Nearly half of patients with advanced and metastatic melanomas harbor a BRAF mutation. Vemurafenib (VEM), a BRAF inhibitor, is used to treat such patients, however, responses to VEM are very short-lived due to intrinsic, adaptive and/or acquired resistance. In this context, we present the action of the B-Raf serine-threonine protein kinase inhibitor (vemurafenib) on the glycans structure and metallomics profiles in melanoma cells without (MeWo) and with (G-361) BRAF mutations. The studies were performed using α1-acid glycoprotein (AGP), a well-known acute-phase protein, and concanavalin A (Con A), which served as the model receptor. The detection of changes in the structure of glycans can be successfully carried out based on the frequency shifts and the charge transfer resistance after interaction of AGP with Con A in different VEM treatments using QCM-D and EIS measurements. These changes were also proved based on the cell ultrastructure examined by TEM and SEM. The LA-ICP-MS studies provided details on the metallomics profile in melanoma cells treated with and without VEM. The studies evidence that vemurafenib modifies the glycans structures and metallomics profile in melanoma cells harboring BRAF mutation that can be further implied in the resistance phenomenon. Therefore, our data opens a new avenue for further studies in the short-term addressing novel targets that hopefully can be used to improve the therapeutic regiment in advanced melanoma patients. The innovating potential of this study is fully credible and has a real impact on the global patient society suffering from advanced and metastatic melanomas. 相似文献
The photocatalytic deactivation of volatile organic compounds and mold fungi using TiO2 modified with mono‐ and bimetallic (Pt, Cu, Ag) particles is reported in this study. The mono‐ and bimetal‐modified (Pt, Cu, Ag) titanium(IV) oxide photocatalysts were prepared by chemical reduction method and characterized using XRD, XPS, DR/UV‐Vis, BET, and TEM analysis. The effect of incident light, type and content of mono‐ and bimetallic nanoparticles deposited on titanium(IV) oxide was studied. Photocatalytic activity of as‐prepared nanocomposites was examined in the gas phase using LEDs array. High photocatalytic activity of Ag/Pt‐TiO2 and Cu/Pt‐TiO2 in the reaction of toluene degradation resulted from improved efficiency of interfacial charge transfer process, which was consistent with the fluorescence quenching effect revealed by photoluminescence (PL) emission spectra. The photocatalytic deactivation of Penicillium chrysogenum, a pathogenic fungi present in the indoor environment, especially in a damp or water‐damaged building using mono‐ and bimetal‐modified (Pt, Cu, Ag) titanium(IV) oxide was evaluated for the first time. TiO2 modified with mono‐ and bimetallic NPs of Ag/Pt, Cu, and Ag deposited on TiO2 exhibited improved fungicidal activity under LEDs illumination than pure TiO2. 相似文献
A series of dual-mode nanomaterials based on Ba2LaV3O11:Yb3+, Er3+, Bi3+, with different bismuth content were synthesized using the hydrothermal method. Various analytical methods, such as x-ray diffraction (XRD) with additional detailed Rietveld analysis, transmission electron microscopy (TEM), inductively coupled plasma mass spectroscopy (ICP-MS) and laser spectroscopy have confirmed that with increasing Bi3+ content, phase purity, optical absorption and luminescence intensity significantly increased. Moreover, a slight luminescence color tunability was observed along with the gradual introduction of bismuth into the host structure since, among the others, the local crystal field around emitting Er3+ ions was changing. The use of ultraviolet and near-infrared excitation wavelengths allowed to obtain a dual mode luminescence, which extended the emission range and demonstrated the possibility of using the studied materials, e.g. in solar cells. 相似文献
The ideal quality control method for pharmaceutical products should be capable of rapid nondestructive testing of intact tablets or capsules. Raman spectroscopy using near-infrared excitation is shown to be capable of obtaining useful spectral data directly from drug formulations in gel capsules and from the gel capsules inside blister packs. The Raman data collected from the capsules inside blister packs containing 0-100 mg of the active ingredient (bucindolol), when coupled with multivariate calibration, resulted in a calibration SEP of 3.36 mg. The largest source of error was found to be due to sample inhomogeneity. Even so, the method is shown to have significant potential as a rapid nondestructive quality control method for pharmaceutical samples. 相似文献
In an empirical user study, we assessed two approaches to ranking the results from a keyword search using semantic contextual match based on Latent Semantic Analysis. These techniques involved searches initiated from words found in a seed document within a corpus. The first approach used the sentence around the search query in the document as context while the second used the entire document. With a corpus of 20,000 documents and a small proportion of relevant documents (<0.1%), both techniques outperformed a conventional keyword search on a recall-based information retrieval (IR) task. These context-based techniques were associated with a reduction in the number of searches conducted, an increase in users’ precision and, to a lesser extent, an increase in recall. This improvement was strongest when the ranking was based on document, rather than sentence, context. Individuals were more effective on the IR task when the lists returned by the techniques were ranked better. User performance on the task also correlated with achievement on a generalized IQ test but not on a linguistic ability test. 相似文献
There is a need for effective vaccine delivery systems and vaccine adjuvants without extraneous excipients that can compromise or minimize their efficacy. Vaccine adjuvants cytosine–phosphate–guanosine oligodeoxynucleotides (CpG ODNs) can effectively activate immune responses to secrete cytokines. However, CpG ODNs are not stable in serum due to enzymatic cleavage and are difficult to transport through cell membranes. Herein, DNA microcapsules made of CpG ODNs arranged into 3D nanostructures are developed to improve the serum stability and immunostimulatory effect of CpG. The DNA microcapsules allow encapsulation and co‐delivery of cargoes, including glycogen. The DNA capsules, with >4 million copies of CpG motifs per capsule, are internalized in cells and accumulate in endosomes, where the Toll‐like receptor 9 is engaged by CpG. The capsules induce up to 10‐fold and 20‐fold increases in tumor necrosis factor (TNF)‐α and interleukin (IL)‐6 secretion, respectively, in RAW264.7 cells compared with CpG ODNs. Furthermore, the microcapsules stimulate TNF‐α and IL‐6 secretion in a concentration‐ and time‐dependent manner. The immunostimulatory activity of the capsules correlates to their intracellular trafficking, endosomal confinement, and degradation, assessed by confocal and super‐resolution microscopy. These DNA capsules can serve as both adjuvants to stimulate an immune reaction and vehicles to encapsulate vaccine peptides/genes to achieve synergistic immune effects. 相似文献
Facilitation is a critical means of supporting creative processes in teams. Previous studies have shown that neutrality is central to effective facilitation but no clear conceptualization of neutrality has been provided to date. The aim of this paper is to explore how neutrality is enacted by facilitators, what its key elements and mechanisms are, and how it is perceived in the creative facilitation context. We adopt a theory building mode and conduct an in‐depth case study, following an innovation project in the IT sector with a series of facilitated creativity workshops. Our results show that neutrality is a multi‐dimensional construct that interacts with several outcome dimensions of facilitation, i.e. people, process, and product. We introduce a pro‐active neutrality framework, which explains the mechanisms of neutrality in facilitation and thereby extend theory on both neutrality and facilitation. We further outline a number of propositions that could be explored by future research as well as provide important creativity management implications that will enhance creativity and innovation in the workplace. 相似文献
Augmented, mixed and virtual reality are changing the way people interact and communicate. Five dimensional communications and services, integrating information from all human senses are expected to emerge, together with holographic communications (HC), providing a truly immersive experience. HC presents a lot of challenges in terms of data gathering and transmission, demanding Artificial Intelligence empowered communication technologies such as 5G. The goal of the paper is to present a model of a context-aware holographic architecture for real time communication based on semantic knowledge extraction. This architecture will require analyzing, combining and developing methods and algorithms for: 3D human body model acquisition; semantic knowledge extraction with deep neural networks to predict human behaviour; analysis of biometric modalities; context-aware optimization of network resource allocation for the purpose of creating a multi-party, from-capturing-to-rendering HC framework. We illustrate its practical deployment in a scenario that can open new opportunities in user experience and business model innovation.