Abstract: Data is migrated. For instance, in response to detection of a failed group in a drive of groups comprising respective blocks, it is determined whether the total number of groups in the drive that have failed is less than a predetermined threshold. Data associated with the failed group is migrated to a reserved group in a reserved space of the drive according to a determination that the total number is less than the predetermined threshold; and a read/write (I/O) request to the failed group is redirected to the reserved group based on a mapping relationship from the failed group to the reserved group. Consequently, data does not need to be repaired on an entire drive due to one failed write request and replacing the drive is avoided, thereby saving resources, time and labor, and improving the impact of the failed write request on the performance of a storage system.

Abstract: The disclosure provides PARP PROTAC molecules comprising a PARP inhibitor linked to an E3 ligase binder, and their use in treating diseases caused by aberrant PARP activation. Such PROTAC molecules produce selective degradation of one or a specific set of PARP proteins with limited effects on the protein level of other PARPs.

Abstract: A mass-spectrometry-based method and substrates are provided herein for large scale kinome activity profiling directly from crude lysates using 90 chemically synthesized peptide substrates with amino acid sequences derived from known phosphoproteins. Quantification of peptide phosphorylation rates was achieved via the use of stable isotope labeled synthetic peptides. A method and substrates for obtaining 90 simultaneous activity measurements in a single-reaction format were developed and validated. The kinome activity profiling strategy was successfully applied with lysates of: cells manipulated by combination of mitogen stimulation, pharmacological perturbation and siRNA-directed kinase knockdown; seven different breast cancer cell lines treated with gefitinib; and each of normal and cancerous tissue samples from renal cell carcinoma patients.

Abstract: A mass-spectrometry-based method and substrates are provided herein for large scale kinome activity profiling directly from crude lysates using 90 chemically synthesized peptide substrates with amino acid sequences derived from known phosphoproteins. Quantification of peptide phosphorylation rates was achieved via the use of stable isotope labeled synthetic peptides. Half of these peptides immediately or rapidly showed robust and site-specific phosphorylation after incubation with serum-starved HEK293 cell lysate. A method and substrates for obtaining 90 simultaneous activity measurements in a single-reaction format were developed and validated. Activating kinase pathways through insulin or EGF stimulation reproducibly altered the phosphorylation rates of peptides derived from known pathway protein substrates.

Abstract: PARylated proteins are enriched by treating cell lysates comprising PARylated proteins and DNA/RNA with an endonuclease that cleaves the DNA/RNA but not the PAR; and separating the PARylated proteins from the cleaved DNA/RNA. PARylation sites are labeled by eluting PARylated proteins from a PAR-affinity substrate with a nucleophilic amine exchange reactant, wherein the reactant labels PARylation sites of the proteins. Specific binding agents are identified by screening compounds for specific binding to a PARylated protein disclosed herein; and identifying one of the compounds as a specific binder of the protein. Antibodies which specifically bind PARylation sites are also disclosed.

Abstract: PARylated proteins are enriched by treating cell lysates comprising PARylated proteins and DNA/RNA with an endonuclease that cleaves the DNA/RNA but not the PAR; and separating the PARylated proteins from the cleaved DNA/RNA. PARylation sites are labeled by eluting PARylated proteins from a PAR-affinity substrate with a nucleophilic amine exchange reactant, wherein the reactant labels PARylation sites of the proteins. Specific binding agents are identified by screening compounds for specific binding to a PARylated protein disclosed herein; and identifying one of the compounds as a specific binder of the protein. Antibodies which specifically bind PARylation sites are also disclosed.

Abstract: PARylated proteins are enriched by treating cell lysates comprising PARylated proteins and DNA/RNA with an endonuclease that cleaves the DNA/RNA but not the PAR; and separating the PARylated proteins from the cleaved DNA/RNA. PARylation sites are labeled by eluting PARylated proteins from a PAR-affinity substrate with a nucleophilic amine exchange reactant, wherein the reactant labels PARylation sites of the proteins. Specific binding agents are identified by screening compounds for specific binding to a PARylated protein disclosed herein; and identifying one of the compounds as a specific binder of the protein. Antibodies which specifically bind PARylation sites are also disclosed.

Abstract: PARylated proteins are enriched by treating cell lysates comprising PARylated proteins and DNA/RNA with an endonuclease that cleaves the DNA/RNA but not the PAR; and separating the PARylated proteins from the cleaved DNA/RNA. PARylation sites are labeled by eluting PARylated proteins from a PAR-affinity substrate with a nucleophilic amine exchange reactant, wherein the reactant labels PARylation sites of the proteins. Specific binding agents are identified by screening compounds for specific binding to a PARylated protein disclosed herein; and identifying one of the compounds as a specific binder of the protein. Antibodies which specifically bind PARylation sites are also disclosed.

Abstract: Provided are over 300 mTOR kinase targets identified by a comprehensive phosphoproteomics assay. Methods of targeting mTOR kinase targets, methods to determine the level of mTOR activity by measuring the level of phosphorylation of an mTOR targeted phosphorylation site, methods for distinguishing different classes of mTOR activity in a cell based on phosphoproteomic analysis of mTOR-targeted proteins are also provided. Also provided is the classification of a hyperproliferative disease based on phosphoproteomic analysis of mTOR-targeted proteins, as well as the personalization of therapeutic methods for the treatment of hyperproliferative disease based on phosphoproteomics. Also provided are therapeutic methods including administering to a subject an mTOR inhibitor, an mTOR inhibitor and an additional kinase inhibitor, or a dual inhibitor of mTOR and an additional kinase based on the phosphorylation levels of mTOR targets determined in the subject.

Abstract: A mass-spectrometry-based method and substrates are provided herein for large scale kinome activity profiling directly from crude lysates using 90 chemically synthesized peptide substrates with amino acid sequences derived from known phosphoproteins. Quantification of peptide phosphorylation rates was achieved via the use of stable isotope labeled synthetic peptides. Half of these peptides immediately or rapidly showed robust and site-specific phosphorylation after incubation with serum-starved HEK293 cell lysate. A method and substrates for obtaining 90 simultaneous activity measurements in a single-reaction format were developed and validated. Activating kinase pathways through insulin or EGF stimulation reproducibly altered the phosphorylation rates of peptides derived from known pathway protein substrates.