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  • 1
    Online Resource
    Online Resource
    Wafer-Scale Growth of Single-Crystal Monolayer Graphene on Reusable Hydrogen-Terminated Germanium
    American Association for the Advancement of Science (AAAS) ; 2014
    In:  Science Vol. 344, No. 6181 ( 2014-04-18), p. 286-289
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 344, No. 6181 ( 2014-04-18), p. 286-289
    Abstract: The uniform growth of single-crystal graphene over wafer-scale areas remains a challenge in the commercial-level manufacturability of various electronic, photonic, mechanical, and other devices based on graphene. Here, we describe wafer-scale growth of wrinkle-free single-crystal monolayer graphene on silicon wafer using a hydrogen-terminated germanium buffer layer. The anisotropic twofold symmetry of the germanium (110) surface allowed unidirectional alignment of multiple seeds, which were merged to uniform single-crystal graphene with predefined orientation. Furthermore, the weak interaction between graphene and underlying hydrogen-terminated germanium surface enabled the facile etch-free dry transfer of graphene and the recycling of the germanium substrate for continual graphene growth.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1252268
    RVK:
    TA 1000
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    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2014
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    detail.hit.zdb_id: 2066996-3
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  • 2
    Online Resource
    Online Resource
    Generation of 3D lacrimal gland organoids from human pluripotent stem cells
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 605, No. 7908 ( 2022-05-05), p. 126-131
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 605, No. 7908 ( 2022-05-05), p. 126-131
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-04613-4
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
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  • 3
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    Online Resource
    Human glioblastoma arises from subventricular zone cells with low-level driver mutations
    Springer Science and Business Media LLC ; 2018
    In:  Nature Vol. 560, No. 7717 ( 2018-8), p. 243-247
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 560, No. 7717 ( 2018-8), p. 243-247
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-018-0389-3
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
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  • 4
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    Online Resource
    Genetic dissection of the biosynthetic route to gentamicin A 2 by heterologous expression of its minimal gene set
    Proceedings of the National Academy of Sciences ; 2008
    In:  Proceedings of the National Academy of Sciences Vol. 105, No. 24 ( 2008-06-17), p. 8399-8404
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 24 ( 2008-06-17), p. 8399-8404
    Abstract: Since the first use of streptomycin as an effective antibiotic drug in the treatment of tuberculosis, aminoglycoside antibiotics have been widely used against a variety of bacterial infections for over six decades. However, the pathways for aminoglycoside biosynthesis still remain unclear, mainly because of difficulty in genetic manipulation of actinomycetes producing this class of antibiotics. Gentamicin belongs to the group of 4,6-disubstituted aminoglycosides containing a characteristic core aminocyclitol moiety, 2-deoxystreptamine (2-DOS), and the recent discovery of its biosynthetic gene cluster in Micromonospora echinospora has enabled us to decipher its biosynthetic pathway. To determine the minimal set of genes and their functions for the generation of gentamicin A 2 , the first pseudotrisaccharide intermediate in the biosynthetic pathway for the gentamicin complex, various sets of candidate genes from M. echinospora and other related aminoglycoside-producing strains were introduced into a nonaminoglycoside producing strain of Streptomyces venezuelae . Heterologous expression of different combinations of putative 2-DOS biosynthetic genes revealed that a subset, gtmB-gtmA-gacH , is responsible for the biosynthesis of this core aminocyclitol moiety of gentamicin. Expression of gtmG together with gtmB-gtmA-gacH led to production of 2′- N -acetylparomamine, demonstrating that GtmG acts as a glycosyltransferase that adds N -acetyl- d -glucosamine (GLcNA) to 2-DOS. Expression of gtmM in a 2′- N -acetylparomamine-producing recombinant S. venezuelae strain generated paromamine. Expression of gtmE in an engineered paromamine-producing strain of S. venezuelae successfully generated gentamicin A 2 , indicating that GtmE is another glycosyltransferase that attaches d -xylose to paromamine. These results represent in vivo evidence elucidating the complete biosynthetic pathway of the pseudotrisaccharide aminoglycoside.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0803164105
    RVK:
    TA 1000
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    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2008
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  • 5
    Online Resource
    Online Resource
    Genomic alterations in BCL2L1 and DLC1 contribute to drug sensitivity in gastric cancer
    Proceedings of the National Academy of Sciences ; 2015
    In:  Proceedings of the National Academy of Sciences Vol. 112, No. 40 ( 2015-10-06), p. 12492-12497
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 40 ( 2015-10-06), p. 12492-12497
    Abstract: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Recent high-throughput analyses of genomic alterations revealed several driver genes and altered pathways in GC. However, therapeutic applications from genomic data are limited, largely as a result of the lack of druggable molecular targets and preclinical models for drug selection. To identify new therapeutic targets for GC, we performed array comparative genomic hybridization (aCGH) of DNA from 103 patients with GC for copy number alteration (CNA) analysis, and whole-exome sequencing from 55 GCs from the same patients for mutation profiling. Pathway analysis showed recurrent alterations in the Wnt signaling [ APC , CTNNB1 , and DLC1 (deleted in liver cancer 1)], ErbB signaling ( ERBB2 , PIK3CA , and KRAS ), and p53 signaling/apoptosis [ TP53 and BCL2L1 (BCL2-like 1)] pathways. In 18.4% of GC cases (19/103), amplification of the antiapoptotic gene BCL2L1 was observed, and subsequently a BCL2L1 inhibitor was shown to markedly decrease cell viability in BCL2L1 -amplified cell lines and in similarly altered patient-derived GC xenografts, especially when combined with other chemotherapeutic agents. In 10.9% of cases (6/55), mutations in DLC1 were found and were also shown to confer a growth advantage for these cells via activation of Rho-ROCK signaling, rendering these cells more susceptible to a ROCK inhibitor. Taken together, our study implicates BCL2L1 and DLC1 as potential druggable targets for specific subsets of GC cases.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1507491112
    RVK:
    TA 1000
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    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
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  • 6
    Online Resource
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    Nanoscale imaging reveals miRNA-mediated control of functional states of dendritic spines
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 19 ( 2019-05-07), p. 9616-9621
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 19 ( 2019-05-07), p. 9616-9621
    Abstract: Dendritic spines are major loci of excitatory inputs and undergo activity-dependent structural changes that contribute to synaptic plasticity and memory formation. Despite the existence of various classification types of spines, how they arise and which molecular components trigger their structural plasticity remain elusive. microRNAs (miRNAs) have emerged as critical regulators of synapse development and plasticity via their control of gene expression. Brain-specific miR-134s likely regulate the morphological maturation of spines, but their subcellular distributions and functional impacts have rarely been assessed. Here, we exploited atomic force microscopy to visualize in situ miR-134s, which indicated that they are mainly distributed at nearby dendritic shafts and necks of spines. The abundance of miR-134s varied between morphologically and functionally distinct spine types, and their amounts were inversely correlated with their postulated maturation stages. Moreover, spines exhibited reduced contents of miR-134s when selectively stimulated with beads containing brain-derived neurotropic factor (BDNF). Taken together, in situ visualizations of miRNAs provided unprecedented insights into the “inverse synaptic-tagging” roles of miR-134s that are selective to inactive/irrelevant synapses and potentially a molecular means for modifying synaptic connectivity via structural alteration.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1819374116
    RVK:
    TA 1000
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    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
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    detail.hit.zdb_id: 1461794-8
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  • 7
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    Online Resource
    Attenuation of Aβ‐Induced Apoptosis of Plant Extract (Saengshik) Mediated by the Inhibition of Mitochondrial Dysfunction and Antioxidative Effect
    Wiley ; 2007
    In:  Annals of the New York Academy of Sciences Vol. 1095, No. 1 ( 2007-01), p. 399-411
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1095, No. 1 ( 2007-01), p. 399-411
    Abstract: Abstract :  Recently, considerable attention has been focused on dietary manipulation of oxidative and/or nitrosative damage on neuronal cells. In this article, a neuroprotective effect of plant (Saengshik) extracts was investigated. Rat pheochromocytoma (PC12), cells treated with β‐amyloid underwent apoptotic death as determined by positive in situ terminal end‐labeling (TUNEL staining), decreased mitochondrial transmembrane potential, and elevated caspase‐3 activity co‐occurring with enhanced MDA accumulation and the reduction of GSH levels. Saengshik pretreatment attenuated β‐amyloid‐induced apoptosis in PC12 cells possibly by inhibiting mitochondrial dysfunction and exerting antioxidant properties. Saengshik pretreatment inhibited the loss of mitochondrial membrane potentials and reduced the activation of caspase‐3. The in vitro antioxidant activities of Saengshik extracts were verified by the 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) method and superoxide dismutase (SOD) mimetic activity. In β‐amyloid‐challenged PC12 cells, Saengshik prevented the production of ROS, decreased the level of MDA, and elevated GSH. The potential of Saengshik as one of the neuroprotective regimens has been suggested through this article, and the combination with defined pharmaceuticals or other dietary antioxidants may provide a better therapeutic or preventive advantage for the management of Alzheimer's disease.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Article
    DOI: 10.1196/annals.1397.043
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 2007
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    detail.hit.zdb_id: 2071584-5
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  • 8
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    Online Resource
    Design of protein-binding proteins from the target structure alone
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 605, No. 7910 ( 2022-05-19), p. 551-560
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 605, No. 7910 ( 2022-05-19), p. 551-560
    Abstract: The design of proteins that bind to a specific site on the surface of a target protein using no information other than the three-dimensional structure of the target remains a challenge 1–5 . Here we describe a general solution to this problem that starts with a broad exploration of the vast space of possible binding modes to a selected region of a protein surface, and then intensifies the search in the vicinity of the most promising binding modes. We demonstrate the broad applicability of this approach through the de novo design of binding proteins to 12 diverse protein targets with different shapes and surface properties. Biophysical characterization shows that the binders, which are all smaller than 65 amino acids, are hyperstable and, following experimental optimization, bind their targets with nanomolar to picomolar affinities. We succeeded in solving crystal structures of five of the binder–target complexes, and all five closely match the corresponding computational design models. Experimental data on nearly half a million computational designs and hundreds of thousands of point mutants provide detailed feedback on the strengths and limitations of the method and of our current understanding of protein–protein interactions, and should guide improvements of both. Our approach enables the targeted design of binders to sites of interest on a wide variety of proteins for therapeutic and diagnostic applications.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-04654-9
    RVK:
    TA 1000
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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    detail.hit.zdb_id: 1413423-8
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  • 9
    Online Resource
    Online Resource
    Phase transition-induced band edge engineering of BiVO 4 to split pure water under visible light
    Proceedings of the National Academy of Sciences ; 2015
    In:  Proceedings of the National Academy of Sciences Vol. 112, No. 45 ( 2015-11-10), p. 13774-13778
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 45 ( 2015-11-10), p. 13774-13778
    Abstract: Through phase transition-induced band edge engineering by dual doping with In and Mo, a new greenish BiVO 4 (Bi 1-X In X V 1-X Mo X O 4 ) is developed that has a larger band gap energy than the usual yellow scheelite monoclinic BiVO 4 as well as a higher (more negative) conduction band than H + /H 2 potential [0 V RHE (reversible hydrogen electrode) at pH 7]. Hence, it can extract H 2 from pure water by visible light-driven overall water splitting without using any sacrificial reagents. The density functional theory calculation indicates that In 3+ /Mo 6+ dual doping triggers partial phase transformation from pure monoclinic BiVO 4 to a mixture of monoclinic BiVO 4 and tetragonal BiVO 4 , which sequentially leads to unit cell volume growth, compressive lattice strain increase, conduction band edge uplift, and band gap widening.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1509674112
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
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    detail.hit.zdb_id: 1461794-8
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  • 10
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    Roles of cell confluency and fluid shear in 3-dimensional intracellular forces in endothelial cells
    Proceedings of the National Academy of Sciences ; 2012
    In:  Proceedings of the National Academy of Sciences Vol. 109, No. 28 ( 2012-07-10), p. 11110-11115
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 109, No. 28 ( 2012-07-10), p. 11110-11115
    Abstract: We use a novel 3D inter-/intracellular force microscopy technique based on 3D traction force microscopy to measure the cell–cell junctional and intracellular tensions in subconfluent and confluent vascular endothelial cell (EC) monolayers under static and shear flow conditions. We found that z-direction cell–cell junctional tensions are higher in confluent EC monolayers than those in subconfluent ECs, which cannot be revealed in the previous 2D methods. Under static conditions, subconfluent cells are under spatially non-uniform tensions, whereas cells in confluent monolayers are under uniform tensions. The shear modulations of EC cytoskeletal remodeling, extracellular matrix (ECM) adhesions, and cell–cell junctions lead to significant changes in intracellular tensions. When a confluent monolayer is subjected to flow shear stresses with a high forward component comparable to that seen in the straight part of the arterial system, the intracellular and junction tensions preferentially increase along the flow direction over time, which may be related to the relocation of adherens junction proteins. The increases in intracellular tensions are shown to be a result of chemo-mechanical responses of the ECs under flow shear rather than a direct result of mechanical loading. In contrast, the intracellular tensions do not show a preferential orientation under oscillatory flow with a very low mean shear. These differences in the directionality and magnitude of intracellular tensions may modulate translation and transcription of ECs under different flow patterns, thus affecting their susceptibility for atherogenesis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1207326109
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2012
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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