Abstract: The invention relates to compounds that inhibit DUBs, particularly USP9X. The invention also includes methods of inhibiting DUBs, including USP9X, and methods of treating cancers.

Abstract: The invention relates to compounds that inhibit DUBs, particularly USP9X. The invention also includes methods of inhibiting DUBs, including USP9X, and methods of treating cancers.

Abstract: The invention relates to compounds that inhibit DUBs, particularly USP9X. The invention also includes methods of inhibiting DUBs, including USP9X, and methods of treating cancers.

Abstract: The invention provides compositions and methods, e.g., assay technologies and their use in biodetection and diagnostics. More particularly, the invention provides compositions and methods based on nucleic acid-templated chemistry in biodetection and profiling of receptors (and their families) and proteins (and their families), and the use of same in diagnostics.

Abstract: The invention provides compositions and methods for the detection and/or quantification of biological targets (e.g., nucleic acids and proteins) by the nucleic acid-templated creation of one or more reaction products, for example, epitopes, enzyme substrates, enzyme activators, and ligands. The reaction products can be detected and/or quantitated after signal amplification using an amplification system.

Abstract: The present invention entails methods and kits for carrying them out based on the discovery that an RNA replicase, such as Q&bgr; replicase, has DNA-dependent RNA polymerase (“DDRP”) activity with nucleic acid segments, including DNA segments and DNA:RNA chimeric segments, which comprise a 2′-deoxyribonucleotide or an analog thereof and which have sequences of RNAs that are autocatalytically replicatable by the replicase.

Abstract: The present invention entails methods, and kits for carrying them out, based on the discovery that an RNA replicase, such as Q&bgr; replicase, has DNA-dependent RNA polymerase (“DDRP”) activity with nucleic acid segments, including DNA segments and DNA:RNA chimeric segments, which comprise a 2′-deoxyribonucleotide or an analog thereof and which have sequences of RNAs that are autocatalytically replicatable by the replicase. The discovery of this DDRP activity provides methods of the invention for nucleic acid amplification wherein a nucleic acid, with a DNA segment with the sequence of an RNA that is autocatalytically replicatable by an RNA replicase, is provided as a substrate for the replicase. The replicase catalyzes synthesis, from the DNA segment, of the RNA, which the replicase then autocatalytically replicates. The invention entails use of the amplification methods in detecting nucleic acid analytes, as in nucleic acid probe hybridization assays.

Abstract: The present invention entails methods, and kits for carrying them out, based on the discovery that an RNA replicase, such as Q&bgr; replicase, has DNA-dependent RNA polymerase (“DDRP”) activity with nucleic acid segments, including DNA segments and DNA:RNA chimeric segments, which comprise a 2′-deoxyribonucleotide or an analog thereof and which have sequences of RNAs that are autocatalytically replicatable by the replicase. The discovery of this DDRP activity provides methods of the invention for nucleic acid amplification wherein a nucleic acid, with a DNA segment with the sequence of an RNA that is autocatalytically replicatable by an RNA replicase, is provided as a substrate for the replicase. The replicase catalyzes synthesis, from the DNA segment, of the RNA, which the replicase then autocatalytically replicates. The invention entails use of the amplification methods in detecting nucleic acid analytes, as in nucleic acid probe hybridization assays.

Abstract: The present invention entails methods, and kits for carrying them out, based on the discovery that an RNA replicase, such as Q.beta. replicase, has DNA-dependent RNA polymerase ("DDRP") activity with nucleic acid segments, including DNA segments and DNA:RNA chimeric segments, which comprise a 2'-deoxyribonucleotide or an analog thereof and which have sequences of RNAs that are autocatalytically replicatable by the replicase. The discovery of this DDRP activity provides methods of the invention for nucleic acid amplification wherein a nucleic acid, with a DNA segment with the sequence of an RNA that is autocatalytically replicatable by an RNA replicase, is provided as a substrate for the replicase.

Abstract: A novel signal amplification system for immunoassays that minimizes non-specific signals is disclosed. Immunoassay methods, reagents and test kits are described for obtaining immunoassays of enhanced sensitivity. The reagents include antibody-variant DNA conjugates, wherein the variant DNA is a substrate for an RNA-dependent RNA polymerase, such as, QB replicase. Immunoassay methods to detect, or to detect and quantitate, analyte in test samples comprise transcribing the variant DNA of said antibody-DNA conjugates that are bound to analyte, to RNA, and replicating the RNA transcripts, wherein the presence or quantity of variant RNA replication products can be correlated with the presence or quantity of analyte in the test samples. Further, methods are provided to detect, or to detect and quantitate, simultaneously two or more analytes in a test sample.

Abstract: New methods are provided for the amplification of a midivariant DNA containing an inserted target specific nucleic acid sequence(s) to enable detection of the presence of a target nucleic acid sequence in a test sample. One method employs midivariant DNA as a template for the synthesis of RNA catalyzed by QB replicase. Two midivariant DNA/probe conjugates including a nonreplicable portion of midivariant DNA and a target specific nucleic acid sequence (probe) are described. An amplification method including the steps of hybridization and ligation of the midivariant DNA/probe conjugates followed by replication of the DNA template has enabled detection of less than 200 template molecules. In a modified amplification method one of the midivariant DNA/probe conjugates further includes a RNA polymerase promoter sequence to enable transcription of the midivariant DNA template into RNA. The sequential ligation-transcription-replication method enables the detection of a single template molecule.

Abstract: A new method has been developed for conducting a gene probe assay. The preferred technique involves (1) using a gene amplification technique (e.g., PCR) to multiply the gene sequence of interest and (2) using a hybridization--ligation detection methodology, wherein the sequences of probes hybridized to the target sequence allow for separation and detection (e.g., probes might contain a combination of magnetic particles and acridinium esters) to determine if a specific sequence is present.

Abstract: The assay described herein is predicated on an observation that when acridinium ester labeled tracers are bound to their corresponding binding conjugate immobilized on a metal oxide solid phase, the measurable chemiluminescent light emission of the labeled tracer bound to the solid phase is quenched as compared to the free fraction tracer that is unattached to the solid phase. According to the invention, a non-separation specific binding assay to detect or quantify the presence of an analyte is provided where the entire reaction mixture is flashed (including unreacted tracer) and modulated signal (because of the quench effect) is associated with a reference, thus determining the amount or presence of said analyte in said sample. Disadvantages inherent in heterogeneous assays employing multiple separations may be avoided using this non-separation method.

Abstract: Novel non-competitive assay techniques have been developed which not only improve sensitivity, but also are convenient and less susceptible to interfering factors. They are compatible with existing instruments and can be run in one or more test tubes. The analyte is reacted with labeled specific binder, after which the mixture is reacted with (1) an insoluble material attached to an analyte derivative and (2) a solid phase carrying a binder. The solid phase is then separated, and the label attached to the solid phase is measured. Variations of the procedure include the use of a reversible bridge for attaching the insoluble material to the analyte mimic and the conduct of the assay in various porous media, such as paper, chromatographic and electrophoretic media, and dipsticks.

Abstract: New methods are provided for the amplification of a midivariant DNA containing an inserted target specific nucleic acid sequence(s) to enable detection of the presence of a target nucleic acid sequence in a test sample. One method employs midivariant DNA as a template for the synthesis of RNA catalyzed by QB replicase. Two midivariant DNA/probe conjugates including a nonreplicable portion of midivariant DNA and a target specific nucleic acid sequence (probe) are described. An amplification method including the steps of hybridization and ligation of the midivariant DNA/probe conjugates followed by replication of the DNA template has enabled detection of less than 200 template molecules. In a modified amplification method one of the midivariant DNA/probe conjugates further includes a RNA polymerase promoter sequence to enable transcription of the midivariant DNA template into RNA. The sequential ligation-transcription-replication method enables the detection of a single template molecule.