Abstract: The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.

Abstract: Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human beta-2 microglobulin gene. The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified T cells having reduced cell-surface expression of beta-2 microglobulin.

Abstract: The present disclosure provides novel co-stimulatory domains useful in genetically-modified cells to promote cell proliferation and/or promote cytokine secretion after antigen recognition. For example, disclosed herein are genetically-modified cells comprising a chimeric antigen receptor or an inducible regulatory construct incorporating the co-stimulatory domains disclosed herein. Also disclosed herein are plasmids and viral vectors comprising a nucleic acid sequence encoding the co-stimulatory domains, and methods of administering compositions comprising the novel co-stimulatory domains to subjects in order to reduce the symptoms, progression, or occurrence of disease, such as cancer.

Abstract: The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.

Abstract: The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.

Abstract: An apparatus is provided, where the apparatus includes a plurality of components; a first circuitry to generate a clock signal, and to supply the clock signal to the plurality of components; a second circuitry to estimate, for each of two or more components of the plurality of components, a corresponding duty cycle of the clock signal received at the corresponding component, wherein two or more duty cycles corresponding to the two or more components are determined; a third circuitry to determine an average of the two or more duty cycles; and a fourth circuitry to correct a duty cycle of the clock signal generated by the first circuitry, based at least in part on the average.

Abstract: A single sign-on facility providing access across multiple application instances is described. The facility receives sign-in data from a user that includes a sign-in name and password. The facility generates a modified sign-in name by adding information identifying a particular application instance to the received sign-in name. The facility then acts on behalf of the user based upon the generated modified sign-in name and the received password.

Abstract: The present invention encompasses methods for reducing the number of target cells in a subject, such as cancer cells. The methods include administration of genetically-modified human immune cells expressing a chimeric antigen receptor or exogenous T cell receptor, which have specificity for an antigen on the target cells Administration of the genetically-modified immune cells can be preceded by the administration of a lymphodepletion region and/or an immunosuppression regimen, to improve efficacy of the therapy and persistence of the cells in vivo.

Abstract: A customer order prediction system can include a computing device configured to obtain customer order data characterizing a customer’s interaction with an electronic marketplace and to obtain environmental data characterizing at least one event expected to effect the customer’s ordering behavior. The computing device can be further configured to generate feature data based on the customer data and the environmental data wherein the feature data organizes the customer data and the environmental data based on characteristics of an order size estimation model. The computing device is also configured to determine a predicted customer order size using the order size estimation model and to adjust a delivery availability of the electronic marketplace based on the predicted order size.

Abstract: A woven fabric seam area is provided including a top surface and a bottom surface, with the woven fabric being formed of warp yarns interwoven with weft yarns in a repeating pattern, and either the warp yarns or the weft yarns are formed at least in part of a laser energy absorbent material. Within the fabric seam area yarns formed of laser energy transparent material can be bonded to yarns being formed at least in part of a laser energy absorbent material by laser welds in order to maintain or achieve a desired flexibility and/or shear resistance of the fabric. A method of forming such a fabric seam area is also provided.

Abstract: An approach generates a speed profile for one or more delivery locations. The speed profile corresponds to location data of a delivery order for a respective delivery location, and indicates a plurality of events associated with a movement of a delivery order to the respective delivery location. The approach generates, based on the speed profile and location data corresponding to the delivery order, feature data of the respective delivery location. The approach applies a machine learning model to the generated feature data to output a door-step time prediction for the respective delivery location. The door-step time prediction is based on a time difference between timestamps of two events of the plurality of events associated with the movement of the delivery order. The approach generates a planned delivery route for the one or more delivery locations, based on the one or more delivery locations and respective the door-step time predictions.

Abstract: Techniques are disclosed for advantageously forecasting an inventory of a product having a particular duration (e.g., video content). The technique can include determining the particular configuration (e.g., maximum number of impressions, maximum amount of time permitted) of breaks identified within an impression log. Based on the number of breaks and the configurations of the breaks, the technique can forecast a future inventory of the product. In some implementations, the disclosed technique can identify an amount of a previous break that was not filled with video content. These forecasts can enable product sellers to better communicate with their customers, negotiate supply contracts, price their products, plan for business operations, etc.

Abstract: Aspects of the subject disclosure may include, for example, receiving a request to forecast allocations for a new descriptor, the new descriptor differing from preexisting descriptors, each of the preexisting descriptors being associated with a subset of locations of a network of locations, each location corresponding to an electronic segment in electronic canvases, and the new descriptor being associated with a new subset of locations of the network of locations, identifying one or more affected descriptors having one or more overlapping subsets of locations of the network of locations and one or more non-overlapping subsets of locations of the network of locations, determining a forecast of allocated locations in each of the one or more affected descriptors; identifying, according to the forecast, at least a portion of allocated locations in the one or more overlapping subsets of locations that are displaceable resulting in a number of displaceable allocations, and determining, according to the number of di

Abstract: The present invention encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, using particular lymphodepletion regimens in combination with particular populations of chimeric antigen receptor T cells expressing anti CD19 CAR PBCAR0191, anti CD20 CAR PBCAR20A or anti BCMA CAR PBCAR269A.

Abstract: Provided herein are compositions and methods for the treatment of a disease, such as cancer, using a chimeric antigen receptor or genetically-modified cells comprising a chimeric antigen receptor having specificity for CD20. The invention provides polynucleotides encoding such chimeric antigen receptors, and genetically-modified cells comprising such chimeric antigen receptors. Also provided are methods for making such genetically-modified cells and pharmaceutical compositions comprising the same. The invention further provides methods for treating a disease (e.g., cancer) in a subject by administering such genetically-modified cells or compositions. The main embodiments concern CARs with an scFv specific for CD20, the hinge and transmembrane domains from CD8, the costimulatory cytoplasmic or signalling domain from co-stimulatory molecules Novell (N1) or Novel6 (N6) and the CD3zeta intracellular signaling domain.

Abstract: Aspects of the subject disclosure may include, for example, receiving a request to forecast allocations for a new descriptor, the new descriptor differing from preexisting descriptors, each of the preexisting descriptors being associated with a subset of locations of a network of locations, each location corresponding to an electronic segment in electronic canvases, and the new descriptor being associated with a new subset of locations of the network of locations, identifying one or more affected descriptors having one or more overlapping subsets of locations of the network of locations and one or more non-overlapping subsets of locations of the network of locations, determining a forecast of allocated locations in each of the one or more affected descriptors; identifying, according to the forecast, at least a portion of allocated locations in the one or more overlapping subsets of locations that are displaceable resulting in a number of displaceable allocations, and determining, according to the number of di

Abstract: The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.

Abstract: The present invention provides compositions and methods for inducing antigen-specific tolerance in a subject. In one embodiment, the present invention provides a composition comprising an apoptotic body and an epitope of an antigen. Also provided herein are methods of preparing and administering the composition. The composition and methods provided herein can induce antigen-specific tolerance in a subject.

Abstract: The present disclosure provides nucleic acid molecules encoding an engineered antigen receptor, such as a chimeric antigen receptor or exogenous T cell receptor, and an inhibitory nucleic acid molecule, such as an RNA interference molecule. The present disclosure further relates to nucleic acids, DNA constructs, vectors, pharmaceutical compositions, genetically-modified cells, and methods of treatment that utilize the nucleic acid molecules of the invention.