Abstract: Provided are methods for isolating T-cells with T cell receptors (TCRs) optimized for reactivity to specific peptides and decreased cross-reactivity to non-target peptides. Advantageously, TCRs of the invention can be optimized to target cancer antigens and peptides while having reducing reactivity to healthy cells. Methods of the invention utilize a novel combination of culturing conditions that increase T-cell activation and allow for validation of TCR activity. Culturing conditions of the invention further reduce culturing times generally needed to achieve expanded reactive T-cells. Because of the robust nature of the activation and validation conditions of the present invention, variants of identified TCRs can also be optimized and validated for their response to peptides, including cancer peptides.

Abstract: Systems and methods include a computer-implemented method for generating and using a graph/document structure to store reservoir simulation results. A graph is generated that represents reservoir simulation results of a reservoir simulation performed on a reservoir using a reservoir simulation model. The graph represents a full set of relational data and non-relational data included in the reservoir simulation results. The graph stores graph information and relational data in a graph/document structure. Objects of the reservoir, elements of the reservoir simulation results, and inputs of the reservoir simulation model are represented as vertices in the graph. Relationships between vertices are represented as edges in the graph. An edge is defined by a pair of vertices in the graph.

Abstract: A method for enhancing the allocation of fluid flow rates among a plurality of well bores in fluid communication with at least one subterranean reservoir is disclosed. An objective function and system equations are generated which utilize constraint violation penalties associated with soft constraints. The soft constraints are constraints which may be violated if necessary to arrive at a feasible solution to optimizing the objective function and the system equations. The fluid flow rates are then allocated among the well bores as determined by the optimizing of the objective function and system equations. Fluid flow rates among well bores, particularly those exhibiting similar fluid characteristics, may be related to one another. Initial flow rates of components (oil, gas, and water) and pressures in the well bores may be determined by an initial simulation run.