336 research outputs found
Electronic properties of a-CNx thin films: An x-ray-absorption and photoemission spectroscopy study
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Hydrodynamics of a 5D Einstein-dilaton black hole solution and the corresponding BPS state
We apply the potential reconstruction approach to generate a series of
asymptotically AdS (aAdS) black hole solutions, with a self-interacting bulk
scalar field. Based on the method, we reproduce the pure AdS solution as a
consistency check and we also generate a simple analytic 5D black hole
solution. We then study various aspects of this solution, such as temperature,
entropy density and conserved charges. Furthermore, we study the hydrodynamics
of this black hole solution in the framework of fluid/gravity duality, e.g. the
ratio of the shear viscosity to the entropy density. In a degenerate case of
the 5D black hole solution, we find that the c function decreases monotonically
from UV to IR as expected. Finally, we investigate the stability of the
degenerate solution by studying the bosonic functional energy of the gravity
and the Witten-Nester energy . We confirm that the degenerate solution
is a BPS domain wall solution. The corresponding superpotential and the
solution of the killing spinor equation are found explicitly.Comment: V2: 23 pages, no figure, minor changes, typos corrected, new
references and comments added, version accepted by JHE
High Speed Cycle-Approximate Simulation of Embedded Cache-Incoherent and Coherent Chip-Multiprocessors
Overexpression of ฮฒ2-microglobulin is associated with poor survival in patients with oral cavity squamous cell carcinoma and contributes to oral cancer cell migration and invasion
ฮฒ2-Microglobulin (ฮฒ2M), a component of MHC class I molecules, is believed to be associated with tumour status in various cancers. In this study, we examined the expression of ฮฒ2M at different malignant stages of oral cavity squamous cell carcinoma (OCSCC). To determine the possible correlation between ฮฒ2M expression and various clinical characteristics, 256 samples from patients with OCSCC were evaluated by immunohistochemical staining. Strong ฮฒ2M expression was significantly correlated with a relatively advanced tumour stage (P<0.001), positive nodal status (P<0.001), and TNM stage (P<0.001). The cumulative 5-year survival rate was significantly correlated with a relatively advanced tumour stage (P<0.001), positive nodal status (P<0.001), TNM stage (P<0.001), and strong expression of ฮฒ2M (P<0.001). Thus, elevated ฮฒ2M expression is an indicator of poor survival (P<0.001). In addition, we extended our analysis of ฮฒ2M expression to the FaDu and SCC25 oral cancer cell lines. ฮฒ2-Microglobulin expression was positively correlated with cell migration and invasion in ฮฒ2M-overexpressing transfectants in Transwell chambers. The suppression of ฮฒ2M expression using small interfering RNA (siRNA) was sufficient to decrease cell migration and invasion in vitro. Taken together, our results suggest that ฮฒ2M expression in the tissues is associated with survival and may be involved in tumour progression and metastasis in OCSCC
Evaluation of subcortical grey matter abnormalities in patients with MRI-negative cortical epilepsy determined through structural and tensor magnetic resonance imaging
Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures
DNA double-strand breaks (DSBs) are a serious threat to the cell, for if not or miss-repaired, they can lead to chromosomal aberration, mutation and cancer. DSBs in human cells are repaired via non-homologous DNA end joining (NHEJ) and homologous recombination repair pathways. In the former process, the structure of DNA termini plays an important role, as does the genetic constitution of the cells, through being different in normal and pathological cells. In order to investigate the dependence of NHEJ on DSB structure in normal and cancer cells, we used linearized plasmids with various, complementary or non-complementary, single-stranded or blunt DNA termini, as well as whole-cell extract isolated from normal human lymphocytes, chronic myeloid leukemia K562 cells and lung cancer A549 cells. We observed a pronounced variability in the efficacy of NHEJ reaction depending on the type of ends. Plasmids with complementary and blunt termini were more efficiently repaired than the substrate with 3' protruding single-strand ends. The hierarchy of the effectiveness of NHEJ was on average, from the most effective to the least, A549/ normal lymphocytes/ K562. Our results suggest that the genetic constitution of the cells together with the substrate terminal structure may contribute to the efficacy of the NHEJ reaction. This should be taken into account on considering its applicability in cancer chemo- or radiotherapy by pharmacologically modulating NHEJ cellular responses
Analysis of Epitopes on Dengue Virus Envelope Protein Recognized by Monoclonal Antibodies and Polyclonal Human Sera by a High Throughput Assay
Dengue virus is the leading cause of arboviral diseases worldwide. The envelope protein is the major target of neutralizing antibodies and vaccine development. While previous studies have reported several epitopes on envelope protein, the possibility of interdomain epitopes and the relationship of epitopes to neutralizing potency remain unexplored. We developed a high throughput dot blot assay by using 67 alanine mutants of surface-exposed envelope residues as a systematic approach to identify epitopes recognized by mouse monoclonal antibodies and polyclonal human sera. Our results suggested the presence of interdomain epitopes more frequent than previously appreciated. Compared with monoclonal antibodies generated by traditional protocol, the potent neutralizing monoclonal antibodies generated by a new protocol showed several unique features of their epitopes. Moreover, the predominant epitopes of antibodies against envelope protein in polyclonal sera can be identified by this assay. These findings have implications for future development of epitope-specific diagnostics and epitope-based dengue vaccine, and add to our understanding of humoral immune responses to dengue virus at the epitope level
Humoral Immune Responses of Dengue Fever Patients Using Epitope-Specific Serotype-2 Virus-Like Particle Antigens
Dengue virus (DENV) is a serious mosquito-borne pathogen causing significant global disease burden, either as classic dengue fever (DF) or in its most severe manifestation dengue hemorrhagic fever (DHF). Nearly half of the world's population is at risk of dengue disease and there are estimated to be millions of infections annually; a situation which will continue to worsen with increasing expansion of the mosquito vectors and epidemic DF/DHF. Currently there are no available licensed vaccines or antivirals for dengue, although significant effort has been directed toward the development of safe and efficacious dengue vaccines for over 30 years. Promising vaccine candidates are in development and testing phases, but a better understanding of immune responses to DENV infection and vaccination is needed. Humoral immune responses to DENV infection are complex and may exacerbate pathogenicity, yet are essential for immune protection. In this report, we develop DENV-2 envelope (E) protein epitope-specific antigens and measure immunoglobulin responses to three distinct epitopes in DENV-2 infected human serum samples. Immunoglobulin responses to DENV-2 infection exhibited significant levels of individual variation. Antibody populations targeting broadly cross-reactive epitopes centered on the fusion peptide in structural domain II were large, highly variable, and greater in primary than in secondary DENV-2 infected sera. E protein domain III cross-reactive immunoglobulin populations were similarly variable and much larger in IgM than in IgG. DENV-2 specific domain III IgG formed a very small proportion of the antibody response yet was significantly correlated with DENV-2 neutralization, suggesting that the highly protective IgG recognizing this epitope in murine studies plays a role in humans as well. This report begins to tease apart complex humoral immune responses to DENV infection and is thus important for improving our understanding of dengue disease and immunological correlates of protection, relevant to DENV vaccine development and testing
Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics
<p>Abstract</p> <p>Background</p> <p>Tumor initiating stem-like cells (TISCs) are a subset of neoplastic cells that possess distinct survival mechanisms and self-renewal characteristics crucial for tumor maintenance and propagation. The induction of epithelial-mesenchymal-transition (EMT) by TGFฮฒ has been recently linked to the acquisition of TISC characteristics in breast cancer. In HCC, a TISC and EMT phenotype correlates with a worse prognosis. In this work, our aim is to elucidate the underlying mechanism by which cells acquire tumor initiating characteristics after EMT.</p> <p>Methods</p> <p>Gene and protein expression assays and Nanog-promoter luciferase reporter were utilized in epithelial and mesenchymal phenotype liver cancer cell lines. EMT was analyzed with migration/invasion assays. TISC characteristics were analyzed with tumor-sphere self-renewal and chemotherapy resistance assays. <it>In vivo </it>tumor assay was performed to investigate the role of Snail1 in tumor initiation.</p> <p>Conclusion</p> <p>TGFฮฒ induced EMT in epithelial cells through the up-regulation of Snail1 in Smad-dependent signaling. Mesenchymal liver cancer post-EMT demonstrates TISC characteristics such as tumor-sphere formation but are not resistant to cytotoxic therapy. The inhibition of <it>Snail1 </it>in mesenchymal cells results in decreased <it>Nanog </it>promoter luciferase activity and loss of self-renewal characteristics <it>in vitro</it>. These changes confirm the direct role of Snail1 in some TISC traits. <it>In vivo</it>, the down-regulation of <it>Snail1 </it>reduced tumor growth but was not sufficient to eliminate tumor initiation. In summary, TGFฮฒ induces EMT and TISC characteristics through Snail1 and Nanog up-regulation. In mesenchymal cells post-EMT, Snail1 directly regulates <it>Nanog </it>expression, and loss of Snail1 regulates tumor growth without affecting tumor initiation.</p
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