Multi-detection and polarisation contrast in scannning near-field optical microscopy in reflection

A new type of NSOM probe has been developed, with a design based o­n the probes used in Atomic Force Microscopy. The probe consists of a cantilever with at its end a conical tip. This tip has been metal-coated to provide an aperture. With the cantilevered probe, the problem of breaking of the tip due to high normal forces is solved. In operation, the tip is scanned in contact with the sample while regulating the force between the tip and the sample with a beam deflection technique, which allows to simultaneously make an optical and a topographical image of the sample. The probes are made using micromechanical techniques, which allows batch fabrication of the probes. Testing of the probes is done in a transmission NSOM set-up in which the sample is scanned while the tip and the optical path are kept fixed. Using an opaque sample with submicron holes, the new probes have been tested, resulting an optical image with a simultaneously measured topographical image

A systematic search for novae in M31 on a large set of digitized archival Schmidt plates

This paper reports on the detection of optical novae in our neighbour galaxy M31 based on digitized historical Tautenburg Schmidt plates. The accurate positions of the detected novae lead to a much larger database when searching for recurrent novae in M31. We conducted a systematic search for novae on 306 digitized Tautenburg Schmidt plates covering a time span of 36 years from 1960 to 1996. From the database of both ~ 300 000 light curves and about one million detections on only one plate per colour band, nova candidates were efficiently selected by automated algorithms and subsequently individually inspected by eye. We report the detection of 84 nova candidates. We found 55 nova candidates from the automated analysis of the light curves. Among these, 22 were previously unknown, 12 were known but not identified on Tautenburg Schmidt plates before, and 21 novae had been previously discovered on Tautenburg plates. An additional 29 known novae could be confirmed by the detailed investigation of single detections. One of our newly discovered nova candidates shows a high position coincidence with a nova detected about 30 years earlier. Therefore, this object is likely to be a recurrent nova. Furthermore, we re-investigated all 41 nova candidates previously found on Tautenburg plates and confirm all but two. Positions are given for all nova candidates with a typical accuracy of ~ 0.4 arcsec. We present light curves and finding charts as online material. The analysis of the plates has shown the wealth of information still buried in old plate archives. Extrapolating from this survey, digitization of other historical M31 plate archives (e.g. from the Mount Wilson or Asiago observatories) for a systematic nova search looks very promising.Comment: 29 pages, 14 figures, 19 tables, accepted for publication in A&A. Figs 6-14 are reduced in resolution due to the restrictions on space available on astro-ph; v2: minor grammatical change

Endothelin receptor B antagonists decrease glioma cell viability independently of their cognate receptor

Background: Endothelin receptor antagonists inhibit the progression of many cancers, but research into their influence on glioma has been limited. Methods: We treated glioma cell lines, LN-229 and SW1088, and melanoma cell lines, A375 and WM35, with two endothelin receptor type B (ETRB)-specific antagonists, A-192621 and BQ788, and quantified viable cells by the capacity of their intracellular esterases to convert non-fluorescent calcein AM into green-fluorescent calcein. We assessed cell proliferation by labeling cells with carboxyfluorescein diacetate succinimidyl ester and quantifying the fluorescence by FACS analysis. We also examined the cell cycle status using BrdU/propidium iodide double staining and FACS analysis. We evaluated changes in gene expression by microarray analysis following treatment with A-192621 in glioma cells. We examined the role of ETRB by reducing its expression level using small interfering RNA (siRNA). Results: We report that two ETRB-specific antagonists, A-192621 and BQ788, reduce the number of viable cells in two glioma cell lines in a dose- and time-dependent manner. We describe similar results for two melanoma cell lines. The more potent of the two antagonists, A-192621, decreases the mean number of cell divisions at least in part by inducing a G2/M arrest and apoptosis. Microarray analysis of the effects of A-192621 treatment reveals up-regulation of several DNA damage-inducible genes. These results were confirmed by real-time RT-PCR. Importantly, reducing expression of ETRB with siRNAs does not abrogate the effects of either A-192621 or BQ788 in glioma or melanoma cells. Furthermore, BQ123, an endothelin receptor type A (ETRA)-specific antagonist, has no effect on cell viability in any of these cell lines, indicating that the ETRB-independent effects on cell viability exhibited by A-192621 and BQ788 are not a result of ETRA inhibition. Conclusion: While ETRB antagonists reduce the viability of glioma cells in vitro, it appears unlikely that this effect is mediated by ETRB inhibition or cross-reaction with ETRA. Instead, we present evidence that A-192621 affects glioma and melanoma viability by activating stress/DNA damage response pathways, which leads to cell cycle arrest and apoptosis. This is the first evidence linking ETRB antagonist treatment to enhanced expression of DNA damage-inducible genes

Unsupervised Domain Adaptation for Multispectral Pedestrian Detection

Multimodal information (e.g., visible and thermal) can generate robust pedestrian detections to facilitate around-the-clock computer vision applications, such as autonomous driving and video surveillance. However, it still remains a crucial challenge to train a reliable detector working well in different multispectral pedestrian datasets without manual annotations. In this paper, we propose a novel unsupervised domain adaptation framework for multispectral pedestrian detection, by iteratively generating pseudo annotations and updating the parameters of our designed multispectral pedestrian detector on target domain. Pseudo annotations are generated using the detector trained on source domain, and then updated by fixing the parameters of detector and minimizing the cross entropy loss without back-propagation. Training labels are generated using the pseudo annotations by considering the characteristics of similarity and complementarity between well-aligned visible and infrared image pairs. The parameters of detector are updated using the generated labels by minimizing our defined multi-detection loss function with back-propagation. The optimal parameters of detector can be obtained after iteratively updating the pseudo annotations and parameters. Experimental results show that our proposed unsupervised multimodal domain adaptation method achieves significantly higher detection performance than the approach without domain adaptation, and is competitive with the supervised multispectral pedestrian detectors

Comparison of various methods to delineate blood vessels in retinal images

The blood vessels in the human retina are easily visualisable via digital fundus photography and provide an excellent window to the health of a patient affected by diseases of blood circulation such as diabetes. Diabetic retinopathy is identifiable through lesions of the vessels such as narrowing of the arteriole walls, beading of venules into sausage like structures and new vessel growth as an attempt to reperfuse ischaemic regions. Automated quantification of these lesions would be beneficial to diabetes research and to clinical practice, particularly for eye-screening programmes for the detection of eye-disease amongst diabetic persons

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway.

Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation

Differential bioreactivity of neutral, cationic and anionic polystyrene nanoparticles with cells from the human alveolar compartment: robust response of alveolar type 1 epithelial cells

BACKGROUND: Engineered nanoparticles (NP) are being developed for inhaled drug delivery. This route is non-invasive and the major target; alveolar epithelium provides a large surface area for drug administration and absorption, without first pass metabolism. Understanding the interaction between NPs and target cells is crucial for safe and effective NP-based drug delivery. We explored the differential effect of neutral, cationic and anionic polystyrene latex NPs on the target cells of the human alveolus, using primary human alveolar macrophages (MAC) and primary human alveolar type 2 (AT2) epithelial cells and a unique human alveolar epithelial type I-like cell (TT1). We hypothesized that the bioreactivity of the NPs would relate to their surface chemistry, charge and size as well as the functional role of their interacting cells in vivo. METHODS: Amine- (ANP) and carboxyl- surface modified (CNP) and unmodified (UNP) polystyrene NPs, 50 and 100 nm in diameter, were studied. Cells were exposed to 1–100 μg/ml (1.25-125 μg/cm(2); 0 μg/ml control) NP for 4 and 24 h at 37 °C with or without the antioxidant, N-acetyl cysteine (NAC). Cells were assessed for cell viability, reactive oxygen species (ROS), oxidised glutathione (GSSG/GSH ratio), mitochondrial integrity, cell morphology and particle uptake (using electron microscopy and laser scanning confocal microscopy). RESULTS: ANP-induced cell death occurred in all cell types, inducing increased oxidative stress, mitochondrial disruption and release of cytochrome C, indicating apoptotic cell death. UNP and CNP exhibited little cytotoxicity or mitochondrial damage, although they induced ROS in AT2 and MACs. Addition of NAC reduced epithelial cell ROS, but not MAC ROS, for up to 4 h. TT1 and MAC cells internalised all NP formats, whereas only a small fraction of AT2 cells internalized ANP (not UNP or CNP). TT1 cells were the most resistant to the effects of UNP and CNP. CONCLUSION: ANP induced marked oxidative damage and cell death via apoptosis in all cell types, while UNP and CNP exhibited low cytotoxicity via oxidative stress. MAC and TT1 cell models show strong particle-internalization compared to the AT2 cell model, reflecting their cell function in vivo. The 50 nm NPs induced a higher bioreactivity in epithelial cells, whereas the 100 nm NPs show a stronger effect on phagocytic cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0091-7) contains supplementary material, which is available to authorized users