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  • 1
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    Oxford [England] ; New York, N.Y. [USA] : Oxford University Press
    Keywords: Conflict management. ; Ethnic relations. ; Gestion des conflits. ; Group identity. ; Identité collective. ; Relations interethniques.
    Notes: Introduction : social identity and intergroup conflict / Lee Jussim, Richard D. Ashmore, and David Wilder / Ingroup identification and intergroup conflict : when does ingroup love become outgroup hate? / Marilynn B. Brewer -- Ethnic identity, national identity, and intergroup conflict : the significance of personal experiences / Thomas Hylland Eriksen -- The meaning of american national identity : patterns of ethnic conflict and consensus / Jack Citrin, Cara Wong, and Brian Duff -- Communal and national identity in a multiethnic state : a comparison of three perspectives / Jim Sidanius and John R. Petrocik -- Social and role identities and political violence : identity as a window on violence in northern ireland / Robert W. White -- Individual and group identities in genocide and mass killing / Ervin Staub -- The role of national identity in conflict resolution : experiences from Israeli-Palestinian problem-solving workshops / Herbert C. Kelman -- Conclusion : toward a social identity framework for intergroup conflict / Richard D. Ashmore, Lee Jussim, David Wilder, and Jessica Heppen
    Pages: xii, 270 p.
    ISBN: 0-19-530241-9
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  • 2
    Publication Date: 2018-07-31
    Description: Background/Aim: High expression of the Bcl-2-interacting cell death suppressor (BIS), an anti-apoptotic protein, in various human cancers is linked to a poor outcome. The purpose of this study was to clarify whether BIS is associated with the migration and invasive characteristics of A549 cells. Materials and Methods: BIS-knockout (KO) cells were prepared by the CRISPR/Cas9 method. The aggressive behaviors of A549 cells were analyzed by wound healing and a transwell invasion assay as well as 3D spheroid culture. Results: BIS depletion resulted in significant inhibition of the migration and invasive potential of A549 cells which was accompanied by an increased ratio of E-cadherin/N-cadherin and a decrease in the mRNA levels of Zeb1, Snail, Slug and MMP-2. NF-B activity was suppressed in BIS-KO A549 cells due to the decrease in p65 protein levels, but not in mRNA levels. Conclusion: BIS regulates cell invasion and the induction of the epithelial-mesenchymal transition (EMT) phenotype in A549 cells probably via the NF-B signaling pathway.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 3
    Publication Date: 2018-09-08
    Description: Background/Aim: High expression of the Bcl-2-interacting cell death suppressor (BIS), an anti-apoptotic protein, in various human cancers is linked to a poor outcome. The purpose of this study was to clarify whether BIS is associated with the migration and invasive characteristics of A549 cells. Materials and Methods: BIS-knockout (KO) cells were prepared by the CRISPR/Cas9 method. The aggressive behaviors of A549 cells were analyzed by wound healing and a transwell invasion assay as well as 3D spheroid culture. Results: BIS depletion resulted in significant inhibition of the migration and invasive potential of A549 cells which was accompanied by an increased ratio of E-cadherin/N-cadherin and a decrease in the mRNA levels of Zeb1, Snail, Slug and MMP-2. NF-ĸB activity was suppressed in BIS-KO A549 cells due to the decrease in p65 protein levels, but not in mRNA levels. Conclusion: BIS regulates cell invasion and the induction of the epithelial-mesenchymal transition (EMT) phenotype in A549 cells probably via the NF-ĸB signaling pathway.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 4
    Publication Date: 2018-01-04
    Description: Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter ( d max ) of 3 to 7 cm. Experimental Design: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA ± LTLD. The 701 enrolled patients had to have ≤4 unresectable HCC lesions, at least one of which had a d max of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy. Results: The primary endpoint was not met; in intention-to-treat analysis, the PFS HR of RFA + LTLD versus RFA alone was 0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was 0.95 (95% CI, 0.76–1.20; P = 0.67). Among 285 patients with a solitary HCC lesion who received ≥45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41–0.96; P 〈 0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin. Conclusions: Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion ≥45 minutes. Clin Cancer Res; 24(1); 73–83. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 5
    Publication Date: 2018-11-06
    Description: The variable lymphocyte receptor (VLR) B of jawless vertebrates functions as a secreted Ab of jawed vertebrates and has emerged as an alternative Ab with a single polypeptide chain. After observing an upregulated VLRB response in hagfish immunized with avian influenza virus (AIV) subtype H9N2, we screened AIV H9N2–specific VLRB using a mammalian expression system. To improve the binding avidity of the Ag-specific VLRB to the Ag, we enabled multimerization of the VLRB by conjugating it with C-terminal domain of human C4b-binding protein. To dramatically enhance the expression and secretion of the Ag-specific VLRB, we introduced a glycine–serine linker and the murine Ig leader sequence. The practical use of the Ag-specific VLRB was also demonstrated through various immunoassays, detected by anti-VLRB Ab (11G5). Finally, we found that the Ag-specific VLRB decreased the infectivity of AIV H9N2. Together, our findings suggest that the generated Ag-specific VLRB could be used for various immunoapplications.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 6
    Publication Date: 2018-01-03
    Description: Simultaneous sequencing of the genome and transcriptome at the single-cell level is a powerful tool for characterizing genomic and transcriptomic variation and revealing correlative relationships. However, it remains technically challenging to analyze both the genome and transcriptome in the same cell. Here, we report a novel method for simultaneous isolation of genomic DNA and total RNA (SIDR) from single cells, achieving high recovery rates with minimal cross-contamination, as is crucial for accurate description and integration of the single-cell genome and transcriptome. For reliable and efficient separation of genomic DNA and total RNA from single cells, the method uses hypotonic lysis to preserve nuclear lamina integrity and subsequently captures the cell lysate using antibody-conjugated magnetic microbeads. Evaluating the performance of this method using real-time PCR demonstrated that it efficiently recovered genomic DNA and total RNA. Thorough data quality assessments showed that DNA and RNA simultaneously fractionated by the SIDR method were suitable for genome and transcriptome sequencing analysis at the single-cell level. The integration of single-cell genome and transcriptome sequencing by SIDR (SIDR-seq) showed that genetic alterations, such as copy-number and single-nucleotide variations, were more accurately captured by single-cell SIDR-seq compared with conventional single-cell RNA-seq, although copy-number variations positively correlated with the corresponding gene expression levels. These results suggest that SIDR-seq is potentially a powerful tool to reveal genetic heterogeneity and phenotypic information inferred from gene expression patterns at the single-cell level.
    Electronic ISSN: 1549-5469
    Topics: Biology , Medicine
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  • 7
    Publication Date: 2018-01-03
    Description: Off-target binding in the basal ganglia is commonly observed in the 18 F-AV-1451 PET studies of the elderly. We sought to investigate the relationship between this phenomenon in the basal ganglia and iron accumulation using iron-sensitive R 2 * MRI. Methods: Fifty-nine healthy controls and 61 patients with Alzheimer disease and mild cognitive impairment underwent 18 F-AV-1451 PET and R 2 * MRI studies. A correlation analysis was performed for age, 18 F-AV-1451 binding, and R 2 * values. Results: There was an age-related increase in both 18 F-AV-1451 binding in the basal ganglia and R 2 * values in the putamen in both the controls and the Alzheimer disease/mild cognitive impairment patients. 18 F-AV-1451 binding in the basal ganglia increased with R 2 * values. Conclusion: Off-target 18 F-AV-1451 binding in the basal ganglia is associated with the age-related increases in iron accumulation. Postmortem studies are required to further investigate the nature of this association.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 8
    Publication Date: 2018-08-01
    Description: Guidance molecules, receptors, and downstream signaling pathways involved in the asymmetric neuronal cell migration and process outgrowth have been identified from genetic studies using model organisms, most of which are evolutionarily conserved. In the nematode Caenorhabditis elegans , the roles of Wnt ligands and their receptors in the polarization of specific sets of neurons along the anterior-posterior (A-P) body axis have been well elucidated, but their downstream effectors are relatively unknown. Here, we report yap-1 , encoding an evolutionarily conserved transcriptional co-activator, as a novel player in the Wnt-mediated asymmetric development of specific neurons in C. elegans . We found that the loss of yap-1 activity failed to restrict the dendritic extension of ALM neurons to the anterior orientation, which is similar to the phenotype caused by defective cwn-1 and cwn-2 Wnt gene activities. Cell-specific rescue experiments showed that yap-1 acts in the cell autonomous manner to polarize ALM dendrites. We also found that subcellular localization of YAP-1 was spatio-temporally regulated. The loss of yap-1 in Wnt-deficient mutants did not increase the severity of the ALM polarity defect of the mutants. Wnt-deficient animals displayed abnormal subcellular localization of YAP-1 in touch receptor neurons, suggesting that yap-1 may act downstream of the cwn-1 / cwn-2 Wnt ligands for the ALM polarization process. Together, we have identified a new role for YAP-1 in neuronal development and our works will contribute to further understanding of intracellular events in neuronal polarization during animal development.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 9
    Publication Date: 2018-04-03
    Description: Monocarboxylate transporters (MCT) are transmembrane proteins that control the lactate metabolism and are associated with poor prognosis in solid tumors, including colorectal cancer. Here, we aimed to investigate the biological and clinical role of MCTs in colorectal cancer and to assess the potential of therapeutic application. A total of 16 human colorectal cancer cell lines, 11 patient-derived cells from malignant ascites [patient-derived cells (PDC)], and 39 matched pairs of primary colorectal cancer and normal colorectal tissues were used to assess the role of MCT in vitro and in vivo . siRNA methodology was used to determine the effect of MCT inhibition and molecular mechanism of hypoxia- and angiogenesis-related factors in addition to MCT4. The effect of MCT inhibition was confirmed in mouse xenograft models. MCT4 expression in surgical tissue was evaluated by IHC and used for survival analysis. Expression of MCTs was demonstrated in colorectal cancer cell lines. siRNA-mediated MCT silencing caused significant decline of cell proliferation both in vitro and in vivo . An additive effect of MCT inhibition was induced by combined treatment with chemotherapy or radiotherapy. In particular, the expression of MCT4 was markedly increased in PDCs, and MCT4 inhibition significantly decreased PDC proliferation. Hypoxia-inducible factor 1-α (HIF1α) was also highly expressed in PDCs, whereas HIF1α knockdown reduced MCT4 expression and of other angiogenesis-related mediators. The patients with high MCT4 expression by IHC showed shorter relapse-free survival compared with low expression. These findings suggest that MCT4 may represent a new therapeutic target for colorectal cancer with peritoneal carcinomatosis and serve as a prognostic indicator. Mol Cancer Ther; 17(4); 838–48. ©2018 AACR .
    Print ISSN: 1535-7163
    Electronic ISSN: 1538-8514
    Topics: Medicine
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  • 10
    Publication Date: 2018-04-19
    Description: Aim To canvass the UK pathology community to ascertain current levels of digital pathology usage in clinical and academic histopathology departments, and prevalent attitudes to digital pathology. Methods A 15-item survey was circulated to National Health Service and academic pathology departments across the UK using the SurveyMonkey online survey tool. Responses were sought at a departmental or institutional level. Where possible, departmental heads were approached and asked to complete the survey, or forward it to the most relevant individual in their department. Data were collected over a 6-month period from February to July 2017. Results 41 institutes from across the UK responded to the survey. 60% (23/39) of institutions had access to a digital pathology scanner, and 60% (24/40) had access to a digital pathology workstation. The most popular applications of digital pathology in current use were undergraduate and postgraduate teaching, research and quality assurance. Investigating the deployment of digital pathology in their department was identified as a high or highest priority by 58.5% of institutions, with improvements in efficiency, turnaround times, reporting times and collaboration in their institution anticipated by the respondents. Access to funding for initial hardware, software and staff outlay, pathologist training and guidance from the Royal College of Pathologists were identified as factors that could enable respondent institutions to increase their digital pathology usage. Conclusion Interest in digital pathology adoption in the UK is high, with usage likely to increase in the coming years. In light of this, pathologists are seeking more guidance on safe usage.
    Keywords: Open access
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
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