Abstract: This disclosure relates to compounds of Formula (A): Formula (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; Formula (I) in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.

Abstract: An electronic data document (EDD) and related system and method for use in a computerized clinical trial verification system is provided. In an exemplary embodiment, the EDD is authenticated by the creator and validated by the receiver, and comprises an image of a source document (SD) that comprises a masked record of at least one interaction between a clinical trial investigator and a patient enrolled in a clinical trial, at least one revealed portion of the SD that includes evidence relevant to at least one question in a clinical trial questionnaire, and at least one annotation connecting the revealed portion to the at least one question. A computerized system and method for allowing a clinical trial investigator to answer questions from a clinical trial questionnaire pertinent to a clinical trial of a medical treatment using encrypted and partially masked electronic documents comprising images of original patient records is provided.

Abstract: This invention provides Degronimers that have E3 Ubiquitin Ligase targeting moieties (Degrons) that can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation. The invention also provides Degrons that can be used to treat disorders mediated by cereblon or an Ikaros family protein, and methods of use and compositions thereof as well as methods for their preparation.

Abstract: This invention provides Degronimers that have carbon-linked E3 Ubiquitin Ligase targeting moieties (Degrons), which can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation.

Abstract: An advantageous morphic form of Compound 1 which is also known as CFT7455 and is (S)-3-(6-(4-(morpholinomethyl)benzyl)-2-oxobenzo[cd]indol-1(2H)-yl)piperidine-2,6-dione and methods to prepare Compound 1 for therapeutic applications are provided. This invention also provides new dosage regimens for administering Compound 1.

Abstract: A device may identify a plurality of sources for outputs that the device is configured to provide. The plurality of sources may include at least one of a particular application in the device, an operating system of the device, a particular area within a display of the device, or a particular graphical user interface object. The device may also assign a set of distinct voices to respective sources of the plurality of sources. The device may also receive a request for speech output. The device may also select a particular source that is associated with the requested speech output. The device may also generate speech having particular voice characteristics of a particular voice assigned to the particular source.

Abstract: Provided herein are compounds, compositions, and methods useful for degrading protein tyrosine phosphatase, e.g., protein tyrosine phosphatase non-receptor type 2 (PTPN2) and/or protein tyrosine phosphatase non-receptor type 1 (PTPN1), and for treating related diseases favorably responsive to PTPN1 or PTPN2 inhibitor treatment, e.g., a cancer 5 or a metabolic disease.

Abstract: This disclosure relates to compounds of Formula (A): IRAK-L-DSM (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.

Abstract: This invention provides heterocyclic compounds that bind to E3 Ubiquitin Ligase (typically through cereblon) (“Degrons”), which can be used as is or linked to a Targeting Ligand for a selected Target Protein for therapeutic purposes and methods of use and compositions thereof as well as methods for their preparation.

Abstract: A fuel nozzle apparatus includes: an outer body having an exterior surface and a plurality of openings in the exterior surface. An inner body is disposed inside the outer body, cooperating with the outer body to define an annular space. A main injection ring is disposed in the annular space and includes an array of fuel posts extending outward therefrom, each fuel post including a perimeter wall defining a lateral surface and a recessed floor. Each fuel post is aligned with one of the openings and separated from the opening by a perimeter gap defined between the opening and the lateral surface. A main fuel gallery extends within the main injection ring. The main injection ring includes plurality of main fuel orifices, each main fuel orifice communicating with the main fuel gallery and extending through one of the fuel posts.

Abstract: This invention provides compounds that have spirocyclic E3 Ubiquitin Ligase targeting moieties (Degrons), which can be used as is or linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation.

Abstract: This invention provides amine-linked C3-glutarimide Degronimers for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation, wherein the C3-glutarimide Degronimers have the formula:

Abstract: A backwater flow detection device for detecting backwater flow between a building and a sewer conduit using air pressure detection in air pockets in the sewer conduit. The backwater flood detection device detects backwater flow events including backflow events from a sewer line as well as wastewater blockage events that can result in wastewater backflow into a building. The water detection sensor allows the homeowner or building manager to be warned when there is an issue with backwater flow in or near the building, and also with the backwater valve.

Abstract: Heat exchanger assemblies including turning vanes are taught herein. In preferred embodiments, the heat exchanger assembly comprises: an inlet duct; a heat exchanger coupled to the inlet duct and a plurality of turning vanes coupled to the heat exchanger and protruding into the inlet duct. The intake plane of the heat exchanger is at an angle between 0 degrees and 90 degrees to the primary flow direction of the inlet duct. The plurality of turning vanes comprise: a straight leading edge of length L that is parallel to the primary flow direction of the inlet duct; a convex lower surface that transitions a bottom of the leading edge to an upper wall of a lower channel of the heat exchanger; and a concave upper surface that transitions a distal point of the turning vane to a second channel of the heat exchanger.

Abstract: This invention provides Degronimers that have carbon-linked E3 Ubiquitin Ligase targeting moieties (Degrons), which can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation.

Abstract: A device may identify a plurality of sources for outputs that the device is configured to provide. The plurality of sources may include at least one of a particular application in the device, an operating system of the device, a particular area within a display of the device, or a particular graphical user interface object. The device may also assign a set of distinct voices to respective sources of the plurality of sources. The device may also receive a request for speech output. The device may also select a particular source that is associated with the requested speech output. The device may also generate speech having particular voice characteristics of a particular voice assigned to the particular source.

Abstract: The invention provides tricyclic compounds that degrade neosubstrates for use in the treatment of disorders described herein, including, for example, abnormal cellular proliferation, neurodegenerative diseases, and autoimmune diseases.

Abstract: The present invention provides an electronic data document (EDD) and related system and method for use in a computerized clinical trial verification system. In an exemplary embodiment, the EDD is authenticated by the creator and validated by the receiver, and comprises an image of a source document (SD) that comprises a masked record of at least one interaction between a clinical trial investigator and a patient enrolled in a clinical trial, at least one revealed portion of the SD that includes evidence relevant to at least one question in a clinical trial questionnaire, and at least one annotation connecting the revealed portion to the at least one question. The present invention provides a computerized system and method for allowing a clinical trial investigator to answer questions from a clinical trial questionnaire pertinent to a clinical trial of a medical treatment using encrypted and partially masked electronic documents comprising images of original patient records.

Abstract: A system for growing plants and monitoring the growth of plants, comprising a gardening system and a server. The gardening system comprises a frame that defines a housing for receiving a tray of plants. The gardening system also has a lighting subsystem and watering subsystem to provide light and water to the plants. Sensors and cameras of the gardening system may capture data corresponding to the conditions of the gardening system and health of the plant. Based on the captured data, the server may use machine learning to determine optimal plant growing thresholds, and may send a control command to a controller of the gardening system to change one or more conditions of the gardening system. The plants grown by the system may be nutritious, and the bioavailability of the nutrients of the plants may be increased.

Abstract: Heterobifunctional compounds for targeted protein degradation that include a tricyclic cereblon binder linked to an appropriate protein targeting ligand to degrade a targeted disease-mediating protein of interest are provided.