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  • 1
    Online Resource
    Online Resource
    Direct mapping of bending and torsional dynamics in individual nanostructures
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 25 ( 2023-06-20)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 25 ( 2023-06-20)
    Abstract: Investigating coherent acoustic vibrations in nanostructured materials provides fundamental insights into optomechanical responses and microscopic energy flow. Extensive measurements of vibrational dynamics have been performed for a wide variety of nanoparticles and nanoparticle assemblies. However, virtually all of them show that only the dilation modes are launched after laser excitations, and the acoustic bending and torsional motions, which are commonly observed in photoexcited chemical bonds, are absent. Unambiguous identification and refined characterization of these “missing” modes have been a long-standing issue. In this report, we investigated the acoustic vibrational dynamics of individual Au nanoprisms on free-standing graphene substrates using an ultrafast high-sensitivity dark-field imaging approach in four-dimensional transmission electron microscopy. Following optical excitations, we observed low-frequency multiple-mode oscillations and higher superposition amplitudes at nanoprism corners and edges on the subnanoparticle level. In combination with finite-element simulations, we determined that these vibrational modes correspond to out-of-plane bending and torsional motions, superimposed by an overall tilting effect of the nanoprisms. The launch and relaxation processes of these modes are highly pertinent to substrate effects and nanoparticle geometries. These findings contribute to the fundamental understanding about acoustic dynamics of individual nanostructures and their interaction with substrates.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2221956120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    Quantum computational advantage using photons
    American Association for the Advancement of Science (AAAS) ; 2020
    In:  Science Vol. 370, No. 6523 ( 2020-12-18), p. 1460-1463
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 370, No. 6523 ( 2020-12-18), p. 1460-1463
    Abstract: Quantum computers promise to perform certain tasks that are believed to be intractable to classical computers. Boson sampling is such a task and is considered a strong candidate to demonstrate the quantum computational advantage. We performed Gaussian boson sampling by sending 50 indistinguishable single-mode squeezed states into a 100-mode ultralow-loss interferometer with full connectivity and random matrix—the whole optical setup is phase-locked—and sampling the output using 100 high-efficiency single-photon detectors. The obtained samples were validated against plausible hypotheses exploiting thermal states, distinguishable photons, and uniform distribution. The photonic quantum computer, Jiuzhang , generates up to 76 output photon clicks, which yields an output state-space dimension of 10 30 and a sampling rate that is faster than using the state-of-the-art simulation strategy and supercomputers by a factor of ~10 14 .
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abe8770
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2020
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    detail.hit.zdb_id: 2066996-3
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  • 3
    Online Resource
    Online Resource
    3D printing of inorganic nanomaterials by photochemically bonding colloidal nanocrystals
    American Association for the Advancement of Science (AAAS) ; 2023
    In:  Science Vol. 381, No. 6665 ( 2023-09-29), p. 1468-1474
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 381, No. 6665 ( 2023-09-29), p. 1468-1474
    Abstract: Ligand photochemistry of colloidal nanocrystals enables 3D laser direct printing of various inorganic nanomaterials.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.adg6681
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
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  • 4
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    Online Resource
    Therapeutic reversal of Huntington’s disease by in vivo self-assembled siRNAs
    Oxford University Press (OUP) ; 2021
    In:  Brain Vol. 144, No. 11 ( 2021-12-16), p. 3421-3435
    Details
    In: Brain, Oxford University Press (OUP), Vol. 144, No. 11 ( 2021-12-16), p. 3421-3435
    Abstract: Huntington’s disease is an autosomal-dominant neurodegenerative disease caused by CAG expansion in exon 1 of the huntingtin (HTT) gene. Since mutant huntingtin (mHTT) protein is the root cause of Huntington’s disease, oligonucleotide-based therapeutic approaches using small interfering RNAs (siRNAs) and antisense oligonucleotides designed to specifically silence mHTT may be novel therapeutic strategies for Huntington’s disease. Unfortunately, the lack of an effective in vivo delivery system remains a major obstacle to realizing the full potential of oligonucleotide therapeutics, especially regarding the delivery of oligonucleotides to the cortex and striatum, the most severely affected brain regions in Huntington’s disease. In this study, we present a synthetic biology strategy that integrates the naturally existing exosome-circulating system with artificial genetic circuits for self-assembly and delivery of mHTT-silencing siRNA to the cortex and striatum. We designed a cytomegalovirus promoter-directed genetic circuit encoding both a neuron-targeting rabies virus glycoprotein tag and an mHTT siRNA. After being taken up by mouse livers after intravenous injection, this circuit was able to reprogramme hepatocytes to transcribe and self-assemble mHTT siRNA into rabies virus glycoprotein-tagged exosomes. The mHTT siRNA was further delivered through the exosome-circulating system and guided by a rabies virus glycoprotein tag to the cortex and striatum. Consequently, in three mouse models of Huntington’s disease treated with this circuit, the levels of mHTT protein and toxic aggregates were successfully reduced in the cortex and striatum, therefore ameliorating behavioural deficits and striatal and cortical neuropathologies. Overall, our findings establish a convenient, effective and safe strategy for self-assembly of siRNAs in vivo that may provide a significant therapeutic benefit for Huntington’s disease.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awab354
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 5
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    Online Resource
    Lead halide–templated crystallization of methylamine-free perovskite for efficient photovoltaic modules
    American Association for the Advancement of Science (AAAS) ; 2021
    In:  Science Vol. 372, No. 6548 ( 2021-06-18), p. 1327-1332
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 372, No. 6548 ( 2021-06-18), p. 1327-1332
    Abstract: Upscaling efficient and stable perovskite layers is one of the most challenging issues in the commercialization of perovskite solar cells. Here, a lead halide–templated crystallization strategy is developed for printing formamidinium (FA)–cesium (Cs) lead triiodide perovskite films. High-quality large-area films are achieved through controlled nucleation and growth of a lead halide• N -methyl-2-pyrrolidone adduct that can react in situ with embedded FAI/CsI to directly form α-phase perovskite, sidestepping the phase transformation from δ-phase. A nonencapsulated device with 23% efficiency and excellent long-term thermal stability (at 85°C) in ambient air (~80% efficiency retention after 500 hours) is achieved with further addition of potassium hexafluorophosphate. The slot die–printed minimodules achieve champion efficiencies of 20.42% (certified efficiency 19.3%) and 19.54% with an active area of 17.1 and 65.0 square centimeters, respectively.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abh1035
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2021
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  • 6
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    Online Resource
    Whole-brain mapping of histaminergic projections in mouse brain
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 14 ( 2023-04-04)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 14 ( 2023-04-04)
    Abstract: Histamine is a conserved neuromodulator in mammalian brains and critically involved in many physiological functions. Understanding the precise structure of the histaminergic network is the cornerstone in elucidating its function. Herein, using histidine decarboxylase (HDC)-CreERT2 mice and genetic labeling strategies, we reconstructed a whole-brain three dimensional (3D) structure of histaminergic neurons and their outputs at 0.32 × 0.32 × 2 μm 3 pixel resolution with a cutting-edge fluorescence microoptical sectioning tomography system. We quantified the fluorescence density of all brain areas and found that histaminergic fiber density varied significantly among brain regions. The density of histaminergic fiber was positively correlated with the amount of histamine release induced by optogenetic stimulation or physiological aversive stimulation. Lastly, we reconstructed a fine morphological structure of 60 histaminergic neurons via sparse labeling and uncovered the largely heterogeneous projection pattern of individual histaminergic neurons. Collectively, this study reveals an unprecedented whole-brain quantitative analysis of histaminergic projections at the mesoscopic level, providing a foundation for future functional histaminergic study.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2216231120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
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    SSG: 11
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Quantum teleportation of physical qubits into logical code spaces
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 36 ( 2021-09-07)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 36 ( 2021-09-07)
    Abstract: Quantum error correction is an essential tool for reliably performing tasks for processing quantum information on a large scale. However, integration into quantum circuits to achieve these tasks is problematic when one realizes that nontransverse operations, which are essential for universal quantum computation, lead to the spread of errors. Quantum gate teleportation has been proposed as an elegant solution for this. Here, one replaces these fragile, nontransverse inline gates with the generation of specific, highly entangled offline resource states that can be teleported into the circuit to implement the nontransverse gate. As the first important step, we create a maximally entangled state between a physical and an error-correctable logical qubit and use it as a teleportation resource. We then demonstrate the teleportation of quantum information encoded on the physical qubit into the error-corrected logical qubit with fidelities up to 0.786. Our scheme can be designed to be fully fault tolerant so that it can be used in future large-scale quantum technologies.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2026250118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
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    SSG: 11
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  • 8
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    Online Resource
    A high-resolution summary of Cambrian to Early Triassic marine invertebrate biodiversity
    American Association for the Advancement of Science (AAAS) ; 2020
    In:  Science Vol. 367, No. 6475 ( 2020-01-17), p. 272-277
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 367, No. 6475 ( 2020-01-17), p. 272-277
    Abstract: One great challenge in understanding the history of life is resolving the influence of environmental change on biodiversity. Simulated annealing and genetic algorithms were used to synthesize data from 11,000 marine fossil species, collected from more than 3000 stratigraphic sections, to generate a new Cambrian to Triassic biodiversity curve with an imputed temporal resolution of 26 ± 14.9 thousand years. This increased resolution clarifies the timing of known diversification and extinction events. Comparative analysis suggests that partial pressure of carbon dioxide ( P co 2 ) is the only environmental factor that seems to display a secular pattern similar to that of biodiversity, but this similarity was not confirmed when autocorrelation within that time series was analyzed by detrending. These results demonstrate that fossil data can provide the temporal and taxonomic resolutions necessary to test (paleo)biological hypotheses at a level of detail approaching those of long-term ecological analyses.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aax4953
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2020
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  • 9
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    Small-molecule inhibitors for the Prp8 intein as antifungal agents
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 2 ( 2021-01-12)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 2 ( 2021-01-12)
    Abstract: Self-splicing proteins, called inteins, are present in many human pathogens, including the emerging fungal threats Cryptococcus neoformans ( Cne ) and Cryptococcus gattii ( Cga ), the causative agents of cryptococcosis. Inhibition of protein splicing in Cryptococcus sp. interferes with activity of the only intein-containing protein, Prp8, an essential intron splicing factor. Here, we screened a small-molecule library to find addititonal, potent inhibitors of the Cne Prp8 intein using a split-GFP splicing assay. This revealed the compound 6G-318S, with IC 50 values in the low micromolar range in the split-GFP assay and in a complementary split-luciferase system. A fluoride derivative of the compound 6G-318S displayed improved cytotoxicity in human lung carcinoma cells, although there was a slight reduction in the inhibition of splicing. 6G-318S and its derivative inhibited splicing of the Cne Prp8 intein in vivo in Escherichia coli and in C. neoformans . Moreover, the compounds repressed growth of WT C. neoformans and C. gattii . In contrast, the inhibitors were less potent at inhibiting growth of the inteinless Candida albicans . Drug resistance was observed when the Prp8 intein was overexpressed in C. neoformans , indicating specificity of this molecule toward the target. No off-target activity was observed, such as inhibition of serine/cysteine proteases. The inhibitors bound covalently to the Prp8 intein and binding was reduced when the active-site residue Cys1 was mutated. 6G-318S showed a synergistic effect with amphotericin B and additive to indifferent effects with a few other clinically used antimycotics. Overall, the identification of these small-molecule intein-splicing inhibitors opens up prospects for a new class of antifungals.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2008815118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
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  • 10
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    Online Resource
    CAG RNAs induce DNA damage and apoptosis by silencing NUDT16 expression in polyglutamine degeneration
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 19 ( 2021-05-11)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 19 ( 2021-05-11)
    Abstract: DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington’s disease (HD). In this study, we showed that the expression of untranslatable expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the Nudix hydrolase 16 ( NUDT16 ) gene was down-regulated in mutant CAG RNA-expressing cells. The loss of NUDT16 function results in a misincorporation of damaging nucleotides into DNAs and leads to DNA damage. We showed that small CAG (sCAG) RNAs, species generated from expanded CAG transcripts, hybridize with CUG-containing NUDT16 mRNA and form a CAG-CUG RNA heteroduplex, resulting in gene silencing of NUDT16 and leading to the DNA damage and cellular apoptosis. These results were further validated using expanded CAG RNA-expressing mouse primary neurons and in vivo R6/2 HD transgenic mice. Moreover, we identified a bisamidinium compound, DB213, that interacts specifically with the major groove of the CAG RNA homoduplex and disfavors the CAG-CUG heteroduplex formation. This action subsequently mitigated RNA-induced silencing complex (RISC)-dependent NUDT16 silencing in both in vitro cell and in vivo mouse disease models. After DB213 treatment, DNA damage, apoptosis, and locomotor defects were rescued in HD mice. This work establishes NUDT16 deficiency by CAG repeat RNAs as a pathogenic mechanism of polyQ diseases and as a potential therapeutic direction for HD and other polyQ diseases.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2022940118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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