Antibodies that bind ICOS (Inducible T cell Co-Stimulator). Therapeutic use of anti-ICOS antibodies for modulating the ratio between regulatory T cells and effector T cells, to stimulate the immune system of patients, including use in treating cancers. Methods of producing anti-ICOS antibodies, including species cross-reactive antibodies, using transgenic knock-out mice.

A system for assaying forces applied by cells includes an optically transparent substrate comprising a soft material having a Young's modulus within the range of about 3 kPa to about 100 kPa. An array of molecular patterns is disposed on a surface of the optically transparent substrate, the molecular patterns include fluorophore-conjugated patterns adherent to cells. The system includes at least one light source configured to excite the fluorophore-conjugated patterns and an imaging device configured to capture fluorescent light emitted from the fluorophore-conjugated patterns. Dimensional changes in the size of the patterns are used to determine contractile forces imparted by cells located on the patterns.

Provided herein are methods for analysis of target cells on a population or individual basis, including before and after contact with a stimulus in order to determine the effect of such stimulus on the target cells. Also provided are devices for performing such methods. The analysis methods involve identifying and measuring or tracking morphological changes that occur in target cells over a period of time. Tracking is accomplished using imaging systems capable of imaging target cells individually over a period of time either continuously or at discrete intervals of time.

Disclosed herein is method and system for determining quality of semen sample. Trajectories of objects, identified in each of plurality of image frames of semen sample, are generated by tracking movement of the objects across image frames, and compensating a drift velocity of the semen sample. Further, generated trajectories are classified into sperm and non-sperm trajectories. Finally, total concentration estimate and total motility estimate of the semen sample are computed to generate a semen quality index, which indicates quality of the semen sample. In an embodiment, the method of present disclosure uses a multi-level Convolutional Neural Network (CNN) analysis technique for effectively classifying the object trajectories into sperm and non-sperm objects. Also, since the present method includes estimating and compensating drift velocity in the semen sample, it enhances overall accuracy of motility estimation and semen quality analysis.

Systems and methods for determining whether a set of test perturbations discriminates over a null distribution for an on target effect against a first component of an entity are disclosed. The perturbations are perturbations of the first component and the entity comprises a plurality of components. For each perturbation in the set, a corresponding vector comprising a plurality of elements, is obtained. Each element comprises a distribution metric of measurements of a feature across instances of the entity upon exposure to the respective perturbation or (ii) a distribution metric of a respective dimension reduction component computed using the measurement of the plurality of features across instances of the entity upon the perturbation exposure. A composite metric is computed, using the vectors, and compared to a null distribution. When the composite metric is differentiated from the null distribution, the set of perturbations is deemed to discriminate the on target effect against the first component over the null distribution.

Compositions and methods for inducing PD-L1 internalization are disclosed. The methods include reducing the amount of cell surface PD-L1 by contacting a cell expressing PD-L1 with a compound that binds to cell surface PD-L1 and induces PD-L1 internalization. Compounds that induce PD-L1 internalization can be used to enhance, stimulate and/or increase an immune response and treat a PD-1-related disease or condition.

The present disclosure generally relates to a cell culturing system, and specifically to a three-dimensional cell culturing system for neuronal cells that promotes both structural and functional characteristics that mimic those of in vivo peripheral fibers, including cell myelination. Using a dual hydrogel construct and spheroids comprising neuronal cells, the present disclosure provides methods, devices, and systems for in vitro spatially-controlled, three-dimensional models that permit intra- and extra-cellular electro-physiological measurements and recordings. The three-dimensional hydrogel constructs allow for flexibility in incorporated cell types, geometric fabrication, and electrical manipulation, providing viable systems for culture, perturbation, and testing of biomimetic neural growth with physiologically-relevant results.

Embodiments herein described provide methods for determining phenotypic parameters of cell populations and expressing them in terms of tensors that can be compared with one another. Embodiments provide methods for determining phenotypic parameters of cell populations in response to an agent. Embodiments provide methods for comparing effects of an agent on phenotypic parameters to effects of reference standards whose in vivo effects are known. Embodiments provide methods for predicting the effect of an agent by the comparison with the known effects of reference standards. Embodiments provide methods for classifying agents by their effects on phenotypic parameters. Embodiments provide software and computer systems for calculating multiparametric tensors, compressing their complexity and comparing them after compression.

A system for assaying forces applied by cells includes an optically transparent substrate comprising a soft material having a Young's modulus within the range of about 3 kPa to about 100 kPa. An array of molecular patterns is disposed on a surface of the optically transparent substrate, the molecular patterns include fluorophore-conjugated patterns adherent to cells. The system includes at least one light source configured to excite the fluorophore-conjugated patterns and an imaging device configured to capture fluorescent light emitted from the fluorophore-conjugated patterns. Dimensional changes in the size of the patterns are used to determine contractile forces imparted by cells located on the patterns.

Compositions and methods for inducing PD-L1 internalization are disclosed. The methods include reducing the amount of cell surface PD-L1 by contacting a cell expressing PD-L1 with a compound that binds to cell surface PD-L1 and induces PD-L1 internalization. Compounds that induce PD-L1 internalization can be used to enhance, stimulate and/or increase an immune response and treat a PD-1-related disease or condition.