Abstract: The present application is directed to a therapeutically useful compound, comprised of two monomers that are linked to each other through two or more reversible covalent bonds. Each monomer is a polyfunctionalized molecule comprising a bioorthogonal linker element and ligand or pharmacophore, wherein the linker and ligand/pharmacophore are covalently coupled to each other either directly or through an optional connector moiety.

Abstract: The present application is directed to a therapeutically useful monomer comprising a linker element and an E3 ubiquitin ligase binding moiety. The linker and the E3 ubiquitin ligase binding moiety are covalently coupled to each other either directly or through an optional connector moiety.

Abstract: The present invention relates to methods for identifying and/or quantifying low abundance, nucleotide base mutations, insertions, deletions, translocations, splice variants, miRNA variants, alternative transcripts, alternative start sites, alternative coding sequences, alternative non-coding sequences, alternative splicings, exon insertions, exon deletions, intron insertions, or other rearrangement at the genome level and/or methylated or hydroxymethylated nucleotide bases, as well as markers to identify early cancer, monitor cancer treatment, and identify early cancer recurrence.

Abstract: The present invention relates to methods for identifying and/or quantifying low abundance, nucleotide base mutations, insertions, deletions, translocations, splice variants, miRNA variants, alternative transcripts, alternative start sites, alternative coding sequences, alternative non-coding sequences, alternative splicings, exon insertions, exon deletions, intron insertions, or other rearrangement at the genome level and/or methylated nucleotide bases.

Abstract: Described herein are silyl monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. Such multimer forming associations of monomers may be promoted by the proximal binding of the monomers to their target biomolecule(s). In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

Abstract: Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

Abstract: Described herein are silyl monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. Such multimer forming associations of monomers may be promoted by the proximal binding of the monomers to their target biomolecule(s). In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

Abstract: Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

Abstract: The present invention is directed to method of using a collection of monomers capable of forming multimers as a fluorescence reporter in different applications such as ligand detection/screening, disease diagnosis, drug discovery or screening, fluorescent labeling and imaging, or other fluorescent methodologies. Each monomer in the collection includes one or more ligand elements useful for binding to a target molecule with a dissociation constant of less than 300 ?M and a linker element connected to the ligand elements directly or indirectly through a connector. Association of linker elements of different combinations of monomers, with their ligand elements bound to the target molecule to form a multimer, will generate a unique fluorescent signature different from that produced by those monomers either alone or in association with each other in the absence of the target molecule, when subjected to electromagnetic excitement.

Abstract: Described herein are silyl monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. Such multimer forming associations of monomers may be promoted by the proximal binding of the monomers to their target biomolecule(s). In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

Abstract: Closures for containers and methods for using same are provided. In a general embodiment/the present disclosure provides a closure having a top portion (12), a bottom portion (14) and a side portion (16), an aperture (18) extending though the closure, a projection (20) extending from the closure and at least two rib members (36) on an interior of the projection. The projection may also include a cover (22). In another embodiment, a method for using a closure includes inserting a. spike member into a projection, piercing a membrane that hermetically seals a medical container, pushing rib members within the projection to center the spike member inserted into the projection, and tearing the membrane to create a vent hole in the membrane.