Abstract: A sensor is provided including a polymer capable of having an alterable measurable property from the group of luminescence and electrical conductivity, the polymer having an intermediate combination of a recognition element, a tethering element and a property-altering element bound thereto and capable of altering the measurable property, the intermediate combination adapted for subsequent separation from the polymer upon exposure to an agent having an affinity for binding to the recognition element whereupon the separation of the intermediate combination from the polymer results in a detectable change in the alterable measurable property, and, detecting said detectable change in the alterable measurable property.

Abstract: Novel methods are provided for identifying heterozygous carriers of autosomal recessive disorders such as Ataxia telangiectasia.

Abstract: The invention relates to polynucleotides for HSV detection and the use of these polypeptides in kits and methods for HSV detection.

Abstract: Solid support assays using non-standard bases are described. A capture oligonucleotide comprising a molecular recognition sequence is attached to a solid support and hybridized with a target oligonucleotide. In some instances, the molecular recognition sequence includes one or more non-standard bases and hybridizes to a complementary tagging sequence of the target oligonucleotide. In other instances, incorporation of a non-standard base (e.g., via PCR or ligation) is used in the assay.

Abstract: A method for dry detection/quantification of targeted nucleotide chains, comprising the steps of: (1) realizing a state in which a hybrid (C) of a certain amount of targeted nucleotide chain (A), which is derived from a sample solution and subjected to detection or quantification, and a probe nucleotide chain (B), which has a base sequence complementary to a specific site of the base sequence of the targeted nucleotide chain, is formed on a solid-phase substrate by mutually reacting the two types of nucleotide chains with each other, and in which there exists a fluorescence dye (D), which acts on the hybrid (C), thereby emits fluorescence or increases its fluorescence intensity, and is capable of continuing to emit fluorescence even in the dried state while acting on the hybrid; (2) drying the hybrid (C) and the fluorescence dye (D) on the substrate; and (3) measuring the fluorescence emitted from the fluorescence dye (D), as a measuring means, after the drying operation.

Abstract: The invention relates to polynucleotides for HSV detection and the use of these polypeptides in kits and methods for HSV detection.

Abstract: Green fluorescent protein (GFP) is widely used as a reporter in determining gene expression and protein localization. The present invention provides fusion proteins with a half life of ten hours or less with several embodiments having half lives of 4 hours or less. Such proteins may be constructed by fusing C-terminal amino acids of the degradation domain of mouse ornithine decarboxylase (MODC), which contains a PEST sequence, to the C-terminal end of an enhanced variant of GFP (EGFP). Fluorescence intensity of the fusion protein in transfected cells is similar to that of EGFP, but the fusion protein, unlike EGFP, is unstable in the presence of cycloheximide. Specific mutations in the MODC region have resulted in mutants with varying half lives, useful for a variety of purposes.

Abstract: Kits for the multiplexed detection of known, selected nucleotide target sequences are provided. Detection involves the release of identifying tags as a consequence of target recognition. The kits include sets of electrophoretic tag probes or e-tag probes, capture agent and optionally a nuclease. The e-tag probes comprise a detection region and a mobility-defining region called the mobility modifier, both linked to a target-binding moiety. In using the kits, the target-binding moiety of the e-tag probes hybridizes to complementary target sequences followed by nuclease cleavage of the e-tag probes and release of detectable e-tags or e-tag reporters. The mixture is exposed to a capture agent which binds uncleaved and/or partially cleaved e-tag probes, followed by electrophoretic separation. In a multiplexed assay, different released e-tag reporters may be separated and detected providing for target identification.

Abstract: Compounds having structure (1) wherein R1 is —H a protecting group, a linker or a binding partner; and R2 and R34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.

Abstract: The present invention provides modified oligonucleotide primers designed to incorporate a cleavable moiety so that a 3? portion of the primer (linked to an extension product) can be released from an upstream 5? portion of the primer. Upon selective cleavage of the cleavable site, primer extension products that contain about five or fewer base pairs of the primer sequence are released, to provide more useful sizing and sequence information per fragment than extension products containing the entire primer.

Abstract: The invention relates to a novel labeling reactant of formula (I) suitable for labeling an oligonucleotide wherein: R is a temporary protecting group. A is either a phosphorylating moiety or a solid support tethered to a bridge point Z via a linker arm E. E? is a linker arm between G and Z. G is a bivalent aromatic structure, tethered to two iminodiacetic acid ester groups N(COOR??)2 or G is a structure selected from a group consisting of G is a protected functional group. The invention further concerns a method for direct attachment of a conjugate group to an oligonucleotide structure enabling the attachment of a desired number of these groups during chain assembly. The method comprises a Mitsonobu alkylation.

Abstract: 2-(6-Cyano-1-hexyn-1-yl)adenosine, 2-(6-cyano-1-hexyn-1-yl)adenosine 5?-monophosphate, or salts thereof; and drugs containing the same as an active ingredient. The compounds have excellent effects of lowering ocular tension, promoting blood flow in retina, and protecting optic nerve failure and are highly soluble in water. Owing to these characteristics, the compounds are useful as drugs such as remedies for glaucoma and ocular hypertension.

Abstract: A compound of formula 1-[3,4-dihydroxy-5-(2-hydroxyethyl)tetrahydrofuran-2-yl]pryimidine-2,4(1H,3H)-dione has inhibitory effects of matrix metalloproteinase-2 (gelatinase A) enzyme and binding of TNF? to TNF?-RI.

Abstract: The invention is directed to methods for the non-radioactive labeling, detection, quantitation and isolation of nascent proteins translated in a cellular or cell-free translation system. tRNA molecules are misaminoacylated with non-radioactive markers which may be non-native amino acids, amino acid analogs or derivatives, or substances recognized by the protein synthesizing machinery. Markers may comprise cleavable moieties, detectable labels, reporter properties wherein markers incorporated into protein can be distinguished from unincorporated markers, or coupling agents which facilitate the detection and isolation of nascent protein from other components of the translation system. The invention also comprises proteins prepared using misaminoacylated tRNAs which can be utilized in pharmaceutical compositions for the treatment of diseases and disorders in humans and other mammals, and kits which may be used for the detection of diseases and disorders.

Abstract: Linked nucleosides having at least one functionalized nucleosid that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2?-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining linked nucleosides are 2?-deoxy-2?-fluoro, 2?-O-methoxy, 2?-O-ethoxy, 2?-O-propoxy, 2?-O-aminoalkoxy or 2?-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3? or the 5? positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.

Abstract: Probe sets for the multiplexed detection of known, selected nucleotide target sequences are provided. Detection involves the release of identifying tags as a consequence of target recognition. The probe sets include electrophoretic tag probes or “e-tag probes”, comprising a detection region and a mobility-defining region called the mobility modifier, both linked to a target-binding moiety. The target-binding moiety of the e-tag probes hybridizes to complementary target sequences followed by nuclease cleavage of the e-tag probes and release of detectable e-tags or e-tag reporters. The mixture is exposed to a capture agent which binds uncleaved and/or partially cleaved e-tag probes, followed by electrophoretic separation. In a multiplexed assay, different released e-tag reporters may be separated and detected providing for target identification.

Abstract: The present invention relates to detection or genotyping (or other sample analysis) of target nucleic acids following immobilization of the target nucleic acids onto a surface. The target nucleic acids can be re-used multiple times, thus conserving sample materials and simplifying sample preparation.

Abstract: The present invention pertains to a method for determining the sequence of a polynucleotide, the method relying on the detection of a conformational change in an enzyme that interacts with and processes along the polynucleotide. The detection of a conformational change may be carried out by measuring changes in a fluorophore bound to the enzyme.

Abstract: The present invention relates to fluorescent probes which can be used in multicolor fluorescence in situ hybridization, and mainly chromosome painting. The probes intended for labeling a chromosome are such that they are composed of a set of DNA segments which are more represented in certain chromosome bands and which are obtained by IRS-PCR amplification from said chromosomes using PCR primers specific for the repeated and dispersed Alu and LINE DNA sequences. The invention comprises, in addition, methods of producing said probes, multicolor FISH methods which can use said probes as well as diagnostic kits comprising them. Finally, the invention comprises combinations of fluorophores and optical filters.

Abstract: The present invention concerns oligonucleotides containing one or more modified nucleotides which increase the binding affinity of the oligonucleotides to target nucleic acids having a complementary nucleotide base sequence. These modified oligonucleotides hybridize to the target sequence at a faster rate than unmodified oligonucleotides having an identical nucleotide base sequence. Such modified oligonucleotides include oligonucleotides containing at least one 2?-O-methylribofuranosyl moiety joined to a nitrogenous base. Oligonucleotides can be modified in accordance with the present invention to preferentially bind RNA targets. The present invention also concerns methods of using these modified oligonucleotides and kits containing the same.

Abstract: The invention comprises novel methods and strategies to detect and/or quantify nucleic acid analytes. The methods involve nucleic acid probes with covalently conjugated dyes, which are attached either at adjacent nucleotides or at the same nucleotide of the probe and novel linker molecules to attach the dyes to the probes. The nucleic acid probes generate a fluorescent signal upon hybridization to complementary nucleic acids based on the interaction of one of the attached dyes, which is either an intercalator or a DNA groove binder, with the formed double stranded DNA. The methods can be applied to a variety of applications including homogeneous assays, real-time PCR monitoring, transcription assays, expression analysis on nucleic acid microarrays and other microarray applications such as genotyping (SNP analysis). The methods further include pH-sensitive nucleic acid probes that provide switchable fluorescence signals that are triggered by a change in the pH of the medium.

Abstract: Disclosed are methods for identifying nucleic acid sequences which are of different abundances in different nucleic acid source populations, e.g. differentially expressed genes or genomic variations among individuals or populations of individuals. In one embodiment, probes derived from the source nucleic acid populations are derivatized with a terminal sample ID (SID) sequence characteristic of that population. Upon competitive hybridization of the probes to a reference or index nucleic acid library containing all the sequences in the populations being compared, the SID tags remain single stranded, and those from the different sources are then annealed to one another. Unhybridized (remainder) SID sequences are then quantified. By labeling such remainder SID sequences with a fluorescent dye, FACS sorting of beads containing the hybridized probes can be carried out. The signal ratio upon which such sorting is based is enhanced compared to competitive hybridization using labeled probes without SID sequences.

Abstract: External control reagents for nucleic acid amplification are provided that verify the absence or presence of specific target sequences, and correct primers and probes. A single-stranded, external control polynucleotide is amplified with primers of the same sequence as target primers. Probes with detectable labels and sequences specific for target and external control polynucleotides allow for detection and measurement. The primers and the detectable probe are adjacent or substantially adjacent when hybridized to the external control polynucleotide. Target and control amplicons may be detected by increased fluorescence induced by polymerase-mediated 5? nuclease cleavage or hybridization of a self-quenching probe complementary to both target and external control polynucleotides. A kit of PCR reagents can be dispensed into vessels for rapid and accurate nucleic acid amplification assay, with real-time or end-point measurements.

Abstract: An automated analyzer for performing multiple diagnostic assays simultaneously includes multiple stations, or modules, in which discrete aspects of the assay are performed on fluid samples contained in reaction receptacles. The analyzer includes stations for automatically preparing a specimen sample, incubating the sample at prescribed temperatures for prescribed periods, preforming an analyte isolation procedure, and ascertaining the presence of a target analyte. An automated receptacle transporting system moves the reaction receptacles from one station to the next.

Abstract: The invention provides novel dye-labeled ribonucleotide analogs and methods for synthesizing those analogs. The compounds of the invention are especially useful for DNA sequencing by the polymerase chain reaction.

Abstract: A process for substantially enhancing the regio and stereoselective synthesis of 9-?-anomeric nucleoside analogs is described. The introduction of the sugar moiety onto a 6-substituted purine base was preformed so that only the 9-?-D- or L-purine nucleoside analogs were obtained. This regio and stereoselective introduction of the sugar moiety allows the synthesis of nucleoside analogs and in particular 2?-deoxy, 3?-deoxy, 2?-deoxy-2?-?-fluoro and 2?,3?-dideoxy-2?-?-fluoro purine nucleoside analogs in high yield without virtually any formation of the 7-positional isomers. The compounds are drugs or intermediates to drugs.

Abstract: Novel compounds are provided which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group. The protecting group has the general formula Ar—C(R1)(R2)—O—C(O)— wherein: Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogous derivative thereof; R1 and R2 are independently H, optionally substituted alkyl, alkenyl or alkynyl, optionally substituted aryl or optionally substituted heteroaromatic, or a vinylogous derivative of the foregoing; and X is a leaving group, a chemical fragment linked to Ar—C(R1)(R2)—O—C(O)— via a heteroatom, or a solid support; provided that when Ar is 1-pyrenyl and R1 and R2 are H, X is not linked to Ar—C(R1)(R2)—O—C(O)— via a nitrogen atom.

Abstract: The invention relates to a functionalized compound of general formula (I): in which W represents a nucleotide analog, L represents a linker arm comprising at least four atoms, R1 represents a linear or branched alkyl chain, A functionalized polynucleotide comprising at least one said compound and a labeled functionalized polynucleotide comprising at least one functionalized compound corresponding to the formula (I?). A method for detecting a target nucleic acid using a said compound is described.

Abstract: This invention relates to non-radioactive markers that facilitate the detection and analysis of nascent proteins translated within cellular or cell-free translation systems. Nascent proteins containing these markers can be rapidly and efficiently detected, isolated and analyzed without the handling and disposal problems associated with radioactive reagents. Preferred markers are dipyrrometheneboron difluoride (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dyes.

Abstract: A method for detecting white spot syndrome virus (WSSV) in a sample includes the steps of (a) adding to the sample a thermostable polymerase, appropriate nucleoside triphosphates, a nucleic-acid-binding fluorescent entity, and a pair of primers substantially complementary to a target nucleic acid having the sequence shown in SEQ ID NO: 1 or the complement of the target nucleic acid; (b) thermally cycling the sample between at least a denaturation temperature and an elongation temperature; (c) illuminating the sample with a selected wavelength of light that is absorbed by the fluorescent entity during the thermally cycling step; (d) determining the amount of fluorescence generated by the fluorescent entity; and (e) detecting the presence of the target nucleic acid by analyzing the amount of luminescence determined after at least one amplification cycle. The invention further provides kits for detection of WSSV in samples.

Abstract: Oligonucleotide-folate conjugates are described wherein folates are conjugated to one or more sites on an oligonucleotide including the 2?-, 3?-, 5?-, nucleobase and internucleotide linkage sites. The folate can be attached via the ?- or ?-carboxylate, optionally through a linking group. Methods for the regiospecific synthesis of the conjugates are disclosed. Also disclosed are nucleosidic and non-nucleosidic linkers conjugated to folic acid and related folates.

Abstract: A method for screening molecule which have a synthetic lethal property when in combination with a gene of interest carrying a non-lethal mutation, said method comprising the steps of: transfecting a first reporter gene into mammalian cells having a genome comprising a gene of interest which carries a non-lethal mutation, or a genome which is null of said gene of interest; selecting clones stably expressing said fist reporter gene; introducing into said cells a survival plasmid comprising a functioning copy of said gene of interest, a second reporter gene, selectable marker, an origin of DNA replication and a nuclear antigen gene essential for replication of the plasmid within said cells, wherein said survivsal plasmid is autonomously replicating and spontaneously lost from said cells; growing said cells in the presence of a selection compound which selects for said selectable marker; selecting cell clones stably expressing said second reporter gene and said functioning copy of said gene of interest; removing

Abstract: The invention provides methods for detecting contamination in a PCR reaction. Methods of the invention are especially useful for detection of contamination in heterogeneous samples containing a rare nucleic acid to be detected.

Abstract: Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. The heterocyclic derivative containing compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

Abstract: The present invention provides a DNA base sequencing system having a compact, simple and convenient structure. In one embodiment of the present invention, a reaction chamber module for pyrosequencing in which a multiple number of reaction vessels (reaction chambers) 10 and reagent-introducing narrow tubes 6 are integrated is formed in a device board 5. Reagents held in reagent reservoirs 1, 2, 3 and 4 mounted separately from this reaction chamber module are introduced into the reaction vessels 10 via reagent-introducing narrow tubes (capillaries) 6. The reagent-introducing narrow tubes (capillaries) 6 at the area of 2 cm from the reaction vessels 10 are structured with narrow capillaries having an inner diameter of about 0.1 mm and the conductance of these capillaries for the reagent solution determines the injection speed of the solution. Using the present invention, many kinds of DNAs can be analyzed simultaneously.

Abstract: One of the major peanut allergens, Ara h I, was selected from cDNA expression library clones using Ara h I specific oligo-nucleotides and polymerase chain reaction technology. The Ara h I clone identified a 2.3 kb mRNA species on a Northern blot containing peanut poly A+RNA. DNA sequence analysis of the cloned inserts revealed that the Ara h I allergen has significant homology with the vicilin seed storage protein family found in most higher plants. The isolation of the Ara h I clones allowed the synthesis of this protein in E. coli cells and subsequent recognition of this. recombinant protein in immunoblot analysis using serum IgE from patients with peanut hypersensitivity.

Abstract: Methods and compositions to label oligonucleotides and analogs directly on a solid-support having the structure where S is a solid-support, A is a cleavable linker, X is a moiety with three or more attachment sites, L is a label, Y is a nucleophile, i.e. O, NH, NR or S, and P1 is an acid cleavable protecting group are provided. The labelled solid-support is reacted in a cyclical fashion to synthesize a labelled oligonucleotide on a solid-support in the 5′ to 3′ direction, having the structure: Labelled oligonucleotides are also synthesized by reacting: (i) a label reagent bearing functionality consisting of carboxylic acid, sulfonic acid, phosphonic acid, or phosphoric acid, (ii) an oligonucleotide on solid support with nucleophilic functionality, and (iii) a coupling reagent, whereby an ester, amide, thioester, sulfonamide, sulfonate, phosphonate, phosphoramidate, phosphorothioate, or phosphate bond is formed.

Abstract: The invention relates to a novel labeling reactant of formula (I) suitable for labeling an oligonucleotide 1

Abstract: Novel compounds having a fluorescence quencher as a leaving group are disclosed. Nucleic acids and other molecules containing a fluorophore and a fluorescence quencher are disclosed as an embodiment of this invention. The use of the oligonucleotides in enzyme-free oligonucleotide ligation reactions results in an increase in fluorescence when the oligonucleotide also contains a nearby fluorophore. The ligation reactions can be performed in solution, on surfaces, or in cells.

Abstract: Methods are provided for preparing nucleic acid arrays on a support. In these methods a plurality of nucleic acids are synthesized on the support and the synthesis steps include oxidizing a phosphite triester nucleic acid linkage to a phosphate triester nucleic acid linkage using a solution about 0.005 to about 0.05 M iodine in a mixture comprising water and organic solvent.

Abstract: This invention provides for labeling reagents, labeled targets and processes for preparing labeling reagents. The labeling reagents can take the form of cyanine dyes, xanthene dyes, porphyrin dyes, coumarin dyes or composite dyes. These labeling reagents are useful for labeling probes or targets, including nucleic acids and proteins. These reagents can be usefully applied to protein and nucleic acid probe based assays. They are also applicable to real-time detection processes.

Abstract: The present invention concerns methods and compositions involving labeled, double-stranded RNA (dsRNA), including siRNA, capable of triggering RNA-mediated interference (RNAi) in a cell. Compositions of the invention include labeled dsRNA for RNAi, which may be a single strand of RNA that basepairs with itself or two separate RNA strands. In some embodiments, the label is fluorescent. The present invention further concerns methods for preparing such composition and kits for implementing such methods. Other methods of the invention include ways of using labeled dsRNA for RNAi.

Abstract: The present invention relates to a method for labeling a nucleic acid characterized in that a ratio of signal intensities of each of labels of the labeled nucleic acids prepared from the same nucleic acid used as a template is substantially the same, irrelevant to the kinds of nucleic acids used as the template, a labeled nucleic acid prepared by the method, and a kit used for the method.

Abstract: The invention relates to compositions and methods useful in the labeling and identification of proteins. The invention provides for highly soluble zwitterionic dye molecules where the dyes and associated side groups are non-titratable and maintain their net zwitterionic character over a broad pH range, for example, between pH 3 and 12. These dye molecules find utility in a variety of applications, including use in the field of proteomics.

Abstract: Provided are compositions and assay kits comprising functionalized nanocrystals having extending therefrom a plurality of polynucleotide strands of known sequence; wherein primary dots are used to operably link to a molecular probe, and secondary dots comprise a plurality of polynucleotide strands which are complementary to the plurality of polynucleotide strands of the primary dots. Also provided is a method for detecting the presence or absence of target molecule in a sample comprising operably linking primary dots to molecular probe, contacting the complex formed with the sample, contacting the sample with successive additions of secondary dots and primary dots. If target molecule is present in the sample, the primary dots and secondary dots will form dendrimers that can be detected by fluorescence emission.

Abstract: Materials and methods for incorporating adenosine derivatives into the 5′ end of transcribed RNA are disclosed. Adenosine derivatives include naturally occurring compounds such as Coenzyme A, NAD, and FAD, as well as various non-naturally occurring compounds. The derivatives can be used to impart desirable properties to the RNA such as fluorescence, the ability to bind to receptors or ligands, and improved catalytic activity.

Abstract: The present invention relates to methods for the detection of polymorphism in polynucleotides by using hybridization of fragments of segments of a polynucleotide suspected of containing a polymorphism with an oligonucleotide having a sequence complementary to a fragment identifying the polymorphism and subsequent detection of incorporated labels in the oligonucleotide-fragment duplex.

Abstract: Selectively functionalized oligonucleotides, methods for making same, and compounds useful therefor are disclosed. The oligonucleotides can be selectively functionalized with a first conjugate group at the 3′-terminial position and optionally functionalized with a second conjugate group at the 5′-terminal position and/or one or more internucleotides. Alternatively, the oligonucleotides can be selectively functionalized with a first conjugate group at the 5′-terminal position and optionally functionalized with a second conjugate group at one or more internucleotides. In yet another embodiment, the oligonucleotides can be functionalized with a first conjugate group at one or more internucleotides and with a second conjugate group at one or more different internucleotides.

Abstract: The invention relates to a quality control method for manufacturing biopolymer arrays comprising (a) synthesizing a plurality of different biopolymer species on an array from monomeric or oligomeric building blocks comprising detectable protecting groups; (b) optionally carrying out a determination of the detectable protecting groups on the array after synthesis; (c) cleaving off the detectable protecting groups; and (d) carrying out a determination of the detectable protecting groups on the array after cleavage in order to determine the efficacy of deprotection.

Abstract: A novel method for the labeling of oligonucleotides which results in the economical synthesis of 5′ labeled molecules. A set of suitably protected and carefully selected set of amino linkers, a modified deprotination/cleavage protocol and standard coupling methodologies to are used to allow for the convergent synthesis of any number of labeled oligonucleotides.