Abstract: A process to obtain linear double-stranded covalently closed DNA “dumbbell” constructs from plasmids by restriction digest, subsequent ligation with hairpin oligodesoxyribonucleotides, optionally in the presence of restriction enzyme, and a final digestion with endo- and exonucleolytic enzymes that degrade all contaminating polymeric DNA molecules but the desired construct. The invention also provides a process to obtain said dumbbell constructs employing endonuclease class II enzymes. Furthermore, the invention provides a process to obtain linear, covalently closed DNA molecules, such as plasmids, free from contamination by genomic DNA, by submitting the DNA preparation to a facultative endonucleolytic degradation step and an obligatory exonucleolytic degradation step.

Abstract: Arrays of polynucleotide or polypeptide target molecules immobilized on a surface of a substrate where the target molecules are arranged in the array according to intensity of organism expression of cognate probe molecules which hybridize to the target molecules. For instance, target molecules having a higher than average indicia of hybridization, e.g. at least a factor of 2, are segregated at a peripheral region of the substrate and at a lower surface density. Preferred arrays can contain animal, plant or microorganism target molecules including Aspergillus nidulans. Diagnostic arrays can comprise targets from mixed species, e.g. human, mouse and virus; plant breeding arrays can comprise targets from mixed plants, e.g. Arabidopsis thaliana, maize, soy, cotton, wheat, rice, canola and potato.

Abstract: Disclosed is a process of performing Sexual PCR which includes generating random polynucleotides by interrupting or blocking synthesis or amplification process to slow or halt synthesis or amplification of at least one polynucleotides, optionally amplifying the polynucleotides, and reannealing the polynucleotides to produce random mutant polynucleotides. Also provided are vector and expression vehicles including such mutant polynucleotides, polypeptides expressed by the mutant polynucleotides and a method for producing random polypeptides.

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: The present invention provides methods for the determination of the structure of biomolecular targets, as well as the site and nature of the interaction between ligands and biomolecular targets. The present invention also provides methods for the determination of the relative affinity of a ligand for the biomolecular target it interacts with. Also provided are methods for screening ligand or combinatorial libraries of compounds against one or more than one biological target molecules. The methods of the invention also allow determination of the relative binding affinity of combinatorial and other compounds for a biomolecular target. The present invention further provides methods for the use of mass modifying tags for screening multiple biomolecular targets. In a preferred embodiment, ligands which have great specificity and affinity for molecular interaction sites on biomolecules, especially RNA can be identified.

Abstract: This invention discloses a method for preparing a complex comprised of a VEGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound by identifying a VEGF Nucleic Acid Ligand by SELEX methodology and associating the VEGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further discloses Complexes comprising one or more VEGF Nucleic Acid Ligands in association with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further includes a Lipid construct comprising a VEGF Nucleic Acid Ligand or Complex and methods for making the same.

Abstract: In accordance with the present invention, there are provided nucleic acids encoding human metabotropic glutamate receptor subtypes and the proteins encoded thereby. In a particular embodiment, the invention nucleic acids encode mGluR1, mGluR2, mGluR3 and mGluR5 subtypes of human metabotropic glutamate receptors. In addition to being useful for the production of metabotropic glutamate receptor subtypes, these nucleic acids are also useful as probes, thus enabling those skilled in the art, without undue experimentation, to identify and isolate related human receptor subunits. In addition to disclosing novel metabotropic glutamate receptor subtypes, the present invention also comprises methods for using such receptor subtypes to identify and characterize compounds which affect the function of such receptors, e.g., agonists, antagonists, and modulators of glutamate receptor function.

Abstract: The complete sequence of the canine von Willebrand Factor cDNA and deduced amino acid sequence is provided. The mutation which causes von Willebrand's Disease in Scottish Terriers, a single base deletion in exon 4, has also been determined. Methods for detecting carriers of the defective vWF gene are also provided.

Abstract: Methods are described for the identification and preparation of high-affinity Nucleic Acid Ligands to Complement System Proteins. Methods are described for the identification and preparation of high affinity Nucleic Acid Ligands to Complement System Proteins C1q, C3 and C5. Included in the invention are specific RNA ligands to C1q, C3 and C5 identified by the SELEX method.

Abstract: The present invention concerns new compositions and methods for the detection of pathological events. It more specifically concerns methods for the detection in vitro of the presence of a pathology or a pathological event in a subject, comprising taking a sample of blood cells from the subject and determining, in this sample, the presence of blood cells presenting a physiological state characteristic of the pathology. The invention also concerns the tools, kits and compositions for the implementation of such methods, as well as their uses in the field of human and animal health, or in experimental research for example.

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 non-volatile antifuse memories or volatile memories, such as EEPROMS, DRAMS or flash memory. 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 is provided for making synthetic capped RNAs. These compounds serve as substrates for the virally encoded endonuclease associated with influenza virus. We are able to assay for this unique and specific viral activity of cleavage of a capped RNA in vitro. Therefore, screening of inhibitors of this activity is possible. In addition, short non-extendible (due to their length or because of the modification of the 3′-end of the oligo, i.e. 3′-dA) RNAs are potent inhibitors of the cleavage of capped RNAs by influenza endonuclease. Finally, these compounds may be used to investigate viral and cellular mechanisms of transcription/translation or mRNA maturation.

Abstract: The present invention relates of the mammalian HKNG1 gene, a gene associated with bipolar affective disorder (BAD) in humans. The invention relates, in particular, to methods for the diagnostic evaluation, genetic testing and prognosis of HKNG1 neuropsychiatric disorders including schizophrenia, attention deficit disorder, a schizoaffective disorder, a bipolar affective disorder or a unipolar affective disorder.

Abstract: The invention provides methods for the production of polynucleotides with a desired property (e.g., conferring a desired phenotype and/or encoding polypeptide with a desired property) which is selectable or can be screened for. The method includes making insertions and/or deletions at random sites in DNA segments in a population. In some embodiments the random insertions and deletions are made recursively.

Abstract: The present invention provides nucleic acid markers for rice blast resistance genes Pi-ta and Pi-ta2, which hybridize with any RFLP probes isolated from rice genomic DNA and are located within a distance of 2.0 cM from rice blast resistance genes Pi-ta or Pi-ta2. According to the present invention, it becomes possible to easily identify rice blast resistance genes and related genes from rice cultivars containing Pi-ta or Pi-ta2, thus promoting development and breeding of superior cultivars. It becomes also possible to easily carry out a resistance test of rice. This will open up way to create new resistance genes.

Abstract: Methods are described for the isolation of nucleic acid ligands to integrins using the SELEX process. SELEX is an acronym for Systematic Evolution of Ligands by EXponential enrichment. The nucleic acid ligands of the present invention are useful as therapeutic and diagnostic agents.

Abstract: Methods and model systems for identifying and characterizing new therapeutic agents, particularly proteins, which mimic or inhibit the activity of all interferons, Type I interferons, IFN-&agr;, IFN-&bgr;, or IFN-&ggr;. The method comprises administering an interferon selected from the group consisting of IFN-&agr;, IFN &bgr;, IFN-&tgr;, IFN-&ohgr;, IFN-&ggr;, and combinations thereof to cultured cells, administering the candidate agent to a duplicate culture of cells; and measuring the effect of the candidate agent and the interferon on the transcription or translation of one or, preferably, a plurality of the interferon stimulated genes or the interferon repressed genes (hereinafter referred to as “ISG's” and “IRGs”, respectively). The model system is an array with gene probes that hybridize with from about 100 to about 5000 ISG and IRG transcripts.

Abstract: This invention comprises nucleic acid ligand for use as a diagnostic reagent for detecting the presence or absence of a target molecule in a sample, and a diagnostic reagent to measure the amount of a target molecule in a sample. In a preferred embodiment the nucleic acid ligands are identified by the method of the invention referred to as the Systematic Evolution of Ligands by EXponential enrichment (SELEX), wherein a candidate mixture of nucleic acids are iteratively enriched in high affinity nucleic acids and amplified by further partitioning.

Abstract: Methods and compositions are provided for detecting single nucleotide polymorphisms using a pair of oligonucleotides, a primer and a snp detection sequence, where the snp detection sequence hybridizes to the target DNA downstream from the primer and in the direction of primer extension. The snp detection sequence is characterized by having a nucleotide complementary to the snp and adjacent nucleotide complementary to adjacent nucleotides in the target and an electophoretic tag bonded to the 5′-nucleotide. The pair of oligonucleotides is combined with the target DNA under primer extension conditions, where the polymerase has 5′-3′ exonuclease activity. When the snp is present, the electophoretic tag is released from the snp detection sequence, and can be detected by electrophoresis as indicative of the presence of the snp in the target DNA.

Abstract: The invention employs an unlabeled signal primer comprising a 5′ adapter sequence for detection of nucleic acid target sequences. The detection system further comprises a reporter probe, the 3′ end of which hybridizes to the complement of the 5′ adapter sequence of the signal primer to produce a 5′ overhang. Polymerase is used to fill in the overhang and synthesize the complement of the 5′ overhang of the reporter probe. Synthesis of the reporter probe complement is detected, either directly or indirectly, as an indication of the presence of the target.