40 research outputs found

    Fast, multi-band photon detectors based on quantum well devices for beam-monitoring in new generation light sources

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    In order to monitor the photon-beam position for both diagnostics and calibration purposes, we have investigated the possibility to use InGaAs/InAlAs Quantum Well (QW) devices as position-sensitive photon detectors for Free-Electron Laser (FEL) or Synchrotron Radiation (SR). Owing to their direct, low-energy band gap and high electron mobility, such QW devices may be used also at Room Temperature (RT) as fast multi-band sensors for photons ranging from visible light to hard X-rays. Moreover, internal charge-amplification mechanism can be applied for very low signal levels, while the high carrier mobility allows the design of very fast photon detectors with sub-nanosecond response times. Segmented QW sensors have been preliminary tested with 100-fs-wide 400 nm laser pulses and X-ray SR. The reported results indicate that these devices respond with 100 ps rise-times to such ultra-fast laser pulses. Besides, linear scan on the back-pixelated device has shown that these detectors are sensitive to the position of each ultrashort beam bunch

    A ligand discovery toolbox for the WWE domain family of human E3 ligases

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    The WWE domain is a relatively under-researched domain found in twelve human proteins and characterized by a conserved tryptophan-tryptophan-glutamate (WWE) sequence motif. Six of these WWE domain-containing proteins also contain domains with E3 ubiquitin ligase activity. The general recognition of poly-ADP-ribosylated substrates by WWE domains suggests a potential avenue for development of Proteolysis-Targeting Chimeras (PROTACs). Here, we present novel crystal structures of the HUWE1, TRIP12, and DTX1 WWE domains in complex with PAR building blocks and their analogs, thus enabling a comprehensive analysis of the PAR binding site structural diversity. Furthermore, we introduce a versatile toolbox of biophysical and biochemical assays for the discovery and characterization of novel WWE domain binders, including fluorescence polarization-based PAR binding and displacement assays, 15N-NMR-based binding affinity assays and 19F-NMR-based competition assays. Through these assays, we have characterized the binding of monomeric iso-ADP-ribose (iso-ADPr) and its nucleotide analogs with the aforementioned WWE proteins. Finally, we have utilized the assay toolbox to screen a small molecule fragment library leading to the successful discovery of novel ligands targeting the HUWE1 WWE domain

    A multipurpose experimental facility for advanced X-ray Spectrometry applications

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    Ponencia presentada en la European Conference on X-Ray Spectrometry (EXRS). 2014Motivation, Ultra High Vacuum Chamber (UHVC) project: To support/enhance the training of scientists/engineers from developing countries in the operation of synchrotron radiation instrumentation; To provide beam time access for R&D projects and hands-on training in SR-XRS based techniques; To promote networking and knowledge sharing; To increase the quality and the competitiveness of the developing countries to apply beam time proposals at SR facilities; To contribute in the further development of XRS techniques in applications with socioeconomicalrelevance (characterization of energy storage/conversion materials, environmental, biological and biomedical applications)Fil: Leani, Juan José. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Leani, Juan José. Nuclear Science and Instrumentation Laboratory, IAEA Laboratories; Austria.Física Atómica, Molecular y Química (física de átomos y moléculas incluyendo colisión, interacción con radiación, resonancia magnética, Moessbauer Efecto.

    The Anglo-Saxon migration and the formation of the early English gene pool

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    The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture1. The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate2,3,4. Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans—including 278 individuals from England—alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present-day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age France5,6

    Position sensitive photon detectors using epitaxial InGaAs/InAlAs quantum wells

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    This work deals with the investigation of novel position-sensitive devices based on InGaAs/InAlAs quantum wells, which could be applied to several applications of either synchrotron or conventional light sources. Such devices may be used as fast and efficient detectors due to the direct, low-energy band gap and high electron mobility at room temperature. Metamorphic In0.75Ga0.25As/In0.75Al0.25As quantum wells containing a two-dimensional electron gas were grown by molecular beam epitaxy. Two devices with size of 5 7 5 mm2 were prepared by using optical lithography. In the first, the active layers were segmented into four electrically insulated quadrants. Indium ohmic contacts were realized on the corner of each quadrant (for readout) and on the back surface (for bias). In the second, the quantum well was left unsegmented and covered by 400 nm of Al providing a single bias electrode, while four readout electrodes were fabricated on the back side by depositing and segmenting a Ni/Ge/Au layer. Photo-generated carriers can be collected at the readout electrodes by biasing from either the QW side or the back side of the devices during beam exposure. Individual currents obtained from each electrode allow monitoring of both the position and the intensity of the impinging beam for photon energies ranging from visible to hard X-ray. Such detector prototypes were tested with synchrotron radiation. Moreover, the position of the beam can be estimated with a precision of 800 nm in the segmented QW. A lower precision of 10 \u3bcm was recorded in the unsegmented QW due to the charge diffusion through the 500-\u3bcm-thick wafer, with however a lower electronic noise due to the better uniformity of the contacts

    Retrospective evaluation of canine anal sac carcinoma (260 cases) in Brazil: late detection and failures in lymph node evaluation

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    ABSTRACT: Anal sac neoplasms are common in companion animals, and the epidemiological profile has been extensively described in international studies; however, national data are still lacking. Data on the Brazilian reality of anal sac carcinoma cases’ diagnosis and treatment are also scarce. The purpose of this study was to retrospectively evaluate cases of canine anal sac carcinoma and assess the profile of involvement, tumor size, and lymphatic invasion at the time of diagnosis. Information was obtained from Vetpat laboratory database, from 260 cases spanning a 12-year period (2010-2021). In histopathological evaluation at the time of diagnosis, data on sex, age, and race were described, as well as tumor size and lymphatic invasion. The presence of metastasis was also assessed in cases where lymph nodes were sampled. Simple descriptive statistical analysis was used to evaluate the data. Adult and elderly, female, and mixed-breed animals were more involved, indicating differences from international studies that can be attributed to sociocultural factors. In terms of tumor size, it was observed that 93% of the cases had the largest diameter above 2.5cm. Only 7% of the cases had the largest diameter below 2.5cm, demonstrating the often late diagnosis and the importance of rectal palpation examination during the general physical assessment of canine patients, particularly at an advanced age. Regarding lymphatic invasion and affected lymph nodes, 50% of the cases had lymphatic invasion described in the histopathological examination. However, only 5% of the lymph nodes were sent along with the primary tumor, indicating the disease’s aggressive behavior but with possible metastases underdiagnosed
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