414 research outputs found

    On the Licensing of Understating NPIs: Manipulating the domain of degrees for Japanese 'anmari' and 'sonnani'

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    Negative Polarity Items (NPIs) often have an effect of strengthening the statements which contain them. However, there are also NPIs that contribute to make a weaker claim such as all that (Israel 1996, 2006; van Rooy 2003). I analyze two kinds of such NPIs, namely the degree modifier 'a(n)mari' and 'sonnani' in Japanese, which roughly translate as 'very/much' and '(all) that'. In doing so, two points are considered. First, since the NPIs in question are degree modifiers, I would like to adopt a degree-based semantics and combine it with the idea of domain widening proposed for determiner NPIs such as any. In particular, building on a version of Chierchia's (2006) framework, I consider domain widening in terms of domains of degrees. Second, to capture the nature of understatement, I refer to the notion of quality-based strengthening, rather than informativity/entailment-based strengthening (Israel 2006; Krifka 1995; van Rooy 2003)

    Modes of comparison and Question under Discussion: Evidence from `contrastive comparison' in Japanese

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    Based on new empirical evidence from Japanese, we first point out that the previously recognized distinction between explicit comparison and implicit comparison (Kennedy 2009; Sawada 2009) does not fully exhaust the possible types of comparison constructions. The third type of comparison construction, which we call 'contrastive comparison', calls for a finer-grained classification that cross-classifies the three types of comparison constructions in terms of both semantic and pragmatic properties. We will then show that such a refined perspective straightforwardly becomes available once we extend the previous classification with a closer attention to discourse-structural properties of the relevant constructions in terms of the notion of Question under Discussion (Roberts 1996)

    Effect of High Fat Loading in Dahl Salt-Sensitive Rats

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    Salt sensitivity of blood pressure (BP) is speculated to be a characteristic in obesity-induced hypertension. To elucidate the influence of obesity on salt-sensitive hypertension, we examined the effect of fat loading on BP, renal damage, and their progression induced by salt excess in Dahl salt-sensitive (S) rats. High fat (HF: 45% fat diet: 8 weeks) diet increased BP with greater weight gain and visceral fat accumulation than low fat (10% fat) diet. In HF-fed rats, plasma glucose, plasma insulin, and urinary catecholamine increased, and urinary protein tended to be elevated. Moreover, excessive salt (8% salt diet: 8 weeks)-induced hypertension and proteinuria was accelerated in HF-fed rats. Therefore, fat loading increased BP in Dahl S rats possibly through insulin-resistance and sympathetic excitation. Moreover, fat loading accelerated salt-induced BP elevation and renal damage, suggesting excessive intake of both fat and salt, such as a civilized diet, exert the synergic harmful effects

    CaM kinase Iα–induced phosphorylation of Drp1 regulates mitochondrial morphology

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    Mitochondria are dynamic organelles that frequently move, divide, and fuse with one another to maintain their architecture and functions. However, the signaling mechanisms involved in these processes are still not well characterized. In this study, we analyze mitochondrial dynamics and morphology in neurons. Using time-lapse imaging, we find that Ca2+ influx through voltage-dependent Ca2+ channels (VDCCs) causes a rapid halt in mitochondrial movement and induces mitochondrial fission. VDCC-associated Ca2+ signaling stimulates phosphorylation of dynamin-related protein 1 (Drp1) at serine 600 via activation of Ca2+/calmodulin-dependent protein kinase Iα (CaMKIα). In neurons and HeLa cells, phosphorylation of Drp1 at serine 600 is associated with an increase in Drp1 translocation to mitochondria, whereas in vitro, phosphorylation of Drp1 results in an increase in its affinity for Fis1. CaMKIα is a widely expressed protein kinase, suggesting that Ca2+ is likely to be functionally important in the control of mitochondrial dynamics through regulation of Drp1 phosphorylation in neurons and other cell types

    Increased IP-10 production by blood–nerve barrier in multifocal acquired demyelinating sensory and motor neuropathy and multifocal motor neuropathy

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    Objective Dysfunction of the blood–nerve barrier (BNB) plays important roles in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). The aim of the present study was to identify the candidate cytokines/chemokines that cause the breakdown of the BNB using sera from patients with CIDP and MMN. Methods We determined the levels of 27 cytokines and chemokines in human peripheral nerve microvascular endothelial cells (PnMECs) after exposure to sera obtained from patients with CIDP variants (typical CIDP and multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]), MMN and amyotrophic lateral sclerosis (ALS), and healthy controls (HC), using a multiplexed fluorescent bead-based immunoassay system. Results The induced protein (IP)10 level in the cells in both the MADSAM and MMN groups was markedly increased in comparison with the typical CIDP, ALS and HC groups. The other cytokines, including granulocyte colony-stimulating factor, vascular endothelial growth factor (VEGF) and interleukin-7, were also significantly upregulated in the MADSAM group. The increase of IP-10 produced by PnMECs was correlated with the presence of conduction block in both the MADSAM and MMN groups. Conclusion The autocrine secretion of IP-10 induced by patient sera in PnMECs was markedly upregulated in both the MADSAM and MMN groups. The overproduction of IP-10 by PnMECs leads to the focal breakdown of the BNB and may help to mediate the transfer of pathogenic T cells across the BNB, thereby resulting in the appearance of conduction block in electrophysiological studies of patients with MADSAM and MMN

    Fretting fatigue wear behavior of Y-TZP dental ceramics processed by non-conventional microwave sintering

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    This is the peer reviewed version of the following article: PRESENDA-BARRERA, ALVARO, Salvador Moya, Mª Dolores, Vleugels, Jozef , Moreno, Rodrigo, Borrell Tomás, María Amparo. (2017). Fretting fatigue wear behavior of Y-TZP dental ceramics processed by non-conventional microwave sintering.Journal of the American Ceramic Society, 100, 5, 1842-1852. DOI: 10.1111/jace.14769, which has been published in final form at http://doi.org/10.1111/jace.14769. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving[EN] The fretting wear behavior of self-mated Y-TZP dental materials obtained by non-conventional microwave and conventional sintering has been investigated. Two 3Y-TZP materials, a widely utilized commercial dental ceramic (LAVA) and a lab-prepared 3Y-TZP powder based equivalent have been assessed. Relative density and mechanical properties as well as the grain size variations upon sintering have been evaluated. After exposure to selected gross slip regime fretting wear conditions, the wear tracks have been characterized allowing the measurement of the coefficient of friction, track profiles, and pit features. The results indicate thaT microwave sintering results in a similar fretting wear behavior as observed for conventional sintered 3YTZP, since the measured volumetric wear loss is of a comparable order of magnitude. Regarding the influence of the grain size, the analysis revealed that a large grain size (>300 nm) results in an increased wear volume and that a higher resistance to fretting wear is constrained to a midrange particle size. Since the fracture toughness of all investigated ceramic grades was comparable, the influence of the fracture toughness could not be assessed. Abrasive grooving, delamination and microcracking have been identified as major wear mechanisms inside the wear tracks for both conventional and microwave sintered 3Y-TZP. In general, microwave sintering can provide 3Y-TZP dental materials with a comparable fretting wear resistance as that observed for conventional sintering using lower dwell sintering temperatures and a shorter processing time.Spanish Ministry of Economy and Competitiveness MINECO, Grant/Award Number: MAT2015-67586-C3-R; Generalitat Valenciana, Grant/Award Number: GRI-SOLIA/2013/035, GV/2014/009; MINECO, Grant/Award Number: IJCI-2014-19839.Presenda-Barrera, A.; Salvador Moya, MD.; Vleugels, J.; Moreno, R.; Borrell Tomás, MA. (2017). Fretting fatigue wear behavior of Y-TZP dental ceramics processed by non-conventional microwave sintering. Journal of the American Ceramic Society. 100(5):1842-1852. https://doi.org/10.1111/jace.14769S18421852100

    Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma

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    Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBVencoded RNA.We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-a, and arginase 1, suggesting the immune regulatory role of BART miRNAs.The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma.These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV1 B-cell lymphoma. (Blood. 2018;131(23):2552-2567)

    Evaluation of the association between the common E469K polymorphism in the ICAM-1 gene and diabetic nephropathy among type 1 diabetic patients in GoKinD population

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    <p>Abstract</p> <p>Background</p> <p>The ICAM-1 gene is a strong positional and biological candidate for susceptibility to the development of T1D and DN. We have recently demonstrated that SNP rs5498(E469K) confers susceptibility to the development of T1D and might be associated with DN in Swedish Caucasians. The present study aimed to further evaluate the association between the ICAM-1 genetic polymorphisms and DN.</p> <p>Methods</p> <p>Two common non-synonymous SNPs, including rs5498(E469K) and rs1799969(R241G), in the ICAM-1 gene were genotyped in 662 (312 female/350 male) T1D patients with DN and 620 (369/251) without DN. All patients were selected from the GoKinD study.</p> <p>Results</p> <p>Genotype distributions of both SNPs were in Hardy-Weinberg equilibrium but SNP rs5498(E469K) had high heterozygous index. In this SNP, the heterozygosity and positivity for the allele G were found to be significantly associated with DN in female T1D patients (P = 0.010, OR = 0.633, CI 95% 0.447–0.895 and P = 0.026, OR = 0.692, CI 95% 0.500–0.958). Furthermore, the female patients without DN carrying three genotypes A/A, A/G and G/G had different cystatin levels (0.79 ± 0.17, 0.81 ± 0.14 and 0.75 ± 0.12 mg/L, P = 0.021). No significant association of SNP rs1799969 (R241G) with DN was found.</p> <p>Conclusion</p> <p>The present study provides further evidence that SNP rs5498(E469K) in the ICAM-1 gene presents a high heterozygous index and the allele G of this polymorphism may confers the decreased risk susceptibility to the development of DN in female T1D patients among the GoKinD population.</p
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