Abstract: The present invention demonstrates that mitochondrial DNA damage occurs prior to, or simultaneous with, atherosclerotic lesion development, that aortic mitochondrial DNA damage increases with age, and that genotype and diet both influence the level of mitochondrial DNA damage. Hence, the present invention demonstrates that mitochondrial DNA damage occurs early in atherosclerosis, and may be an initiating event in atherogenesis, and provides methods to predict coronary atherosclerotic heart disease based upon the amount of mitochondrial DNA damage.

Abstract: Nucleic acids comprising the RNA component of a mammalian telomerase are useful as pharmaceutical, therapeutic, and diagnostic reagents.

Abstract: The present invention relates to methods, reagents and compositions, for conducting electrochemiluminescence binding assays which improve one or more characteristics of the assay or the instruments used to conduct the assay. The method is achieved using microparticles that include electrically conductive material. The electrically conductive material has one or more copies of an assay ligand immobilized an its outer surface and a plurality of electrochemiluminescent moieties immobilized an its outer surface. The assay ligand may be linked to the electrochemiluminescent moiety.

Abstract: Methods are disclosed for immobilizing a substance to a surface. A surface is employed that comprises a linking group consisting of a first portion comprising a hydrocarbon chain, optionally substituted, and a second portion comprising an alkylene oxide or an alkylene imine wherein the alkylene is optionally substituted. One end of the first portion is attached to the surface and one end of the second portion is attached to the other end of the first portion chain by means of an amine or an oxy functionality. The second portion terminates in an amine or a hydroxy functionality. The surface is reacted with the substance to be immobilized under conditions for attachment of the substance to the surface by means of the linking group. Compositions of matter and reaction systems are also disclosed.

Abstract: The present invention is generally directed to microfluidic systems and methods of using such systems in the determination of the nucleotide sequence of target nucleic acid sequences (referred to herein as the “target”). In particular, the present invention provides methods and systems for determining the relative positions within a target nucleic acid sequence that are occupied by a given nucleotide, e.g., A, T, G or C, by separating mixtures of nested sets of fragments of the target nucleic acid, which sets each include fragments that terminate in a different given nucleotide.

Abstract: Novel xylo nucleoside or xylo nucleotide analogs, polynucleotides comprising xylo nucleotide substitution, processes for their synthesis and incorporation into polynucleotides.

Abstract: Methods and compounds, including compositions therefrom, are provided for determining the sequence of nucleic acid molecules. The methods permit the determination of multiple nucleic acid sequences simultaneously. The compounds are used as tags to generate tagged nucleic acid fragments which are complementary to a selected target nucleic acid molecule. Each tag is correlative with a particular nucleotide and, in a preferred embodiment, is detectable by mass spectrometry. Following separation of the tagged fragments by sequential length, the tags are cleaved from the tagged fragments. In a preferred embodiment, the tags are detected by mass spectrometry and the sequence of the nucleic acid molecule is determined therefrom. The individual steps of the methods can be used in automated format, e.g., by the incorporation into systems.

Abstract: Method and devices for performing chromatographic pattern analysis determine chromatographic variability due to a plurality of sources without requiring identification or characterization of peaks or other chromatographic features, receives data indicative of a standard chromatogram and a first sample chromatogram generated from a first mixture by a High Pressure Liquid Chromatography (HPLC) device and data indicative of a plurality of additional sample chromatograms generated by the HPLC device from a plurality of different mixtures. The method and devices generate from the standard chromatogram, a plurality of sets of chromatographic variability data, each set being indicative of a different effect of the chromatographic variability of the HPLC. The standard chromatogram is modified as a function of the variability data, and a residual value, indicative of a difference between the modified standard chromatograms and the first sample chromatogram is generated.

Abstract: A chemical analog of adenine is provided which can be incorporated into DNA but base pairs as normal, and does not disrupt DNA secondary structure. The analog is cleavable and disrupts functionality with DNA-binding protein. The analog finds use in a technique provided by the invention involving TDI footprinting or adenine-DNA contacts.

Abstract: Conjugates between a minor groove binding molecule, such as the trimer of 1,2-dihydro-(3H)-pyrrolo[3,2-e]indole-7-carboxylate (CDPI3), and an oligonucleotide form unusually stable hybrids with complementary target sequences, in which the tethered CDPI3 group resides in the minor groove of the duplex. These conjugates can be used as probes and primers. Due to their unusually high binding affinity, conjugates as short as 8-mers can be used as amplification primers with high specificity and efficiency. MGB conjugation also increases the discriminatory power of short oligonucleotides, providing enhanced detection of nucleotide sequence mismatches by short oligonucleotides.

Abstract: Nucleic acid analogues provide a particularly useful tool for the preparation of complex polymeric structures of defined geometry because they are relatively stable to reaction conditions for the preparation of such structures and provide the opportunity to introduce reactive groups which would not be possible with usual nucleic acids. These supramolecular structures can be used to form fine networks in nanometer size, for the preparation of e.g., computer chips, new materials/polymers with conductivity and/or insulator properties, and robot arms in nanometer scale.

Abstract: The present invention comprises an improved method of synthesizing oligonucleotides. The method comprises employing dinucleotides (or “dimer blocks”) as the basic synthetic unit building block. The method results in extremely high purity oligonucleotides in which the N−1 content is very low, generally less than 1-2% of the full length, N, oligonucleotide. We have found that synthesis using dinucleotide phosphorothioates results in oligonucleotides having very little phosphodiester content. Furthermore, we have found that the amount of dimer required in each coupling step can be less than about 6 and is preferably about 2 equivalents. Synthesis of oligonucleotides according to the dimer block approach described herein can also be conducted without the capping step that has heretofore been deemed necessary after each coupling.

Abstract: A technique for immobilizing biological molecules, in particular nucleic acid strands, is described. Biological molecules immobilized at surfaces can be used in electron-transfer detection techniques in which a binding partner of a biological molecule is brought into proximity of the surface-immobilized biological molecule, an electrical potential created between the two biologically-binding species, and electron transfer through the species determined. Another technique involves immobilizing a bioligical molecule such as a protein, DNA, etc. at a surface via a self-assembled monolayer, affecting the biological molecule via, for example, biological binding, inducing a change in conformation via a prion, etc., and detecting an electronic property change in the molecule via a change in inpedence associated with an electronic circuit addressed by the biological molecule. These technique facilitates combinatorial array detection articles.

Abstract: Normalization of experimental fragment patterns for nucleic acid polymers having putatively known sequences starts with obtaining at least one raw fragment pattern for the experimental sample. The raw fragment pattern represents the positions of a selected nucleic acid base within the polymer as a function of migration time or distance. This raw fragment pattern is conditioned using conventional baseline correction and noise reduction technique to yield a clean fragment pattern. The clean fragment pattern is then evaluated to determine one or more “normalization coefficients.

Abstract: The present disclosure provides a method for the identification of nucleotide sequences which encode selenoproteins. Nucleotide sequences are translated in all potential reading frames, those with a relatively large number of UGA or TGA codons are noted, and frameshift-dependent open reading frames and SECIS elements are identified as associated with selenoprotein coding sequences, especially those within or overlapping known open reading frames. Further provided are selenoprotein coding sequences which are associated with certain viruses (e.g., HIV and Ebola), cancer-related genes and coding sequences related to normal functioning of the immune system.

Abstract: Methods and compositions are provided for forming complexes intracellularly between dsDNA and oligomers of heterocycles, aliphatic amino acids, particularly omega-amino acids, and a polar end group. By appropriate choice of target sequences and composition of the oligomers, complexes are obtained with low dissociation constants. The formation of complexes can be used for modifying the phenotype of cells, either prokaryotic or eukaryotic, for research and therapy.

Abstract: Methods for creating and using polypeptide probes with high affinity for any desirable coiled coil region are described, as well as heterospecific polypeptide probes directed to the coiled coil region of a target polypeptide. Core residue packing rules are provided for selective amino acid pairing and packing in the hydrophobic core of the interhelical interface.

Abstract: A class of asymmetric monobenzoxanthene compounds useful as fluorescent dyes are disclosed having the structure wherein Y1 and Y2 are individually hydroxyl, amino, imminium, or oxygen, R1-R8 are hydrogen, fluorine, chlorine, alkyl, alkene, alkyne, sulfonate, amino, amido, nitrile, alkoxy, linking group, and combinations thereof, and R9 is acetylene, alkane, alkene, cyano, substituted phenyl, and combinations thereof. The invention further includes novel intermediate compounds useful for the synthesis of asymmetric benzoxanthene compounds having the general structure where substituents R3-R7 correspond to like-referenced substituents in the structure of described above, and Y2 is hydroxyl or amine. In another aspect, the invention includes methods for synthesizing the above dye compounds and intermediates.

Abstract: Methods are provided for identifying nucleic acids. Methods of the invention are useful for identifying and analyzing nucleic acids, especially variants of single nucleotide polymorphisms, that are indicative of disease or the predisposition for disease.

Abstract: A method for producing a Y chromosome specific probe selected from highly repeating sequences on that chromosome is described. There is little or no nonspecific binding to autosomal and X chromosomes, and a very large signal is provided. Inventive primers allowing the use of PCR for both sample amplification and probe production are described, as is their use in producing large DNA chromosome painting sequences.