Abstract: The present invention provides a dry solid medium for storage of genetic material, including RNA and DNA, in a form suitable for subsequent analysis. The invention also provides a dry solid medium including components which function in subsequent analysis of the genetic material using, for example, PCR, reverse transcriptase initiated PCR, LCR, RFLP, or genetic hybridization. The components for subsequent analysis include, for example, nucleotide sequences such as a primer and a target sequence stabilizer.The invention further provides methods for using the dry solid medium of the invention. The invention and methods thereof are particularly suited for analysis in automated systems.

Abstract: Methods are described for the identification and preparation of high-affinity nucleic acid ligands to cytokines. Included in the invention are specific nucleic acid ligands to IFN-gamma, IL-4, IL-10, TNF-alpha, and RANTES.

Abstract: A method for detecting the presence of a double-stranded target nucleic acid sequence contained in fixed cells or cell structures is provided. The method includes the steps of forming the fixed cells or cell structures by fixing cells or cell structures so as to allow a nucleic acid probe to enter, and forming a probe/RecA complex in which a single-stranded probe and RecA protein are stably bound to each other. The probe/RecA complex is allowed to react with the double-stranded target nucleic acid sequence to bind thereto under conditions in which the double-stranded target nucleic acid sequence is not denatured, and by detecting the RecA protein included in the probe/RecA complex, the presence of the double-stranded target nucleic acid sequence is detected.The invention provides a diagnostic method by which the position of a specific gene or its regulatory region in a chromosome and the presence of a nucleic acid sequence derived from virus can be measured or visualized with high sensitivity and with ease.

Abstract: Methods of diagnosing glaucoma, and particularly primary congenital glaucoma, by detecting mutations in a gene associated with glaucoma, such as the CYP1B1 gene, are disclosed. Methods include hybridization analysis, such as Southern or Northern analysis, which use hybridization of a mutant nucleic acid probe to the gene associated with glaucoma; direct mutation analysis by restriction digest; sequencing of the gene associated with glaucoma; hybridization of an allele-specific oligonucleotide with amplified genomic DNA; or identification of the presence of mutant proteins encoded by the gene associated with glaucoma. Kits for use in diagnosis of glaucoma are also described. Methods of treatment of glaucoma, including administration of the protein encoded by the gene associated with glaucoma; administration of genes, gene constructs, or other nucleic acid constructs; or administration of other therapeutic agents, are additionally described.

Abstract: This application provides methods for identifying nucleic acid ligands capable of covalently interacting with targets of interest. The nucleic acids can be associated with various functional units. The method also allows for the identification of nucleic acids that have facilitating activities as measured by their ability to facilitate formation of a covalent bond between the nucleic acid, including its associated functional unit, and its target.

Abstract: Combinations, called matrices with memories, of matrix materials that are encoded with an optically readable code are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The matrix materials may additionally include fluophors or other luminescent moieties to produce luminescing matrices with memories. The memories include electronic and optical storage media and also include optical memories, such as bar codes and other machine-readable codes. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.

Abstract: Nucleic acid ligands containing modified nucleotides are described as are methods for producing such oligonucleotides. Such ligands enrich the chemical diversity of the candidate mixture for the SELEX process. Specific examples are provided of nucleic acids containing nucleotides modified at the 2'- and 5-position. Specific 2-OH and 2'-NH.sub.2 modified RNA ligands to thrombin are described.

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: Reagents and composition for controlling the translation of hepatitis GB virus (HGBV)-A, -B or -C peptides from viral nucleic acid. These reagents and methods comprise control elements of the 5' NTR region of the HGBV-A, -B, or -C viral genome.

Abstract: The present invention provides for a method for generating a directed, recombinant fusion nucleic acid molecule which includes: (A) contacting a first pair of single-stranded primers with a first strand and a second strand of a first nucleic acid molecule and a second pair of single-stranded primers with a first strand and a second strand of a second nucleic acid molecule under hybridization conditions, (B) amplifying the first nucleic acid molecule and the first pair of primers and the second nucleic acid molecule and the second pair of primers under amplification conditions, separately; (C) mixing the amplification products from step (B) and the first primer of the first pair of primers and the second primer of the second pair of primers under hybridization conditions; (D) amplifying the hybridized molecules of step (C) under amplification conditions so as to generate a directed, recombinant fusion nucleic acid molecule so as to generate a directed, recombinant fusion nucleic acid molecule.

Abstract: A new human chitinase having an amino acid sequence as shown in FIG. 1 or FIG. 2. Modified forms of it having a similar chitin-hydrolyzing activity, and antigenic peptides representing one of its epitopes. Recombinant production of the human chitinase by genetically engineered hosts or host cells. Recombinant nucleic acid encoding it, and human chitinase-specific oligonucleotides. Use for therapeutic or prophylactic treatment of humans against infection by chitin-containing pathogens, or for decomposing chitin, e.g. from chitin-based articles. Antibodies binding to the human chitinase. Diagnostic test kits comprising the human chitanase, its antigenic peptides, human chitinase antibodies, recombinant nucleic acid or oligonucleotides.

Abstract: Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The data storage units are preferably non-volatile antifuse memories. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.

Abstract: The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.

Abstract: Biosensor technology based on the labelling entities having particle reporters provides cost competitive readily manufactured assay devices. Sub-micron particles of uniform dimension in metals, polymers, glasses, ceramics and biological structures such as phages are used as the labelling entities. Such reporter particles greatly increase the sensitivity and accuracy, and provide a variety of assay techniques for determining analyte presence in a sample. The particles may have dielectric, paramagnetic and/or phosphorescent properties, such particles are particularly useful in a variety of competition type assays. Novel phosphor and phage particles are provided for use as unique labelling entities.

Abstract: The nucleic acid amplification procedures of the present invention provide methods for amplification of a nucleic acid comprised of a first strand, comprising (a) using the first strand to generate copies of a second strand at a first location, (b) moving the copies of the second strand to a second location, and (c) using the copies of the second strand to generate copies of at least a portion of the first strand. Target nucleic acids used in the context of the present method include RNA or DNA, either single stranded or double stranded, using primer extension or joining-type protocols. Embodiments are set forth for automated forms of the claimed procedures.

Abstract: The invention pertains to methods for detecting the presence or absence of a mutation associated with hypertrophic cardiomyopathy (HC). The methods include providing DNA which encodes a sarcomeric thin filament protein (e.g., .alpha.-tropomyosin or cardiac troponin T) and detecting the presence or absence of a mutation in the amplified product which is associated with HC. DNA encoding an actin-associated protein, a myosin-associated protein, or a sarcomeric protein other than .beta. cardiac heavy chain can also be used in the methods of the present invention. The invention further pertains to methods for diagnosing familial HC (FHC) in a subject. These methods typically include obtaining a sample of DNA which encodes a sarcomeric thin filament protein from a subject being tested for FHC and diagnosing the subject for FHC by detecting the presence or absence of a mutation in the sarcomeric thin filament protein which causes FHC as an indication of the disease.

Abstract: The present invention relates to variant forms of the receptor for the obese gene product. In particular, the invention relates to methods of detecting receptor variants in the reproductive organs for the diagnosis of the cause of infertility. In addition, it relates to methods of inhibiting or down-regulating expression of defective variants in cells to augment their responsiveness to regulation by leptin as well as methods of using compounds to directly activate signal transduction pathways associated with this ligand-receptor system to improve fertility.

Abstract: The present invention provides materials and methods for sensitively and selectively screening biological samples for the presence of Candida albicans, a fungal pathogen of increasing clinical concern. Specifically, nucleic acids, reagents, and primers for DNA amplification are provided that will allow amplification of a 526 base pair oligonucleotide from DNA containing Candida albicans. Methods for using such primers in DNA amplification are also provided.

Abstract: A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Abstract: Kits for synthesizing multiple copies of a target nucleic acid sequence autocatalytically under conditions of substantially constant temperature, ionic strength, and pH are provided in which multiple RNA copies of the target sequence autocatalytically generate additional copies. These methods are useful for generating copies of a nucleic acid target sequence for purposes which include assays to quantitate specific nucleic acid sequences in clinical, environmental, forensic and similar samples, cloning and generating probes.