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  • 1
    Online Resource
    Online Resource
    An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike
    American Association for the Advancement of Science (AAAS) ; 2020
    In:  Science Vol. 370, No. 6523 ( 2020-12-18), p. 1473-1479
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 370, No. 6523 ( 2020-12-18), p. 1473-1479
    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo–electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abe3255
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2020
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 2
    Online Resource
    Online Resource
    Photoelectric conversion on Earth’s surface via widespread Fe- and Mn-mineral coatings
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 20 ( 2019-05-14), p. 9741-9746
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 20 ( 2019-05-14), p. 9741-9746
    Abstract: Sunlight drives photosynthesis and associated biological processes, and also influences inorganic processes that shape Earth’s climate and geochemistry. Bacterial solar-to-chemical energy conversion on this planet evolved to use an intricate intracellular process of phototrophy. However, a natural nonbiological counterpart to phototrophy has yet to be recognized. In this work, we reveal the inherent “phototrophic-like” behavior of vast expanses of natural rock/soil surfaces from deserts, red soils, and karst environments, all of which can drive photon-to-electron conversions. Using scanning electron microscopy, transmission electron microscopy, micro-Raman spectroscopy, and X-ray absorption spectroscopy, Fe and Mn (oxyhydr)oxide-rich coatings were found in rock varnishes, as were Fe (oxyhydr)oxides on red soil surfaces and minute amounts of Mn oxides on karst rock surfaces. By directly fabricating a photoelectric detection device on the thin section of a rock varnish sample, we have recorded an in situ photocurrent micromapping of the coatings, which behave as highly sensitive and stable photoelectric systems. Additional measurements of red soil and powder separated from the outermost surface of karst rocks yielded photocurrents that are also sensitive to irradiation. The prominent solar-responsive capability of the phototrophic-like rocks/soils is ascribed to the semiconducting Fe- and Mn (oxyhydr)oxide-mineral coatings. The native semiconducting Fe/Mn-rich coatings may play a role similar, in part, to photosynthetic systems and thus provide a distinctive driving force for redox (bio)geochemistry on Earth’s surfaces.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1902473116
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet
    American Association for the Advancement of Science (AAAS) ; 2013
    In:  Science Vol. 340, No. 6139 ( 2013-06-21), p. 1459-1463
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 340, No. 6139 ( 2013-06-21), p. 1459-1463
    Abstract: In the past, avian influenza viruses have crossed species barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts. H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type α-2,6-linked sialic acid airway receptor. Using reverse genetics, we systematically created 127 reassortant viruses between a duck isolate of H5N1, specifically retaining its hemagglutinin ( HA ) gene throughout, and a highly transmissible, human-infective H1N1 virus. We tested the virulence of the reassortants in mice as a correlate for virulence in humans and tested transmissibility in guinea pigs, which have both avian and mammalian types of airway receptor. Transmission studies showed that the H1N1 virus genes encoding acidic polymerase and nonstructural protein made the H5N1 virus transmissible by respiratory droplet between guinea pigs without killing them. Further experiments implicated other H1N1 genes in the enhancement of mammal-to-mammal transmission, including those that encode nucleoprotein, neuraminidase, and matrix, as well as mutations in H5 HA that improve affinity for humanlike airway receptors. Hence, avian H5N1 subtype viruses do have the potential to acquire mammalian transmissibility by reassortment in current agricultural scenarios.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1229455
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2013
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 4
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    Online Resource
    The N-Myc-responsive lncRNA MILIP promotes DNA double-strand break repair through non-homologous end joining
    Proceedings of the National Academy of Sciences ; 2022
    In:  Proceedings of the National Academy of Sciences Vol. 119, No. 49 ( 2022-12-06)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 49 ( 2022-12-06)
    Abstract: The protooncoprotein N-Myc, which is overexpressed in approximately 25% of neuroblastomas as the consequence of MYCN gene amplification, has long been postulated to regulate DNA double-strand break (DSB) repair in neuroblastoma cells, but experimental evidence of this function is presently scant. Here, we show that N-Myc transcriptionally activates the long noncoding RNA MILIP to promote nonhomologous end-joining (NHEJ) DNA repair through facilitating Ku70–Ku80 heterodimerization in neuroblastoma cells. High MILIP expression was associated with poor outcome and appeared as an independent prognostic factor in neuroblastoma patients. Knockdown of MILIP reduced neuroblastoma cell viability through the induction of apoptosis and inhibition of proliferation, retarded neuroblastoma xenograft growth, and sensitized neuroblastoma cells to DNA-damaging therapeutics. The effect of MILIP knockdown was associated with the accumulation of DNA DSBs in neuroblastoma cells largely due to decreased activity of the NHEJ DNA repair pathway. Mechanistical investigations revealed that binding of MILIP to Ku70 and Ku80 increased their heterodimerization, and this was required for MILIP-mediated promotion of NHEJ DNA repair. Disrupting the interaction between MILIP and Ku70 or Ku80 increased DNA DSBs and reduced cell viability with therapeutic potential revealed where targeting MILIP using Gapmers cooperated with the DNA-damaging drug cisplatin to inhibit neuroblastoma growth in vivo. Collectively, our findings identify MILIP as an N-Myc downstream effector critical for activation of the NHEJ DNA repair pathway in neuroblastoma cells, with practical implications of MILIP targeting, alone and in combination with DNA-damaging therapeutics, for neuroblastoma treatment.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2208904119
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 5
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    Online Resource
    Diverse Suppressive Influences in Area MT and Selectivity to Complex Motion Features
    Society for Neuroscience ; 2013
    In:  The Journal of Neuroscience Vol. 33, No. 42 ( 2013-10-16), p. 16715-16728
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 33, No. 42 ( 2013-10-16), p. 16715-16728
    Abstract: Neuronal selectivity results from both excitatory and suppressive inputs to a given neuron. Suppressive influences can often significantly modulate neuronal responses and impart novel selectivity in the context of behaviorally relevant stimuli. In this work, we use a naturalistic optic flow stimulus to explore the responses of neurons in the middle temporal area (MT) of the alert macaque monkey; these responses are interpreted using a hierarchical model that incorporates relevant nonlinear properties of upstream processing in the primary visual cortex (V1). In this stimulus context, MT neuron responses can be predicted from distinct excitatory and suppressive components. Excitation is spatially localized and matches the measured preferred direction of each neuron. Suppression is typically composed of two distinct components: (1) a directionally untuned component, which appears to play the role of surround suppression and normalization; and (2) a direction-selective component, with comparable tuning width as excitation and a distinct spatial footprint that is usually partially overlapping with excitation. The direction preference of this direction-tuned suppression varies widely across MT neurons: approximately one-third have overlapping suppression in the opposite direction as excitation, and many other neurons have suppression with similar direction preferences to excitation. There is also a population of MT neurons with orthogonally oriented suppression. We demonstrate that direction-selective suppression can impart selectivity of MT neurons to more complex velocity fields and that it can be used for improved estimation of the three-dimensional velocity of moving objects. Thus, considering MT neurons in a complex stimulus context reveals a diverse set of computations likely relevant for visual processing in natural visual contexts.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.0203-13.2013
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2013
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Inferring Cortical Variability from Local Field Potentials
    Society for Neuroscience ; 2016
    In:  The Journal of Neuroscience Vol. 36, No. 14 ( 2016-04-06), p. 4121-4135
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 36, No. 14 ( 2016-04-06), p. 4121-4135
    Abstract: The responses of sensory neurons can be quite different to repeated presentations of the same stimulus. Here, we demonstrate a direct link between the trial-to-trial variability of cortical neuron responses and network activity that is reflected in local field potentials (LFPs). Spikes and LFPs were recorded with a multielectrode array from the middle temporal (MT) area of the visual cortex of macaques during the presentation of continuous optic flow stimuli. A maximum likelihood-based modeling framework was used to predict single-neuron spiking responses using the stimulus, the LFPs, and the activity of other recorded neurons. MT neuron responses were strongly linked to gamma oscillations (maximum at 40 Hz) as well as to lower-frequency delta oscillations (1–4 Hz), with consistent phase preferences across neurons. The predicted modulation associated with the LFP was largely complementary to that driven by visual stimulation, as well as the activity of other neurons, and accounted for nearly half of the trial-to-trial variability in the spiking responses. Moreover, the LFP model predictions accurately captured the temporal structure of noise correlations between pairs of simultaneously recorded neurons, and explained the variation in correlation magnitudes observed across the population. These results therefore identify signatures of network activity related to the variability of cortical neuron responses, and suggest their central role in sensory cortical function. SIGNIFICANCE STATEMENT The function of sensory neurons is nearly always cast in terms of representing sensory stimuli. However, recordings from visual cortex in awake animals show that a large fraction of neural activity is not predictable from the stimulus. We show that this variability is predictable given the simultaneously recorded measures of network activity, local field potentials. A model that combines elements of these signals with the stimulus processing of the neuron can predict neural responses dramatically better than current models, and can predict the structure of correlations across the cortical population. In identifying ways to understand stimulus processing in the context of ongoing network activity, this work thus provides a foundation to understand the role of sensory cortex in combining sensory and cognitive variables.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.2502-15.2016
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2016
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 7
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    Online Resource
    Secure state estimation for cyber-physical systems by unknown input observer with adaptive switching mechanism
    Elsevier BV ; 2023
    In:  Information Sciences Vol. 647 ( 2023-11), p. 119452-
    Details
    In: Information Sciences, Elsevier BV, Vol. 647 ( 2023-11), p. 119452-
    Type of Medium: Online Resource
    ISSN: 0020-0255
    URL: Article
    DOI: 10.1016/j.ins.2023.119452
    RVK:
    SA 5420
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 218760-7
    detail.hit.zdb_id: 1478990-5
    SSG: 24,1
    SSG: 7,11
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  • 8
    Online Resource
    Online Resource
    Roles of collocation in L2 oral proficiency revisited: Different tasks, L1 vs. L2 raters, and cross-sectional vs. longitudinal analyses
    SAGE Publications ; 2022
    In:  Second Language Research Vol. 38, No. 3 ( 2022-07), p. 531-554
    Details
    In: Second Language Research, SAGE Publications, Vol. 38, No. 3 ( 2022-07), p. 531-554
    Abstract: There is emerging evidence that collocation use plays a primary role in determining various dimensions of L2 oral proficiency assessment and development. The current study presents the results of three experiments which examined the relationship between the degree of association in collocation use (operationalized as t scores and mutual information scores) and the intuitive judgements of L2 comprehensibility (i.e. ease of understanding). The topic was approached from the angles of different task conditions (Study 1), rater background (first language or L1 vs. second language or L2) (Study 2) and cross-sectional vs. longitudinal analyses (Study 3). The findings showed that: (1) collocation emerged as a medium-to-strong determinant of L2 comprehensibility in structured (picture description) compared to free (oral interview) oral production tasks; (2) with sufficient immersion experience, L2 raters can demonstrate as much sensitivity to collocation as L1 raters; and (3) conversational experience is associated with more coherent and mutually-exclusive combinations of words in L2 speech, resulting in greater L2 comprehensibility development.
    Type of Medium: Online Resource
    ISSN: 0267-6583 , 1477-0326
    URL: Article
    DOI: 10.1177/0267658320988055
    RVK:
    EQ 1000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2023712-1
    SSG: 7,11
    SSG: 5,3
    SSG: 7,23
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  • 9
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    Online Resource
    Hierarchical-morphology metafabric for scalable passive daytime radiative cooling
    American Association for the Advancement of Science (AAAS) ; 2021
    In:  Science Vol. 373, No. 6555 ( 2021-08-06), p. 692-696
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 373, No. 6555 ( 2021-08-06), p. 692-696
    Abstract: Incorporating passive radiative cooling structures into personal thermal management technologies could effectively defend humans against intensifying global climate change. We show that large-scale woven metafabrics can provide high emissivity (94.5%) in the atmospheric window and high reflectivity (92.4%) in the solar spectrum because of the hierarchical-morphology design of the randomly dispersed scatterers throughout the metafabric. Through scalable industrial textile manufacturing routes, our metafabrics exhibit desirable mechanical strength, waterproofness, and breathability for commercial clothing while maintaining efficient radiative cooling ability. Practical application tests demonstrated that a human body covered by our metafabric could be cooled ~4.8°C lower than one covered by commercial cotton fabric. The cost-effectiveness and high performance of our metafabrics present substantial advantages for intelligent garments, smart textiles, and passive radiative cooling applications.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abi5484
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2021
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 10
    Online Resource
    Online Resource
    Unique size-dependent nanocatalysis revealed at the single atomically precise gold cluster level
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 42 ( 2018-10-16), p. 10588-10593
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 42 ( 2018-10-16), p. 10588-10593
    Abstract: Atomically precise metal clusters have attracted increasing interest owing to their unique size-dependent properties; however, little has been known about the effect of size on the catalytic properties of metal clusters at the single-cluster level. Here, by real-time monitoring with single-molecule fluorescence microscopy the size-dependent catalytic process of individual Au clusters at single-turnover resolution, we study the size-dependent catalytic behaviors of gold (Au) clusters at the single-cluster level, and then observe the strong size effect on the catalytic properties of individual Au clusters, in both catalytic product formation and dissociation processes. Surprisingly, indicated by both experiments and density functional theory (DFT) calculations, due to such a unique size effect, besides observing the different product dissociation behaviors on different-sized Au clusters, we also observe that small Au clusters [i.e., Au 15 (MPA) 13 ; here, MPA denotes 3-mercaptopropionic acid] catalyze the product formation through a competitive Langmuir–Hinshelwood mechanism, while those relatively larger Au clusters [e.g., Au 18 (MPA) 14 and Au 25( MPA) 18 ] or nanoparticles catalyze the same process through a noncompetitive Langmuir–Hinshelwood mechanism. Such a size effect on the nanocatalysis could be attributed intrinsically to the size-dependent electronic structure of Au clusters. Further analysis of dynamic activity fluctuation of Au clusters reveals more different catalytic properties between Au clusters and traditional Au nanoparticles due to their different size-dependent structures.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1805711115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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