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1.
Science ; 381(6658): 648-653, 2023 Aug 11.
Article in English | MEDLINE | ID: mdl-37561867

ABSTRACT

The efficient, large-scale generation and control of photonic modes guided by van der Waals materials remains as a challenge despite their potential for on-chip photonic circuitry. We report three-atom-thick waveguides-δ waveguides-based on wafer-scale molybdenum disulfide (MoS2) monolayers that can guide visible and near-infrared light over millimeter-scale distances with low loss and an efficient in-coupling. The extreme thinness provides a light-trapping mechanism analogous to a δ-potential well in quantum mechanics and enables the guided waves that are essentially a plane wave freely propagating along the in-plane, but confined along the out-of-plane, direction of the waveguide. We further demonstrate key functionalities essential for two-dimensional photonics, including refraction, focusing, grating, interconnection, and intensity modulation, by integrating thin-film optical components with δ waveguides using microfabricated dielectric, metal, or patterned MoS2.

2.
J Biol Chem ; 299(6): 104838, 2023 06.
Article in English | MEDLINE | ID: mdl-37209821

ABSTRACT

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease that results from mutations in NOTCH3. How mutations in NOTCH3 ultimately result in disease is not clear, although there is a predilection for mutations to alter the number of cysteines of the gene product, supporting a model in which alterations of conserved disulfide bonds of NOTCH3 drives the disease process. We have found that recombinant proteins with CADASIL NOTCH3 EGF domains 1 to 3 fused to the C terminus of Fc are distinguished from wildtype proteins by slowed mobility in nonreducing gels. We use this gel mobility shift assay to define the effects of mutations in the first three EGF-like domains of NOTCH3 in 167 unique recombinant protein constructs. This assay permits a readout on NOTCH3 protein mobility that indicates that (1) any loss of cysteine mutation in the first three EGF motifs results in structural abnormalities; (2) for loss of cysteine mutants, the mutant amino acid residue plays a minimal role; (3) the majority of changes that result in a new cysteine are poorly tolerated; (4) at residue 75, only cysteine, proline, and glycine induce structural shifts; (5) specific second mutations in conserved cysteines suppress the impact of loss of cysteine CADASIL mutations. These studies support the importance of NOTCH3 cysteines and disulfide bonds in maintaining normal protein structure. Double mutant analysis suggests that suppression of protein abnormalities can be achieved through modification of cysteine reactivity, a potential therapeutic strategy.


Subject(s)
CADASIL , Receptor, Notch3 , Humans , CADASIL/genetics , Cysteine/genetics , Cysteine/metabolism , Disulfides , Epidermal Growth Factor/genetics , Mutation , Receptor, Notch3/genetics
3.
Nat Commun ; 13(1): 7826, 2022 Dec 19.
Article in English | MEDLINE | ID: mdl-36535920

ABSTRACT

Twisted 2D materials form complex moiré structures that spontaneously reduce symmetry through picoscale deformation within a mesoscale lattice. We show twisted 2D materials contain a torsional displacement field comprised of three transverse periodic lattice distortions (PLD). The torsional PLD amplitude provides a single order parameter that concisely describes the structural complexity of twisted bilayer moirés. Moreover, the structure and amplitude of a torsional periodic lattice distortion is quantifiable using rudimentary electron diffraction methods sensitive to reciprocal space. In twisted bilayer graphene, the torsional PLD begins to form at angles below 3.89° and the amplitude reaches 8 pm around the magic angle of 1. 1°. At extremely low twist angles (e.g. below 0.25°) the amplitude increases and additional PLD harmonics arise to expand Bernal stacked domains separated by well defined solitonic boundaries. The torsional distortion field in twisted bilayer graphene is analytically described and has an upper bound of 22.6 pm. Similar torsional distortions are observed in twisted WS2, CrI3, and WSe2/MoSe2.

4.
Nano Lett ; 22(17): 7180-7186, 2022 Sep 14.
Article in English | MEDLINE | ID: mdl-36047815

ABSTRACT

Movement of a three-dimensional solid at an air-water interface is strongly influenced by the extrinsic interactions between the solid and the water. The finite thickness and volume of a moving solid causes capillary interactions and water-induced drag. In this Letter, we report the fabrication and dynamical imaging of freely floating MoS2 solids on water, which minimizes such extrinsic effects. For this, we delaminate a synthesized wafer-scale monolayer MoS2 onto a water surface, which shows negligible height difference across water and MoS2. Subsequently patterning by a laser generates arbitrarily shaped MoS2 with negligible in-plane strain. We introduce photoswitchable surfactants to exert a lateral force to floating MoS2 with a spatiotemporal control. Using this platform, we demonstrate a variety of two-dimensional mechanical systems that show reversible shape changes. Our experiment provides a versatile approach for designing and controlling a large array of atomically thin solids on water for intrinsically two-dimensional dynamics and mechanics.

6.
Nat Nanotechnol ; 17(4): 361-366, 2022 04.
Article in English | MEDLINE | ID: mdl-35075299

ABSTRACT

Van der Waals (vdW) solids can be engineered with atomically precise vertical composition through the assembly of layered two-dimensional materials1,2. However, the artisanal assembly of structures from micromechanically exfoliated flakes3,4 is not compatible with scalable and rapid manufacturing. Further engineering of vdW solids requires precisely designed and controlled composition over all three spatial dimensions and interlayer rotation. Here, we report a robotic four-dimensional pixel assembly method for manufacturing vdW solids with unprecedented speed, deliberate design, large area and angle control. We used the robotic assembly of prepatterned 'pixels' made from atomically thin two-dimensional components. Wafer-scale two-dimensional material films were grown, patterned through a clean, contact-free process and assembled using engineered adhesive stamps actuated by a high-vacuum robot. We fabricated vdW solids with up to 80 individual layers, consisting of 100 × 100 µm2 areas with predesigned patterned shapes, laterally/vertically programmed composition and controlled interlayer angle. This enabled efficient optical spectroscopic assays of the vdW solids, revealing new excitonic and absorbance layer dependencies in MoS2. Furthermore, we fabricated twisted N-layer assemblies, where we observed atomic reconstruction of twisted four-layer WS2 at high interlayer twist angles of ≥4°. Our method enables the rapid manufacturing of atomically resolved quantum materials, which could help realize the full potential of vdW heterostructures as a platform for novel physics2,5,6 and advanced electronic technologies7,8.


Subject(s)
Robotic Surgical Procedures , Robotics , Electronics
7.
J Org Chem ; 85(13): 8339-8351, 2020 07 02.
Article in English | MEDLINE | ID: mdl-32462862

ABSTRACT

An efficient general methodology for the synthesis of 4-quinolinyl ethers is demonstrated via a highly reactive SNAr reaction of 4-quinolinyl sulfones with a range of structurally diversified 1°, 2°, and 3° alcohols with a wide substrate scope and high yields. By adapting this methodology, a convergent synthesis of a complex target of HCV NS3/4a protease inhibitor BI 201420 was accomplished.


Subject(s)
Hepatitis C , Viral Nonstructural Proteins , Antiviral Agents , Ethers , Hepacivirus , Humans , Protease Inhibitors/pharmacology , Sulfones
8.
Cell Discov ; 2: 16008, 2016.
Article in English | MEDLINE | ID: mdl-27462455

ABSTRACT

Mixed lineage leukemia protein-1 (MLL1) has a critical role in human MLL1 rearranged leukemia (MLLr) and is a validated therapeutic target. However, its role in regulating global gene expression in MLLr cells, as well as its interplay with MLL1 fusion proteins remains unclear. Here we show that despite shared DNA-binding and cofactor interacting domains at the N terminus, MLL1 and MLL-AF9 are recruited to distinct chromatin regions and have divergent functions in regulating the leukemic transcription program. We demonstrate that MLL1, probably through C-terminal interaction with WDR5, is recruited to regulatory enhancers that are enriched for binding sites of E-twenty-six (ETS) family transcription factors, whereas MLL-AF9 binds to chromatin regions that have no H3K4me1 enrichment. Transcriptome-wide changes induced by different small molecule inhibitors also highlight the distinct functions of MLL1 and MLL-AF9. Taken together, our studies provide novel insights on how MLL1 and MLL fusion proteins contribute to leukemic gene expression, which have implications for developing effective therapies in the future.

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