1,462 research outputs found

    A lost decade for third-wave democracies?

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    By comparing results based on expert and popular surveys, this article finds that popular support for democracy was dwindling even in the decade before expert surveys (such as Freedom in the World and V-Dem) began to show the reality of democratic retreat. Decreasing support for democracy is tied to low satisfaction with how democracy works in practice, and it contributes to the rise of populist leaders who concentrate power in the executive branch. These phenomena reflect the waning capacity of the state to improve governance across all countries. As a result, democracy is likely to face another lackluster decade if both structural and institutional problems are left unsolved

    Assessment of mitochondrial dysfunction and implications in cardiovascular disorders

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    Mitochondria play a pivotal role in cellular function, not only acting as the powerhouse of the cell, but also regulating ATP synthesis, reactive oxygen species (ROS) production, intracellular Ca2+ cycling, and apoptosis. During the past decade, extensive progress has been made in the technology to assess mitochondrial functions and accumulating evidences have shown that mitochondrial dysfunction is a key pathophysiological mechanism for many diseases including cardiovascular disorders, such as ischemic heart disease, cardiomyopathy, hypertension, atherosclerosis, and hemorrhagic shock. The advances in methodology have been accelerating our understanding of mitochondrial molecular structure and function, biogenesis and ROS and energy production, which facilitates new drug target identification and therapeutic strategy development for mitochondrial dysfunction-related disorders. This review will focus on the assessment of methodologies currently used for mitochondrial research and discuss their advantages, limitations and the implications of mitochondrial dysfunction in cardiovascular disorders

    (Z)-Ethyl 2-(2,4-dimethyl­benzyl­idene)-7-methyl-3-oxo-5-phenyl-3,5-dihydro-2H-thia­zolo[3,2-a]pyrimidine-6-carboxyl­ate

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    In the title compound, C25H24N2O3S, the dihedral angles between the thia­zole ring and the phenyl and substituted benzene rings are 84.91 (11) and 11.58 (10)°, respectively. The dihydro­pyrimidine ring adopts a flattened boat conformation. The olefinic double bond is in a Z configuration

    SiRA: Sparse Mixture of Low Rank Adaptation

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    Parameter Efficient Tuning has been an prominent approach to adapt the Large Language Model to downstream tasks. Most previous works considers adding the dense trainable parameters, where all parameters are used to adapt certain task. We found this less effective empirically using the example of LoRA that introducing more trainable parameters does not help. Motivated by this we investigate the importance of leveraging "sparse" computation and propose SiRA: sparse mixture of low rank adaption. SiRA leverages the Sparse Mixture of Expert(SMoE) to boost the performance of LoRA. Specifically it enforces the top kk experts routing with a capacity limit restricting the maximum number of tokens each expert can process. We propose a novel and simple expert dropout on top of gating network to reduce the over-fitting issue. Through extensive experiments, we verify SiRA performs better than LoRA and other mixture of expert approaches across different single tasks and multitask settings

    Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses

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    <p>Abstract</p> <p>Background</p> <p>Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA.</p> <p>Results</p> <p>In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed <it>in vitro</it>. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (<it>P </it>< 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220<sup>+ </sup>cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-A<sup>d</sup>) were increased on CD11c<sup>+ </sup>dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice.</p> <p>Conclusion</p> <p>These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.</p

    Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations

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    Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1–E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer

    Transesterification of palm oil using KF and NaNO3 catalysts supported on spherical millimetric γ-Al2O3

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    The use of spherical millimetric gamma-alumina (γ-Al2O3) as a catalyst support for the production of biodiesel from palm oil is demonstrated. The catalyst support was produced using a dripping method, and KF and NaNO3 catalysts were loaded on the support using the impregnation method. X-ray diffraction (XRD) analysis showed the formation of Na2O and NaAlO2 phases on the NaNO3/γ-Al2O3 catalyst and the formation of K2O and KAlF4 on the KF/γ-Al2O3 catalyst, which were possibly the active sites for the transesterification reaction. The highest number and strength of basic sites generated from the solid phase reaction of the KF/γ-Al2O3 catalyst loaded with 0.24 g kF/g γ-Al2O3 and the NaNO3/γ-Al2O3 catalyst loaded with 0.30 g NaNO3/g γ-Al2O3 were confirmed by temperature programmed desorption of CO2 (CO2-TPD) analysis. The nitrogen adsorption–desorption isotherms also revealed a mesoporous structure of the catalysts. The biodiesel yield was comparable to that produced from smaller catalysts, and this result indicated the potential of the macrospherical catalysts

    Safety and efficacy of endovascular recanalization for symptomatic non-acute atherosclerotic intracranial large artery occlusion

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    Background and objectiveThe optimal treatment for patients with symptomatic non-acute atherosclerotic intracranial large artery occlusion (ILAO) despite medical treatment is not well established. We aimed to assess the safety, efficacy, and feasibility of angioplasty and stenting for these patients.MethodsA total of 251 consecutive patients with symptomatic non-acute atherosclerotic ILAO treated with interventional recanalization were retrospectively collected in our center from March 2015 to August 2021. The rate of successful recanalization, perioperative complications, and follow-up outcomes were evaluated.ResultsSuccessful recanalization was achieved in 88.4% (222/251) of the patients. A total of 24 (24/251, 9.6%) symptomatic complications occurred among 251 procedures. In the 193 patients with clinical follow-up during 19.0 ± 14.7 months, 11 (11/193, 5.7%) patients developed ischemic stroke and four (4/193, 2.1%) patients developed transient ischemic attack (TIA). In the 106 patients with vascular imaging follow-up during 6.8 ± 6.6 months, seven (7/106, 6.6%) patients had restenosis and 10 (10/106, 9.4%) patients had reocclusion.ConclusionThis study suggests that interventional recanalization may be a feasible, basically safe, and an effective alternative in carefully selected patients with symptomatic non-acute atherosclerotic ILAO who have failed medical management
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