923 research outputs found

    The role of primitive part modelling within an integrative simulation environment

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    The component-based modeling approach to the simulation of HVAC systems has been in used for many years. The approach not only supports plant simulation but also allows the integration of the building and plant domains. Frequently, however, the plant models do not match exactly the types being used in a given project and where they do, may not be able to provide the required information. To address such limitations research has been undertaken into alternative approaches. The aim of such research is to provide a modeling approach that is widely applicable and offers efficient code management and data sharing. Primitive Part (PP) modeling is one such effort, which employs generic, process-based elements to attain modeling flexibility. Recent efforts have been on the development of data structure and graphics that facilitates PP auto-connection via computer interface. This paper describes the approach using an example application and its suggested role within an integrative simulation environment

    Dilepton Production at SPS-energy Heavy Ion Collisions

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    The production of dileptons is studied within a hadronic transport model. We investigate the sensitivity of the dilepton spectra to the initial configuration of the hadronic phase in a ultrarelativistic heavy ion collision. Possible in medium correction due to the modifications of pions and the pion form factor in a hadronic gas are discussed.Comment: Dedicated to Gerry Brown in honor of the 32nd celebration of his 39th birthday. 31 pages Latex including 13 eps-figures, uses psfig.sty and epsf.st

    Effects of Allelic Variation in Glutenin Subunits and Gliadins on Baking-Quality in Near-isogenic Lines of Common Wheat cv. Longmai 19

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    Two lines, L-19-613 and L-19-626, were produced from the common wheat cultivar Longmai 19 (L-19) by six consecutive backcrosses using biochemical marker-assisted selection. L-19 (Glu-D1a, Glu-A3c/Gli-A1?; Gli-A1? is a gene coding for unnamed gliadin) and L-19-613 (Glu-D1d, Glu-A3c/Gli-A1?) formed a set of near-isogenic lines (NILs) for HMW-GS, while L-19-613 and L-19-626 (Glu-D1d, Glu-A3e/Gli-A1m) constituted another set of NILs for the LMW-GS/gliadins. The three L-19 NILs were grown in the wheat breeding nursery in 2007 and 2008. The field experiments were designed using the three-column contrast arrangement method with four replicates. The three lines were ranked as follows for measurements of gluten strength, which was determined by the gluten index, Zeleny sedimentation, the stability and breakdown time of the farinogram, the maximum resistance and area of the extensogram, and the P andWvalues of the alveogram: L-19-613 > L-19-626 > L-19. The parameters listed above were significantly different between lines at the 0.05 or 0.01 level. The Glu-D1 and Glu-A3/Gli-A1 loci had additive effects on the gluten index, Zeleny sedimentation, stability, breakdown time, maximum resistance, area, P and W values. Although genetic variation at the Glu-A3/Gli-A1 locus had a great influence on wheat quality, the genetic difference between Glu-D1d and Glu-D1a at the Glu-D1 locus was much larger than that of Glu-A3c/Gli-A1? and Glu-A3e/Gli-A1m at the Glu-A3/Gli-A1 locus. Glu-D1d had negative effects on the extensibility and the L value compared with Glu-D1a. In contrast, Glu-A3c/Gli-A1? had a positive effect on these traits compared with Glu-A3e/Gli-A1m

    Transition from fractal to non-fractal scalings in growing scale-free networks

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    Real networks can be classified into two categories: fractal networks and non-fractal networks. Here we introduce a unifying model for the two types of networks. Our model network is governed by a parameter qq. We obtain the topological properties of the network including the degree distribution, average path length, diameter, fractal dimensions, and betweenness centrality distribution, which are controlled by parameter qq. Interestingly, we show that by adjusting qq, the networks undergo a transition from fractal to non-fractal scalings, and exhibit a crossover from `large' to small worlds at the same time. Our research may shed some light on understanding the evolution and relationships of fractal and non-fractal networks.Comment: 7 pages, 3 figures, definitive version accepted for publication in EPJ

    A preexisting rare PIK3CA e545k subpopulation confers clinical resistance to MEK plus CDK4/6 inhibition in NRAS melanoma and is dependent on S6K1 signaling

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    Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS- mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA E545K mutation as conferring drug resistance. We demonstrate that PIK3CA E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA E545K being nonuniformly distributed. This resistant population rapidly expanded after the initiation of MEKi + CDK4i therapy and persisted in all successive samples even after immune checkpoint therapy and distant metastasis. Functional studies identified activated S6K1 as both a key marker and specific therapeutic vulnerability downstream of PIK3CA E545K -induced resistance. These results demonstrate that difficult-to-detect preexisting resistance mutations may exist more often than previously appreciated and also posit S6K1 as a common downstream therapeutic nexus for the MAPK, CDK4/6, and PI3K pathways. SIGNIFICANCE: We report the first characterization of clinical acquired resistance to MEKi + CDK4i, identifying a rare preexisting PIK3CA E545K subpopulation that expands upon therapy and exhibits drug resistance. We suggest that single-region pretreatment biopsy is insufficient to detect rare, spatially segregated drug-resistant subclones. Inhibition of S6K1 is able to resensitize PIK3CA E545K -expressing NRAS-mutant melanoma cells to MEKi + CDK4i. © 2018 AAC

    Nanoscale study of titanomagnetite from the Panzhihua Layered Intrusion, southwest China: multistage exsolutions record ore formation

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    Titanomagnetite from Fe-Ti-V ores of the Lanjiahuoshan deposit, Panzhihua layered intrusion, Southwest China, was investigated at the nanoscale. The objectives were to establish the composition of exsolution phases and their mutual relationships in order to evaluate the sequence of exsolution among oxide phases, and assess mechanisms of ore formation during magma emplacement. At the micron-scale, titanomagnetite shows crosscutting sets of exsolutions with ilmenite and Al-Mg-Fe-spinel (pleonaste), as well as overprint, both in terms of phase re-equilibration and remobilization of trace elements. Most complex textures were found in titanomagnetite surrounded by ilmenite and this was selected for high-angle annular dark field scanning transmission electron microscopy (HAADF STEM) imaging and STEM energy-dispersive X-ray spectrometry (EDS) spot analysis and mapping on a thin foil prepared in situ on a focused ion beam scanning electron microscope platform. Titanomagnetite revealed two sequential sets of exsolutions, {111} crosscutting {100}, which are associated with changes in phase speciation and trace element distribution patterns. Qandilite is the dominant spinel phase inside titanomagnetite; magnesioferrite is also identified. In contrast, Fe-poor, Al-rich, Mg-bearing spinel is present within ilmenite outside the grain. Vanadium enrichment in newly-formed magnetite lamellae is clear evidence for trace element remobilization. This V-rich magnetite shows epitaxial relationships with ilmenite at the contact with titanomagnetite. Two-fold super-structuring in ilmenite is evidence for non-redox re-equilibration between titanomagnetite and ilmenite, supporting published experimental data. In contrast, the transformation of cubic Ti-rich spinel into rhombohedral ilmenite imaged at the nanoscale represents the “oxy-exsolution” model of titanomagnetite–ilmenite re-equilibration via formation of a transient ulvöspinel species. Nanoscale disorder is encountered as vacancy layers in Ti-rich spinel, and lower symmetry in the Fe-poor, Al-Mg phase, suggesting that slow cooling rates can preserve small-scale phase equilibration. The cooling history of titanomagnetite ore can be reconstructed as three distinct stages, concordant with published models for the magma plumbing system: equilibrium crystallization of Al-rich, Mg-bearing titanomagnetite from cumulus melts at ~55 km, with initial exsolutions occurring above 800 °C at moderate fO2 conditions (Stage 1); crosscutting {111} exsolutions resulting in formation of qandilite, attributable to temperature increase due to emplacement of another batch of melt affecting the interstitial cumulus during uplift. Formation of 2-fold superstructure ilmenite + V-rich magnetite exsolution pairs representing non-redox equilibration indicates resetting of the cooling path at this stage (Stage 2); and ilmenite formation from pre-existing Ti-rich spinel and ulvöspinel, illustrative of redox-driven cooling paths at <10 km (Stage 3). HAADF STEM provides direct imaging of atomic arrangements, allowing recognition of processes not recognizable at the micron-scale, and can thus be used to constrain exsolution models during ore formation.Wenyuan Gao, Cristiana L. Ciobanu, Nigel J. Cook, Ashley Slattery, Fei Huang and Dan Son

    Extensive translation of circular RNAs driven by N6-methyladenosine

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    Extensive pre-mRNA back-splicing generates numerous circular RNAs (circRNAs) in human transcriptome. However, the biological functions of these circRNAs remain largely unclear. Here we report that N6-methyladenosine (m6A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus m6A motifs are enriched in circRNAs and a single m6A site is sufficient to drive translation initiation. This m6A-driven translation requires initiation factor eIF4G2 and m6A reader YTHDF3, and is enhanced by methyltransferase METTL3/14, inhibited by demethylase FTO, and upregulated upon heat shock. Further analyses through polysome profiling, computational prediction and mass spectrometry reveal that m6A-driven translation of circRNAs is widespread, with hundreds of endogenous circRNAs having translation potential. Our study expands the coding landscape of human transcriptome, and suggests a role of circRNA-derived proteins in cellular responses to environmental stress

    Magnetic moments of the low-lying JP= 1/2−J^P=\,1/2^-, 3/2−3/2^- Λ\Lambda resonances within the framework of the chiral quark model

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    The magnetic moments of the low-lying spin-parity JP=J^P= 1/2−1/2^-, 3/2−3/2^- Λ\Lambda resonances, like, for example, Λ(1405)\Lambda(1405) 1/2−1/2^-, Λ(1520)\Lambda(1520) 3/2−3/2^-, as well as their transition magnetic moments, are calculated using the chiral quark model. The results found are compared with those obtained from the nonrelativistic quark model and those of unitary chiral theories, where some of these states are generated through the dynamics of two hadron coupled channels and their unitarization

    Suppressing CMB Quadrupole with a Bounce from Contracting Phase to Inflation

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    Recent released WMAP data show a low value of quadrupole in the CMB temperature fluctuations, which confirms the early observations by COBE. In this paper, a scenario, in which a contracting phase is followed by an inflationary phase, is constructed. We calculate the perturbation spectrum and show that this scenario can provide a reasonable explanation for lower CMB anisotropies on large angular scales.Comment: 5 pages, 3 figure
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