Abstract: Provided herein are compounds of Formula (I) and Formula (II) and stereoisomers, tautomers, and pharmaceutically acceptable salts or solvates thereof. Also provided are pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition by using the compounds and pharmaceutical compositions.

Abstract: In a system for identifying a subset of compounds in a plurality of compounds, the identifying includes obtaining via high throughput screening, for each compound, a vector including a set of elements. Each element includes a measurement of a different feature of an instance of a cell context upon exposure to the compound. The obtaining is repeated for a plurality of cell contexts to obtain a plurality of vectors for each compound across different cell contexts. The vectors are combined for each compound to form a combined vector for each compound, thereby forming a plurality of combined vectors representing different compounds. The plurality of compounds is pruned to the subset of compounds based on a similarity between respective combined vectors in the plurality of combined vectors corresponding to compounds in the plurality of compounds. The subset is used as a reduced size smart compound library to perform pharmaceutical drug discovery.

Abstract: Methods and systems for evaluating a query perturbation, in a cell based assay representing a test state, are provided. Control data points having dimensions representing measurements of different features across control cell aliquots are obtained. Test data points having dimensions representing measurements of different features across test cell aliquots are obtained. A composite test vector is computed between measures of central tendency across the control data points and measures of central tendency across the test data points. Query perturbation data points having dimensions representing measurements of different features across perturbation cell aliquots are obtained. A composite query perturbation vector is computed between measures of central tendency across the control data points and measures of central tendency across the plurality of query perturbation data points.

Abstract: In a method of molecular scaffold hopping an interface of a scheduler computer sends instructions, prepared by the scheduler computer, to a job runner computer to perform a plurality of separate computational tasks. Each of the separate computational tasks includes calculating one or more chemical properties for a query molecule or molecules in a library of molecules. One or more of the plurality of separate computational tasks performed on the job runner computer are preemptible computing instances. Status indicators sent from the job runner computer are received by the interface for each of the plurality of separate computational tasks. The indicators are one of: incomplete, completed, or failed computing instances. The interface resends the instructions to the job runner computer that correspond to the separate computational tasks having the failed computing instance indicator to increase fault-tolerance against the separate computational tasks not attaining the completed computing instance indicator.

Abstract: The disclosure provides methods and systems for identifying a subset of compounds in a plurality of compounds. The identifying includes obtaining, for each compound, a vector including a set of elements, where each element includes a measurement of a different feature of an instance of a cell context upon exposure to the compound. The identifying includes repeating the obtaining for a plurality of cell contexts, to obtain a plurality of vectors for each compound across different cell contexts. The identifying includes combining the vectors for each compound to form a combined vector for each compound, thereby forming a plurality of combined vectors representing different compounds. The identifying includes pruning the plurality of compounds to the subset of compounds based on a similarity between respective combined vectors in the plurality of combined vectors corresponding to compounds in the plurality of compounds.

Abstract: Methods and compositions are provided for treating lysosomal storage diseases and symptoms thereof. The methods include administering a PKC inhibitor, a GSK3? inhibitor, or an inhibitor of both.

Abstract: In a method of molecular scaffold hopping an interface of a scheduler computer sends instructions, prepared by the scheduler computer, to a job runner computer to perform a plurality of separate computational tasks. Each of the separate computational tasks includes calculating one or more chemical properties for a query molecule or molecules in a library of molecules. One or more of the plurality of separate computational tasks performed on the job runner computer are preemptible computing instances. Status indicators sent from the job runner computer are received by the interface for each of the plurality of separate computational tasks. The indicators are one of: incomplete, completed, or failed computing instances. The interface resends the instructions to the job runner computer that correspond to the separate computational tasks having the failed computing instance indicator to increase fault-tolerance against the separate computational tasks not attaining the completed computing instance indicator.

Abstract: An electronic monitor can monitor experimental animals in a cage. The cage has one or more walls that enclose a living space for the experimental animals. The electronic monitor is coupled to the cage. The electronic monitor may include a housing adapted to be mechanically coupled to the cage in a predefined position relative to the cage. A substantially sterile barrier is provided between the living space and the external environment in this coupled state. The walls of the cage may include a signal-interface section. An electromagnetic detector may be coupled to the housing to have a line-of-sight through the signal-interface section and into the living space of the cage. The electromagnetic detector is adapted to detect electromagnetic radiation that is transmitted through the signal-interface section. A controller processes a signal received from the electromagnetic detector to determine a status of the experimental animals or the living space.

Abstract: In a method of molecular scaffold hopping an interface of a scheduler computer sends instructions, prepared by the scheduler computer, to a job runner computer to perform a plurality of separate computational tasks. Each of the separate computational tasks includes calculating one or more chemical properties for a query molecule or molecules in a library of molecules. One or more of the plurality of separate computational tasks performed on the job runner computer are preemptible computing instances. Status indicators sent from the job runner computer are received by the interface for each of the plurality of separate computational tasks. The indicators are one of: incomplete, completed, or failed computing instances. The interface resends the instructions to the job runner computer that correspond to the separate computational tasks having the failed computing instance indicator to increase fault-tolerance against the separate computational tasks not attaining the completed computing instance indicator.

Abstract: The disclosure provides methods and systems for identifying a subset of compounds in a plurality of compounds. The identifying includes obtaining, for each compound, a vector including a set of elements, where each element includes a measurement of a different feature of an instance of a cell context upon exposure to the compound. The identifying includes repeating the obtaining for a plurality of cell contexts, to obtain a plurality of vectors for each compound across different cell contexts. The identifying includes combining the vectors for each compound to form a combined vector for each compound, thereby forming a plurality of combined vectors representing different compounds. The identifying includes pruning the plurality of compounds to the subset of compounds based on a similarity between respective combined vectors in the plurality of combined vectors corresponding to compounds in the plurality of compounds.

Abstract: In a method of molecular scaffold hopping an interface of a scheduler computer sends instructions, prepared by the scheduler computer, to a job runner computer to perform a plurality of separate computational tasks. Each of the separate computational tasks includes calculating one or more chemical properties for a query molecule or molecules in a library of molecules. One or more of the plurality of separate computational tasks performed on the job runner computer are preemptible computing instances. Status indicators sent from the job runner computer are received by the interface for each of the plurality of separate computational tasks. The indicators are one of: incomplete, completed, or failed computing instances. The interface resends the instructions to the job runner computer that correspond to the separate computational tasks having the failed computing instance indicator to increase fault-tolerance against the separate computational tasks not attaining the completed computing instance indicator.

Abstract: A system for determining a goodness of a deep learning model comprises a memory coupled with a processor. The processor accesses a first set of vectors representative of images of a biological assay. The vectors of the first set of vectors are outputs of a first deep learning model. The processor creates a first distribution of a first plurality of pairwise comparisons of vectors, of the first set of vectors, which were generated from image pairs with similar cell perturbations. The processor creates a second distribution of a second plurality of pairwise comparisons of vectors, of the first set of vectors, which were generated from image pairs with dissimilar cell perturbations. The processor determines a difference between the first distribution and the second distribution and uses the difference to make a determination of goodness of the deep learning model as applied to the biological assay.

Abstract: A system for selecting CRISPR guides for knocking out one or more target genes in a target cell from a multiplicity of candidate guides comprises a memory and a processor. The processor determines whether the candidate guide meets a plurality of thresholds. The thresholds are associated with: a transcript support level; targeting a consensus sequence of a target gene; which exon of the target gene is targeted; targeting of a primary transcript, targeting of a common isoform; a precomputed prediction of editing outcomes; mapping to an expressed sequence; fraction of gene expression attributable to targeted transcripts; a common SNP overlap threshold; which exon of the target gene is targeted; overlap of a selected guide; predicted frameshift percentage; maximum and minimum GC content; off target score; where a coding sequence is targeted. In response to meeting the thresholds, the processor selects the candidate guide as a selected CRISPR guide.

Abstract: Methods of measuring attributes of animal urine, using a test pad comprising multiple test patches and urine detection patches in a BAYER pattern is described. The pad comprises different test patches, each surrounded by urine detection patches. When a camera, electronics and software automatically detect fresh urine from a color change of a detection patch, nearby test patches are read with a color camera, after a specific time delay, and compared to color reference spots. Multiple layers and isolation zones in the test pad allow urine to enter the test and detection patches, while keeping urine puddles from spreading. Once used, detection and test patches are not used again. An array of many detection and test patches allows the test pad to be used for multiple urine samples in one vivarium cage before replacing. Embodiments use a mix of IR and white light, and IR cameras and color cameras.

Abstract: The disclosure provides methods and systems for identifying a subset of compounds in a plurality of compounds. The identifying includes obtaining, for each compound, a vector including a set of elements, where each element includes a measurement of a different feature of an instance of a cell context upon exposure to the compound. The identifying includes repeating the obtaining for a plurality of cell contexts, to obtain a plurality of vectors for each compound across different cell contexts. The identifying includes combining the vectors for each compound to form a combined vector for each compound, thereby forming a plurality of combined vectors representing different compounds. The identifying includes pruning the plurality of compounds to the subset of compounds based on a similarity between respective combined vectors in the plurality of combined vectors corresponding to compounds in the plurality of compounds.

Abstract: In various embodiments, an experiment analysis application detects executional artifacts in experiments involving microwell plates. The experiment analysis application computes one or more sets of spatial features based on one or more heat maps associated with a microwell plate. The experiment analysis application then aggregates the set(s) of spatial features to generate a feature vector. The experiment analysis application inputs the feature vector into a trained classifier. In response, the trained classifier generates a label indicating that the microwell plate is associated with a first executional artifact.

Abstract: Evaluating an effect of one or more perturbations on cells of a first cell type is described. One method includes obtaining a screen definition for a screen, where the screen includes a cell-based assay that is run on a temporarily contiguous basis using a plurality of multi-well plates. The method includes obtaining control vectors including measurements of corresponding features of cells in control wells. The method includes obtaining test vectors including measurements of corresponding features of cells in test wells. The method includes forming a variability model based on a variance across the of control vectors, and embedding test vectors onto the variability model, thereby obtaining a set of variability model values. The method includes using the set of variability model values to resolve an effect of at least one data perturbation in the plurality of data perturbations on the first cell type.

Abstract: The disclosure provides methods and systems for identifying a subset of compounds in a plurality of compounds. The identifying includes obtaining, for each compound, a vector including a set of elements, where each element includes a measurement of a different feature of an instance of a cell context upon exposure to the compound. The identifying includes performing the obtaining for a plurality of cell contexts, to obtain a plurality of vectors for each compound across different cell contexts. The identifying includes combining the vectors for each compound to form a combined vector for each compound, thereby forming a plurality of combined vectors representing different compounds. The identifying includes pruning the plurality of compounds to the subset of compounds based on a similarity between respective combined vectors in the plurality of combined vectors corresponding to compounds in the plurality of compounds.

Abstract: A method of measuring efficacy of test treatment of an autoimmune disease in an animal in a vivarium is described. Animal activity data is collected at multiple times during the night. Sequential time regions of the night are identified as high-activity, activity-drop, or low-activity regions. Embodiments are described to quantify a drop, during the night, of an animal's activity level. These quantified activity-drop scalars for consecutive nights are accumulated in an animal health dataset. This dataset is compared to healthy animals, a standard of care or a reference treatment for the first disease to determine efficacy of the test treatment. One embodiment quantifies an activity-drop by fitting straight-line curves through the data in the three nightly regions. Other embodiment uses a Fourier transform on a circle, LASSO, RANSAC or regression analyses for curve fitting. Another embodiment compares areas under data curves in the regions. Animals may be housed in cages with other animals.