4,102 research outputs found

    Multi-seeded melt growth (MSMG) of bulk Y-Ba-Cu-O using thin-film seeds

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    Y-Ba-Cu-O (YBCO) and Sm-Ba-Cu-O (SmBCO) thin films have been used for the first time as heterogeneous seeds to multi-seed successfully the melt growth of bulk YBCO in a multi-seeded melt growth (MSMG) process. The use of thin film seeds, which may be prepared with highly controlled orientation (i.e. with a well-defined a-b plane and precisely known a-direction), is based on their superheating properties and reduces significantly contamination of the bulk sample by the seed material. A variety of grain boundaries were obtained by varying the angle between the seeds. Microstructural studies indicate that the extent of residual melt deposited at the grain boundary decreases with increasing grain boundary contact angle. It is established that the growth front proceeds continuously at the (110)/(110) grain boundary without trapping liquid, which leads to the formation of a clean grain boundary

    Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

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    Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron

    Activated protein C, severe sepsis and 28-day mortality

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    Protein C (PC) de ciency is prevalent in severe sepsis, studies showing that more than 80% of patients with severe sepsis have a baseline PC level below the lower limit of normal [1,2]. The aim of the study was to relate the anticoagulation activity evaluated by PC, with clinical parameters and 28-day mortality.Ye

    Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

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    PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

    Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

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    "© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)

    Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

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    Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative realtime PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p<0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p<0.05). SLC2A3 was related to grade and invasion type (p<0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p<0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811), and by grant fromtheNational Science Council, Poland (N403 043 32/2326)

    Theories for influencer identification in complex networks

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    In social and biological systems, the structural heterogeneity of interaction networks gives rise to the emergence of a small set of influential nodes, or influencers, in a series of dynamical processes. Although much smaller than the entire network, these influencers were observed to be able to shape the collective dynamics of large populations in different contexts. As such, the successful identification of influencers should have profound implications in various real-world spreading dynamics such as viral marketing, epidemic outbreaks and cascading failure. In this chapter, we first summarize the centrality-based approach in finding single influencers in complex networks, and then discuss the more complicated problem of locating multiple influencers from a collective point of view. Progress rooted in collective influence theory, belief-propagation and computer science will be presented. Finally, we present some applications of influencer identification in diverse real-world systems, including online social platforms, scientific publication, brain networks and socioeconomic systems.Comment: 24 pages, 6 figure

    On renormalization group flows and the a-theorem in 6d

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    We study the extension of the approach to the a-theorem of Komargodski and Schwimmer to quantum field theories in d=6 spacetime dimensions. The dilaton effective action is obtained up to 6th order in derivatives. The anomaly flow a_UV - a_IR is the coefficient of the 6-derivative Euler anomaly term in this action. It then appears at order p^6 in the low energy limit of n-point scattering amplitudes of the dilaton for n > 3. The detailed structure with the correct anomaly coefficient is confirmed by direct calculation in two examples: (i) the case of explicitly broken conformal symmetry is illustrated by the free massive scalar field, and (ii) the case of spontaneously broken conformal symmetry is demonstrated by the (2,0) theory on the Coulomb branch. In the latter example, the dilaton is a dynamical field so 4-derivative terms in the action also affect n-point amplitudes at order p^6. The calculation in the (2,0) theory is done by analyzing an M5-brane probe in AdS_7 x S^4. Given the confirmation in two distinct models, we attempt to use dispersion relations to prove that the anomaly flow is positive in general. Unfortunately the 4-point matrix element of the Euler anomaly is proportional to stu and vanishes for forward scattering. Thus the optical theorem cannot be applied to show positivity. Instead the anomaly flow is given by a dispersion sum rule in which the integrand does not have definite sign. It may be possible to base a proof of the a-theorem on the analyticity and unitarity properties of the 6-point function, but our preliminary study reveals some difficulties.Comment: 41 pages, 5 figure

    Biochemical properties of Paracoccus denitrificans FnrP:Reactions with molecular oxygen and nitric oxide

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    In Paracoccus denitrificans, three CRP/FNR family regulatory proteins, NarR, NnrR and FnrP, control the switch between aerobic and anaerobic (denitrification) respiration. FnrP is a [4Fe-4S] cluster containing homologue of the archetypal O2 sensor FNR from E. coli and accordingly regulates genes encoding aerobic and anaerobic respiratory enzymes in response to O2, and also NO, availability. Here we show that FnrP undergoes O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion that involves up to 2 O2 per cluster, with significant oxidation of released cluster sulfide to sulfane observed at higher O2 concentrations. The rate of the cluster reaction was found to be ~6-fold lower than that of E. coli FNR, suggesting that FnrP can remain transcriptionally active under microaerobic conditions. This is consistent with a role for FnrP in activating expression of the high O2 affinity cytochrome c oxidase under microaerobic conditions. Cluster conversion resulted in dissociation of the transcriptionally active FnrP dimer into monomers. Therefore, along with E. coli FNR, FnrP belongs to the subset of FNR proteins in which cluster type is correlated with association state. Interestingly, two key charged residues, Arg140 and Asp154, that have been shown to play key roles in the monomer-dimer equilibrium in E. coli FNR are not conserved in FnrP, indicating that different protomer interactions are important for this equilibrium. Finally, the FnrP [4Fe-4S] cluster is shown to undergo reaction with multiple NO molecules, resulting in iron nitrosyl species and dissociation into monomers
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