Abstract: The invention imparts new properties to nucleic acid aptamers, which may enhance its function as therapeutic drugs or the like. Also provided is a covalent drug having the new properties as an anti-SARS-COV-2 drug. Specifically, an aptamer-based multiwarhead covalent drug having multiple covalent binding warheads is provided. In particular, an aptamer-based multiwarhead covalent drug targeting SARS-COV-2 is provided. A pharmaceutical composition comprising the multiwarhead nucleic acid aptamer and a method of producing the multiwarhead nucleic acid aptamer are also provided.

Abstract: Provided is a novel drug modality which at least partially overcomes the shortcomings of the conventional covalent drugs. A neutralizable covalent drug compound comprising a nucleic acid aptamer and a fluorosulfonyl group linked to the nucleic acid aptamer via a linker is provided. A composition comprising the compound and a method of producing the compound are also provided. Also provided is a neutralizable covalent drug system, comprising the compound or the composition and an oligonucleotide complementary to the nucleic acid aptamer.

Abstract: A method (of manufacturing a semiconductor device) includes, for a layout diagram stored on a non-transitory computer-readable medium, the semiconductor device being based on the layout diagram, the layout diagram including a first level of metallization (M_1st level) and a first level of interconnection (VIA_1st level) thereover corresponding to a first layer of metallization and a first layer of interconnection thereover in the semiconductor device, generating the layout diagram including: selecting a candidate pattern in the layout diagram, the candidate pattern being a first conductive pattern in the M_1st level (first M_1st pattern); determining that the candidate pattern satisfies one or more criteria; and increasing a size of the candidate pattern thereby revising the layout diagram.

Abstract: A method (of manufacturing a semiconductor device) includes, for a layout diagram stored on a non-transitory computer-readable medium, the semiconductor device being based on the layout diagram, the layout diagram including a first level of metallization (M_1st level) and a first level of interconnection (VIA_1st level) thereover corresponding to a first layer of metallization and a first layer of interconnection thereover in the semiconductor device, generating the layout diagram including: selecting a candidate pattern in the layout diagram, the candidate pattern being a first conductive pattern in the M_1st level (first M_1st pattern); determining that the candidate pattern satisfies one or more criteria; and increasing a size of the candidate pattern thereby revising the layout diagram.

Abstract: A method (of manufacturing a semiconductor device) includes, for a layout diagram stored on a non-transitory computer-readable medium, generating the layout diagram including: selecting a candidate pattern in the layout diagram, the candidate pattern being a first conductive pattern in the M_2nd level (first M_2nd pattern) or a first conductive pattern in the M_1st level (first M_1st pattern); determining that the candidate pattern satisfies one or more criteria; and changing a size of the candidate pattern thereby revising the layout diagram.

Abstract: A method (of manufacturing a semiconductor device) includes, for a layout diagram stored on a non-transitory computer-readable medium, generating the layout diagram including: selecting a candidate pattern in the layout diagram, the candidate pattern being a first conductive pattern in the M_2nd level (first M_2nd pattern) or a first conductive pattern in the M_1st level (first M_1st pattern); determining that the candidate pattern satisfies one or more criteria; and changing a size of the candidate pattern thereby revising the layout diagram.

Abstract: A replacement heart valve implant may include an expandable anchor member actuatable between a delivery configuration and a deployed configuration, a plurality of locking mechanisms configured to maintain the expandable anchor member in the deployed configuration, one or more valve leaflets attached to each of the plurality of locking mechanisms, and at least one polymeric laminate corresponding to each locking mechanism, each of the at least one polymeric laminate sized and configured for mounting between a first portion of the corresponding locking mechanism and the expandable anchor member.

Abstract: Aspects of the present invention include methods and compositions related to the production and use of clonal lineages of embryonic progenitor cell lines derived from differentiating cultures of primordial stem cells. In particular, said methods and compositions relate to methods of differentiating cells in the presence of agents that inhibit the signaling of the TGF beta family members of growth factors and the applications of said cell lines in the treatment of diseases such as degenerative muscle disorders, cancer, and vascular disease.

Abstract: A laminating machine configured to apply a film to a media. The laminating machine includes a first roller and a second roller. The first and second rollers together define an in-feed nip point where the first and second rollers contact each other. An in-feed location is defined as a point on the first roller where coupled media and film first contacts the first roller. An in-feed angle is defined as the angle between a line that extends from the center of the first roller to the in-feed location and a line that extends from the center of the first roller to the in-feed nip point, and the in-feed angle is greater than about 10 degrees.

Abstract: A laminating machine configured to apply a film to a media. The laminating machine includes a pair of first rollers that define an in-feed nip, and a pair of second rollers that define an out-feed nip. The laminating machine further includes a threading member movable from the in-feed nip toward the out-feed nip, and wherein the threading member is configured to engage the film.

Abstract: A segmented-mirror vertical cavity surface emitting laser includes an active portion with an active region having at least one quantum well and a lateral dimension. A first mirror stack is positioned on a first opposed major surface of the active portion and extends laterally beyond the lateral dimension of the active region. A second mirror stack is positioned on the opposed major surface and extends laterally beyond the lateral dimension of the active region. The second mirror stack is segmented into two or more zones. In the case where there are two zones, in the first zone there would be a first reflectivity and a first thermal impedance, and in the second zone there would be a second reflectivity lower than the first reflectivity and a second thermal impedance lower than the first thermal impedance.