Abstract: The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer.

Abstract: Cinnoline compounds of formula (I): variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the cinnoline compounds.

Abstract: The invention relates to heterocyclic compounds, pharmaceutically acceptable salts thereof, and pharmaceutical preparations thereof. Also described herein are compositions and the use of such compounds in methods of treating diseases and conditions mediated by deficient CFTR activity, in particular cystic fibrosis.

Abstract: The invention relates to inhibitors of glucosylceramide synthase (GCS) of the Formula I: represented by the following structural formula or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein, useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer.

Abstract: The invention relates to heterocyclic compounds, pharmaceutically acceptable salts thereof, and pharmaceutical preparations thereof. Also described herein are compositions and the use of such compounds in methods of treating diseases and conditions mediated by deficient CFTR activity, in particular cystic fibrosis.

Abstract: Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

Abstract: Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

Abstract: Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

Abstract: Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

Abstract: Methods and apparatus are provided for controlling wireless signal transmissions, wherein problematic symbol patterns are relocated to an erasure region of a data packet prior to erasure encoding and transmission. Relocating the problematic symbol patterns is done so that, when the resulting erasure codeword is punctured and transmitted, the problematic patterns are not transmitted. Yet, those patterns can be restored by the decoder at the receiving device using an erasure decoder in accordance with erasure decoding techniques, e.g., punctured low-density parity-check (LDPC) decoding techniques. In this manner, problematic symbol patterns that may be corrupting during transmission due to noise are removed (punctured) prior to transmission, then restored by the decoder during decoding.

Abstract: Systems and methods for read level tracking and optimization are described. Pages from a wordline of a flash memory device read and the raw page data read from the wordline may be buffered in a first set of buffers. The raw page data for each of the pages may be provided to a decoder for decoding and the decoded page data for each of the pages buffered in a second set of buffers. First bin identifiers may be identified for memory cells of the wordline based on the raw page data and second bin identifiers may be identified for the memory cells of the wordline based on the decoded page data. Cell-level statistics may be accumulated based on the first bin identifiers and the second bin identifiers, and a gradient may be determined for respective read levels based on decoding results for each of the pages and the cell-level statistics. Settings for the read levels may be configured in the flash memory device based on the determined gradients.

Abstract: In one aspect, a computerized method for managing tombstones in a node of a Distributed Database Base System (DDBS) includes the step of providing a rule that, for a namespace in a record of the node of the DDBS that allows expiration, mandates that a later generation's expiration time of the namespace never decreases. The computerized method includes the step of determining that an administrator of the DDBS has set an expiration time of the namespace to infinity. The computerized method includes the step of implementing a background process of the DDBS, wherein the background process scans a DDBS node's drive and flags a set of extant tombstones that are no longer covering viable namespaces or viable records. The computerized method includes the step of deleting all the flagged tombstones.

Abstract: Methods and apparatus are provided for controlling wireless signal transmissions, wherein problematic symbol patterns are relocated to an erasure region of a data packet prior to erasure encoding and transmission. Relocating the problematic symbol patterns is done so that, when the resulting erasure codeword is punctured and transmitted, the problematic patterns are not transmitted. Yet, those patterns can be restored by the decoder at the receiving device using an erasure decoder in accordance with erasure decoding techniques, e.g., punctured low-density parity-check (LDPC) decoding techniques. In this manner, problematic symbol patterns that may be corrupting during transmission due to noise are removed (punctured) prior to transmission, then restored by the decoder during decoding.

Abstract: Isoquinoline compounds and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the isoquinoline compounds.

Abstract: Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. Disclosed herein are compounds and methods to recover wild-type function of p53 mutants using x-ray co-crystal structures of mutant p53 and compounds of the disclosure. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

Abstract: Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

Abstract: A data storage system and method are provided for storing data in non-volatile memory devices. Binary data is received for storage in a non-volatile memory device. The binary data is converted into non-binary data comprising base-X values, where X is an integer greater than two. The non-binary data is encoded to generate a codeword and the codeword is written to a wordline of the non-volatile memory device.

Abstract: Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

Abstract: Cinnoline compounds of formula (I): variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the cinnoline compounds.

Abstract: The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer.