Abstract: An aspect of the present disclosure relates to methods and constructs for modulating gene expression in a cell. In some cases, the constructs are configured to drive expression of one or more genes (e.g., transgenes comprising a tolerogenic factor,) off inducible gene promoters. In some embodiments, the cell-specific promoter is an immune cell gene promoter. In some embodiments, the cell-specific promoter comprises a sequence having 95%, 97%, 99% or 100% sequence identity to a 60, 70, 80, 90, 100, 200, 500, 1,000, 1,500 or 2,000 base pair long fragment of any one of SEQ ID NO: 5 to 57.

Abstract: A digital twin system controls a computing system and comprises a digital twin comprising a virtual model of the computing system including hardware and software entities and their environment. The virtual model incorporates three-dimensional physical dimensions of the hardware and emulates the behaviour of the computing system. The digital twin system performs communications with the computing system including receipt of real-time information regarding performance of the computing system and sensed conditions of the computing system and its environment. The digital twin system comprises a machine learning system trained on (i) historical and real-time performance data; and (ii) historical and real-time sensed data of the computing system and its environment. The digital twin system comprises an orchestrator that determines an action for the computing system and its environment and that supports selected system management objective(s).

Abstract: A computer-implemented method for 3D reconstruction of a target is provided, comprising obtaining an initial global reconstruction of the target in a 3D space, inferred by a global machine learning model; providing, to a user, an initial visualisation of the target based on the reconstruction; receiving, from the user, at least one indication of at least one point of interest in the visualisation; resampling at least one first subsection of the target based on the at least one point of interest to obtain local data, wherein the local data is associated with the subsection based on spatial information that associates the local data with a point in 3D space; inputting the resampled local data and spatial information into a local feature machine learning model to obtain at least one 3D reconstruction of the target, wherein the local feature machine learning model has been trained to output a target reconstruction from local data of resampled subsections, and wherein the 3D coordinate system of the local 3D recon

Abstract: Disclosed herein are methods and compositions for engineering cells to express a CAR where the cells also have inactivated TCR, HPRT, PD1, CISH and/or HLA genes, using engineered nucleases comprising at least one DNA binding domain and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided.

Abstract: The present disclosure provides mammalian cells such as regulatory T cells containing a transgene in the FOXP3 genomic locus. Also provided are methods of generating the cells and methods of using the cells to treat patients in need of immunosuppression.

Abstract: An automated equipment installation verification system to automatically verify correctness of installation actions of an operative installing an item of equipment, the system comprising: a logic unit (804) that executes a rule engine to apply at least one rule to a measure of correctness of each of a plurality of physical acts performed by the operative according to a sequence of stepwise actions to be performed by the operative in the installation of the equipment to determine a degree of correctness of an installation of the equipment, each measure of correctness being determined by a classifier trained to determine a degree of correctness of a respective act based on sensor data corresponding to the act.

Abstract: A digital twin system is provided for controlling a computing system including multiple hardware and software entities. The digital twin system comprises: a digital twin comprising a virtual model of the computing system including the multiple hardware and software entities and their environment. The virtual model incorporates three-dimensional physical dimensions of the hardware, the virtual model being configured to emulate the behaviour of the computing system. The digital twin system further comprises a communications interface for performing bi-directional communications with the computing system. The communications include receipt of real-time information regarding performance of the computing system and sensed conditions of the computing system and its environment. The digital twin system also comprises a machine learning system trained on (i) historical and real-time performance data; and (ii) historical and real-time sensed data of the computing system and its environment.

Abstract: The present disclosure relates to predicting blockages in underground ducts. According to one aspect, there is provided a computer-implemented method of identifying one or more locations along a route for an underground duct which indicate a blockage risk, the route extending between two ends, the method including obtaining a terrain elevation profile for the route; estimating a duct elevation profile for the route based on the terrain elevation profile; and predicting one or more blockage risk locations along the route by determining where water entering the duct from each of the two ends would settle, based on the duct elevation profile.

Abstract: A computer implemented method of allocating a set of communications network resources to resource consumers in a digital communications system can include generating a set of multiple allocation schemes; iteratively applying a genetic algorithm to the set of allocation schemes to generate, at each iteration, a new set of allocation schemes as a generation of allocation schemes based on a preceding generation; and, responsive to a predetermined stopping condition for the iteration, assigning resource consumers to resources in the communications system in accordance with an allocation scheme in a most recent generation determined to satisfy a ranking condition.

Abstract: Nucleases and methods of using these nucleases for alteration of a CFTR gene and generation of cells and animal models.

Abstract: A computer implemented method of allocating a set of communications network resources to resource consumers in a digital communications system can include generating a set of multiple allocation schemes; iteratively applying a genetic algorithm to the set of allocation schemes to generate, at each iteration, a new set of allocation schemes as a generation of allocation schemes based on a preceding generation; and, responsive to a predetermined stopping condition for the iteration, assigning resource consumers to resources in the communications system in accordance with an allocation scheme in a most recent generation determined to satisfy a ranking condition.

Abstract: A computer implemented method of navigating a digital representation of a spatial environment by a user in which a portion of the digital representation is rendered by a rendering computer system for visualization by the user. The method including accessing a digital model of the spatial environment including a specification of each of a plurality of virtual resources in the spatial environment, each specification identifying at least a location of a resource in the spatial environment and at least one trigger criterion for determining when a resource is accessed by the user; monitoring the satisfaction of trigger criteria for the plurality of virtual resources; and responsive to the monitoring, determining the portion of the digital representation for rendering by the rendering computer system for visualization by the user.

Abstract: A computer implemented method to specify a software defined network (SDN) for deployment by an SDN controller, the SDN controller being adapted to configure a plurality of physical network components to deliver communication services, the method including generating a model of the physical network components by accessing each of a plurality of data sources; defining the model including an indication of a location, type and interconnections of physical components based on the data sources; associating each indication in the model with a degree of confidence of accuracy of the indication based on the degree of confidence information from the data sources; accessing a set of rules defining relationships between types of physical component; refining the model based on the rules including adjusting a degree of confidence of accuracy of indications in the model based on satisfaction of the rules; and selecting a subset of network components in the refined model for inclusion in the SDN specification.

Abstract: A computer implemented method to generate a three-dimensional (3D) data model of a two-dimensional (2D) floor plan, the floor plan being constituted as a digital image including indications of types of building elements, is disclosed.

Abstract: A computer implemented method of allocating a set of communications network resources to resource consumers in a digital communications system can include generating a set of multiple allocation schemes; iteratively applying a genetic algorithm to the set of allocation schemes to generate, at each iteration, a new set of allocation schemes as a generation of allocation schemes based on a preceding generation; and, responsive to a predetermined stopping condition for the iteration, assigning resource consumers to resources in the communications system in accordance with an allocation scheme in a most recent generation determined to satisfy a ranking condition.

Abstract: Provided herein are improved methods and compositions for generating CD4-positive effector T cells and regulatory T cells and methods of use thereof.

Abstract: Nucleases and methods of using these nucleases for alteration of a CFTR gene and generation of cells and animal models.

Abstract: Disclosed herein are methods and compositions for inactivating TCR and/or HLA genes, using engineered nucleases comprising at least one DNA binding domain and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided.

Abstract: The present disclosure is in the field of genome engineering, particularly targeted genetic modification of a CISH gene.

Abstract: Described herein are lipid nanoparticles comprising cationic lipids and other lipids and also comprising engineered nucleases facilitate transfer of nucleic acids to cells.