1,485 research outputs found

    Image processing methods to elucidate spatial characteristics of retinal microglia after optic nerve transection

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    Retinal structure and function preservation by polysaccharides of wolfberry in a mouse model of retinal degeneration

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    Inhibition of TGF-B signaling in combination with TLR7 ligation re-programs a tumoricidal phenotype in tumor-associated macrophages

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    Inadequate immunity that occurs in a tumor environment is in part due to the presence of M2-type tumor-associated macrophages (TAMs). TGF-beta has a multi-functional role in tumor development including modulating the biological activity of both the tumor and TAMs. In this study, using an in vitro TAM/tumor cell co-culture system ligation of TLR7, which is expressed on TAMs but not the tumor cells, in the presence of TGF-beta receptor I inhibitor re-programmed the phenotype of the TAMs. In part they adopted the phenotype characteristic of M1-type macrophages, namely they had increased tumoricidal activity and elevated expression of iNOS, CD80 and MHC class II, while TGF-beta secretion was reduced. The reprogrammed phenotype was accompanied by enhanced NF-kappaB nuclear translocation. The pro-angiogenesis factor VEGF was down-regulated and in vivo the number of CD31-positive tumor capillaries was also reduced. Furthermore, in vivo we observed that TLR7 ligation/TGF-beta receptor I inhibition increased tumor apoptosis and elevated the number of CD4+, CD8+, and CD19+ cells as well as neutrophils infiltrating the tumor. Our data demonstrate that selective TLR stimulation with TGF-beta inhibition can reprogram TAMs towards an M1-like phenotype and thereby provides new perspectives in cancer therapy.postprin

    Study of transforming growth factor alpha for the maintenance of human embryonic stem cells

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    Human embryonic stem cells (hESCs) have great potential for regenerative medicine as they have selfregenerative and pluripotent properties. Feeder cells or their conditioned medium are required for the maintenance of hESC in the undifferentiated state. Feeder cells have been postulated to produce growth factors and extracellular molecules for maintaining hESC in culture. The present study has aimed at identifying these molecules. The gene expression of supportive feeder cells, namely human foreskin fibroblast (hFF-1) and non-supportive human lung fibroblast (WI-38) was analyzed by microarray and 445 genes were found to be differentially expressed. Gene ontology analysis showed that 20.9% and 15.5% of the products of these genes belonged to the extracellular region and regulation of transcription activity, respectively. After validation of selected differentially expressed genes in both human and mouse feeder cells, transforming growth factor a (TGFa) was chosen for functional study. The results demonstrated that knockdown or protein neutralization of TGFa in hFF-1 led to increased expression of early differentiation markers and lower attachment rates of hESC. More importantly, TGFa maintained pluripotent gene expression levels, attachment rates and pluripotency by the in vitro differentiation of H9 under non-supportive conditions. TGFa treatment activated the p44/42MAPK pathway but not the PI3K/Akt pathway. In addition, TGFa treatment increased the expression of pluripotent markers, NANOG and SSEA-3 but had no effects on the proliferation of hESCs. This study of the functional role of TGFa provides insights for the development of clinical grade hESCs for therapeutic applications. © The Author(s) 2012. © Springer-Verlag 2012.published_or_final_versio

    Local proliferation is the main source of rod microglia after optic nerve transection

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    Aharonov-Bohm interference in topological insulator nanoribbons

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    Topological insulators represent novel phases of quantum matter with an insulating bulk gap and gapless edges or surface states. The two-dimensional topological insulator phase was predicted in HgTe quantum wells and confirmed by transport measurements. Recently, Bi2Se3 and related materials have been proposed as three-dimensional topological insulators with a single Dirac cone on the surface and verified by angle-resolved photoemission spectroscopy experiments. Here, we show unambiguous transport evidence of topological surface states through periodic quantum interference effects in layered single-crystalline Bi2Se3 nanoribbons. Pronounced Aharonov-Bohm oscillations in the magnetoresistance clearly demonstrate the coverage of two-dimensional electrons on the entire surface, as expected from the topological nature of the surface states. The dominance of the primary h/e oscillation and its temperature dependence demonstrate the robustness of these electronic states. Our results suggest that topological insulator nanoribbons afford novel promising materials for future spintronic devices at room temperature.Comment: 5 pages, 4 figures, RevTex forma

    An assessment of the quality of randomised controlled trials conducted in China

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    Background: Despite the rapid increase in research in China, little is known about the quality of clinical trials conducted there.Methods: A systematic review and critical appraisal of randomised controlled trials (RCTs) conducted in China and published in 2004 was undertaken to describe their characteristics, assess the quality of their reporting, and where possible, the quality of their conduct. Randomised controlled trials in all disease areas and types of interventions, which took place in China and included Chinese citizens were identified using PubMed and hand searching the Journal Series of the Chinese Medical Association. Quality was assessed against a subset of criteria adapted from the CONSORT statement.Results: Three hundred and seven RCTs were included. One hundred and ninety-nine (64.8%) failed to report methods of randomization and 254 (82.4%) did not mention blinding of either participants or investigators. Reporting of baseline characteristics, primary outcome and length of follow-up was inadequate in a substantial proportion of studies. Fewer than 11% of RCTs mentioned ethical approval and only 18.0% adequately discussed informed consent. However, dropout rates were very favourable with nearly 44% of trials reporting a zero dropout rate.Conclusion: Reporting of RCTs in China requires substantial improvement to meet the targets of the CONSORT statement. The conduct of Chinese RCTs cannot be directly inferred from the standard of reporting; however without good reporting the methods of the trials cannot be clearly ascertained

    Occurrence of False Positive Results for the Detection of Carbapenemases in Carbapenemase-Negative Escherichia coli and Klebsiella pneumoniae Isolates

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    Adequate detection of the production of carbapenemase in Enterobacteriaceae isolates is crucial for infection control measures and the appropriate choice of antimicrobial therapy. In this study, we investigated the frequency of false positive results for the detection of carbapenemases in carbapenemase-negative Escherichia coli and Klebsiella pneumoniae clinical isolates by the modified Hodge test (MHT). Three hundred and one E. coli and K. pneumoniae clinical isolates were investigated. All produced extended spectrum β-lactamases (ESBLs) but were susceptible to carbapenems. Antimicrobial susceptibility testing was performed by the disk diffusion and agar dilution methods. The MHT was performed using the standard inoculum of test organisms recommended by the CLSI. Genes that encoded ESBLs and carbapenemases were identified by PCR and DNA sequencing. Among the 301 clinical isolates, none of the isolates conformed to the criteria for carbapenemase screening recommended by the CLSI. The susceptibility rates for imipenem, meropenem, and ertapenem all were 100.0%, 100.0%, and 100.0%, respectively. Of the 301 E. coli and K. pneumoniae isolates, none produced carbapenemase. The MHT gave a positive result for 3.3% (10/301) of the isolates. False positive results can occur when the MHT is used to detect carbapenemase in ESBL-producing isolates and clinical laboratories must be aware of this fact

    Solitary waves in the Nonlinear Dirac Equation

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    In the present work, we consider the existence, stability, and dynamics of solitary waves in the nonlinear Dirac equation. We start by introducing the Soler model of self-interacting spinors, and discuss its localized waveforms in one, two, and three spatial dimensions and the equations they satisfy. We present the associated explicit solutions in one dimension and numerically obtain their analogues in higher dimensions. The stability is subsequently discussed from a theoretical perspective and then complemented with numerical computations. Finally, the dynamics of the solutions is explored and compared to its non-relativistic analogue, which is the nonlinear Schr{\"o}dinger equation. A few special topics are also explored, including the discrete variant of the nonlinear Dirac equation and its solitary wave properties, as well as the PT-symmetric variant of the model
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