| 1. |
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| 2. |
- Gou, De Hai, et al.
(author)
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Inhibition of copper transporter 1 prevents α-synuclein pathology and alleviates nigrostriatal degeneration in AAV-based mouse model of Parkinson's disease
- 2021
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In: Redox Biology. - : Elsevier BV. - 2213-2317. ; 38
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Journal article (peer-reviewed)abstract
- The formation of α-synuclein aggregates is a major pathological hallmark of Parkinson's disease. Copper promotes α-synuclein aggregation and toxicity in vitro. The level of copper and copper transporter 1, which is the only known high-affinity copper importer in the brain, decreases in the substantia nigra of Parkinson's disease patients. However, the relationship between copper, copper transporter 1 and α-synuclein pathology remains elusive. Here, we aim to decipher the molecular mechanisms of copper and copper transporter 1 underlying Parkinson's disease pathology. We employed yeast and mammalian cell models expressing human α-synuclein, where exogenous copper accelerated intracellular α-synuclein inclusions and silencing copper transporter 1 reduced α-synuclein aggregates in vitro, suggesting that copper transporter 1 might inhibit α-synuclein pathology. To study our hypothesis in vivo, we generated a new transgenic mouse model with copper transporter 1 conditional knocked-out specifically in dopaminergic neuron. Meanwhile, we unilaterally injected adeno-associated viral human-α-synuclein into the substantia nigra of these mice. Importantly, we found that copper transporter 1 deficiency significantly reduced S129-phosphorylation of α-synuclein, prevented dopaminergic neuronal loss, and alleviated motor dysfunction caused by α-synuclein overexpression in vivo. Overall, our data indicated that inhibition of copper transporter 1 alleviated α-synuclein mediated pathologies and provided a novel therapeutic strategy for Parkinson's disease and other synucleinopathies.
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| 3. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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| 4. |
- Ades, M., et al.
(author)
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Global Climate : in State of the climate in 2019
- 2020
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In: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
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Journal article (peer-reviewed)
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| 5. |
- Ades, M., et al.
(author)
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GLOBAL CLIMATE
- 2020
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In: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
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Journal article (peer-reviewed)
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| 6. |
- Botvinik-Nezer, Rotem, et al.
(author)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Journal article (peer-reviewed)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 7. |
- Chen, Si, 1981, et al.
(author)
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Sn-3.0Ag-0.5Cu Nanocomposite Solder Reinforced With Bi2Te3 Nanoparticles
- 2015
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In: IEEE Transactions on Components, Packaging and Manufacturing Technology. - : Institute of Electrical and Electronics Engineers (IEEE). - 2156-3985 .- 2156-3950. ; 5:8, s. 1186-1196
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Journal article (peer-reviewed)abstract
- Nanocomposite solders are regarded as one of the most promising interconnect materials for the high-density electronic packaging due to their high mechanical strength and fine microstructure. However, the developments of nanocomposite solders have been limited by the inadequate compatibility between nanoparticles and solder matrix with respect to density, hardness, coefficient of thermal expansion, and surface activity. The compatibility issue will lead to a huge loss of nanoparticles from the solder matrix after the reflow soldering process. The thermal fatigue resistance of solder joint will also become degraded. Therefore, aiming to solve this problem, a novel nanocomposite solder consisting of Bi2Te3 semiconductor nanoparticles and Sn-3.0Ag-0.5Cu (SAC305) solder is presented. The effect of nanoparticles on the viscosity of solder paste and the void content of solder bump was first studied. Then, a series of analysis on the composition and microstructure of the solder bump were completed using transmission electron microscopy, X-ray diffraction, inductively coupled plasma-mass spectrometry, scanning electron microscopy, and energy dispersive X-ray spectroscopy. The survival rate of nanoparticles in the solder bump after reflow soldering process reaches as high as 80%. The refined microstructure was observed from the cross section of the nanocomposite solders. The shear test showed that the average mechanical strength of SAC305 solder after the addition of Bi2Te3 nanoparticles was higher. Meanwhile, no thermal fatigue resistance degradation was detected in the nanocomposite solder after 1000 thermal cycles in the range of -40 degrees C to 115 degrees C.
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| 8. |
- Hou, Zi Yong, et al.
(author)
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Effect of Holding Temperature on Microstructure and Mechanical Properties of High-Strength Multiphase Steel
- 2016
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In: Steel Research International. - : Wiley-VCH Verlagsgesellschaft. - 1611-3683 .- 1869-344X. ; 87:9, s. 1203-1212
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Journal article (peer-reviewed)abstract
- Isothermal holding following intercritical annealing is usually used in microstructure control, e.g., fractions and stabilities of retained-austenite (RA). Fe-0.22C-2.5Mn-0.47Si-0.41Cr-0.02Nb (mass%) steel is subjected to intercritical annealing and isothermal treatment at 250, 300, 350, and 400 degrees C to elucidate the impact on microstructures and mechanical properties by means of electron microscopy and uniaxial tensile test, respectively. The results show that the isothermal holding temperature is vital for the formed phases, including the morphology, volume fraction, and carbon content of RA in the processed steels. The tensile test results indicate that the mechanical properties including Ultra-tensile strength (UTS), Yield strength (YS), as well as Total Elongation (TEL) are attributed to the synthetic action of all constituents of phase morphology and corresponding fractions, e.g., hard-to-soft phase ratio, morphology and fraction of RA, dispersed precipitates. An excellent combination of strength-ductility of the present multiphase steel has been explained in terms of their specific microstructure.
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| 9. |
- Kang, Nai-xin, et al.
(author)
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Anemoside B4 inhibits enterovirus 71 propagation in mice through upregulating 14-3-3 expression and type I interferon responses
- 2022
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In: Acta Pharmacologica Sinica. - : Springer Nature. - 1671-4083 .- 1745-7254. ; 43, s. 977-991
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Journal article (peer-reviewed)abstract
- Enterovirus 71 (EV71) is the major pathogens of human hand, foot, and mouth disease (HFMD). EV71 efficiently escapes innate immunity responses of the host to cause infection. At present, no effective antiviral drugs for EV71 are available. Anemoside B4 (B4) is a natural saponin isolated from the roots of Pulsatilla chinensis (Bunge) Regel. P. chinensis extracts that shows a wide variety of biological activities. In this study, we investigated the antiviral activities of B4 against EV71 both in cell culture and in suckling mice. We showed that B4 (12.5-200 mu M) dose dependently increased the viability of EV71-infected RD cells with an IC50 value of 24.95 +/- 0.05 mu M against EV71. The antiviral activity of B4 was associated with enhanced interferon (IFN)-beta response, since knockdown of IFN-beta abolished its antiviral activity. We also confirmed that the enhanced IFN response was mediated via activation of retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) pathway, and it was executed by upregulation of 14-3-3 protein, which disrupted the interaction between yes-associated protein (YAP) and interferon regulatory factor 3 (IRF3). By using amino acids in cell culture (SILAC)-based proteomics profiling, we identified the Hippo pathway as the top-ranking functional cluster in B4-treated EV71-infected cells. In vivo experiments were conducted in suckling mice (2-day-old) infected with EV71 and subsequently B4 (200 mg center dot kg(-1) center dot d(-1), i.p.) was administered for 16 days. We showed that B4 administration effectively suppressed EV71 replication and improved muscle inflammation and limb activity. Meanwhile, B4 administration regulated the expressions of HFMD biomarkers IL-10 and IFN-gamma, attenuating complications of EV71 infection. Collectively, our results suggest that B4 could enhance the antiviral effect of IFN-beta by orchestrating Hippo and RLRs pathway, and B4 would be a potential lead compound for developing an anti-EV71 drug.
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| 10. |
- Kerrebrouck, Joris Van, et al.
(author)
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726.7-Gb/s 1.5-μm single-mode VCSEL discrete multi-tone transmission over 2.5-km multicore fiber
- 2018
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In: 2018 Optical Fiber Communications Conference and Exposition, OFC 2018 - Proceedings. - : Institute of Electrical and Electronics Engineers Inc.. - 9781943580385 ; , s. 1-3
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Conference paper (peer-reviewed)abstract
- A 107Gb/s net-rate DMT optical signal was generated using a single-mode long-wavelength VCSEL with a modulation bandwidth of 23 GHz. We experimentally demonstrated a total net-rate up to 726.7Gb/s at 1.5μm over 2.5km 7-core dispersion-uncompensated MCF.
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| 11. |
- Lawniczak, Mara K. N., et al.
(author)
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Standards recommendations for the Earth BioGenome Project
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4
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Journal article (peer-reviewed)abstract
- A global international initiative, such as the Earth BioGenome Project (EBP), requires both agreement and coordination on standards to ensure that the collective effort generates rapid progress toward its goals. To this end, the EBP initiated five technical standards committees comprising volunteer members from the global genomics scientific community: Sample Collection and Processing, Sequencing and Assembly, Annotation, Analysis, and IT and Informatics. The current versions of the resulting standards documents are available on the EBP website, with the recognition that opportunities, technologies, and challenges may improve or change in the future, requiring flexibility for the EBP to meet its goals. Here, we describe some highlights from the proposed standards, and areas where additional challenges will need to be met.
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| 12. |
- Newton-Cheh, Christopher, et al.
(author)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Journal article (peer-reviewed)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 13. |
- Olsen, Jogvan Magnus Haugaard, et al.
(author)
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Dalton Project : A Python platform for molecular- and electronic-structure simulations of complex systems
- 2020
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 152:21
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Journal article (peer-reviewed)abstract
- The Dalton Project provides a uniform platform access to the underlying full-fledged quantum chemistry codes Dalton and LSDalton as well as the PyFraME package for automatized fragmentation and parameterization of complex molecular environments. The platform is written in Python and defines a means for library communication and interaction. Intermediate data such as integrals are exposed to the platform and made accessible to the user in the form of NumPy arrays, and the resulting data are extracted, analyzed, and visualized. Complex computational protocols that may, for instance, arise due to a need for environment fragmentation and configuration-space sampling of biochemical systems are readily assisted by the platform. The platform is designed to host additional software libraries and will serve as a hub for future modular software development efforts in the distributed Dalton community.
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| 14. |
- Peng, Shi-Yu, et al.
(author)
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Reduced motor cortex GABABR function following chronic alcohol exposure
- 2021
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In: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; 26:2, s. 383-395
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Journal article (peer-reviewed)abstract
- The GABA(B) receptor (GABA(B)R) agonist baclofen has been used to treat alcohol and several other substance use disorders (AUD/SUD), yet its underlying neural mechanism remains unclear. The present study aimed to investigate cortical GABA(B)R dynamics following chronic alcohol exposure. Ex vivo brain slice recordings from mice chronically exposed to alcohol revealed a reduction in GABA(B)R-mediated currents, as well as a decrease of GABA(B1/2)R and G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) activities in the motor cortex. Moreover, our data indicated that these alterations could be attributed to dephosphorylation at the site of serine 783 (ser-783) in GABA(B2) subunit, which regulates the surface expression of GABA(B)R. Furthermore, a human study using paired-pulse-transcranial magnetic stimulation (TMS) analysis further demonstrated a reduced cortical inhibition mediated by GABA(B)R in patients with AUD. Our findings provide the first evidence that chronic alcohol exposure is associated with significantly impaired cortical GABA(B)R function. The ability to promote GABA(B)R signaling may account for the therapeutic efficacy of baclofen in AUD.
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| 15. |
- Roy, Sushmita, et al.
(author)
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Identification of functional elements and regulatory circuits by Drosophila modENCODE.
- 2010
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
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Journal article (peer-reviewed)abstract
- To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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| 16. |
- Song, Dong Yan, et al.
(author)
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α-Synuclein induces deficiency in clathrin-mediated endocytosis through inhibiting synaptojanin1 expression
- 2023
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In: Journal of Neurochemistry. - 0022-3042. ; 167:3, s. 461-484
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Journal article (peer-reviewed)abstract
- Parkinson's disease (PD) is an age-related chronic neurological disorder, mainly characterized by the pathological feature of α-synuclein (α-syn) aggregation, with the exact disease pathogenesis unclear. During the onset and progression of PD, synaptic dysfunction, including dysregulation of axonal transport, impaired exocytosis, and endocytosis are identified as crucial events of PD pathogenesis. It has been reported that over-expression of α-syn impairs clathrin-mediated endocytosis (CME) in the synapses. However, the underlying mechanisms still needs to be explored. In this study, we investigated the molecular events underlying the synaptic dysfunction caused by over-expression of wild-type human α-syn and its mutant form, involving series of proteins participating in CME. We found that excessive human α-syn causes impaired fission and uncoating of clathrin-coated vesicles during synaptic vesicle recycling, leading to reduced clustering of synaptic vesicles near the active zone and increased size of plasma membrane and number of endocytic intermediates. Furthermore, over-expressed human α-syn induced changes of CME-associated proteins, among which synaptojanin1 (SYNJ1) showed significant reduction in various brain regions. Over-expression of SYNJ1 in primary hippocampal neurons from α-syn transgenic mice recovered the synaptic vesicle density, clustering and endocytosis. Using fluorescence-conjugated transferrin, we demonstrated that SYNJ1 re-boosted the CME activity by restoring the phosphatidylinositol-4,5-bisphosphate homeostasis. Our data suggested that over-expression of α-syn disrupts synaptic function through interfering with vesicle recycling, which could be alleviated by re-availing of SYNJ1. Our study unrevealed a molecular mechanism of the synaptic dysfunction in PD pathogenesis and provided a potential therapeutic target for treating PD.
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| 17. |
- Wang, Anci, et al.
(author)
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Performance optimization of electric vehicle battery thermal management based on the transcritical CO2 system
- 2023
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In: Energy. - : Elsevier BV. - 0360-5442. ; 266
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Journal article (peer-reviewed)abstract
- Thermal management of electric vehicles, especially battery thermal management, is critical to driving range and operational safety. To find a vehicle thermal management system with higher energy efficiency and environmental protection, an environmentally-friendly and efficient battery and cabin parallel cooling thermal management system was evaluated with CO2 as the working fluid. First, different control strategies of the evaporation temperature were compared regarding the battery cooling performance. Then, the effect of the battery cooling evaporation temperature on the coefficient of performance (COP) was explored. It was found that the maximum COP increased by 8.38% as the evaporation temperature decreased from 17 to 5.8 °C. Besides, it was found that the optimal battery cooling evaporation temperature range is 10.2–11 °C when the battery heating power is 0.4 kW. The vapor quality at the cold plate outlet should be lower than 0.95. Finally, the battery cooling performance under variable operating conditions was investigated. The influence of operating parameters on the battery cooling evaporation temperature and CO2 outlet vapor quality was also analyzed. Simulation results showed that the optimum evaporation temperature range varied significantly under different working conditions. The vapor quality at the cold plate outlet decreased slightly with the evaporation temperature.
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| 18. |
- Wang, Guan, et al.
(author)
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Transient analyses for China initiative Accelerator Driven System using the extended BELLA code
- 2023
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In: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 190
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Journal article (peer-reviewed)abstract
- China initiative Accelerator Driven System (CiADS) is a 10 MW lead-bismuth eutectic (LBE) cooled subcritical reactor loaded with UO2 fuels in the first phase, which is designed to demonstrate the engineering feasibility of the ADS concept. The transient analyses were performed to show the safety potential and dynamic characteristics of the CiADS subcritical reactor using the extended BELLA code. Typical scenarios, such as beam-trip transients, unprotected beam overpower (UBOP), unprotected and protected loss of flow (ULOF and PLOF), unprotected and protected loss of heat sink (ULOHS and PLOHS) and self-defined station blackout (SBO), were analyzed and simulated. The results indicate that, as a low-power reactor, the CiADS subcritical reactor has a large margin to avoid severe damage in the core. Short-term cladding failure caused by thermal fatigue under frequent beam trips may not happen since the variations of temperatures are relatively small. However, accelerated LBE corrosion combined with accumulated creep tends to be a risk under ULOF and ULOHS.
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| 19. |
- Wang, Kai, et al.
(author)
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Zinc anode based alkaline energy storage system: Recent progress and future perspectives of zinc–silver battery
- 2024
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In: Energy Storage Materials. - 2405-8297. ; 69
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Research review (peer-reviewed)abstract
- Rechargeable zinc-based batteries have come to the forefront of energy storage field with a surprising pace during last decade due to the advantageous safety, abundance and relatively low cost, making them important supplements of lithium-ion batteries. As a significant role in zinc-based batteries, zinc-silver battery owns the advantages of high specific energy density, stable working voltage, high charging efficiency, safety and environmental friendliness, and it has been widely used in military such as in aerospace, deep water manned and civil field such as energy supply for watch and hearing aid. However, it is still suffering from a few drawbacks such as unsatisfactory cycle life, low utilization of the cathode. This review introduces the basic principles of zinc-silver batteries and elaborates the battery configurations aiming to understand its working mechanisms as well as the related issues. Most importantly, the very recent research updates and the concerns have arisen in the development are summarized from conventional cell to flexible device and hybrid device. Finally, the challenges and perspectives of zinc-silver batteries are further prospected to give a broad idea to readers new in the area and trigger inspirations for motivated researchers to further widen the utilization of silver-zinc batteries.
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| 20. |
- Xiong, Sangqi, et al.
(author)
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A combined machine learning and density functional theory study of binary Ti-Nb and Ti-Zr alloys: Stability and Young’s modulus
- 2020
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In: Computational materials science. - : Elsevier. - 0927-0256 .- 1879-0801. ; 184
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Journal article (peer-reviewed)abstract
- The multicomponent Ti alloys, specifically the β-phase, have experienced a strong growth over the last decades, due to their outstanding properties of ultra-high strength and low Young’s modulus. These properties play a significant role in many aerospace and biomedical applications. Selection and optimization of multicomponent alloys is challenging due to the vast chemical and compositional space. Here we investigate the use of machine learning techniques informed by density functional calculations to guide the selection of Nb- and Zr-based Ti binary alloys. From the cubic structures obtained from high throughput calculations and literature, we identify several structures with Young’s moduli below 40 GPa. The multivariant decision tree methods provide efficient surrogate models to identify structure variables have high influences on the energetic stability and Young’s modulus. We implement a workflow of incorporating DFT provided results and machine learning method to explore the chemical and composition space of other binary and multicomponent alloys, to eventually accelerate the material design via taking advantages of identified key variables.
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| 21. |
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