Abstract: Extracellular protein degraders and compositions are provided that have a potent asialoglycoprotein receptor (ASGPR) Binding Ligand bound to an Extracellular Protein Targeting Ligand for the selective degradation of the Target Extracellular Protein, for example immunoglobulin in vivo to treat disorders mediated by the extracellular protein.

Abstract: Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

Abstract: Heteroaryl sulfonyl compounds and compositions that have a KRAS Recognition Moiety bound to an electrophile for the selective covalent modification of KRAS, for example a mutant KRAS, to treat KRAS-mediated disorders are described.

Abstract: Heteroaryl sulfonyl compounds and compositions that have a CDK2 Recognition Moiety bound to an electrophile for the selective covalent modification of CDK2 to treat CDK2-mediated disorders are described.

Abstract: Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

Abstract: Provided herein are methods, oligonucleotides, and compositions for modulating levels of at least one target protein in a cell, e.g., by reducing levels of the mRNA of the target protein or inhibiting translation of the mRNA. In some embodiments, the target protein can be the ubiquitin ligase polypeptide, including, but not limited to WWP1, WWP2, and NEDD4. Also provided herein are methods, oligonucleotides, and compositions for treating, ameliorating, delaying or reducing a symptom of a cancer. The present disclosure also relates to compounds, methods and compositions for modulating at least one target protein selected from ubiquitin protein ligase. Also provided herein are compounds, methods, and compositions for treating, ameliorating, delaying or reducing a symptom of a cancer or a viral infection. In particular, the present disclosure is directed to specific small-molecule modulators of HECT domain E3 ligases that are useful in the therapy and diagnosis of cancer and viral infection.

Abstract: Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

Abstract: The invention provides substituted imidazole carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat a medical disorder, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.

Abstract: The invention provides substituted, saturated and unsaturated N-heterocyclic carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.

Abstract: The invention provides substituted benzimidazole carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat a medical disorder, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.

Abstract: Methods and apparatus automatically classify intravascular plaque using features extracted from intravascular optical coherence tomography (IVOCT) imagery. One example apparatus includes an image acquisition circuit that accesses a set of IVOCT images, a pre-processing circuit that generates a blood vessel mask based on the IVOCT images, a feature extraction circuit that defines a three dimensional (3D) volume of interest centered on a location in a member of the set of IVOCT images, a classification circuit that generates a classification based on a probability that a voxel represents a type of plaque, and a visualization circuit that provides a visualization, substantially in real time, of a member of the set of IVOCT images and the classification, where the visualization includes a sector classification image, a labeled image, or a 3D visualization. A prognosis or treatment plan may be provided based on the visualization or the classification.

Abstract: This disclosure provides systems and methods to automatically classify stent struts as covered or uncovered and to measure the thickness of tissue coverage. As one example, the method includes storing three-dimensional image data acquired intravascularly via an optical coherence tomography (OCT) apparatus and detecting struts based on analysis of the image data. Image data corresponding to each of the detected struts is further analyzed automatically to compute an indication of tissue coverage for the stent.

Abstract: Methods and apparatus automatically classify intravascular plaque using features extracted from intravascular optical coherence tomography (IVOCT) imagery. One example apparatus includes an image acquisition circuit that accesses a set of IVOCT images, a pre-processing circuit that generates a blood vessel mask based on the IVOCT images, a feature extraction circuit that defines a three dimensional (3D) volume of interest centered on a location in a member of the set of IVOCT images, a classification circuit that generates a classification based on a probability that a voxel represents a type of plaque, and a visualization circuit that provides a visualization, substantially in real time, of a member of the set of IVOCT images and the classification, where the visualization includes a sector classification image, a labeled image, or a 3D visualization. A prognosis or treatment plan may be provided based on the visualization or the classification.

Abstract: This disclosure provides systems and methods to automatically classify stent struts as covered or uncovered and to measure the thickness of tissue coverage. As one example, the method includes storing three-dimensional image data acquired intravascularly via an optical coherence tomography (OCT) apparatus and detecting struts based on analysis of the image data. Image data corresponding to each of the detected struts is further analyzed automatically to compute an indication of tissue coverage for the stent.

Abstract: Architecture for generating responses to search engine queries. Question/answer pairs are used to provide a predefined question hierarchy to facilitate a search. Informative terms and one or more questions are associated with each question node of the hierarchy. A question posed is mapped into the hierarchy to the most similar question class node, as determined by passages of the question and/or comparing the informative terms of the question and the question/answer node. Weighted informative terms associated with that node are then returned, and can be used by an automatic question answering system to more effectively find an answer to a question.

Abstract: The invention features contacting (in vitro or in vivo) a receptor-binding ligand with an organic molecule, which can be a small molecule (i.e., an organic molecule that is not a peptide), or a peptide that noncovalently binds to the ligand and either another ligand for the receptor (either a second copy of the first ligand, or a second, different ligand), the receptor itself, or both. Exemplary ligand/receptor pairs include FGF-2/FGF-R1 and EPO/EPO-R. The invention further features pharmaceutical compositions and methods of using such compositions for treating various medical conditions.

Abstract: The invention is directed to methods of inhibiting the rate at which superoxide dismutse-1 (SOD) aggregates using compounds that stabilize SOD dimers. The methods are useful in the study and therapy of amyotrophic lateral sclerosis. The invention also includes assays that can be used to identify compounds that stabilize dimers and SOD molecules that have been modified for use in these assays.

Abstract: Architecture for generating responses to search engine queries. Question/answer pairs are used to provide a predefined question hierarchy to facilitate a search. Informative terms and one or more questions are associated with each question node of the hierarchy. A question posed is mapped into the hierarchy to the most similar question class node, as determined by passages of the question and/or comparing the informative terms of the question and the question/answer node. Weighted informative terms associated with that node are then returned, and can be used by an automatic question answering system to more effectively find an answer to a question.