Abstract: Tricyclic cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway for therapeutic applications are described.

Abstract: Compounds of Formula I, Formula II, and Formula III and the pharmaceutically acceptable salts thereof are disclosed. The variables X, a, b, c, d, R1-4, R10-15 and R17-22 are disclosed herein. The compounds are useful for treating cancer disorders, especially those involving M2 phenotype of macrophages. Pharmaceutical compositions containing compounds of Formula I or Formula II or Formula III and methods of treatment comprising administering compounds of Formula I and Formula II and Formula III are also disclosed.

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 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: 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: 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 method for implementing a targeted medical outputs is disclosed. The method may comprise: receiving first user data associated with a user from an external server; receiving second user data associated with the user from an internal server; processing the first user data and the second user data at a data fabric structure to generate domains; receiving the domains as an input at a machine learning model trained to generate a machine learning output; receiving at a database cube the machine learning output; performing one or more database cube processing operations on the machine learning output to generate a database cube output; transmitting the database cube output to one or more outputs, identified based on the one or more markers.

Abstract: A method includes: initializing a list of token embeddings, each of the token embeddings corresponding to a tokenized word from text in a corpus of text; generating a graph for a group of consecutive words s from the text, said graph including binary relations between pairs of tokenized words of the group of consecutive words; selecting the token embeddings representing the words of the group of consecutive words from the list of token embeddings; computing a tensor of binary relations as the product between a matrix of the selected token embeddings and a tensor representing discourse relations, the computed tensor representing the binary relations between the pairs of tokenized words; computing a loss using the computed tensor; optimizing the list of token embeddings using the computed loss. The above may be repeated until the computed loss is within a predetermined range.

Abstract: Pharmaceutical Degraders and Degrons for use in therapeutic applications are described herein.

Abstract: An enzyme responsive shape memory polymer formed from a glassy, cross-linked shape memory polymer that incorporates ester bonds that are responsive to the present of an enzyme. PCL-based polyurethanes (featuring simple alternation of PCL diol and lysine-based diisocyanate) are degradable by Amano lipase PS. A non-degradable thermoplastic elastomer may be dual electrospun with a polycaprolactone based TPU with the fixing phase compressed so that the composite is ready for enzymatically triggered contraction. Alternatively, the elastomer may be a PCL copolymer-based polyurethane amorphous elastomer that is both degradable and elastomeric and put into compression so that upon enzymatic degradation of the elastomeric phase the scaffold expands.

Abstract: This invention provides pharmaceutical protein degraders and E3 ubiquitin ligase binders for therapeutic applications as described further herein.

Abstract: This invention provides amine-linked C3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, 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: A computer-implemented method for implementing a data fabric structure is disclosed. The method may comprise: receiving user data associated with a user from an external server via a secure network connection; storing the user data on a cloud-based data lake; transmitting the user data to a staging table; adding, to the staging table, user identification data and metadata; modifying the user data based on a determined correlation between the user data, the user identification data, and metadata to generate modified user data; comparing the modified user data and prior user data to determine a difference; upon determining the difference does not exceed a threshold, extracting, using a trained machine learning model, relevant data from the modified user data; formatting the relevant data into atomic data; generating a plurality of domains based on the atomic data, and presenting via a graphical user interface, graphical depictions of the plurality of domains.

Abstract: A method for outputting new target populations for system initiation using a first machine learning model and a second machine learning model, the method comprising: receiving, user data; storing the user data; identifying a target population based on the user data to select groups of individuals not currently serviced by a specific provider; identifying a population criteria for the target population; applying a population criteria to target population user data of the target population; determining that the population criteria for the target population is above a first threshold population criteria; receiving initiated population data for an initiated population; and determining that the system initiation meets an improvement threshold probability to improve the population criteria by a second threshold amount.

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: A braille cell and associated braille pin support and pin actuation assemblies are disclosed. The braille cell can include a frame, braille pins movable up and down between raised and lowered positions, and a pin actuation assembly to individually move the pins. The braille cell can include support arms, each of which having a base end connected to the frame and a pin end connected to and following a motion of a respective pin between its raised and lowered positions. The pin actuation assembly can include pin actuation units, each having a motor with a rotatable motor shaft and multiple cams mounted on the shaft, each for selectively actuating a respective pin. Each pin actuation unit can also include an angular position sensing system for monitoring, for example magnetically, a passage of the shaft through a reference angular position, and deriving information about a current angular position of the shaft.

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: A heat exchanger comprising a plurality of A channels in a heat exchanger matrix running in a first direction wherein each A channel is formed along its length as a waveform with an identical wavelength, channel width, wave angle, and wall thickness. Adjacent A channels running in an orthogonal direction are 180 degrees out of phase. The plurality of A channels form the plurality of B channels running in a cross-flow direction with the outer walls of the A channels. The B channels exist as the negative space between adjacent 180 degree out of phase A channels.

Abstract: Pharmaceutical Degraders and Degrons for use in therapeutic applications are described herein.