100 research outputs found

    Pixel sensitivity variation in a CdTe-Medipix2 detector using poly-energetic x-rays

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    We have a 1-mm-thick cadmium telluride (CdTe) sensor bump-bonded to a Medipix2 readout chip. This detector has been characterized using a poly-energetic x-ray beam. Open beam images (i.e. without an attenuating specimen between the x-ray source and the detector) have been acquired at room temperature using the MARS-CT system. Profiles of various rows and columns were analyzed for one hundred, 35-ms exposures taken with a bias voltage of -300 V (operating in electron collection mode). A region of increased sensitivity is observed around the edges of the detector. A reasonably periodic, repeatable variation in pixel sensitivity is observed. Some small regions with very low sensitivity and others with zero signals are also observed. Surrounding these regions are circular rings of pixels with higher counts. At higher flux (higher tube current in the x-ray source) there is evidence of saturation of the detector assembly. In this paper we present our understanding of the origin of these features and demonstrate the improved image quality obtained after correcting for these variations

    Characterization of photon counting pixel detectors based on semi-insulating GaAs sensor material

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    Hybrid semiconductor pixel detectors are considered of high interest for synchrotron applications like diffraction and imaging experiments. However, at photon energies above 30 keV, high-Z sensor materials have to be used due to the weak absorption of the most commonly used sensor material, for instance silicon wafers with a thickness of a few hundred μm. Besides materials like CdTe and Ge, semi-insulating, chromium compensated SI-GaAs(Cr) proves to be a promising sensor material for applications with X-rays in the mid-energy range up to ~60 keV. In this work, material characterisation of SI-GaAs(Cr) wafers by electrical measurements and synchrotron white beam topography as well as the characterization and application of pixel detector assemblies based on Medipix readout chips bump-bonded to 500 μm thick SI-GaAs(Cr) sensors are presented. The results show a very homogeneous material with high resistivity and good electrical properties of the electrons as well as a very promising imaging performance of the detector assemblies

    The impact of different calibration matrices on the determination of insulin-like growth factor 1 by high-resolution-LC-MS in acromegalic and growth hormone deficient patients

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    Objectives: Calibration is an important source of variability in liquid chromatography mass spectrometry (LC-MS) methods for insulin-like growth factor 1 (IGF-1). This study investigated the impact of different calibrator matrices on IGF-1 measurements by LC-MS. Moreover, the comparability of immunoassays and LC-MS was assessed. Design & Methods: Calibrators from 12.5 to 2009 ng/ml were prepared by spiking WHO international Standard (ID 02/254 NIBSC, UK) into the following matrices: native human plasma, fresh charcoal-treated human plasma (FCTHP), old charcoal-treated human plasma, deionized water, bovine serum albumin (BSA), and rat plasma (RP). A validated in-house LC-MS method was calibrated repeatedly with these calibrators. Then, serum samples from 197 growth hormone excess and deficiency patients were analysed with each calibration. Results: The seven calibration curves had different slopes leading to markedly different patient results. The largest differences in IGF-1 concentration from the median (interquartile range) was observed with the calibrator in water and the calibrator in RP (336.4 [279.6–417.0] vs. 112.5 [71.2–171.2], p < 0.001). The smallest difference was observed with calibrators in FCTHP and BSA (141.8 [102.0–198.5] vs. 127.9 [86.9–186.0], p < 0.049). Compared to LC-MS with calibrators in FCTHP, immunoassays showed relevant proportional bias (range: −43% to −68%), constant bias (range: 22.84 to 57.29 ng/ml) and pronounced scatter. Comparing the immunoassays with each other revealed proportional bias of up to 24%. Conclusions: The calibrator matrix is critical for the measurement of IGF-1 by LC-MS. Regardless of the calibrator matrix, LC-MS shows poor agreement with immunoassays. Also, the agreement between different immunoassays is variable

    Metabolic enhancement of mammalian developmental pausing

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    The quest to model and modulate embryonic development became a recent cornerstone of stem cell and developmental biology. Mammalian developmental timing is adjustable in vivo by preserving preimplantation embryos in a dormant state called diapause. Inhibition of the growth regulator mTOR (mTORi) pauses mouse development in vitro, yet constraints to pause duration are unrecognized. By comparing the response of embryonic and extraembryonic stem cells to mTORi-induced pausing, we identified lipid usage as a bottleneck to developmental pausing. Enhancing fatty acid oxidation (FAO) boosts embryo longevity, while blocking it reduces the pausing capacity. Genomic and metabolic analyses of single embryos point toward a deeper dormant state in FAO-enhanced pausing and reveal a link between lipid metabolism and embryo morphology. Our results lift a constraint on in vitro embryo survival and suggest that lipid metabolism may be a critical metabolic transition relevant for longevity and stem cell function across tissues

    Estrogens Determine Adherens Junction Organization and E-Cadherin Clustering in Breast Cancer Cells via Amphiregulin

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    Estrogens play an important role in the development and progression of human cancers, particularly in breast cancer. Breast cancer progression depends on the malignant destabilization of adherens junctions (AJs) and disruption of tissue integrity. We found that estrogen receptor alpha (ER alpha) inhibition led to a striking spatial reorganization of AJs and microclustering of E-Cadherin (E-Cad) in the cell membrane of breast cancer cells. This resulted in increased stability of AJs and cell stiffness and a reduction of cell motility. These effects were actomyosindependent and reversible by estrogens. Detailed investigations showed that the ERa target gene and epidermal growth factor receptor (EGFR) ligand Amphiregulin (AREG) essentially regulates AJ reorganization and E-Cad microclustering. Our results not only describe a biological mechanism for the organization of AJs and the modulation of mechanical properties of cells but also provide a new perspective on how estrogens and anti-estrogens might influence the formation of breast tumors
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