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Next-generation megawatt-scale neutrino beams open the way to studying neutrino-nucleus scattering using gaseous targets for the first time. This represents an opportunity to improve the knowledge of neutrino cross sections in the energy region between hundreds of MeV and a few GeV, of interest for the upcoming generation of long-baseline neutrino oscillation experiments. The challenge is to accurately track and (especially) time the particles produced in neutrino interactions in large and seamless volumes down to few-MeV energies. We propose to accomplish this through an optically-read time projection chamber (TPC) filled with high-pressure argon and equipped with both tracking and timing functions. In this work, we present a detailed study of the time-tagging capabilities of such a device, based on end-to-end optical simulations that include the effect of photon propagation, photosensor response, dark count rate and pulse reconstruction. We show that the neutrino interaction time can be reconstructed from the primary scintillation signal with a precision in the range of 1–2.5 ns ( σ ) for point-like deposits with energies down to 5 MeV. A similar response is observed for minimum-ionizing particle tracks extending over lengths of a few meters. A discussion on previous limitations towards such a detection technology, and how they can be realistically overcome in the near future thanks to recent developments in the field, is presented. The performance demonstrated in our analysis seems to be well within reach of next-generation neutrino-oscillation experiments, through the instrumentation of the proposed TPC with conventional reflective materials and a silicon photomultiplier array behind a transparent cathode.

Argon gas doped with 1% wavelength-shifter (CF\\(_4\\)) has been employed in an optical time projection chamber (OTPC) to image cosmic radiation. We present results obtained during the system commissioning, performed with two stacked glass-THGEMs and an EMCCD camera at 1 bar. Preliminary estimates indicate that the combined optical gain was of the order of 10\\(^6\\) (ph/e), producing sharp and high-contrast raw images without resorting to any filtering or post-processing. A first assessment of the impact of pressurization showed no change in the attainable gains when operating at 1.5 bar

Next-generation megawatt-scale neutrino beams open the way to studying neutrino-nucleus scattering using gaseous targets for the first time. This represents an opportunity to improve the knowledge of neutrino cross sections in the energy region between hundreds of MeV and a few GeV, of interest for the upcoming generation of long-baseline neutrino oscillation experiments. The challenge is to accurately track and (especially) time the particles produced in neutrino interactions in large and seamless volumes down to few-MeV energies. We propose to accomplish this through an optically-read time projection chamber (TPC) filled with high-pressure argon and equipped with both tracking and timing functions. In this work, we present a detailed study of the time-tagging capabilities of such a device, based on end-to-end optical simulations that include the effect of photon propagation, photosensor response, dark count rate and pulse reconstruction. We show that the neutrino interaction time can be reconstructed from the primary scintillation signal with a precision in the range of 1-2.5 ns (\\(\\)) for point-like deposits with energies down to 5 MeV. A similar response is observed for minimum-ionizing particle tracks extending over lengths of a few meters. A discussion on previous limitations towards such a detection technology, and how they can be realistically overcome in the near future thanks to recent developments in the field, is presented. The performance demonstrated in our analysis seems to be well within reach of next-generation neutrino-oscillation experiments, through the instrumentation of the proposed TPC with conventional reflective materials and a silicon photomultiplier array behind a transparent cathode.

The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and disease-related end points. Here, we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy. The αvβ6 integrin is key in activating the pro-fibrotic cytokine TGFβ in idiopathic pulmonary fibrosis. Here, the authors show an inhaled small molecule αvβ6 inhibitor GSK3008348 induces prolonged inhibition of TGFβ signaling pathways in human and murine models of lung fibrosis via αvβ6 degradation.

Background: Surgical resection for pancreatic ductal adenocarcinoma (PDAC) entails the excision of the primary tumour and regional lymphadenectomy. This traditional strategy is challenged by the high rate of early recurrence, suggesting inadequate disease staging. Novel methods of intra-operative staging are needed to allow surgical resection to be tailored to the disease’s biology. Methods: A search of published articles on the PubMed and Embase databases was performed using the terms ‘pancreas’ OR ‘pancreatic’ AND ‘intra-operative staging/detection’ OR ‘guided surgery’. Articles published between January 2000 and June 2023 were included. Technologies that offered intra-operative staging and tailored treatment were curated and summarised in the following integrative review. Results: lymph node (LN) mapping and radioimmunoguided surgery have shown promising results but lacked practicality to facilitate real-time intra-operative staging for PDAC. Fluorescence-guided surgery (FGS) offers high contrast and sensitivity, enabling the identification of cancerous tissue and positive LNs with improved precision following intravenous administration of a fluorescent agent. The unique properties of optical coherence tomography and ultrasound elastography lend themselves to be platforms for virtual biopsy intra-operatively. Conclusions: Accurate intra-operative staging of PDAC, localisation of metastatic LNs, and identification of extra-pancreatic disease remain clinically unmet needs under current detection methods and staging standards. Tumour-specific FGS combined with other diagnostic and therapeutic modalities could improve tumour detection and staging in patients with PDAC.