Abstract: Methods are described for detecting protein-protein interactions, among two populations of proteins, each having a complexity of at least 1,000. For example, proteins are fused either to the DNA-binding domain of a transcriptional activator or to the activation domain of a transcriptional activator. Two yeast strains, of the opposite mating type and carrying one type each of the fusion proteins are mated together. Productive interactions between the two halves due to protein-protein interactions lead to the reconstitution of the transcriptional activator, which in turn leads to the activation of a reporter gene containing a binding site for the DNA-binding domain. This analysis can be carried out for two or more populations of proteins.

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: A method for detecting the presence of micronuclei in cells of an organism comprises the steps of (a) isolating cells of the organism, (b) exposing the cells to a hybridization probe, the hybridization probe comprising digested, labeled whole genomic DNA, the digested genomic DNA being labeled with a first binding member capable of specifically binding with a second binding member, whereby, as a result of exposing the cells to the hybridization probe, the hybridization probe binds hybridizes with DNA in the cells, including DNA contained in micronuclei, if present, (c) exposing the cells to a compound comprising the second binding member coupled to an enzyme capable of reacting with a chromogenic substrate to convert the chromogenic substrate into a colored pigment, whereby, as a result of exposing the cells to the compound, the compound binds to the hybridization probe that is hybridized with the DNA in the cells, (d) exposing the cells to the chromogenic substrate, whereby the chromogenic substrate is c

Abstract: Serial analysis of gene expression, SAGE, a method for the rapid quantitative and qualitative analysis of transcripts is provided. Short defined sequence tags corresponding to expressed genes are isolated and analyzed. Sequencing of over 1,000 defined tags in a short period of time (e.g., hours) reveals a gene expression pattern characteristic of the function of a cell or tissue. Moreover, SAGE is useful as a gene discovery tool for the identification and isolation of novel sequence tags corresponding to novel transcripts and genes.

Abstract: The present invention provides a method of transcriptionally modulating the expression of a gene-of-interest. The method comprises contacting a cell which is capable of expressing the gene with an amount of a molecule effective to transcriptionally modulate expression of the gene and thereby affect the level of the protein encoded by the gene which is expressed by the cell. Molecules useful in the practice of the invention are characterized as follows (a) do not naturally occur in the cell, (b) bind to DNA or RNA or bind to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the cell. Additionally, this invention provides a method for determining whether a molecule known to be a modulator of protein biosynthesis is capable of transcriptionally modulating expression of a gene-of-interest.

Abstract: This invention is directed towards a method for obtaining nucleic acid ligands against target proteins without directly purifying the target proteins. The method used in the invention is called SELEX, which is an acronym for Systematic Evolution of Ligands by EXponential enrichment. The nucleic acid ligands of the invention are useful as diagnostic and therapeutic agents for diseases in which the targets proteins play a causative role.

Abstract: The present invention relates, in general, to a process of enzymatically synthesizing nucleic acids containing nucleotides that are resistant to degradation. The invention further relates to methods of utilizing such nucleic acids in DNA and RNA amplification and sequencing, gene therapy and molecular detection protocols.

Abstract: Methods for detecting cancer that include hybridizing a set of chromosomal probes to a biological sample obtained from a patient, and identifying if aneusomic cells are present in a selected subset of cells obtained from the biological sample are described. A set of chromosomal probes and kits for detecting cancer that include sets of chromosomal probes, are also described.

Abstract: This invention discloses high-affinity oligonucleotide ligands to complex tissue targets, specifically nucleic acid ligands having the ability to bind to complex tissue targets, and the methods for obtaining such ligands. Tissue targets comprise cells, subcellular components, aggregates or cells, collections of cells, and higher ordered structures. Specifically, nucleic acid ligands to red blood cells ghosts, endothelia of the blood brain and CSF-blood barriers, glioblastomas, and lymphomas are described.

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: Methods are disclosed for identifying an RNA fragment that mimics the structure of a defined or undefined target RNA molecule to which a compound binds inside of a cell resulting in retardation of cell growth or cell death. Methods using these RNA fragments for identifying unknown compounds of pharmaceutical interest, and for identifying unknown RNA targets for use in treating disease are disclosed. These methods and compositions are used in screening for novel antibiotics, bacteriostatics, or modifications thereof or for identifying compounds useful to alter expression levels of proteins encoded by mRNA. The methods involve providing random DNA fragments from DNA which encodes RNA target molecules, cloning such fragments to create a plasmid library of same; transfecting cells which contain the native RNA target molecule with the plasmid library and exposing the cells to one or more of test compounds.

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: A method of fabricating deposits of non-volatile substances, including biomacromolecules, in the form of spots and filing on a substrate surface by electrospray, where the deposits are used to determine the interaction of the deposited non-volatile substances to other substances. Also included in this method is the mass fabrication on a single chip of an array of single and multicomponent microsamples.

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: Methods are described for the identification and preparation of high-affinity nucleic acid ligands to TGF&bgr;2. Included in the invention are specific RNA ligands to TGF&bgr;2 identified by the SELEX method. Also included are RNA ligands that inhibit the interaction of TGF&bgr;2 with its receptor.

Abstract: A group of oligonucleotides for the identification of sequences in a sample comprising human histamine H2 receptor DNA, cDNA or RNA originating from a tissue sample or body fluid is employed in the diagnosis and/or treatment of human neurological and psychiatric disorders, particularly schizophrenia, and diseases of other systems or organs of the human body. The oligonucleotides, suitable for use as primers for the amplification of DNA corresponding to a region of a human histamine H2 receptor, have nucleotide sequences selected from: 5′ACACCAGCCTGGATGTGA 3′(as listed in SEQ ID NO:12), 5′TCACATCCAGGCTGGTCT 3′ (as listed in SEQ ID NO:13), 5′ CAATCATACCACCTCTAA 3′ (as listed in SEQ ID NO:14), 5′ ACACAAACGCGGTGAAGT 3′(as listed in SEQ ID NO:15). Also described is a diagnostic kit comprising one or more of the above mentioned oligonucleotides.

Abstract: The present invention includes methods for the identification and production of improved nucleic acid ligands based on the SELEX process. Also included are nucleic acid ligands to the HIV-RT protein identified according to the methods described therein.

Abstract: The accumulation of homoplasmic somatic mutations has been observed in the mitochondrial DNA of certain tumor cells. The presence or recurrence of a tumor can be detected by determining the presence of single basepair mutations in the mitochondrial genome from a cell sample of a patient.

Abstract: The present invention relates to a linear DNA vector and to a method for identifying chromosomal regions having a physical proximity within a living cell, and/or for locating in chromosomes of a living cell a DNA double strand break having a physical proximity with a known non-repetitive DNA sequence. The linear DNA vector has a first end which comprises a nucleotide sequence capable of homologous recombination to a first region of a cell chromosome which comprises a known non-repetitive DNA sequence. The linear DNA vector also has a second end which comprises a nucleotide sequence non-homologous to the chromosomes of the cell and being capable of illegitimate integration with a second region of a chromosome in physical proximity to the first chromosomal region.

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.