic use. This study investigates the effect of the pandemic on childhood incidence of otitis media (OM) and associated antibiotic prescribing in a large primary care-based cohort in the Netherlands. / Material and Methods: Retrospective observational cohort study using routine health care data from the Julius General Practitioners’ Network (JGPN). All children aged 0-12 registered in 62 practices before the COVID-19 pandemic (1 March 2019 - 29 February 2020) and/or during the pandemic (1 March 2020 - 28 February 2021) were included. Data on acute otitis media (AOM), otitis media with effusion (OME), ear discharge episodes and associated antibiotic prescriptions were extracted. Incidence rates per 1,000 child years (IR), incidence rate ratios (IRR) and incidence rate differences (IRD) were compared between the two study periods. / Results: OM episodes declined considerably during the COVID-19 pandemic: IR pre-COVID-19 vs COVID-19 for AOM 73.7 vs 27.1 [IRR 0.37]; for OME 9.6 vs 4.1 [IRR 0.43]; and for ear discharge 12.6 vs 5.8 [IRR 0.46]. The absolute number of AOM episodes in which oral antibiotics were prescribed declined accordingly (IRD pre-COVID-19 vs COVID-19: -22.4 per 1,000 child years), but the proportion of AOM episodes with antibiotic prescription was similar in both periods (47% vs 46%, respectively). / Discussion: GP consultation for AOM, OME and ear discharge declined by 63%, 57% and 54% respectively in the Netherlands during the COVID-19 pandemic. Similar antibiotic prescription rates before and during the pandemic indicate that the case-mix presenting to primary care did not considerably change. Our data therefore suggest a true decline as a consequence of infection control measures introduced during the pandemic

    The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis

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    Acknowledgements We wish to thank Jorge Galán, Gregory Pazour, Derek Toomre, Giuliano Callaini, Joel Rosenbaum, Alessandra Boletta and Francesco Blasi for generously providing reagents and for productive discussions, and Sonia Grassini for technical assistance. The work was carried out with the financial support of Telethon (GGP11021) and AIRC.Peer reviewedPostprin

    A Role for Drosophila dFoxO and dFoxO 5′UTR Internal Ribosomal Entry Sites during Fasting

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    One way animals may cope with nutrient deprivation is to broadly repress translation by inhibiting 5′-cap initiation. However, under these conditions specific proteins remain essential to survival during fasting. Such peptides may be translated through initiation at 5′UTR Internal Ribosome Entry Sites (IRES). Here we show that the Drosophila melanogaster Forkhead box type O (dFoxO) transcription factor is required for adult survival during fasting, and that the 5′UTR of dfoxO has the ability to initiate IRES-mediated translation in cell culture. Previous work has shown that insulin negatively regulates dFoxO through AKT-mediated phosphorylation while dFoxO itself induces transcription of the insulin receptor dInR, which also harbors IRES. Here we report that IRES-mediated translation of both dFoxO and dInR is activated in fasted Drosophila S2 cells at a time when cap-dependent translation is reduced. IRES mediated translation of dFoxO and dInR may be essential to ensure function and sensitivity of the insulin signaling pathway during fasting

    The genomic features that affect the lengths of 5’ untranslated regions in multicellular eukaryotes

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    <p>Abstract</p> <p>Background</p> <p>The lengths of 5’UTRs of multicellular eukaryotes have been suggested to be subject to stochastic changes, with upstream start codons (uAUGs) as the major constraint to suppress 5’UTR elongation. However, this stochastic model cannot fully explain the variations in 5’UTR length. We hypothesize that the selection pressure on a combination of genomic features is also important for 5’UTR evolution. The ignorance of these features may have limited the explanatory power of the stochastic model. Furthermore, different selective constraints between vertebrates and invertebrates may lead to differences in the determinants of 5’UTR length, which have not been systematically analyzed.</p> <p>Methods</p> <p>Here we use a multiple linear regression model to delineate the correlation between 5’UTR length and the combination of a series of genomic features (G+C content, observed-to-expected (OE) ratios of uAUGs, upstream stop codons (uSTOPs), methylation-related CG/UG dinucleotides, and mRNA-destabilizing UU/UA dinucleotides) in six vertebrates (human, mouse, rat, chicken, African clawed frog, and zebrafish) and four invertebrates (fruit fly, mosquito, sea squirt, and nematode). The relative contributions of each feature to the variation of 5’UTR length were also evaluated.</p> <p>Results</p> <p>We found that 14%~33% of the 5’UTR length variations can be explained by a linear combination of the analyzed genomic features. The most important genomic features are the OE ratios of uSTOPs and G+C content. The surprisingly large weightings of uSTOPs highlight the importance of selection on upstream open reading frames (which include both uAUGs and uSTOPs), rather than on uAUGs <it>per se</it>. Furthermore, G+C content is the most important determinants for most invertebrates, but for vertebrates its effect is second to uSTOPs. We also found that shorter 5’UTRs are affected more by the stochastic process, whereas longer 5’UTRs are affected more by selection pressure on genomic features.</p> <p>Conclusions</p> <p>Our results suggest that upstream open reading frames may be the real target of selection, rather than uAUGs. We also show that the selective constraints on genomic features of 5’UTRs differ between vertebrates and invertebrates, and between longer and shorter 5’UTRs. A more comprehensive model that takes these findings into consideration is needed to better explain 5’UTR length evolution.</p

    Implied Contribution Under the Federal Securities Laws: A Reassessment

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    Exposure to a strong T-helper 2 (Th2)-like environment during fetal development may promote allergy development. Increased cord blood (CB) levels of the Th2-associated chemokine CCL22 were associated with allergy development during the first 2 y of life. The aim of the present study was to determine whether CB Th1- and Th2-associated chemokine levels are associated with allergy development during the first 6 y of life, allowing assessment of respiratory allergic symptoms usually developing in this period. The CB levels of cytokines, chemokines, and total IgE were determined in 56 children of 20 women with allergic symptoms and 36 women without allergic symptoms. Total IgE and allergen-specific IgE antibody levels were quantified at 6, 12, 24 mo, and 6 y of age. Increased CB CCL22 levels were associated with development of allergic sensitization and asthma and increased CCL17 levels with development of allergic symptoms, including asthma. Sensitized children with allergic symptoms showed higher CB CCL17 and CCL22 levels and higher ratios between these Th2-associated chemokines and the Th1-associated chemokine CXCL10 than nonsensitized children without allergic symptoms. A pronounced Th2 deviation at birth, reflected by increased CB CCL17 and CCL22 levels, and increased CCL22/CXCL10 and CCL17/CXCL10 ratios might promote allergy development later in life

    Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS

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    In contrast to cutaneous melanoma, there is no evidence that BRAF mutations are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway in uveal melanoma, although there is increasing evidence that this pathway is activated frequently in the latter tumours. In this study, we performed mutation analysis of the RAS and BRAF genes in a panel of 11 uveal melanoma cell lines and 19 primary uveal melanoma tumours. In addition, Western blot and immunohistochemical analyses were performed on downstream members of the MAPK pathway in order to assess the contribution of each of these components. No mutations were found in any of the three RAS gene family members and only one cell line carried a BRAF mutation (V599E). Despite this, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), ERK and ELK were constitutively activated in all samples. These data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma

    Effects of new polymorphisms in the bovine myocyte enhancer factor 2D (MEF2D) gene on the expression rates of the longissimus dorsi muscle

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    Myocyte enhancer factor 2D (MEF2D), a product of the MEF2D gene, belongs to the myocyte enhancer factor 2 (MEF2) protein family which is involved in vertebrate skeletal muscle development and differentiation during myogenesis. The aim of the present study was to search for polymorphisms in the bovine MEF2D gene and to analyze their effect on MEF2D mRNA and on protein expression levels in the longissimus dorsi muscle of Polish Holstein–Friesian cattle. Overall, three novel variations, namely, insertion/deletion g.−818_−814AGCCG and g.−211C<A transversion in the promoter region as well as g.7C<T transition in the 5′untranslated region (5′UTR), were identified by DNA sequencing. A total, 375 unrelated bulls belonging to six different cattle breeds were genotyped, and three combined genotypes (Ins-C-C/Ins-C-C, Del-A-T/Del-A-T and Ins-C-C/Del-A-T) were determined. The frequency of the combined genotype Ins-C-C/Ins-C-C and Del-A-T/Del-A-T was varied between the breeds and the average frequency was 0.521 and 0.037, respectively. Expression analysis showed that the MEF2D variants were highly correlated with MEF2D mRNA and protein levels in the longissimus dorsi muscle of Polish Holstein–Friesian bulls carrying the three different combined genotypes. The highest MEF2D mRNA and protein levels were estimated in the muscle of bulls with the Ins-C-C/Ins-C-C homozygous genotype as compared to the Del-A-T/Del-A-T homozygotes (P < 0.01) and Ins-C-C/Del-A-T heterozygotes (P < 0.05). A preliminary association study showed no significant differences in the carcass quality traits between bulls with various MEF2D combined genotypes in the investigated population of Polish Holstein–Friesian cattle

    5′UTR Variants of Ribosomal Protein S19 Transcript Determine Translational Efficiency: Implications for Diamond-Blackfan Anemia and Tissue Variability

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    Background: Diamond-Blackfan anemia (DBA) is a lineage specific and congenital erythroblastopenia. The disease is associated with mutations in genes encoding ribosomal proteins resulting in perturbed ribosomal subunit biosynthesis. The RPS19 gene is mutated in approximately 25 % of DBA patients and a variety of coding mutations have been described, all presumably leading to haploinsufficiency. A subset of patients carries rare polymorphic sequence variants within the 59untranslated region (59UTR) of RPS19. The functional significance of these variants remains unclear. Methodology/Principal Findings: We analyzed the distribution of transcriptional start sites (TSS) for RPS19 mRNAs in testis and K562 cells. Twenty-nine novel RPS19 transcripts were identified with different 59UTR length. Quantification of expressed w.t. 59UTR variants revealed that a short 59UTR correlates with high levels of RPS19. The total levels of RPS19 transcripts showed a broad variation between tissues. We also expressed three polymorphic RPS19 59UTR variants identified in DBA patients. The sequence variants include two insertions (c.-147_-146insGCCA and c.-147_-146insAGCC) and one deletion (c.-144_-141delTTTC). The three 59UTR polymorphisms are associated with a 20–30 % reduction in RPS19 protein levels when compared to the wild-type (w.t.) 59UTR of corresponding length. Conclusions: The RPS19 gene uses a broad range of TSS and a short 59UTR is associated with increased levels of RPS19. Comparisons between tissues showed a broad variation in the total amount of RPS19 mRNA and in the distribution of TS
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