Abstract: The invention relates two general methods for performing PCR amplification, combined with the detection and analysis of the PCR products on a microchip. In the first method, the amplification occurs both outside and within a plurality of gel pads on a microchip, with at least one oligonucleotide primer immobilized in a gel pad. In the second method, PCR amplification also takes place within gel pads on a microchip, but the pads are surrounded by a hydrophobic liquid such as that which separates the individual gel pads into environments which resemble micro-miniaturized test tubes.

Abstract: The invention provides a novel nucleic acid binding assay, which is useful for assessing the sequence-dependence of the binding of ligands to nucleic acid molecules, as well as for determining the affinity of the binding interaction. The invention also provides a selection method based on this nucleic acid binding assay. This selection method allows co-selection of ligands and the nucleic acid molecules that they bind. Additionally, the invention provides kits that can be used for carrying out the methods of the invention.

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: Cells collected from bladder washings or urine may be analyzed by in situ hybridization. Such analysis includes detection of bladder cancer or carcinoma-in-situ.

Abstract: The invention relates to a protein VanB involved, in Gram-positive bacteria, in resistance to glycopeptides, particularly to vancomycine, said resistance being of the type inducible by the vancomycine and non-inducible by teicoplanine. The invention also relates to the utilisation of fragments of nucleotides of the gene van B for the detection of resistances to glycopeptides.

Abstract: The present invention relates to a process for screening for a gene involving a coronary artery spasm-associated disease, which comprises detecting the presence of the relevant nucleotide substituents in the endothelial nitric oxide synthase (eNOS) gene. The present invention provides the ready diagnosis of a coronary artery spasm-associated disease such as angina, which cannot be conveniently screened by the conventional methods.

Abstract: Disclosed is a method of producing random polynucleotides by introducing two or more related polynucleotides into a suitable host cell such that a hybrid polynucleotide is generated by recombination and reductive reassortment. Also provided are vector and expression vehicles including such polynucleotides, polypeptides expressed by the hybrid polynucleotides and a method for screening for hybrid polypeptides.

Abstract: The VSET method comprises: providing a polynucleotide acid sample comprising at least one target site, and a first region of nucleotides immediately adjacent to the target site; preferably genomic DNA; preferably amplifying the polynucleotide; then combining the polynucleotide sample with: three dideoxynucletides selected from the group of ddGTP, ddATP, ddCTP, and ddTTP; and one deoxynucleotide selected from the group consisting of and dGTP, dATP, dCTP, and dTTP wherein the nucleotide of the deoxynucleotide is not the same as the nucleotide in the dideoxynulceotide; and a mini-sequencing primer complementary to the first region of nucleotides; extending the mini-sequencing primer with a dideoxynucletide or deoxynulceotide whose base is complementary to the base at the target site, to provide extension products; and then identifying the extension products, preferably by (MALDI-TOF) mass spectrometry.

Abstract: Disclosed is an in vitro process for synthesizing DNA encoding a family of antigen-combining proteins. This process involves obtaining DNA containing genes encoding antigen-combining proteins and then combining these genes with sequence specific primers. These primers can be oligonucleotides homologous to conserved regions of the genes. The genes and primers are then subjected to sequence specific gene amplification.

Abstract: The present invention relates to a novel gene, NBS1, and its gene product, nibrin. In addition, it relates to methods for detecting mutations or polymorphisms of the gene that are associated with Nijmegen breakage syndrome in patients. Such mutations may be used to diagnose a predisposition to the development of certain pathological conditions in these patients.

Abstract: A process for the production of a naturally folded eukaryotic polypeptide containing two or several cysteines linked by disulfide bridges by a) culturing prokaryotic cells in which the said prokaryotic cells contain an expression vector which codes for the said polypeptide which contains a prokaryotic signal sequence at the N-terminus, b) secreting the polypeptide into the periplasm or the medium, c) cleaving the signal sequence and isolating the polypeptide from the periplasm or the medium, which is characterized in that a nucleic acid coding for a molecular chaperone is additionally expressed in the said prokaryotic cell and the chaperone is secreted into the periplasm, is suitable for the recombinant production of polypeptides in prokaryotes in a high yield.

Abstract: Detection of probe fragment products of basepair mismatch cleavage indicate the presence and sequence of target DNA. Detection of the target is enhanced by amplification through recycling targets by maintaining an assay temperature between the melting point of the target/probe DNA duplex and that of the target/product complex, in the presence of an amplifier comprising ammonium acetate or an amine derivative (for example, diethylamine, piperidine or ammonium carbonate). Cleavage reduces the size of the duplex, and thus lowering its melting point. The amplifier releases the target from the complex, thereby permitting further catalysis of cleavage and effectively amplifying the signal to be detected.

Abstract: A method of using micromechanical devices as sensors for detecting chemical interactions between naturally occurring bio-polymers which are non-identical binding partners is provided. The method is useful whether the reactions occur through electrostatic forces or other forces. Induced stress, heat, or change in mass is detected where a binding partner is placed on a cantilever for possible reaction with an analyte molecules (i.e., a non-identical binding partner). The method is particularly useful in determining DNA hybridization but may be useful in detecting interaction in any chemical assay.

Abstract: Amplification of chromosomal DNA in situ to increase the amount of DNA associated with a chromosome or chromosome region is described. The amplification of chromosomal DNA in situ provides for the synthesis of Fluorescence in situ Hybridization (FISH) painting probes from single dissected chromosome fragments, the production of cDNA libraries from low copy mRNAs and improved in Comparative Genomic Hybridization (CGH) procedures.

Abstract: The invention provides fast and highly accurate mass spectrometer based processes for detecting a particular nucleic acid sequence in a biological sample. Depending on the sequence to be detected, the processes can be used, for example, to diagnose a genetic disease or chromosomal abnormality; a predisposition to a disease or condition, infection by a pathogenic organism, or for determining identity or heredity.

Abstract: A process for instabilizing viral quasi-species-distributions under avoidance of resistance phenomena by replication of the nucleic acids of the viruses present in the quasi-species-distribution by of a defective replication system, a) whereby the defective replication system has a rate of misincorporation for nucleotides above the rate of misincorporation of the viral wild-type-replication system and, whereby the viruses are replicated by the replication system having the higher rate of misincorporation at least as effectively as it is done by the replication system of the wild-type virus, b) and/or negative influence of the replication of the consensus-sequence (nucleic acid sequence of the wild-type virus) in relation to other replicatable nucleic acids.

Abstract: The present invention relates to a novel human antimicrobial peptide which is a member of the defensin superfamily. In particular, isolated nucleic acid molecules are provided encoding the human antimicrobial peptide. Antimicrobial peptide are also provided as are vectors, host cells and recombinant methods for producing the same. Also provided are diagnostic methods for detecting disorders related to the immune system and therapeutic methods for such disorders.

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: Sequencing of a selected region of a target nucleic acid polymer in a natural abundance DNA sample can be performed in a single vessel by combining the sample with a sequencing mixture containing a primer pair, a thermally stable polymerase such as Thermo Sequenase™ which incorporates dideoxynucleotides into an extending nucleic acid polymer at a rate which is no less than about 0.4 times the rate of incorporation of deoxynucleotides, nucleotide feedstocks, and a chain terminating nucleotide. The reaction mixture also includes an unconventional nucleotide and an appropriate enzyme for degradation of nucleic acid polymers containing the unconventional nucleotide. The mixture is processed through multiple thermal cycles for annealing, extension and denaturation to produce a product mixture which is analyzed by electrophoresis.

Abstract: Methods are provided for identifying agents that modulate the expression of genes, such as genes encoding tumor suppressor or tumor-promoting proteins. The methods generally comprise screening candidate agents for the ability to enhance expression of a tumor suppressor gene, such as mda-7, or for the ability to inhibit expression of a tumor-promoting gene within a cell. Modulating agents may be used, for example, within anti-cancer therapies.