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Clinical evidence shows that following initial response to treatment, drug-resistant cancer cells frequently evolve and, eventually, most tumors become resistant to all available therapies. We compiled a focused library consisting of >500 commercially available or newly synthetized 8-hydroxyquinoline (8OHQ) derivatives whose toxicity is paradoxically increased rather than decreased by the activity of P-glycoprotein (Pgp), a transporter conferring multidrug resistance (MDR). Here, we deciphered the mechanism of action of NSC297366 that shows exceptionally strong Pgp-potentiated toxicity. Treatment of cells with NSC297366 resulted in changes associated with the activity of potent anticancer iron chelators. Strikingly, iron depletion was more pronounced in MDR cells due to the Pgp-mediated efflux of NSC297366–iron complexes. Our results indicate that iron homeostasis can be targeted by MDR-selective compounds for the selective elimination of multidrug resistant cancer cells, setting the stage for a therapeutic approach to fight transporter-mediated drug resistance.Significance:Modulation of the MDR phenotype has the potential to increase the efficacy of anticancer therapies. These findings show that the MDR transporter is a “double-edged sword” that can be turned against resistant cancer.

A commercial Empyrean X-ray diffractometer was adapted for combined grazing incidence X-ray fluorescence analysis (GIXRF) measurements with X-ray reflectivity (XRR) measurements. An energy-dispersive silicon drift detector was mounted and integrated in the angle-dependent data acquisition of the Empyrean. Different monochromator/X-ray optics units have been compared with the values obtained by the Atominstitut GIXRF + XRR spectrometer. Data evaluation was performed by JGIXA, a special software for combined GIXRF + XRR data fitting, developed at Atominstitut. A sample consisting of a ~50 nm nickel layer on a silicon substrate was used to compare the performance criteria (i.e. divergence and intensity) of the incident beam optics. An Empyrean X-ray diffractometer was successfully refitted to measure both GIXRF and XRR data.

BACKGROUND The elemental composition of herbal infusions and teas has not been sufficiently investigated. It could potentially be used for defining fingerprints for individual herbal / tea infusions, differentiation of botanical families, detecting the influence of packaging, and other purposes. The objective of this study was to determine the elemental composition, including the trace element content, of various herbal infusions and teas by means of total reflection X‐ray fluorescence analysis (TXRF), with a chemometrics approach using principal component analysis (PCA). RESULTS This study determined the elemental composition of various herbal infusions and teas, including trace elements, using total reflection X‐ray fluorescence (TXRF). The methodology for the sample preparation was established, including the multiple‐steepings procedure for the two tea samples (Oolong and Pu‐erh). Data from 29 samples were collected. We hypothesized that the elemental content of infusions could reflect certain features, such as the influence of processing and the type of tea. CONCLUSION A chemometric approach (PCA) was applied, and differences between teas and herbal infusions were found. This was further corroborated by explicit differentiation of one botanical family, Theaceae. The influence of packaging (tea bags) on herbal material was identified. The three types of tea (Camellia sinensis) appeared to be separated with PCA, and elemental concentrations in Pu‐erh changed with multiple steepings.

Gadolinium-based contrast agents (GBCAs) are frequently used in patients undergoing magnetic resonance imaging. In GBCAs gadolinium (Gd) is present in a bound chelated form. Gadolinium is a rare-earth element, which is normally not present in human body. Though the blood elimination half-life of contrast agents is about 90 minutes, recent studies demonstrated that some tissues retain gadolinium, which might further pose a health threat due to toxic effects of free gadolinium. It is known that the bone tissue can serve as a gadolinium depot, but so far only bulk measurements were performed. Here we present a summary of experiments in which for the first time we mapped gadolinium in bone biopsy from a male patient with idiopathic osteoporosis (without indication of renal impairment), who received MRI 8 months prior to biopsy. In our studies performed by means of synchrotron radiation induced micro- and submicro-X-ray fluorescence spectroscopy (SR-XRF), gadolinium was detected in human cortical bone tissue. The distribution of gadolinium displays a specific accumulation pattern. Correlation of elemental maps obtained at ANKA synchrotron with qBEI images (quantitative backscattered electron imaging) allowed assignment of Gd structures to the histological bone structures. Follow-up beamtimes at ESRF and Diamond Light Source using submicro-SR-XRF allowed resolving thin Gd structures in cortical bone, as well as correlating them with calcium and zinc.

X-ray imaging methods are used in many fields of research, as they allow a non-destructive investigation of the elemental content of various samples. As for every imaging method, for X-ray imaging the optics are of crucial importance. However, these optics can be very expensive and laborious to build, as the requirements on surface roughness and precision are extremely high. Angles of reflection and refraction are often in the range of a few mrad, making a compact design hard to achieve. In this work we present a possibility to simplify X-ray imaging. We have adapted the coded aperture method, a high energy radiation imaging method that has its origins in astrophysics, to full field X-ray fluorescence imaging. In coded aperture imaging, an object is projected through a known mask, the coded aperture, onto an area sensitive detector. The resulting image consists of overlapping projections of the object and a reconstruction step is necessary to obtain the information from the recorded image. We recorded fluorescence images of different samples with an energy-dispersive 2D detector (pnCCD) and investigated different reconstruction methods. With a small coded aperture with 12 holes we could significantly increase the count rate compared to measurements with a straight polycapillary optic. We show that the reconstruction of two different samples is possible with a deconvolution approach, an iterative algorithm and a neural network. These results demonstrate that X-ray fluorescence imaging with coded apertures has the potential to deliver good results without scanning and with an improved count rate, so that measurement times can be shortened compared to established methods.

Imaging with X-rays is a challenging field, due to the optical properties of X-rays. The fabrication of appropriate optics is usually expensive and requires an elaborate manufacturing process. One simpler and less expensive possibility of imaging high energy radiation is coded aperture imaging, a technique well established in astrophysics and also used in nuclear medicine or radiation detection, e.g., for nuclear decommissioning. Our aim is to adapt coded aperture imaging for X-ray fluorescence spectroscopy in the nearfield. In this work we show theoretical considerations and preliminary simulations of image formation through a coded aperture and three different reconstruction methods to prepare the experiments. We used a new mask based on an inverted modified uniformly redundant array (MURA) that could be used for the construction of a decoding mask for all investigated geometrical arrangements. The most commonly used reconstruction method, convoluting the detected image with a decoding mask, does not always deliver satisfactory results. This is more noticeable for small distances between the object, mask and detector. Hence, we developed two new reconstruction methods, one based on iterative algebraic optimization and another one based on a genetic algorithm. Both show good performance even in those cases where the convolution method fails. This provides a basis for further investigations of the ideal parameters for near field coded aperture imaging and refinements of the algorithms. We performed first measurements with a coded aperture at the BAMline at BESSY II and could successfully reconstruct a test object from the obtained recorded images.

In 2020, the International Commission on Radiation UnitsMeasurements ICRU has released Report 95 on "Operational Quantities for External Radiation Exposure". This publication introduced a new measurand, namely ambient dose H

In this proof-of-principle study, we established and implemented a cross-modality imaging (CMI) pipeline to characterize and compare bisphosphonate (BIS)-treated jawbones of Sprague-Dawley rats after tooth extraction after physical therapies (photobiomodulation and extracorporeal shockwave therapy (PBMT and ESWT)). We showcase the feasibility of such a CMI approach and its compatibility across imaging modalities to probe the same region of interest (ROI) of the same jawbone. Jawbones were imaged in toto in 3D using micro-Computed Tomography to identify ROIs for subsequent sequential 2D analysis using well-established technologies such as Atomic Force Microscopy and Scanning Electron Microscopy, and recent imaging approaches in biomedical settings, such as micro-X-Ray Fluorescence Spectroscopy. By combining these four modalities, multiscale information on the morphology, topography, mechanical stiffness (Young's modulus), and calcium, zinc and phosphorus concentrations of the bone was collected. Based on the CMI pipeline, we characterized and compared the jawbones of a previously published clinically relevant rat model of BIS-related osteonecrosis of the jawbone (BRONJ) before and after treatment with BISs, PBMT and ESWT. While we did not find that physical therapies altered the mechanical and elemental jawbone parameters with significance (probably due to the small sample size of only up to 5 samples per group), both ESWT and PBMT reduced pore thicknesses and bone-to-enamel distances significantly compared to the controls. Although focused on BIS-treated jawbones, the established CMI platform can be beneficial in the study of bone-related diseases in general (such as osteoarthritis or -porosis) to acquire complementary hallmarks and better characterize disease status and alleviation potentials.

Stabilization capacity of 5% by weight lignite added in three particle size ranges (

In this work, a new setup for dispersive XAFS measurements is presented. This reproducible and scanning-free setup yields both time- and laterally-resolved XAFS experiments in a ‘single-shot’. It allows a straightforward adjustment for probing different elements covering many relevant applications in materials science. An incoming energetic broadband beam is diffracted by a Si (111) crystal after passing through the sample and collected by an area sensitive detector. Depending on the energy range of the incoming beam, XANES and/or EXAFS spectra can be recorded with a time resolution down to 1 s. The feasibility of this setup was demonstrated at the BAMline at BESSY II (Berlin, Germany) with reference Fe and Cu foils and the results are hereby presented and discussed. Additionally, an application where time resolution on the second scale is required is briefly evaluated. The presented example concerns studying early stages of zinc(II)2-methylimidazolate (ZIF-8) crystallization. This is particularly important for biomedical applications.

In imaging, penetration depth comes at the expense of lateral resolution, which restricts the scope of 3D in-vivo imaging of small animals at micrometer resolution. Bioimaging will need to expand beyond correlative light and electron microscopy (CLEM) approaches to combine insights about in-vivo dynamics in a physiologically relevant 3D environment with ex-vivo information at micrometer resolution (or beyond) within the spatial, structural and biochemical contexts. Our report demonstrates the immense potential for biomedical discovery and diagnosis made available by bridging preclinical in-vivo imaging with ex-vivo biological microscopy to zoom in from the whole organism to individual structures and by adding localized spectroscopic information to structural and functional information. We showcase the use of two novel imaging pipelines to zoom into mural lesions (occlusions/hyperplasia and micro-calcifications) in murine vasculature in a truly correlative manner, that is using exactly the same animal for all integrated imaging modalities. This correlated multimodality imaging (CMI) approach includes well-established technologies such as Positron Emission Tomography (microPET), Autoradiography, Magnetic Resonance Imaging (microMRI) and Computed Tomography (microCT), and imaging approaches that are more novel in the biomedical setting, such as X-Ray Fluorescence Spectroscopy (microXRF) and High Resolution Episcopic Microscopy (HREM). Although the current pipelines are focused on mural lesions, they would also be beneficial in preclinical and clinical investigations of vascular diseases in general.

In imaging, penetration depth comes at the expense of lateral resolution, which restricts the scope of 3D in-vivo imaging of small animals at micrometer resolution. Bioimaging will need to expand beyond correlative light and electron microscopy (CLEM) approaches to combine insights about in-vivo dynamics in a physiologically relevant 3D environment with ex-vivo information at micrometer resolution (or beyond) within the spatial, structural and biochemical contexts. Our report demonstrates the immense potential for biomedical discovery and diagnosis made available by bridging preclinical in-vivo imaging with ex-vivo biological microscopy to zoom in from the whole organism to individual structures and by adding localized spectroscopic information to structural and functional information. We showcase the use of two novel imaging pipelines to zoom into mural lesions (occlusions/hyperplasia and micro-calcifications) in murine vasculature in a truly correlative manner, that is using exactly the same animal for all integrated imaging modalities. This correlated multimodality imaging (CMI) approach includes well-established technologies such as Positron Emission Tomography (microPET), Autoradiography, Magnetic Resonance Imaging (microMRI) and Computed Tomography (microCT), and imaging approaches that are more novel in the biomedical setting, such as X-Ray Fluorescence Spectroscopy (microXRF) and High Resolution Episcopic Microscopy (HREM). Although the current pipelines are focused on mural lesions, they would also be beneficial in preclinical and clinical investigations of vascular diseases in general.

Confocal micro-x-ray fluorescence (μXRF) is a powerful tool to analyze the spatial distribution of major, minor, and trace elements in three dimensions. Typical (confocal) μXRF measurements in the lab use polychromatic excitation, complicating quantification and fundamental parameter-based corrections and furthermore deteriorating peak-to-background ratios due to scattered bremsstrahlung. The goal for the new setup was to remedy these problems, without sacrificing spatial resolution, and keep it flexible for different excitation energies and transportation to other sources. The source assembly consists of a water-cooled fine-focus x-ray diffraction tube and a parallel beam-mirror, which produces a quasi-parallel, monochromatic beam. The presented results were obtained using a 2 kW molybdenum tube and a mirror for Mo-Kα. The confocal setup itself consists of two polycapillary half-lenses, one for the source side and the other for the detector side, where a 50 mm2 silicon drift detector is mounted. Both polycapillaries have a focus size of ∼15 μm for Mo-Kα. The second polycapillary can also be exchanged for a custom-designed collimator in order to perform non-confocal μXRF. Details of the technical setup and results from technical and biological samples are presented. Detection limits for selected elements from Ca to Pb in the confocal and non-confocal mode were established (e.g., 1 μg/g non-confocal and 20 μg/g confocal for As) using the NIST standard reference materials (SRMs) 621 and 1412. Furthermore, the results of the measurements of SRM 621 were evaluated using the fundamental parameter based quantification software ATI-QUANT. The results are compared with the certified values and generally are in good agreement.

Resistance to chemotherapeutic agents is a major obstacle in cancer treatment. A recently proposed strategy is to target the collateral sensitivity of multidrug resistant (MDR) cancer. Paradoxically, the toxicity of certain metal chelating agents is increased, rather than decreased, by the function of P-glycoprotein (Pgp), which is known to confer resistance by effluxing chemotherapeutic compounds from cancer cells. We have recently characterized and compared the solution&rsquo, s chemical properties including ligand protonation and the metal binding properties of a set of structurally related 8-hydroxyquinoline derived Mannich bases. Here we characterize the impact of the solution stability and redox activity of their iron(III) and copper(II) complexes on MDR-selective toxicity. Our results show that the MDR-selective anticancer activity of the studied 8-hydroxyquinoline derived Mannich bases is associated with the iron deprivation of MDR cells and the preferential formation of redox-active copper(II) complexes, which undergo intracellular redox-cycling to induce oxidative stress.

Liposomes containing copper and the copper ionophore neocuproine were prepared and characterized for in vitro and in vivo anticancer activity. Thermosensitive PEGylated liposomes were prepared with different molar ratios of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and hydrogenated soybean phosphatidylcholine (HSPC) in the presence of copper(II) ions. Optimal, temperature dependent drug release was obtained at 70:30 DPPC to HSPC weight ratio. Neocuproine (applied at 0.2 mol to 1 mol phospholipid) was encapsulated through a pH gradient while using unbuffered solution at pH 4.5 inside the liposomes, and 100 mM HEPES buffer pH 7.8 outside the liposomes. Copper ions were present in excess, yielding 0.5 mM copper-(neocuproine)2 complex and 0.5 mM free copper. Pre-heating to 45 &deg, C increased the toxicity of the heat-sensitive liposomes in short-term in vitro experiments, whereas at 72 h all investigated liposomes exhibited similar in vitro toxicity to the copper(II)-neocuproine complex (1:1 ratio). Thermosensitive liposomes were found to be more effective in reducing tumor growth in BALB/c mice engrafted with C26 cancer cells, regardless of the mild hyperthermic treatment. Copper uptake of the tumor was verified by PET/CT imaging following treatment with [64Cu]Cu-neocuproine liposomes. Taken together, our results demonstrate the feasibility of targeting a copper nanotoxin that was encapsulated in thermosensitive liposomes containing an excess of copper.

Total reflection X-ray fluorescence (TXRF) is ideally suited for the inspection of silicon wafer surfaces in the ultra trace regime. Detection limits in the range of 1010 atoms⋅ cm−2 for metals are achievable by straight TXRF. The determination of surface contaminations on silicon wafers is of great importance to the semiconductor industry as the purity of the wafers has a direct impact on the quality and yield of the end product. The ATOMIKA 8300W spectrometer can perform a position sensitive analysis and thus provide data which can be used to track down the source of the contamination and possibly improve the manufacturing process. The quantification procedure uses an external standard technique and is described in detail. To bring the spectrometer back into operation, the functionality of its components had to be checked and most importantly a new reference wafer had to be prepared and validated. This was done by intentionally contaminating a blank wafer with a known amount of a certified nickel standard. The new reference wafer was then validated by using it to analyze and quantify blank wafers contaminated with a known quantity of the CRM NIST 1640. The achieved detection limit for nickel is comparable to results previously recorded using the ATOMIKA 8030W spectrometer. The 8300 W spectrometer was successfully put into operation and shows satisfactory reproducibility data, allowing the use in an accredited laboratory.

This paper investigates in detail a sample preparation procedure for the total-reflection X-ray fluorescence (TXRF) analysis of airborne particles using a three-stage Dekati™ PM10 cascade impactor. The impactor was modified in such a way, that 30 mm diameter quartz reflectors suitable for TXRF spectrometers can be inserted as collection plates below the impactor's nozzle arrays with cut-off diameters of 10, 2.5 and 1 μm. Smaller particles are collected in a backup filter, which can be analyzed using classical energy-dispersive XRF. As an internal standard 5 ng Y were pipetted centrally onto each reflector after collection. The reflector surface has to be coated in order to reduce particle bounce-off. Two surface coatings, silicone oil and petroleum jelly (“Vaseline”), were compared in this study. Before TXRF analysis this coating layer was removed by low-temperature oxygen plasma ashing. A new approach was introduced, which involves masking of the quartz reflectors in order to remove the outer ring of the spot pattern, which consists of two concentric circles, and to produce a sample, which lies entirely inside the detectable area. Results of this approach were compared to those obtained from unmasked samples and discussed in detail. Angle scans show residue-like behavior of the samples in each stage. Samples were taken on the roof of the Atominstitut building in January 2017 on 10 days during working hours.

The aim of the work is to present a systematic evaluation of the analytical capabilities of the new X-ray fluorescence facility jointly operated between the International Atomic Energy Agency and the Elettra Sincrotrone Trieste for multipurpose total reflection X-ray fluorescence analysis. The analytical performance of the XRF beamline end-station (IAEAXspe) was systematically evaluated under TXRF excitation geometry by analyzing different types of aqueous (lake, waste and fresh water) and solid (soil, vegetal, biological) certified reference materials using an excitation energy of 13.0 keV (for the purpose of multielemental analysis). The results obtained for both types of samples in terms of limits of detection and accuracy were also compared with those obtained using laboratory X-ray tube based TXRF systems with different features (including Mo and W X-ray tube systems). Taking advantage of the possibility to work under high vacuum, the IAEAXspe set-up instrumental sensitivity was also determined using an excitation energy of 6.2 keV to explore the possibilities for light elements determination. A clear improvement of the element detection limits is achieved when comparing this facility to conventional X-ray tube based TXRF systems highlighting the benefits of using the monoenergetic synchrotron exciting radiation and the ultra-high vacuum chamber in comparison with conventional laboratory systems. The results of the present work are discussed in view of further exploitation of the facility for different environmental and biological related applications. Fil: Marguí, Eva. Universidad de Girona; España Fil: Hidalgo, Manuela. Universidad de Girona; España Fil: Migliori, Alessandro. IAEA Laboratories; Austria Fil: Leani, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. IAEA Laboratories; Austria Fil: Queralt, Ignasi. Consejo Superior de Investigaciones Científicas; España Fil: Kallithrakas Kontos, Nikolaos. Technical University of Crete; Grecia Fil: Streli, Christina. Technische Universitat Wien; Austria Fil: Prost, Josef. Technische Universitat Wien; Austria Fil: Karydas, Andreas Germanos. IAEA Laboratories; Austria. National Centre for Scientific Research; Grecia

In the present study, several Cu chelators [2,2′-biquinoline, 8-hydroxiquinoline (oxine), ammonium pyrrolidinedithiocarbamate (APDTC), Dp44mT, dithizone, neocuproine] were used to study Cu uptake, depletion and localization in different cancer cell lines. To better understand the concentration dependent fluctuations in the Cu intracellular metal content and Cu-dependent in vitro antiproliferative data, the conditional stability constants of the Cu complex species of the investigated ligands were calculated. Each investigated chelator increased the intracellular Cu content on HT-29 cells causing Cu accumulation depending on the amount of the free Cu(II). Copper accumulation was 159 times higher for Dp44mT compared to the control. Investigating a number of other transition metals, intracellular accumulation of Cd was observed only for two chelators. Intracellular Zn content slightly decreased (cca. 10%) for MCF-7 cells, while a dramatic decrease was observed on MDA-MB-231 ones (cca. 50%). A similar decrease was observed for HCT-116, while Zn depletion for HT-29 corresponded to cca. 20%. The IC50 values were registered for the investigated four cell lines at increasing external Cu(II) concentration, namely, MDA-MB-231 cells had the lowest IC50 values for Dp44mT ranging between 7 and 35 nM. Thus, Zn depletion could be associated with lower IC50 values. Copper depletion was observed for all ligands being less pronounced for Dp44mT and neocuproine. Copper localization and its colocalization with Zn were determined by μ-XRF imaging. Loose correlation (0.57) was observed for the MCF-7 cells independently of the applied chelator. Similarly, a weak correlation (0.47) was observed for HT-29 cells treated with Cu(II) and oxine. Colocalization of Cu and Zn in the nucleus of HT-29 cells was observed for Dp44mT (correlation coefficient of 0.85).

Combining strong signal amplification made possible by Gaseous Electron Multipliers (GEMs) with the high spatial resolution provided by optical readout, highly performing radiation detectors can be realized. An optically read out GEM-based Time Projection Chamber (TPC) is presented. The device permits 3D track reconstruction by combining the 2D projections obtained with a CCD camera with timing information from a photomultiplier tube. Owing to the intuitive 2D representation of the tracks in the images and to automated control, data acquisition and event reconstruction algorithms, the optically read out TPC permits live display of reconstructed tracks in three dimensions. An Ar/CF4 (80/20%) gas mixture was used to maximize scintillation yield in the visible wavelength region matching the quantum efficiency of the camera. The device is integrated in a UHV-grade vessel allowing for precise control of the gas composition and purity. Long term studies in sealed mode operation revealed a minor decrease in the scintillation light intensity.

A method has been developed for the quantitative elemental analysis of Mentha longifolia L. leaves collected from different cities in Saudi Arabia using total reflection X-ray fluorescence. Using a microwave digestion system, 100 mg of each sample was completely digested using 3 mL of nitric acid and 2 mL of hydrogen peroxide. The stabilization of the digested samples on the silicon reflectors was studied using a silicone solution and polyvinyl alcohol. 5 µL of either silicone solution or polyvinyl alcohol (1% m/v) was pipetted and dried on the silicon reflector prior to the deposition of the digested samples. It was recognized that there is some enhancement on the intensity of the peak area with the silicone solution at photon energies less than 11 keV. However, the obtained results confirm the ability of using silicone solution or polyvinyl alcohol (1% m/v) as the stabilizer prior to the deposition of the sample droplet on the quartz reflector. However, the silicone solution was more applicable....

Evaluation of in vitro cytotoxicity of several Cu chelating agents - 2,2′-biquinoline, 8-hydroxyquinoline (oxine), ammonium pyrrolidinedithiocarbamate (APDTC), di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT), dithizone and neocuproine – on HT-29 human colon adenocarcinoma as well as long term in vitro cytostatic effect were assessed in the presence of Cu(II) ions. Intracellular Cu accumulation was observed for each chelating agent. Cytotoxicity was also investigated on HCT-15 and HCT-116 human colon adenocarcinomas, HT-1080 human fibrosarcoma, A-375 malignant melanoma, MCF-7, MDA-MB-231 and ZR-75-1 human breast adenocarcinomas as well as MeT-5A and P31wt mesothelioma. For both short and long term antiproliferative studies, each chelating agent proved to be much more effective in the presence of Cu(II) ions. Generally, the following cytotoxicity order could be established on each cell line: Dp44mT > neocuproine > APDTC > oxine > 2,2′ biquinoline ≈ dithizone. The IC 50 values even showed one order of magnitude difference among the cell lines. Considerable differences were also observed for colony formation and spheroid growth inhibition. Thus, for Dp44mT and neocuproine, practically no resistant cell line could be developed, whereas for the rest of the chelating agents the long term survival was ensured. By raising the Cu(II) concentration from 0.5 μM to 50 μM, dramatically higher apoptotic processes were induced for Dp44mT and oxine after just 20 min. Elevated Cu(II) concentration activated reactive oxygen species generation. The investigated chelating agents restored the DNA damage caused by free Cu(II). Thus, DNA is not the target of the intracellular Cu accumulation. However, DNA intercalation was observed for the Cu(II) and neocuproine combination.

Matrix-assisted laser desorption/ionisation mass spectrometric imaging (MALDI MSI) is a technique that provides localized information on intact molecules in a sample. Micro X-ray fluorescence (μXRF) imaging allows the examination of the spatial distribution of elements in a sample without any morphological changes. These methods have already been applied separately to different tissues, organs, plants and bacterial films, but, to the best of our knowledge, they have yet to be coupled in a multimodal analysis. In this proof-of-principle study, we established and tested sample preparation strategies, allowing the multimodal analysis of lipids (sphingomyelin and phosphatidylcholines) and elements relevant to bone structures as calcium, phosphorous and sulphur in the very same sample section of a chicken phalanx without tissue decalcification. The results of the investigation of such parameters as adhesive tapes supporting tissue sections, and the sequence of the imaging experiments are presented. We show specific lipid distributions in skin, cartilage, muscle, nail, and the intact morphology of bone by calcium and phosphorus imaging. A combination of molecular and elemental imaging was achieved, thus, providing now for the first time the possibility of gathering MALDI MSI and μXRF information from the very same sample without any washing steps omitting therefore the analytical artifacts that inevitably occur in approaches using consecutive tissue sections. The proposed combination can benefit in research studies regarding bone diseases, osteoporosis, osteoarthritis, cartilage failure, bone/tendon distinguishing, where elemental and lipid interaction play an essential role.

The nuclide-specific dose rate constant, formerly called gamma ray constant, is one of the most important quantities in practical radiation protection dosimetry. For radiation sources with known radionuclide composition and activity, the expected dose rates at various distances can easily be calculated with reasonable approximations. In addition, they serve as a planning basis for the design of shielding of radiation application rooms and facilities. In this study, dose rate constants were calculated using the most recent conversion coefficients and the most suitable spectral data for more than 400 radionuclides using different calculation approaches. In addition this paper provides a critical review of currently published dose rate constants for the ambient dose equivalent H∗(10).

Total arsenic (As) as well as As(III) and As(V) species were monitored in drinking water with elevated As content sampled at waterworks of four settlements located in Hungary by means of on-site, solid phase extraction with a strong anion exchanger followed by As determination by either high-resolution continuum source graphite furnace atomic absorption spectrometry (HR-CS-GFAAS) or total-reflection X-ray fluorescence spectrometry (TXRF). Total As concentrations in well water samples varied between 40 μg/L and 120 μg/L. Additionally, the occurrence of As(III) in each studied well water exceeded 80% of the total As content. On the other hand, As(V) was found to be the predominant species (≈ 90%) in water samples with reduced As concentrations (i.e., after treatments at waterworks) below the health limit value of 10 μg/L prescribed by the 98/83/EC Council Directive. Moreover, As could not be detected in the As(III)-associated fractions of several samples. Generally, a reasonable agreement was found between the results obtained with HR-CS-GFAAS and TXRF. Nevertheless, As concentrations in the As(III)-associated fractions collected after the flocculation and coagulation steps were below the detection limit of the TXRF method at a higher extent. Preliminary application of this simple As speciation approach enables a proper choice of reagents and their dosage for similar water treatment technologies and hence, a reduction in the water treatment costs. The current SPE method coupled off-line to cost-effective atomic spectrometric detection for monitoring inorganic As species in waters represents an alternative approach to conventional As speciation methods, thus it could be extensively exploited for routine analysis in water quality control laboratories.

This review covers developments in and applications of XRF techniques such as EDXRF, WDXRF, TXRF, XRF microscopy using technologies such as synchrotron sources, X-ray optics, X-ray tubes and detectors in laboratory, mobile and hand-held systems.

Clinical evidence shows that following initial response to treatment, drug-resistant cancer cells frequently evolve and, eventually, most tumors become resistant to all available therapies. We compiled a focused library consisting of >500 commercially available or newly synthetized 8-hydroxyquinoline (8OHQ) derivatives whose toxicity is paradoxically increased rather than decreased by the activity of P-glycoprotein (Pgp), a transporter conferring multidrug resistance (MDR). Here, we deciphered the mechanism of action of NSC297366 that shows exceptionally strong Pgp-potentiated toxicity. Treatment of cells with NSC297366 resulted in changes associated with the activity of potent anticancer iron chelators. Strikingly, iron depletion was more pronounced in MDR cells due to the Pgp-mediated efflux of NSC297366–iron complexes. Our results indicate that iron homeostasis can be targeted by MDR-selective compounds for the selective elimination of multidrug resistant cancer cells, setting the stage for a therapeutic approach to fight transporter-mediated drug resistance. Significance: Modulation of the MDR phenotype has the potential to increase the efficacy of anticancer therapies. These findings show that the MDR transporter is a “double-edged sword” that can be turned against resistant cancer.

This study examined the chemical speciation of atmospheric particulate matter (PM) samples collected in Ulaanbaatar, Mongolia. The health effects of atmospheric aerosol depend on the particles’ size distribution, elemental composition and chemical species as well as other factors, which vary according to the pollution sources and meteorological conditions. Employing the International Atomic Energy Agency (IAEA) supported X-ray fluorescence (XRF) beamline at Elettra Sincrotrone Trieste, Italy, we used a small incidence angle for the synchrotron emission radiation in this ultra-high-vacuum environment to analyze the fine and the coarse mode (PM2.5 and PM2.5-10, respectively) through X-ray absorption near-edge structure (XANES) spectroscopy, which was applied to the K-edges of the chromium (Cr) and zinc (Zn) in PM samples selected via energy-dispersive XRF (EDXRF) analysis for their high concentrations of these transition metals. The spectroscopic results identified trivalent chromium sulfate [Cr2(SO4)3] and chromium oxide (Cr2O3) compounds as the major chemical forms of Cr in both the coarse and the fine PM fraction. Furthermore, both fractions contained abundances of sulfate (ZnSO4) and silicate (Zn2SiO4) compounds, but only the fine mode contained Zn oxalate (ZnC2O4), whereas only the coarse mode contained Zn chloride (ZnCl2). These Cr and Zn species seemed to originate from local anthropogenic sources, e.g., combustion products or traffic-related resuspended road dust. Our findings, which are based on the first chemical speciation analysis from Ulaanbaatar, provide insight into the physiochemical characteristics of atmospheric aerosols as well as information on the potential sources of Cr and Zn species bound to fine and coarse PM.

The interest about coatings devoted to biomedical applications has been continuously increasing during the last years. Several literature studies address the modification of surface properties, and the improvement of biocompatibility of implant surfaces by coatings. Among the other properties, adhesion and uniform coverage are desired. Another challengeable issue for biomedical applications is metal release from implant alloy into tissue environment. Indeed, severe adverse reactions may occur, including inflammation, fibrosis, thrombosis, infections and, last but non least, metallosis. Clinical cases of this pathology have been already observed with orthopaedic implants made with CoCrMo alloys. On these purposes several materials and coating techniques have been investigated. Recently, nanomaterials have also been considered. Atomic Layer Deposition (ALD) is a synthesis technique for nanomaterials, that is raising interest in the field of biomedical application, due to its unique properties. ALD allows conformal coating by ultrathin layers with high adhesion and well-defined thickness, at the nanometer scale. Oxide compounds may be easily deposited by ALD, even at low temperature. Among these, TiO2 is one of the most attractive functional oxide for such application, due to its high durability, good corrosion resistance, and well-tested biocompatibility. Indeed, TiO2 is already used to coat biomedical alloys and implants to improve short and long term body responses. In this work we study the effect of TiO2 layers deposited by ALD against metal release from CoCrMo alloy implants. Implant samples are coated with different thicknesses of TiO2, ranging from 10 to 200nm. Micro X-Ray Fluorescence is used to map the metal distribution in the bone surrounding the implant, after 1 and 2 months respectively from implantation. It is observed that the presence of TiO2 may prevent the metal transfer into the bone. Results show that Co and Cr has cluster distribution in the tissue surrounding the uncoated implant, with a number of particles that significantly increases with time. While, a decreasing gradient distribution from the alloy surface is evident in all the coated implant samples. In particular, the thicker the coating layer, the lower is the metal concentration in the surrounding tissue. The distribution of Mo is much uniform and extended with respect to Co and Cr. Metal transport increases with time, only in uncoated samples. It is also observed that corrosion of coated implants is delayed. The content of metals at a fixed distance from the implant surface increases with time. However, the mechanism of metal transport through the coating layer is not clear. For this reason a further "proof of concept" test is designed, to study the transport kinetics of ionic species into water through TiO2 coatings, deposited by ALD. Results show zero order kinetics. This model experiment demonstrates that the release of ionic species occur by a mechanism of diffusion through a continuous layer. This work figures out two important benefits of TiO2 coating obtained by ALD on the surface of CoCrMo implant: i. it shows a barrier effect against metal movement from the implant toward the tissue; ii. it protects the implant material against corrosion in this biological environment. Clinical benefits or antibacterial effects should be further investigated. From another point of view, this study highlights that ALD allows a very precise control of ionic species diffusion by means of layer thickness. This ability can be strongly exploited in the field of controlled release. The combination of these effects may be successfully used to obtain layer by layer structures with tunable properties, making ALD a powerful tool for biomedical applications.

This review describes advances in the XRF group of techniques published approximately between April 2015 and March 2016. Fundamental contributions in the instrumentation sections include the development of synchrotron radiation sources, semiconductor design technology and evaluating the quality of in situ hand-held XRF results. A bench top TXRF spectrometer for the measurement of the elements from carbon to uranium is described that offers achievable detection limits that range from ng g−1 to μg g−1. The applications sections aim to give a representative overview of the range of applications that use XRF techniques with an emphasis on papers that describe technical or application innovation. Sample size investigated ranged from the planet Mercury down to nano-gram quantities of cement secreted by settlement stage barnacle larvae. The archaeological and cultural heritage section this year includes an authentic report on the use of cannabis as a filler in ancient lime plaster and heartening news that the construction of an underground parking garage in the centre of Zurich (Switzerland) unearthed the remains of seven Neolithic settlements from the 4th and 3rd millennium BC. The X-ray excitation of iron present in ancient iron-gall inks was presented as a step toward the non-invasive reading of fragile and/or unopenable documents. Feedback from readers of this review is most welcome and the review coordinator may be contacted using the email address provided.

In the present work, the elemental composition of airborne particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) collected from urban and residential areas of Jordan was determined and the associated pollution sources were identified. The sampling was performed in sites located in Zarqa and Amman during the winter and spring seasons of 2014/2015. The quantitative elemental analysis of nineteen (19) elements was carried out using an energy dispersive X-ray fluorescence (EDXRF) spectrometer utilizing the polarization geometry and the three secondary targets (CaF2, Ge and Mo). Remarkable enhancement in terms of analytical range, low Z-elements quantification (including Al, Na and Cl), and limits of detection were achieved. The total concentration of the PM2.5 samples in winter is higher than its concentration during spring due to the lower dispersion of atmospheric aerosols. Despite the lower concentration of PM2.5 collected from the urban location, Zarqa, high concentrations of the elements Ca, V, Cu, Zn and Pb were recognized which could be an indication to the industrial and anthropogenic activities at Zarqa. The average concentration of Ca in the urban area is approximately twice the concentration in the residential site which indicates the heavy cement industries at Zarqa city. A similar concentration of S was found in both locations which indicates the same anthropogenic sources such as consuming fuels and electrical power plants. The average percentages of the total detected elements at Amman and Zarqa are equal to 48% and 86% from the total mass concentration, respectively, which confirm the heavy anthropogenic activities at Zarqa. Based on the calculations of Pearson's correlation coefficients and the principle component analysis, source apportionments of the detected elements in the two locations were evaluated.

This article presents results from an experimental setup for a dual energy-band vacuum spectrometer for total-reflection X-ray fluorescence analysis allowing simultaneous efficient excitation of low, medium, and high Z elements. The spectrometer is equipped with an air-cooled 35 W low power Rh X-ray tube and a 17 mm2 silicon drift detector with a thin 8 µm beryllium window. A Pd/B4C multilayer monochromator is used at the same time as a Bragg reflector for Rh-Kα radiation and as a high-energy cut-off reflector above 5 keV, where the characteristic Rh-L radiation is totally reflected and present in the spectrum of the exciting radiation. This leaves one broad low energy band below 5 keV and one high energy band around the energy of Rh-Kα. As Rh-L radiation would be absorbed on its path through air, a new beam entrance system was designed in order to guide the Rh-L photons into the vacuum chamber for efficient excitation of low Z elements. With this setup, elements down to sodium (Z = 11, E = 1.04 keV) could be detected. First results are presented, and spectra obtained in air as well as in vacuum are compared and discussed. Detection limits in the range of 1000 µg/kg for Na and around 140 µg/kg for Mg were achieved using the NIST SRM 1640 (trace elements in water).

Gaseous Electron Multipliers (GEM) are well known for stable operation at high particle fluxes. We present a study of the intrinsic limits of GEMdetectors when exposed to very high particle fluxes of the order of MHz/mm2. We give an interpretation to the variations of the effective gain, which, as a function of the particle flux, first increases and then decreases. We also discuss the reduction of the ion back-flow with increasing flux. We present measurements and simulations of a triple GEM detector, describing its behaviour in terms of accumulation of positive ions that results in changes of the transfer fields and the amplification fields. The behaviour is expected to be common to all multi-stage amplification devices where the efficiency of transferring the electrons from one stage to the next one is not 100%.

The aim of this work was to compare different excitation modes for the analysis of light elements from carbon (Z = 6) upwards using a total reflection X-ray fluorescence analysis (TXRF) vacuum chamber which allows the attachment of different X-ray tubes and detectors. In the first set of experiments, two water-cooled high-power X-ray tubes with Cr (Z = 25) and Cu (Z = 29) anodes, respectively, were compared with an air-cooled low-power tube with Mo anode (Z = 42) and a thin Be window for the transmission of Mo-L lines. In the first two cases, monochromatic Kα radiation was used for excitation, while in the case of the Mo tube the multilayer acted as a cut-off reflector and part of the Mo bremsstrahlung continuum together with the Mo-L series were used for excitation. Multi-element standards containing elements ranging from Na (Z = 11) to Ti (Z = 22) were analyzed by a silicon drift detector (SDD) with a 300 nm ultrathin polymer window (UTW). Detection limits were calculated and compared for the three excitation modes. The second set of experiments was performed using an air-cooled low-power X-ray tube with Rh anode (Z = 45) in order to show that a conventional SDD with a 25 μm beryllium window can be used for the detection of elements from Na upwards. The use of compact air-cooled low-power X-ray tubes together with Peltier-cooled SDDs with UTW should lead to the development of highly sensitive tabletop vacuum TXRF spectrometers with a design optimized for the analysis of light elements. Detection limits as achieved by vacuum chambers using conventional water-cooled high-power tubes (e.g. Streli et al., 2004) are realistically achievable with the new approach.

X-ray fluorescence (XRF) is a well-established method for quantitative elemental analysis. For accurate quantification, secondary excitation has to be taken into account. In this paper, the secondary excitation process was discussed for analysis by confocal micro-XRF. Experimental depth profiles were shown for a layered sample of Co and Cu. An additional peak was observed in the depth profile of Co, and it was explained by secondary excitation process. Additionally, a Mosaic model was proposed for quantification of confocal micro- XRF analysis.

Absorption effects in total reflection X-ray fluorescence (TXRF) analysis are important to consider, especially if external calibration is to be applied. With a color X-ray camera (CXC), that enables spatially and energy resolved XRF analysis, the absorption of the primary beam was directly visualized for μL-droplets and an array of pL-droplets printed on a Si-wafer with drop-on-demand technology. As expected, deposits that are hit by the primary beam first shade subsequent droplets, leading to a diminished XRF signal. This shading effect was quantified with enhanced precision making use of sub-pixel analysis that improves the spatial resolution of the camera. The measured absorption was compared to simulated results using three different model calculations. It was found they match very well (average deviation < 10%). Thus errors in quantification due to absorption effects can be accounted for in a more accurate manner.

This review covers developments in and applications of XRF techniques such as EDXRF, WDXRF, TXRF, XRF microscopy using technologies such as synchrotron sources, X-ray optics, X-ray tubes and detectors in laboratory, mobile and hand-held systems.

The distribution and speciation of zinc were studied in the body of female specimens of the soil-inhabiting, plant-feeding nematode, Xiphinema vuittenezi treated with nano-ZnO and its bulk counterpart. Lyophilized nematodes were studied by X-ray absorption near edge structure spectrometry (XANES) in order to characterize the zinc speciation. Furthermore, in the cross-sections prepared by focused ion beam technique, elemental maps were obtained using the electron probe microanalysis (EPMA) technique. XANES spectra were collected from three different regions (head, midbody and tail region) of nematodes in case of two different treatments (50 mg/L bulk and nano-ZnO suspension, 24 h long treatment). The sample spectra were fitted by the spectra of several reference compounds, the main components of the fitted spectra are the following in all cases: bulk/nano-ZnO; Zn–His and Zn 3 (PO 4 ) 2 ∗ xH 2 O. Consequently, partial biotransformation takes place for both treatments, histidine- and phosphate-rich ligands play dominant role in the binding of zinc. According to the result of the EPMA analysis, it can be established that the distribution of zinc correlates with the calcium and phosphorus distribution for both treatments. Considering the results of the investigations performed by the two microanalytical techniques, it is likely that calcium phosphate granules were formed in order to bind zinc and hereby to take part in zinc detoxification. Apparent difference in the behavior of bulk and nano-sized ZnO in the body of the investigated nematodes was not found.