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  • 1
    Publication Date: 2018-04-14
    Description: We report a general strategy for obtaining high-quality, large-area metal-chalcogenide semiconductor films from precursors combining chelated metal salts with chalcoureas or chalcoamides. Using conventional organic solvents, such precursors enable the expeditious formation of chalco-gels, which are easily transformed into the corresponding high-performance metal-chalcogenide thin films with large, uniform areas. Diverse metal chalcogenides and their alloys (MQ x : M = Zn, Cd, In, Sb, Pb; Q = S, Se, Te) are successfully synthesized at relatively low processing temperatures (〈400°C). The versatility of this scalable route is demonstrated by the fabrication of large-area thin-film transistors (TFTs), optoelectronic devices, and integrated circuits on a 4-inch Si wafer and 2.5-inch borosilicate glass substrates in ambient air using CdS, CdSe, and In 2 Se 3 active layers. The CdSe TFTs exhibit a maximum field-effect mobility greater than 300 cm 2 V –1 s –1 with an on/off current ratio of 〉10 7 and good operational stability (threshold voltage shift 〈 0.5 V at a positive gate bias stress of 10 ks). In addition, metal chalcogenide–based phototransistors with a photodetectivity of 〉10 13 Jones and seven-stage ring oscillators operating at a speed of ~2.6 MHz (propagation delay of 〈 27 ns per stage) are demonstrated.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 2
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    The International Institute of Anticancer Research (IIAR)
    Publication Date: 2018-01-28
    Description: Ursolic acid (UA) is a natural pentacyclic triterpene that has various biological activities, including anticancer and anti-inflammatory effects. This study investigated the ability of UA to cause cell death in pheochromocytoma (PC-12) cells. UA was cytotoxic to PC-12 cells (half-maximum inhibitory concentration=53.2 μM) and significantly reduced the clonogenic ability of PC-12 cells. It also triggered apoptosis by reducing the level of B-cell lymphoma 2 (BCL2), activating caspase-3, and inducing cleavage of poly (ADP-ribosyl) polymerase. To investigate the effects of UA treatment on the induction and progression of autophagy, the levels of p62 and the conversion of the microtubule-associated protein light chain 3 (LC3)-I to LC3-II, which are important markers of autophagic flux, were monitored. UA treatment induced the accumulation of p62 and increased the LC3-II/LC3-I ratio. These results demonstrate that UA treatment induced autophagy, but the downstream signaling pathway was blocked. In summary, this study shows that UA kills PC-12 cells by inducing apoptosis and impairing autophagy progression.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 3
    Publication Date: 2018-01-25
    Description: Recent advances in wearable electronics combined with wireless communications are essential to the realization of medical applications through health monitoring technologies. For example, a smart contact lens, which is capable of monitoring the physiological information of the eye and tear fluid, could provide real-time, noninvasive medical diagnostics. However, previous reports concerning the smart contact lens have indicated that opaque and brittle components have been used to enable the operation of the electronic device, and this could block the user’s vision and potentially damage the eye. In addition, the use of expensive and bulky equipment to measure signals from the contact lens sensors could interfere with the user’s external activities. Thus, we report an unconventional approach for the fabrication of a soft, smart contact lens in which glucose sensors, wireless power transfer circuits, and display pixels to visualize sensing signals in real time are fully integrated using transparent and stretchable nanostructures. The integration of this display into the smart lens eliminates the need for additional, bulky measurement equipment. This soft, smart contact lens can be transparent, providing a clear view by matching the refractive indices of its locally patterned areas. The resulting soft, smart contact lens provides real-time, wireless operation, and there are in vivo tests to monitor the glucose concentration in tears (suitable for determining the fasting glucose level in the tears of diabetic patients) and, simultaneously, to provide sensing results through the contact lens display.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 4
    Publication Date: 2018-03-30
    Description: Background/Aim: Microtubule-associated protein 1 light chain 3B (LC3B), an autophagy marker, has been used as a promising marker in various cancer types. However, the expression of LC3B in muscle-invasive bladder cancer (MIBC) and its prognostic significance have not been investigated. Recent studies pointed to the involvement of ESRRA in regulating autophagy via both transcriptional and post-translational control. In the current study, prognostic importance of LC3B and ESRRA in MIBC was investigated. Patients and Methods: We immunohistochemically studied the expression of LC3B and ESRRA in 56 MIBC samples. Results: LC3B was stained high in 16 patients (28.6%) and low or negative in 40 patients (71.4%). ESRRA expression was high for 20 patients (35.7%) and low for 36 patients (64.3%). Both LC3B (p=0.003) and ESRRA (p=0.026) expression correlated significantly with disease-free survival rates. Double-positive LC3B and ESRRA correlated with poor overall survival (p=0.007) and disease-free survival (p=0.001) in MIBC patients. Conclusion: LC3B and ESRRA might be a useful prognostic factor in patients with MIBC. The co-expression of LC3B and ESRRA might be a prognostic and therapeutic target for patients with bladder cancer.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 5
    Publication Date: 2018-05-31
    Description: Background/Aim: MicroRNAs (miRNAs) are closely associated with a number of cellular processes, including cell development, differentiation, proliferation, carcinogenesis, and apoptosis. The aim of the present study was to elucidate the molecular mechanisms underlying the tumor suppressor activity of miRNA-203 (miR-203) in YD-38 human oral cancer cells. Materials and Methods: Polymerase chain reaction analysis, MTT assay, DNA fragmentation assay, fluorescence-activated cell-sorting analysis, gene array, immunoblotting, and luciferase assay were carried out in YD-38 cells. Results: miR-203 expression was significantly down-regulated in YD-38 cells compared to expression levels in normal human oral keratinocytes. miR-203 decreased the viability of YD-38 cells in a time- and dose-dependent manner. In addition, over-expression of miR-203 significantly increased not only DNA segmentation, but also the apoptotic population of YD-38 cells. These results indicate that miR-203 overexpression induces apoptosis in YD-38 cells. Target gene array analysis revealed that the expression of the polycomb complex protein gene Bmi-1, a representative oncogene, was significantly down-regulated by miR-203 in YD-38 cells. Moreover, both mRNA and protein levels of Bmi-1 were significantly reduced in YD-38 cells transfected with miR-203. These results indicate that Bmi-1 is a target gene of miR-203. A luciferase reporter assay confirmed that miR-203 suppressed Bmi-1 expression by directly targeting the 3’-untranslated region. Conclusion: miR-203 induces apoptosis in YD-38 cells by directly targeting Bmi-1, which suggests its possible application as an anti-cancer therapeutic.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 6
    Publication Date: 2018-08-02
    Description: Jinwoo Seong, Nam-Shik Kim, Jee-Ah Kim, Wonbin Lee, Ji-Yun Seo, Min Kyu Yum, Ji-Hoon Kim, Inkuk Park, Jong-Seol Kang, Sung-Hwan Bae, Cheol-Heui Yun, and Young-Yun Kong Mammary glands develop through primary ductal elongation and side branching to maximize the spatial area. Although primary ducts are generated by bifurcation of terminal end buds, the mechanism through which side branching occurs is still largely unclear. Here, we show that inhibitor of DNA-binding 2 (ID2) drives side branch formation through the differentiation of K6 + bipotent progenitor cells (BPs) into CD61 + luminal progenitor cells (LPs). Id2 -null mice had side-branching defects, along with developmental blockage of the differentiation of K6 + BPs into CD61 + LPs. Notably, CD61 + LPs were found in budding and side branches, but not in terminal end buds. Hormone reconstitution studies using ovariectomized MMTV-hemagglutinin-nuclear localized sequence-tagged Id2 transgenic mice revealed that ID2 is a key mediator of progesterone, which drives luminal lineage differentiation and side branching. Our results suggest that CD61 is a marker of side branches and that ID2 regulates side branch formation by inducing luminal lineage commitment from K6 + BPs to CD61 + LPs.
    Print ISSN: 0950-1991
    Electronic ISSN: 1477-9129
    Topics: Biology
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  • 7
    Publication Date: 2018-11-02
    Description: Purpose: M2-type TAMs are increasingly implicated as a crucial factor promoting metastasis. Numerous cell types dictate monocyte differentiation into M2 TAMs via a complex network of cytokine-based communication. Elucidating critical pathways in this network can provide new targets for inhibiting metastasis. In this study, we focused on cancer cells, CAFs, and monocytes as a major node in this network. Experimental Design: Monocyte cocultures with cancer-stimulated CAFs were used to investigate differentiation into M2-like TAMs. Cytokine array analyses were employed to discover the CAF-derived regulators of differentiation. These regulators were validated in primary CAFs and bone marrow-derived monocytes. Orthotopic, syngeneic colon carcinoma models using cotransplanted CAFs were established to observe effects on tumor growth and metastasis. To confirm a correlation with clinical evidence, meta-analyses were employed using the Oncomine database. Results: Our coculture studies identify IL6 and GM-CSF as the pivotal signals released from cancer cell–activated CAFs that cooperate to induce monocyte differentiation into M2-like TAMs. In orthotopic, syngeneic colon carcinoma mouse models, cotransplanted CAFs elevated IL6 and GM-CSF levels, TAM infiltration, and metastasis. These pathologic effects were dramatically reversed by joint IL6 and GM-CSF blockade. A positive correlation between GM-CSF and IL6 expression and disease course was observed by meta-analyses of the clinical data. Conclusions: Our studies indicate a significant reappraisal of the role of IL6 and GM-CSF in metastasis and implicate CAFs as the "henchmen" for cancer cells in producing an immunosuppressive tumor ecological niche. Dual targeting of GM-CSF and IL6 is a promising new approach for inhibiting metastasis. Clin Cancer Res; 24(21); 5407–21. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 8
    Publication Date: 2018-03-27
    Description: Photoactivatable drugs for nicotinic optopharmacology Photoactivatable drugs for nicotinic optopharmacology, Published online: 26 March 2018; doi:10.1038/nmeth.4637 Optopharmacological manipulation with ‘caged’ glutamate and GABA has enabled the study of these ligands’ cognate receptors, but other ligands such as tertiary amine drugs have not been amenable to caging. A new strategy yields a photoactivatable nicotine, PA-Nic, which allows manipulation of nicotinic acetylcholine receptors.
    Print ISSN: 1548-7091
    Electronic ISSN: 1548-7105
    Topics: Biology , Medicine
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  • 9
    Publication Date: 2018-04-10
    Description: Introduction Although recurrence rate among cases of resected pancreatic cancer are as high as 85%, an optimal treatment for recurrent pancreatic cancer (RePC) has not been established. Previous evidence regarding RePC is scarce, and randomised controlled trials (RCTs) are particularly lacking. The evidence mapping (EM) method has been introduced as a tool intended to complement the conventional systematic review (SR) and meta-analysis (MA) and is suitable for this issue. This review aims to investigate the optimal treatment options for RePC, using a newly developed automatic EM tool. Method and analysi s All study types, including RCTs, non-randomised studies and other forms of observational studies will be included in the SR-EM. The Medline, Embase, Cochrane library and Scopus databases will be searched for reports of five treatment options for local and metastatic recurrences, including re-resection, chemotherapy, radiotherapy, best supportive care and other novel treatments, published from database inception to 30 April 2017. References from relevant studies will be searched manually. If meta-analysis is feasible, the primary outcome measure will be median overall survival. Two independent authors will select the studies and assess the risk of bias, and a third author will resolve discrepancies in consensus meeting. To visualise EM, we will use a novel web-based and open-access mapping programme, Plotting E-Map (PLOEM) ( http://plotting-e-map.com ). If eligible combinations of interventions for quantitative comparison are identified, we will conduct subgroup MAs using random-effect models and I 2 statistics. Publication bias will be visualised using funnel plots. Ethics and dissemination This study will not use primary data, and therefore formal ethical approval is not required. The findings will be disseminated through peer-reviewed journals and committee conferences. PROSPEROregistration number CRD42016049178 .
    Keywords: Open access, Oncology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 10
    Publication Date: 2018-04-27
    Description: Memory resides in engram cells distributed across the brain. However, the site-specific substrate within these engram cells remains theoretical, even though it is generally accepted that synaptic plasticity encodes memories. We developed the dual-eGRASP (green fluorescent protein reconstitution across synaptic partners) technique to examine synapses between engram cells to identify the specific neuronal site for memory storage. We found an increased number and size of spines on CA1 engram cells receiving input from CA3 engram cells. In contextual fear conditioning, this enhanced connectivity between engram cells encoded memory strength. CA3 engram to CA1 engram projections strongly occluded long-term potentiation. These results indicate that enhanced structural and functional connectivity between engram cells across two directly connected brain regions forms the synaptic correlate for memory formation.
    Keywords: Neuroscience
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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