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    10784 research outputs found

    Ligation of multiple protein domains using orthogonal inteins with non-native splice junctions

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    Publisher Copyright: © 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.Protein splicing is a self-catalyzed process in which an internal protein domain (the intein) is excised from its flanking sequences, linking them together with a canonical peptide bond. Trans-inteins are separated in two different precursor polypeptide chains that must assemble to catalytically self-excise and ligate the corresponding flanking exteins to join even when expressed separately either in vitro or in vivo. They are very interesting to construct full proteins from separate domains because their common small size favors chemical synthesis approaches. Therefore, trans-inteins have multiple applications such as protein modification and purification, structural characterization of protein domains or production of intein-based biosensors, among others. For many of these applications, when using more than one trans-intein, orthogonality between them is a critical issue to ensure the proper ligation of the exteins. Here, we confirm the orthogonality (lack of cross-reactivity) of four different trans- or split inteins, gp41-1, gp41-8, IMPDH-1 and NrdJ-1 both in vivo and in vitro, and built different constructs that allow for the sequential fusion of up to four protein fragments into one final spliced product. We have characterized the splicing efficiency of these constructs. All harbor non-native extein residues at the splice junction between the trans-intein and the neighboring exteins, except for the essential Ser + 1. Our results show that it is possible to ligate four different protein domains using inteins gp41-1, IMPDH-1 and NrdJ-1 with non-native extein residues to obtain a final four-domain spliced product with a not negligible yield that keeps its native sequence.Peer reviewe

    Ferromagnetic Order in 2D Layers of Transition Metal Dichlorides

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    Publisher Copyright: © 2024 The Authors. Advanced Materials published by Wiley-VCH GmbH.Magnetism in two dimensions is traditionally considered an exotic phase mediated by spin fluctuations, but far from collinearly ordered in the ground state. Recently, 2D magnetic states have been discovered in layered van der Waals compounds. Their robust and tunable magnetic state by material composition, combined with reduced dimensionality, foresee a strong potential as a key element in magnetic devices. Here, a class of 2D magnets based on metallic chlorides is presented. The magnetic order survives on top of a metallic substrate, even down to the monolayer limit, and can be switched from perpendicular to in-plane by substituting the metal ion from iron to nickel. Using functionalized STM tips as magnetic sensors, local exchange fields are identified, even in the absence of an external magnetic field. Since the compounds are processable by molecular beam epitaxy techniques, they provide a platform with large potential for incorporation into current device technologies.Peer reviewe

    DONES EVO: Risk mitigation for the IFMIF-DONES facility

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    Publisher Copyright: © 2024 The Author(s)The International Fusion Materials Irradiation Facility- DEMO Oriented Neutron Source (IFMIF-DONES) is a scientific infrastructure aimed to provide an intense neutron source for the qualification of materials to be used in future fusion power reactors. Its implementation is critical for the construction of the fusion DEMOnstration Power Plant (DEMO). IFMIF-DONES is a unique facility requiring a broad set of technologies. Although most of the necessary technologies have already been validated, there are still some aspects that introduce risks in the evolution of the project. In order to mitigate these risks, a consortium of companies, with the support of research centres and the funding of the CDTI (Centre for the Development of Industrial Technology and Innovation), has launched the DONES EVO Programme, which comprises six lines of research: • Improvement of signal transmission and integrity (planning and integration risks) • Optimisation of RF conditioning processes (planning and reliability risks) • Development of a reliable beam extraction device (reliability risks) • Development of technologies for the production of medical isotopes (reliability risks) • Improvement of critical parts of the lithium purification system (safety and reliability risks) • Validation of the manufacture of critical components with special materials (reliability risk).DONES EVO will focus on developing the appropriate response to the risks identified in the IFMIF-DONES project through research and prototyping around the associated technologies. This contribution will present a discussion of the risks, the proposed response to them and the evolution of the technologies involved, following selected experiments carried out throughout the project.Peer reviewe

    Printed Optical Sensors Towards Breathing Detection

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    Publisher Copyright: © 2024 SBMO.This work demonstrates the possibility of fabricating optical sensors by printing the corresponding sensitive optical waveguides directly onto a flat substrate. Specifically, humidity-sensitive polymeric waveguides have been printed towards breathing sensing. The optical sensitive waveguides manufactured are compact, ensuring coupling with the input and output optical fibers. The response of the printed optical sensor was evaluated to humidity variations. Unlike the traditional manufacturing process, any modification in the material, structure, dimensions, etc. of the sensitive optical waveguide can be carried out in a simple, low cost and extremely fast way.Peer reviewe

    Thermal conductivity of layered minerals using molecular dynamics simulation: A case study on calcium sulfates

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    Publisher Copyright: © 2024 The AuthorsLayered minerals containing inter-layer water show directional anisotropy. In previous work, the authors have shown that this inter-layer water affects the mechanical performance of these minerals. Even though difference in thermal conductivity of minerals has been alluded to in experimental literature due to presence of water molecules within crystal, a detailed coordinated theoretical study has not been carried out. In this work, a molecular dynamics study has been presented on sulfates of calcium to demonstrate that thermal conductivity is indeed reduced with the presence of inter-layer water. The correlation between the vibration of different molecular groups to the thermal transport mechanism of the material has been investigated. It has been observed that vibration modes of H2O molecules have a negligible contribution to thermal transport eventually reducing thermal conductivity perpendicular to the water layer. Even though calcium sulfate has been chosen for this study, it can be anticipated that similar behaviors can be observed with other minerals in which inter-layer water is present. This study represents a detailed structure–property correlation in the thermal transport mechanism through layered minerals.This research was also carried out under the umbrella of the project PoroPCM ( PCI2019-103657 ) funded by MCIN/AEI/10.13039/ 501100011033 and co-founded by the European Union (Programaci’ on Conjunta Internacional 2019) and the projects MIRACLE ( GA 964450 ) and NRG-STORAGE ( GA 870114 ) funded by the European Commission . We also acknowledge the Transnational Common Laboratory (LTC) Aquitaine-Euskadi Network in Green Concrete. We also acknowledge the Rockfish supercomputing facility of Johns Hopkins University, USA, and the Param Shakti supercomputing facility of IIT Kharagpur, India for providing the computational platform for this work. This work was born under the umbrella of the project “Photonic Metaconcrete with Infrared RAdiative Cooling Capacity for Large Energy Savings (MIRACLE: GA 964450)” funded by the European Union (Programaci’ on Conjunta Internacional 2019) . This research was also carried out under the umbrella of the project PoroPCM (PCI2019-103657) funded by MCIN/AEI/10.13039/ 501100011033 and co-founded by the European Union (Programaci’ on Conjunta Internacional 2019) and the projects MIRACLE (GA 964450) and NRG-STORAGE (GA 870114) funded by the European Commission. We also acknowledge the Transnational Common Laboratory (LTC) Aquitaine-Euskadi Network in Green Concrete. We also acknowledge the Rockfish supercomputing facility of Johns Hopkins University, USA, and the Param Shakti supercomputing facility of IIT Kharagpur, India for providing the computational platform for this work. This work was born under the umbrella of the project “Photonic Metaconcrete with Infrared RAdiative Cooling Capacity for Large Energy Savings (MIRACLE: GA 964450)” funded by the European Union (Programaci’ on Conjunta Internacional 2019).Peer reviewe

    Detection, exploitation and mitigation of memory errors

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    Publisher Copyright: © The Author(s) 2024. Published by Oxford University Press. All rights reserved.Software vulnerabilities are the root cause for a multitude of security problems in computer systems. Owing to their efficiency and tight control over low-level system resources, the C and C++ programming languages are extensively used for a myriad of purposes, from implementing operating system kernels to user-space applications. However, insufficient or improper memory management frequently leads to invalid memory accesses, eventually resulting in memory corruption vulnerabilities. These vulnerabilities are used as a foothold for elaborated attacks that bypass existing defense methods. In this paper, we summarise the main memory safety violation types (i.e. memory errors), and analyse how they are exploited by attackers and the main mitigation methods proposed in the research community. We further systematise the most relevant techniques with regards to memory corruption identification in current programs.Peer reviewe

    Biosensing based on lossy mode resonances

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    Publisher Copyright: © 2023 Elsevier B.V.Lossy mode resonance (LMR)-based sensors have experienced an important development in the last decade. Among the different domains in which LMR-based sensors have been used, biosensing is one of the fields that has attracted more interest in recent years. Here, LMR properties and some biosensing concepts are reviewed in the first place. Then, the progress of LMR-based biosensors is described, starting with cladding-removed multimode fibers (CRMMF), and evolving towards the employment of D-shaped single mode fibers, which have led to better biosensors in terms of performance and limit of detection (LOD). More recent advances, such as the development of biosensors that combine the optical and electrochemical domains, or the introduction of planar waveguides as the biosensor substrate, are also discussed. In all the cases, examples of biosensors are included, indicating the detected biomarker, biofunctionalization protocol, dynamic range, LOD, and specificity assays. Finally, some conclusions about LMR-based biosensors are presented, as well as future perspectives and some ideas to advance in this field.Peer reviewe

    Machine learning classification meets migraine: recommendations for study evaluation

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    Publisher Copyright: © The Author(s) 2024.The integration of machine learning (ML) classification techniques into migraine research has offered new insights into the pathophysiology and classification of migraine types and subtypes. However, inconsistencies in study design, lack of methodological transparency, and the absence of external validation limit the impact and reproducibility of such studies. This paper presents a framework of six essential recommendations for evaluating ML-based classification in migraine research: (1) group homogenization by clinical phenotype, attack frequency, comorbidity, therapy, and demographics; (2) defining adequate sample size; (3) quality control of collected and preprocessed data; (4) transparent training, testing, and performance evaluation of ML models, including strategies for data splitting, overfitting control, and feature selection; (5) interpretability of results with clinical relevance; and (6) open data and code sharing to facilitate reproducibility. These recommendations aim to balance the trade-off between model generalization and precision while encouraging collaborative standardization across the ML and headache communities. Furthermore, this framework intends to stimulate discussion toward forming a consortium to establish definitive guidelines for ML-based classification research in migraine field.Peer reviewe

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