330 research outputs found

    Partial Disorder in the Periodic Anderson Model on a Triangular Lattice

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    We report our theoretical results on the emergence of a partially-disordered state at zero temperature and its detailed nature in the periodic Anderson model on a triangular lattice at half filling. The partially-disordered state is characterized by coexistence of a collinear antiferromagnetic order on an unfrustrated honeycomb subnetwork and nonmagnetic state at the remaining sites. This state appears with opening a charge gap between a noncollinear antiferromagnetic metal and Kondo insulator while changing the hybridization and Coulomb repulsion. We also find a characteristic crossover in the low-energy excitation spectrum as a result of coexistence of magnetic order and nonmagnetic sites. The result demonstrates that the partially-disordered state is observed distinctly even in the absence of spin anisotropy, in marked contrast to the partial Kondo screening state found in the previous study for the Kondo lattice model.Comment: 4 pages, 4 figures, accepted for publication in J. Phys. Soc. Jp

    Thermal Properties of Heavy Fermion Compound YbP

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    Low-temperature specific heat and its field-dependence up to 16 T was measured in a stoichiometric single crystal of YbP. A sharp peak was observed at {\it T}N_{\rm N} = 0.53 K in zero magnetic field. Application of external field seems to induce a new magnetic phase above 11 T. The field dependence of the transition temperature in the high-field phase is different from that of the low field phase. The linear coefficient of the electronic specific heat is estimated as 120 mJ/mole K2^{2} from low temperature specfic heat, suggesting heavy Fermion state in YbP.Comment: to be published in J.Phys.Soc.Jpn on May, 200

    Correcting for optical aberrations using multilayer displays

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    Optical aberrations of the human eye are currently corrected using eyeglasses, contact lenses, or surgery. We describe a fourth option: modifying the composition of displayed content such that the perceived image appears in focus, after passing through an eye with known optical defects. Prior approaches synthesize pre-filtered images by deconvolving the content by the point spread function of the aberrated eye. Such methods have not led to practical applications, due to severely reduced contrast and ringing artifacts. We address these limitations by introducing multilayer pre-filtering, implemented using stacks of semi-transparent, light-emitting layers. By optimizing the layer positions and the partition of spatial frequencies between layers, contrast is improved and ringing artifacts are eliminated. We assess design constraints for multilayer displays; autostereoscopic light field displays are identified as a preferred, thin form factor architecture, allowing synthetic layers to be displaced in response to viewer movement and refractive errors. We assess the benefits of multilayer pre-filtering versus prior light field pre-distortion methods, showing pre-filtering works within the constraints of current display resolutions. We conclude by analyzing benefits and limitations using a prototype multilayer LCD.National Science Foundation (U.S.) (Grant IIS-1116452)Alfred P. Sloan Foundation (Research Fellowship)United States. Defense Advanced Research Projects Agency (Young Faculty Award)Vodafone (Firm) (Wireless Innovation Award

    Modeling Firm Heterogeneity in International Trade: Do Structural Effects Matter?

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    This paper analyzes the qualitative properties of a multisectoral, multiregional computable general equilibrium model where some industries include heterogeneous firms as in Melitz (2003). The model, formulated according to Roson and Oyamada (2014), adds endogenous productivity effects to a standard Walras-Ricardian framework. We argue that the in- clusion of such effects changes the magnitude and distribution of welfare benefits obtainable by reductions in trade barriers, due to of comparative advantages. We illustrate the point through a numerical example, in which alternative model formulations are assessed. A standard neoclassic GE model, a basic Melitz model and a hybrid model are then compared. The three model versions are all calibrated with the same data set and an identical simulation experiment (a 50% reduction of transport costs between two regions) is carried out in the three cases. The results show that the hybrid model displays the largest welfare gains, as it combines Ricardian comparative advantages with Melitz average productivity improvements. However, they also show that new effects, not present in the original Ricardo and Melitz frameworks, are at a work

    Towards regulation of Endocrine Disrupting chemicals (EDCs) in water resources using bioassays - A guide to developing a testing strategy

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    Endocrine disrupting chemicals (EDCs) are found in every environmental medium and are chemically diverse. Their presence in water resources can negatively impact the health of both human and wildlife. Currently, there are no mandatory screening mandates or regulations for EDC levels in complex water samples globally. Bioassays, which allow quantifying in vivo or in vitro biological effects of chemicals are used commonly to assess acute toxicity in water. The existing OECD framework to identify single-compound EDCs offers a set of bioassays that are validated for the Estrogen-, Androgen-, and Thyroid hormones, and for Steroidogenesis pathways (EATS). In this review, we discussed bioassays that could be potentially used to screen EDCs in water resources, including in vivo and in vitro bioassays using invertebrates, fish, amphibians, and/or mammalians species. Strengths and weaknesses of samples preparation for complex water samples are discussed. We also review how to calculate the Effect-Based Trigger values, which could serve as thresholds to determine if a given water sample poses a risk based on existing quality standards. This work aims to assist governments and regulatory agencies in developing a testing strategy towards regulation of EDCs in water resources worldwide. The main recommendations include 1) opting for internationally validated cell reporter in vitro bioassays to reduce animal use & cost; 2) testing for cell viability (a critical parameter) when using in vitro bioassays; and 3) evaluating the recovery of the water sample preparation method selected. This review also highlights future research avenues for the EDC screening revolution (e.g., 3D tissue culture, transgenic animals, OMICs, and Adverse Outcome Pathways (AOPs)).This work was supported by the Fonds de recherche du Québec - Nature et technologies (FRQNT-290501) to JR, Natural Sciences and Engineering Research Council (NSERC) of Canada (NSERC-DG-2020-06475), and Canada Research Chairs to VSL (CRC-950-232235). LNM was supported by a H2020-Marie Skłodowska-Curie Action MSCA-IF-RI- 2017 awarded by the European Commission (ref. 797725-EpiSTOX). The authors are grateful to the Intersectorial Centre for Endocrine Disruptor Analysis (ICEDA)'s researcher network that facilitated this Special Issue. We thank Peta Neale that compiled references from the literature for EBT value that can be found in Table 3.Peer reviewe

    Reproducibility of the mfERG between instruments

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    Purpose First, to examine both the reproducibility of the multifocal electroretinogram (mfERG) recorded on different versions of the same instrument, and the repeatability of the mfERG recorded on a single instrument using two different amplifiers. Second, to demonstrate a means by which multicenter and longitudinal studies that use more than one recording instrument can compare and combine data effectively. Methods Three different amplifiers and two mfERG setups, one using VERIS™ 4.3 software (mfERG1) and another using VERIS™ Pro 5.2 software (mfERG2), were evaluated. A total of 73 subjects with normal vision were tested in three groups. Group 1 (n = 42) was recorded using two amplifiers in parallel on mfERG1. Group 2 (n = 52) was recorded on mfERG2 using a single amplifier. Group 3 was a subgroup of 21 subjects from groups 1 and 2 that were tested sequentially on both instruments. A fourth group of 26 subjects with diabetes were also recorded using the two parallel amplifiers on mfERG1. P1 implicit times and N1-P1 amplitudes of the 103 local first order mfERGs were measured, and the differences between the instruments and amplifiers were evaluated as raw scores and Z-scores based on normative data. Measurements of individual responses and measurements averaged over the 103 responses were analyzed. Results Simultaneous recordings made on mfERG1 with the two different amplifiers showed differences in implicit times but similar amplitudes. There was a mean implicit time difference of 2.5 ms between the amplifiers but conversion to Z-scores improved their agreement. Recordings made on different days with the two instruments produced similar but more variable results, with amplitudes differing between them more than implicit times. For local response implicit times, the 95% confidence interval of the difference between instruments was approximately ±1 Z-score (±0.9 ms) in either direction. For local response amplitude, it was approximately ±1.6 Z-scores (±0.3 μV). Conclusions Different amplifiers can yield quite different mfERG P1 implicit times, even with identical band-pass settings. However, the reproducibility of mfERG Z-scores across recording instrumentation is relatively high. Comparison of data across systems and laboratories, necessary for multicenter or longitudinal investigations, is facilitated if raw data are converted into Z-scores based on normative data

    Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells

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    BACKGROUND: We demonstrated that mouse embryonic stem (ES) cells-derived vascular endothelial growth factor receptor-2 (VEGF-R2) positive cells could differentiate into both endothelial cells (EC) and mural cells (MC), and termed them as vascular progenitor cells (VPC). Recently, we have established a method to expand monkey and human ES cells-derived VPC with the proper differentiation stage in a large quantity. Here we investigated the therapeutic potential of human VPC-derived EC and MC for vascular regeneration. METHODS AND RESULTS: After the expansion of human VPC-derived vascular cells, we transplanted these cells to nude mice with hindlimb ischemia. The blood flow recovery and capillary density in ischemic hindlimbs were significantly improved in human VPC-derived EC-transplanted mice, compared to human peripheral and umbilical cord blood-derived endothelial progenitor cells (pEPC and uEPC) transplanted mice. The combined transplantation of human VPC-derived EC and MC synergistically improved blood flow of ischemic hindlimbs remarkably, compared to the single cell transplantations. Transplanted VPC-derived vascular cells were effectively incorporated into host circulating vessels as EC and MC to maintain long-term vascular integrity. CONCLUSIONS: Our findings suggest that the combined transplantation of human ES cells-derived EC and MC can be used as a new promising strategy for therapeutic vascular regeneration in patients with tissue ischemia

    Molecular Modeling Study for Inhibition Mechanism of Human Chymase and Its Application in Inhibitor Design

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    Human chymase catalyzes the hydrolysis of peptide bonds. Three chymase inhibitors with very similar chemical structures but highly different inhibitory profiles towards the hydrolase function of chymase were selected with the aim of elucidating the origin of disparities in their biological activities. As a substrate (angiotensin-I) bound crystal structure is not available, molecular docking was performed to dock the substrate into the active site. Molecular dynamics simulations of chymasecomplexes with inhibitors and substrate were performed to calculate the binding orientation of inhibitors and substrate as well as to characterize conformational changes in the active site. The results elucidate details of the 3D chymase structure as well as the importance of K40 in hydrolase function. Binding mode analysis showed that substitution of a heavier Cl atom at the phenyl ring of most active inhibitor produced a great deal of variation in its orientation causing the phosphinate group to interact strongly with residue K40. Dynamics simulations revealed the conformational variation in region of V36-F41upon substrate and inhibitor binding induced a shift in the location of K40 thus changing its interactions with them. Chymase complexes with the most activecompound and substrate were used for development of a hybrid pharmacophore model which was applied in databases screening. Finally, hits which bound well at the active site, exhibited key interactions and favorable electronic properties were identified as possible inhibitors for chymase. This study not only elucidates inhibitorymechanism of chymase inhibitors but also provides key structural insights which will aid in the rational design of novel potent inhibitors of the enzyme. In general, the strategy applied in the current study could be a promising computational approach and may be generally applicable to drug design for other enzymes

    Mind the gap: connexins and cell–cell communication in the diabetic kidney

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    Connexins, assembled as a hexameric connexon, form a transmembrane hemichannel that provides a conduit for paracrine signalling of small molecules and ions to regulate the activity and function of adjacent cells. When hemichannels align and associate with similar channels on opposing cells, they form a continuous aqueous pore or gap junction, allowing the direct transmission of metabolic and electrical signals between coupled cells. Regulation of gap junction synthesis and channel activity is critical for cell function, and a number of diseases can be attributed to changes in the expression/function of these important proteins. Diabetic nephropathy is associated with several complex metabolic and inflammatory responses characterised by defects at the molecular, cellular and tissue level. In both type 1 and type 2 diabetes, glycaemic injury of the kidney is the leading cause of end-stage renal failure, a consequence of multiple aetiologies, including increased deposition of extracellular matrix, glomerular hyperfiltration, albuminuria and tubulointerstitial fibrosis. In diabetic nephropathy, loss of connexin mediated cell–cell communication within the nephron may represent an early sign of disease; however, our current knowledge of the role of connexins in the diabetic kidney is sparse. This review highlights recent evidence demonstrating that maintenance of connexin-mediated cell–cell communication could benefit region-specific renal function in diabetic nephropathy and suggests that these proteins should be viewed as a tantalising novel target for therapeutic intervention

    Correlations of differentially expressed gap junction connexins cx26, cx30, cx32, cx43 and cx46 with breast cancer progression and prognosis.

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    BACKGROUND AND AIMS: Connexins and their cell membrane channels contribute to the control of cell proliferation and compartmental functions in breast glands and their deregulation is linked to breast carcinogenesis. Our aim was to correlate connexin expression with tumor progression and prognosis in primary breast cancers. MATERIALS AND METHODS: Meta-analysis of connexin isotype expression data of 1809 and 1899 breast cancers from the Affymetrix and Illumina array platforms, respectively, was performed. Expressed connexins were also monitored at the protein level in tissue microarrays of 127 patients equally representing all tumor grades, using immunofluorescence and multilayer, multichannel digital microscopy. Prognostic correlations were plotted in Kaplan-Meier curves and tested using the log-rank test and cox-regression analysis in univariate and multivariate models. RESULTS: The expression of GJA1/Cx43, GJA3/Cx46 and GJB2/Cx26 and, for the first time, GJA6/Cx30 and GJB1/Cx32 was revealed both in normal human mammary glands and breast carcinomas. Within their subfamilies these connexins can form homo- and heterocellular epithelial channels. In cancer, the array datasets cross-validated each other's prognostic results. In line with the significant correlations found at mRNA level, elevated Cx43 protein levels were linked with significantly improved breast cancer outcome, offering Cx43 protein detection as an independent prognostic marker stronger than vascular invasion or necrosis. As a contrary, elevated Cx30 mRNA and protein levels were associated with a reduced disease outcome offering Cx30 protein detection as an independent prognostic marker outperforming mitotic index and necrosis. Elevated versus low Cx43 protein levels allowed the stratification of grade 2 tumors into good and poor relapse free survival subgroups, respectively. Also, elevated versus low Cx30 levels stratified grade 3 patients into poor and good overall survival subgroups, respectively. CONCLUSION: Differential expression of Cx43 and Cx30 may serve as potential positive and negative prognostic markers, respectively, for a clinically relevant stratification of breast cancers
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