148 research outputs found

    Phase separation effects and the nematic-isotropic transition in polymer and low molecular weight liquid crystals doped with nanoparticles

    Get PDF
    Properties of the nematic–isotropic phase transition in polymer and low molecular weight liquid crystals doped with nanoparticles have been studied both experimentally and theoretically in terms of molecular mean-field theory. The variation of the transition temperature and the transition heat with the increasing volume fraction of CdSe quantum dot nanoparticles in copolymer and low molecular weight nematics has been investigated experimentally and the data are interpreted using the results of the molecular theory which accounts for a possibility of phase separation when the system undergoes the nematic–isotropic transition. The theory predicts that the nematic and isotropic phases with different concentrations of nanoparticles may coexist over a broad temperature range, but only if the nanoparticle volume fraction exceeds a certain threshold value which depends on the material parameters. Such unusual phase separation effects are determined by the strong interaction between nanoparticles and mesogenic groups and between nanoparticles themselves

    STUDYING SPECIALIZATION AS A FACTOR IN TOURISM CLUSTER DEVELOPMENT

    Get PDF
    The importance of this research paper is that a significant number of tourism clusters established on the territory of the Russian Federation are not always successful as catalysts for the development of the tourism sector. This study aims to determine methods for conducting research on specialization as a factor in tourism cluster development, taking into consideration the existing research approaches and research findings in this area. The systematic, structural, functional and analysis methods were used, along with a general theoretic approach to researching tourism cluster development. The selected methods made it possible to identify approaches to forming research methodologies for studying tourism cluster specialization. Based on the presented approaches to examining specialization as a factor in the development of tourism clusters, it is possible to choose research methods and the coherence of research activities in this area. The methodology and coherence of research into tourism clusters was determined with a view to detect key development indicators for tourism development and various tourism-related processes taking place on the territory of a tourism cluster. The research findings will provide necessary tools and mechanisms for developing tourism clusters based on the diversification of their specialization. The findings of the study are directed at increasing the effectiveness of decisions taken to assess and forecast tourism cluster development and can also be of use to all those interested in this field. The materials of the present study can be used by regional administrations to monitor and make effective management decisions aimed at improving regional tourism development programs. Experts and scholars could also benefit from the findings of this study to analyze and develop projections and to promote topic-related methodological approaches. The article will be of practical value to specialists in tourism planning, tourism administration and tourism enterprise managers

    2014-2015 Master Class - Raisa Isaacs (Harpsichord)

    Get PDF
    https://spiral.lynn.edu/conservatory_masterclasses/1031/thumbnail.jp

    Phosphorylated Nuclear DICER1 Promotes Open Chromatin State and Lineage Plasticity of AT2 Tumor Cells in Lung Adenocarcinomas

    Get PDF
    KRAS/ERK pathway phosphorylates DICER1, causing its nuclear translocation, and phosphomimetic Dicer1 contributes to tumorigenesis in mice. Mechanisms through which phospho-DICER1 regulates tumor progression remain undefined. While DICER1 canonically regulates microRNAs (miRNA) and epithelial-to-mesenchymal transition (EMT), we found that phosphorylated nuclear DICER1 (phospho-nuclear DICER1) promotes late-stage tumor progression in mice with oncogenic Kras, independent of miRNAs and EMT. Instead, we observe that the murine AT2 tumor cells exhibit altered chromatin compaction, and cells from disorganized advanced tumors, but not localized tumors, express gastric genes. Collectively, this results in subpopulations of tumor cells transitioning from a restricted alveolar to a broader endodermal lineage state. In human LUADs, we observed expression of phospho-nuclear DICER1 in advanced tumors together with the expression of gastric genes. We define a multimeric chromatin-DICER1 complex composed of the Mediator complex subunit 12, CBX1, MACROH2A.1, and transcriptional regulators supporting the model that phospho-nuclear DICER1 leads to lineage reprogramming of AT2 tumor cells to mediate lung cancer progression

    Ligelizumab for Chronic Spontaneous Urticaria

    Get PDF
    Background: In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose–response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists. Methods: In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose–response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial. Results: A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose–response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged. Conclusions: A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332. opens in new tab.

    Geographic gradients in a functional trait: variation of body size and size diversity in ground beetle Poecilus cupreus (Linnaeus, 1758) (Coleoptera, Carabidae)

    Get PDF
    The aim of this study was to test the character of body size variation and its diversity in the widespread ground beetle Poecilus cupreus in geographical gradients. Beetles were sampled in 14 regions of Europe and the Asia, and sampling territories differed by 17° in latitude and 121° in longitude. We measured six linear traits in each captured beetle and formed a data set that included 6745 individuals. In the latitudinal gradient, three of the six traits studied decreased their values (direct trends), and the variability curve of four of the six features studied is hump-shaped with a maximum value in the middle latitudes (polynomial trends). In the longitudinal gradient, three traits decreased their values (direct trends), and the variability of three ones had the form of a concave curve with minimum values in the middle longitudes. The variability coefficients of the features themselves behave differently. Their value increased in the latitudinal gradient and decreased in the longitudinal gradient (direct trends). Polynomial trends show a hump-shaped curve – the greatest variability of feature values is observed in the middle latitudes and middle longitudes. We worked according to a single methodology and our analysis is intraspecific, so we insist that such eco-geographic and morphometric studies be conducted in the same way

    Frequent Long-Range Epigenetic Silencing of Protocadherin Gene Clusters on Chromosome 5q31 in Wilms' Tumor

    Get PDF
    Wilms' tumour (WT) is a pediatric tumor of the kidney that arises via failure of the fetal developmental program. The absence of identifiable mutations in the majority of WTs suggests the frequent involvement of epigenetic aberrations in WT. We therefore conducted a genome-wide analysis of promoter hypermethylation in WTs and identified hypermethylation at chromosome 5q31 spanning 800 kilobases (kb) and more than 50 genes. The methylated genes all belong to α-, β-, and γ-protocadherin (PCDH) gene clusters (Human Genome Organization nomenclature PCDHA@, PCDHB@, and PCDHG@, respectively). This demonstrates that long-range epigenetic silencing (LRES) occurs in developmental tumors as well as in adult tumors. Bisulfite polymerase chain reaction analysis showed that PCDH hypermethylation is a frequent event found in all Wilms' tumor subtypes. Hypermethylation is concordant with reduced PCDH expression in tumors. WT precursor lesions showed no PCDH hypermethylation, suggesting that de novo PCDH hypermethylation occurs during malignant progression. Discrete boundaries of the PCDH domain are delimited by abrupt changes in histone modifications; unmethylated genes flanking the LRES are associated with permissive marks which are absent from methylated genes within the domain. Silenced genes are marked with non-permissive histone 3 lysine 9 dimethylation. Expression analysis of embryonic murine kidney and differentiating rat metanephric mesenchymal cells demonstrates that Pcdh expression is developmentally regulated and that Pcdhg@ genes are expressed in blastemal cells. Importantly, we show that PCDHs negatively regulate canonical Wnt signalling, as short-interfering RNA–induced reduction of PCDHG@ encoded proteins leads to elevated β-catenin protein, increased β-catenin/T-cell factor (TCF) reporter activity, and induction of Wnt target genes. Conversely, over-expression of PCDHs suppresses β-catenin/TCF-reporter activity and also inhibits colony formation and growth of cancer cells in soft agar. Thus PCDHs are candidate tumor suppressors that modulate regulatory pathways critical in development and disease, such as canonical Wnt signaling
    corecore