2,360 research outputs found

    Design and performance of the ENUBET monitored neutrino beam

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    The ENUBET project is aimed at designing and experimentally demonstrating the concept of monitored neutrino beams. These novel beams are enhanced by an instrumented decay tunnel, whose detectors reconstruct large-angle charged leptons produced in the tunnel and give a direct estimate of the neutrino flux at the source. These facilities are thus the ideal tool for high-precision neutrino cross-section measurements at the GeV scale because they offer superior control of beam systematics with respect to existing facilities. In this paper, we present the first end-to-end design of a monitored neutrino beam capable of monitoring lepton production at the single particle level. This goal is achieved by a new focusing system without magnetic horns, a 20 m normal-conducting transfer line for charge and momentum selection, and a 40 m tunnel instrumented with cost-effective particle detectors. Employing such a design, we show that percent precision in cross-section measurements can be achieved at the CERN SPS complex with existing neutrino detectors

    Dem-Aging: autophagy-related pathologies and the "two faces of dementia"

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    Neuronal ceroid lipofuscinosis (NCL) is an umbrella term referring to the most frequent childhood-onset neurodegenerative diseases, which are also the main cause of childhood dementia. Although the molecular mechanisms underlying the NCLs remain elusive, evidence is increasingly pointing to shared disease pathways and common clinical features across the disease forms. The characterization of pathological mechanisms, disease modifiers, and biomarkers might facilitate the development of treatment strategies.The DEM-AGING project aims to define molecular signatures in NCL and expedite biomarker discovery with a view to identifying novel targets for monitoring disease status and progression and accelerating clinical trial readiness in this field. In this study, we fused multiomic assessments in established NCL models with similar data on the more common late-onset neurodegenerative conditions in order to test the hypothesis of shared molecular fingerprints critical to the underlying pathological mechanisms. Our aim, ultimately, is to combine data analysis, cell models, and omic strategies in an effort to trace new routes to therapies that might readily be applied in the most common forms of dementia

    4D Printing of Humidity‐Driven Seed Inspired Soft Robots (Adv. Sci. 9/2023)

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    In article number 2205146, Stefano Mariani, Nicola M. Pugno, Barbara Mazzolai, and co-workers develop a seed-inspired soft robot using 4D printed biodegradable polymers. Driven by humidity changes, the artificial seed adapts its morphology to interact with soil roughness and cracks, exploring a sample soil. In perspective, the soft robot shows great potential as a battery-free wireless tool for environmental monitoring

    4D Printing of Humidity-Driven Seed Inspired Soft Robots

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    Geraniaceae seeds represent a role model in soft robotics thanks to their ability to move autonomously across and into the soil driven by humidity changes. The secret behind their mobility and adaptivity is embodied in the hierarchical structures and anatomical features of the biological hygroscopic tissues, geometrically designed to be selectively responsive to environmental humidity. Following a bioinspired approach, the internal structure and biomechanics of Pelargonium appendiculatum (L.f.) Willd seeds are investigated to develop a model for the design of a soft robot. The authors exploit the re-shaping ability of 4D printed materials to fabricate a seed-like soft robot, according to the natural specifications and model, and using biodegradable and hygroscopic polymers. The robot mimics the movement and performances of the natural seed, reaching a torque value of ≈30 ”N m, an extensional force of ≈2.5 mN and it is capable to lift ≈100 times its own weight. Driven by environmental humidity changes, the artificial seed is able to explore a sample soil, adapting its morphology to interact with soil roughness and cracks

    Monitored neutrino beams and the next generation of high precision cross section experiments

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    The main source of systematic uncertainty on neutrino cross section measurements at the GeV scale originates from the poor knowledge of the initial flux. The reduction of this uncertainty to 1% can be achieved through the monitoring of charged leptons produced in association with neutrinos. The goal of the ENUBET ERC project is to prove the feasibility of such a monitored neutrino beam. In this contribution, the final results of the ERC project, together with the complete assessment of the feasibility of its concept, are presented. An overview of the detector technology for a next generation of high precision neutrino-nucleus cross section measurements, to be performed with the ENUBET neutrino beam, is also given

    Tumor-Infiltrating T Cells in EBV-Associated Gastric Carcinomas Exhibit High Levels of Multiple Markers of Activation, Effector Gene Expression, and Exhaustion

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    Epstein–Barr virus (EBV) is a gamma-herpesvirus associated with 10% of all gastric cancers (GCs) and 1.5% of all human cancers. EBV-associated GCs (EBVaGCs) are pathologically and clinically distinct entities from EBV-negative GCs (EBVnGCs), with EBVaGCs exhibiting differential molecular pathology, treatment response, and patient prognosis. However, the tumor immune landscape of EBVaGC has not been well explored. In this study, a systemic and comprehensive analysis of gene expression and immune landscape features was performed for both EBVaGC and EBVnGC. EBVaGCs exhibited many aspects of a T cell-inflamed phenotype, with greater T and NK cell infiltration, increased expression of immune checkpoint markers (BTLA, CD96, CTLA4, LAG3, PD1, TIGIT, and TIM3), and multiple T cell effector molecules in comparison with EBVnGCs. EBVaGCs also displayed a higher expression of anti-tumor immunity factors (PDL1, CD155, CEACAM1, galectin-9, and IDO1). Six EBV-encoded miRNAs (miR-BARTs 8-3p, 9-5p, 10-3p, 22, 5-5p, and 14-3p) were strongly negatively correlated with the expression of immune checkpoint receptors and multiple markers of anti-tumor immunity. These profound differences in the tumor immune landscape between EBVaGCs and EBVnGCs may help explain some of the observed differences in pathological and clinical outcomes, with an EBV-positive status possibly being a potential biomarker for the application of immunotherapy in GC

    Embedded Software of the KM3NeT Central Logic Board

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    International audienceThe KM3NeT Collaboration is building and operating two deep sea neutrino telescopes at the bottom of the Mediterranean Sea. The telescopes consist of latices of photomultiplier tubes housed in pressure-resistant glass spheres, called digital optical modules and arranged in vertical detection units. The two main scientific goals are the determination of the neutrino mass ordering and the discovery and observation of high-energy neutrino sources in the Universe. Neutrinos are detected via the Cherenkov light, which is induced by charged particles originated in neutrino interactions. The photomultiplier tubes convert the Cherenkov light into electrical signals that are acquired and timestamped by the acquisition electronics. Each optical module houses the acquisition electronics for collecting and timestamping the photomultiplier signals with one nanosecond accuracy. Once finished, the two telescopes will have installed more than six thousand optical acquisition nodes, completing one of the more complex networks in the world in terms of operation and synchronization. The embedded software running in the acquisition nodes has been designed to provide a framework that will operate with different hardware versions and functionalities. The hardware will not be accessible once in operation, which complicates the embedded software architecture. The embedded software provides a set of tools to facilitate remote manageability of the deployed hardware, including safe reconfiguration of the firmware. This paper presents the architecture and the techniques, methods and implementation of the embedded software running in the acquisition nodes of the KM3NeT neutrino telescopes

    Addressing Peripherality in Italy: A Critical Comparison between Inner Areas and Territorial Capital-Based Evaluations

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    As highlighted by the UN 2030 Agenda, sustainable development is a complex and multidimensional issue that can be effectively implemented and reached at the local level. This implies the evaluation of differences and disparities between territories in order to define local priorities and support cohesion policy objectives. This need has been addressed by the Italian "National Strategy for Inner Areas", which aims to support the growth of territories with a continuous economic and population decline. However, Inner Areas are identified by a set of indicators related to the low accessibility to Services of General Interest, neglecting other important factors that contribute to this condition. This paper proposes a critical analysis of this measurement and of the related "territorialization" of Inner Areas, by introducing a more comprehensive assessment model based on the concept of Territorial Capital (TC), which highlights a more nuanced understanding of complexities and diversities related to the potential development of a territory. In particular, the proposed model evaluates eight TC dimensions (human, social, cognitive, infrastructural, productive, relational, environmental and settlement capital), which cover a broad spectrum of Sustainable Development Goals (SDGs). In order to accurately demonstrate the differences between the results of the two evaluation methods, this paper presents the results of a case study application concerning all 377 municipalities, which compose the Autonomous Region of Sardinia (Italy). The findings of this study confirm the potential of an approach based on the Territorial Capital for place-based policymaking. TC, in fact, can become relevant for defining local priorities and supporting complex decisions, allowing governments to better design and tailor interventions for the effective and efficient management of available resources. Furthermore, these results pose new questions for future research developments in the field of sustainable and equitable development

    Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

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    Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)

    The Power Board of the KM3NeT Digital Optical Module: design, upgrade, and production

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    International audienceThe KM3NeT Collaboration is building an underwater neutrino observatory at the bottom of the Mediterranean Sea consisting of two neutrino telescopes, both composed of a three-dimensional array of light detectors, known as digital optical modules. Each digital optical module contains a set of 31 three inch photomultiplier tubes distributed over the surface of a 0.44 m diameter pressure-resistant glass sphere. The module includes also calibration instruments and electronics for power, readout and data acquisition. The power board was developed to supply power to all the elements of the digital optical module. The design of the power board began in 2013, and several prototypes were produced and tested. After an exhaustive validation process in various laboratories within the KM3NeT Collaboration, a mass production batch began, resulting in the construction of over 1200 power boards so far. These boards were integrated in the digital optical modules that have already been produced and deployed, 828 until October 2023. In 2017, an upgrade of the power board, to increase reliability and efficiency, was initiated. After the validation of a pre-production series, a production batch of 800 upgraded boards is currently underway. This paper describes the design, architecture, upgrade, validation, and production of the power board, including the reliability studies and tests conducted to ensure the safe operation at the bottom of the Mediterranean Sea throughout the observatory's lifespa
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