1,200 research outputs found

    Dielectric response of BaTiO electronic states under AC fields via microsecond time-resolved X-ray absorption spectroscopy

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    This research was performed under the approval of the Photon Factory Program Advisory Committee (PF-PAC; Contract Numbers 2015G580, 2017G587, and 2019G614) and was financially supported by JSPS KAKENHI Grant Numbers 18H01153 , 19H02426 , and 18K19126 . The experiment for measuring spectra in Fig. 6 (b) was performed on beamline BM26A (proposal MA 2731) at the European Synchrotron Radiation Facility (ESRF), Grenoble, France. We are grateful to Local Contact at the ESRF for providing assistance in using beamline BM26A. Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART². © 2021 Acta Materialia Inc. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ )For the first time, the dielectric response of a BaTiO thin film under an AC electric field is investigated using microsecond time-resolved X-ray absorption spectroscopy at the Ti K-edge in order to clarify correlated contributions of each constituent atom on the electronic states. Intensities of the pre-edge peak and shoulder structure just below the main edge increase with an increase in the amplitude of the applied electric field, whereas that of the main peak decreases in an opposite manner. Based on the multiple scattering theory, the increase and decrease of the and main peaks are simulated for different Ti off-center displacements. Our results indicate that these spectral features reflect the inter- and intra-atomic hybridization of Ti 3 with O 2 and Ti 4 respectively. In contrast, the shoulder structure is not affected by changes in the Ti off-center displacement but is susceptible to the effect of the corner site Ba ions. This is the first experimental verification of electronic contribution of Ba to polarization reversal.----/ / /---- This is open access article of S. Kato, N. Nakajima, S. Yasui, S. Yasuhara, D. Fu, J. Adachi, H. Nitani, Y. Takeichi, A. Anspoks, Dielectric response of BaTiO3 electronic states under AC fields via microsecond time-resolved X-ray absorption spectroscopy (DOI 10.1016/j.actamat.2021.116681), Acta Materialia, Volume 207, 2021,116681 - under the CC BY license (http://creativecommons.org/licenses/by/4.0/ )Photon Factory Program Advisory Committee (PF-PAC; Contract Numbers 2015G580, 2017G587, and 2019G614); JSPS KAKENHI Grant Numbers 18H01153 , 19H02426 , and 18K19126; Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART²

    Computational Controversy

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    Climate change, vaccination, abortion, Trump: Many topics are surrounded by fierce controversies. The nature of such heated debates and their elements have been studied extensively in the social science literature. More recently, various computational approaches to controversy analysis have appeared, using new data sources such as Wikipedia, which help us now better understand these phenomena. However, compared to what social sciences have discovered about such debates, the existing computational approaches mostly focus on just a few of the many important aspects around the concept of controversies. In order to link the two strands, we provide and evaluate here a controversy model that is both, rooted in the findings of the social science literature and at the same time strongly linked to computational methods. We show how this model can lead to computational controversy analytics that have full coverage over all the crucial aspects that make up a controversy.Comment: In Proceedings of the 9th International Conference on Social Informatics (SocInfo) 201

    Analyzing Ideological Communities in Congressional Voting Networks

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    We here study the behavior of political party members aiming at identifying how ideological communities are created and evolve over time in diverse (fragmented and non-fragmented) party systems. Using public voting data of both Brazil and the US, we propose a methodology to identify and characterize ideological communities, their member polarization, and how such communities evolve over time, covering a 15-year period. Our results reveal very distinct patterns across the two case studies, in terms of both structural and dynamic properties

    Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy.

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    BACKGROUND Virus-like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMVTT -VLPs) that are genetically fused with one of the major peanut allergens, Ara h 2 (CuMVTT -Ara h 2). We previously demonstrated the immunogenicity and the protective capacity of VLP Peanut-based immunization in a murine model for peanut allergy. Moreover, a Phase I clinical trial has been initiated using VLP Peanut material manufactured following a GMP-compliant manufacturing process. Key product characterization studies were undertaken here to understand the role and contribution of critical quality attributes that translate as predictive markers of immunogenicity and protective efficacy for clinical vaccine development. METHOD The role of prokaryotic RNA encapsulated within VLP Peanut on vaccine immunogenicity was assessed by producing a VLP Peanut batch with a reduced RNA content (VLP Peanut low RNA). Immunogenicity and peanut allergen challenge studies were conducted with VLP Peanut low RNA, as well as with VLP Peanut in WT and TLR 7 KO mice. Furthermore, mass spectrometry and SDS-PAGE based methods were used to determine Ara h 2 antigen density on the surface of VLP Peanut particles. This methodology was subsequently applied to investigate the relationship between Ara h 2 antigen density and immunogenicity of VLP Peanut. RESULTS A TLR 7 dependent formation of Ara h 2 specific high-avidity IgG antibodies, as well as a TLR 7 dependent change in the dominant IgG subclass, was observed following VLP Peanut vaccination, while total allergen-specific IgG remained relatively unaffected. Consistently, a missing TLR 7 signal caused only a weak decrease in allergen tolerability after vaccination. In contrast, a reduced RNA content for VLP Peanut resulted in diminished total Ara h 2 specific IgG responses, followed by a significant impairment in peanut allergen tolerability. The discrepant effect on allergen tolerance caused by an absent TLR 7 signal versus a reduced RNA content is explained by the observation that VLP Peanut-derived RNA not only stimulates TLR 7 but also TLR 3. Additionally, a strong correlation was observed between the number of Ara h 2 antigens displayed on the surface of VLP Peanut particles and the vaccine's immunogenicity and protective capacity. CONCLUSIONS Our findings demonstrate that prokaryotic RNA encapsulated within VLP Peanut, including antigen density of Ara h 2 on viral particles, are key contributors to the immunogenicity and protective capacity of the vaccine. Thus, antigenicity and RNA content are two critical quality attributes that need to be determined at the stage of manufacturing, providing robust information regarding the immunogenicity and protective capacity of VLP Peanut in the mouse which has translational relevance to the human setting

    Metabolomics to unveil and understand phenotypic diversity between pathogen populations

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    Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

    The next generation virus‐like particle platform for the treatment of peanut allergy

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    Background: Allergy to peanut is one of the leading causes of anaphylactic reactions among food allergic patients. Immunization against peanut allergy with a safe and protective vaccine holds a promise to induce durable protection against anaphylaxis caused by exposure to peanut. A novel vaccine candidate (VLP Peanut), based on virus‐like particles (VLPs), is described here for the treatment of peanut allergy. Methods and Results: VLP Peanut consists of two proteins: a capsid subunit derived from Cucumber mosaic virus engineered with a universal T‐cell epitope (CuMVTT_{TT}) and a CuMVTT_{TT} subunit fused with peanut allergen Ara h 2 (CuMVTT_{TT}‐Ara h 2), forming mosaic VLPs. Immunizations with VLP Peanut in both naïve and peanut‐sensitized mice resulted in a significant anti‐Ara h 2 IgG response. Local and systemic protection induced by VLP Peanut were established in mouse models for peanut allergy following prophylactic, therapeutic, and passive immunizations. Inhibition of FcγRIIb function resulted in a loss of protection, confirming the crucial role of the receptor in conferring cross protection against peanut allergens other than Ara h 2. Conclusion: VLP Peanut can be delivered to peanut‐sensitized mice without triggering allergic reactions, while remaining highly immunogenic and offering protection against all peanut allergens. In addition, vaccination ablates allergic symptoms upon allergen challenge. Moreover, the prophylactic immunization setting conferred the protection against subsequent peanut‐induced anaphylaxis, showing the potential for preventive vaccination. This highlights the effectiveness of VLP Peanut as a prospective break‐through immunotherapy vaccine candidate toward peanut allergy. VLP Peanut has now entered clinical development with the study PROTECT

    The essential role of multi-point measurements in investigations of turbulence, three-dimensional structure, and dynamics: the solar wind beyond single scale and the Taylor Hypothesis

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    Space plasmas are three-dimensional dynamic entities. Except under very special circumstances, their structure in space and their behavior in time are not related in any simple way. Therefore, single spacecraft in situ measurements cannot unambiguously unravel the full space-time structure of the heliospheric plasmas of interest in the inner heliosphere, in the Geospace environment, or the outer heliosphere. This shortcoming leaves numerous central questions incompletely answered. Deficiencies remain in at least two important subjects, Space Weather and fundamental plasma turbulence theory, due to a lack of a more complete understanding of the space-time structure of dynamic plasmas. Only with multispacecraft measurements over suitable spans of spatial separation and temporal duration can these ambiguities be resolved. We note that these characterizations apply to turbulence across a wide range of scales, and also equally well to shocks, flux ropes, magnetic clouds, current sheets, stream interactions, etc. In the following, we will describe the basic requirements for resolving space-time structure in general, using turbulence' as both an example and a principal target or study. Several types of missions are suggested to resolve space-time structure throughout the Heliosphere.Comment: White Paper submitted to: Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033. arXiv admin note: substantial text overlap with arXiv:1903.0689
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