Abstract: The invention provides labels for electronic detection of individual molecules. The labels are comprised of elements with different electrical properties that affect the electric current flowing through a nanoelectrode. The labels are of polymeric or filamentous structure where the elements are arranged linearly along their length. The arrangement of the elements is predetermined and combinatorial, so that a high diversity of labels can be generated in a manner that resembles barcoding on a nanoscale level. Methods for the synthesis of said barcode labels and for the binding of the barcode labels to individual molecules, their movement past a nanoelectrode, and their detection are also provided.

Abstract: Provided is a polynucleotide dendrimer having a single unique binding site for binding a target molecule, thereby permitting stoichiometric quantification of the dendrimer-bound target molecule. The dendrimer of the invention is useful in conjunction with various methods for detecting, and optionally quantifying, nucleic acids, proteins, polysaccharides, organic compounds, or antigens, among others.

Abstract: Oligonucleotide molecules for the detection of Giardia lamblia (G. lamblia which molecules hybridise under medium to high stringency conditions to unique 18S rDNA/rRNA sequences of G. lamblia, and methods for the detection of the presence of viable cells of G. lamblia in samples using the oligonucleotide molecules.

Abstract: The invention relates to a labeling reactant of formula (I) useful for labeling an oligonucleotide wherein: R is a temporary protecting group. A is either a phosphorylating moiety or a solid support tethered to Z via a linker arm E?. Z is a bridge point and is formed from E is a linker arm between R and Z. E? is a linker arm between Z and Z?. E? is a linker arm between Z and A. E?? is a linker arm between Z? and G. Z? is a purine or pyrimidine base. G is a protected bivalent aromatic structure, tethered to two iminodiacetic acid ester groups N(CH2COOR?)2, or G is a structure selected from the group consisting of or G is a protected functional group, or G is a protected or unprotected organic dye, hapten or a spin label.

Abstract: A nucleic acid primer is bound to a soluble carrier macromolecule, a multitude of primer molecules thus being carried by each carrier macromolecule, and hybridisation of the primer to a template followed by extension of the primer to replicate the template in complementary form is carried out as part of a PCR procedure or other amplification, or to form an extended primer of greater hybridisation affinity. A second primer used in the amplification may also be bound to a carrier macromolecule.

Abstract: In various embodiments of the invention, novel compositions having a polynucleotide bound to a substrate via a cleavable linker are provided, and methods of cleaving a polynucleotide from a substrate are provided.

Abstract: The invention provides methods and kits for determining the presence of polynucleotides in samples. According to certain embodiments, the invention provides methods for determining the presence of target polynucleotides by amplifying the target polynucleotides in the sample, detecting amplification products, and determining the sequence of the amplification products.

Abstract: Methods and compositions for detecting and localizing light originating from a mammal are disclosed. Also disclosed are methods for targeting light emission to selected regions, as well as for tracking entities within the mammal. In addition, animal models for disease states are disclosed, as are methods for localizing and tracking the progression of disease or a pathogen within the animal, and for screening putative therapeutic compounds effective to inhibit the disease or pathogen.

Abstract: Provided is a preparative method for isolating RNA comprising an oligo-or polynucleotide from a sample, which method comprises: (a) treating the sample with a reactant capable of covalently modifying the 2?-OH position of the ribose rings of the RNA under conditions so that a proportion of the 2?-OH positions of the ribose rings bear a substituent; and (b) preparing isolated RNA therefrom by separating material containing the substituent from the sample on the basis of a property of the substituent.

Abstract: The present invention relates to an automated method of transposon-mediated multiplex sequencing of DNA fragments inserted into a vector. It relates more particularity to an increased efficiency in such automated methods, where the increased efficiency is obtained by screening out before the sequencing those constructs in which the transposon inserted into the vector sequence. This prevents a waste of time and resources in performing reactions sequencing the vector instead of the DNA fragments of interest.

Abstract: The present invention relates to a method for determining a nucleotide sequence of a nucleic acid by detecting a single dye molecule.

Abstract: A method for homogeneously assaying biopolymer bonding includes obtaining signals from a test sample before, during and/or after the application of stimulus to the test sample and correlating the signals. The signals, whose magnitude correlate with binding affinity, can be, for example, electrical conductance and/or fluorescent intensity. The stimulus can be, for example, electric voltage and/or laser radiation. Preferably, different types of signals are measured and compared so as to enhance the reliability of the assay.

Abstract: The present invention provides a labeled nucleoside having formula: where X represents an aliphatic diamine, and the labeling moiety comprises a label and a spacer, where the spacer is coupled at one end to a platinum atom and at the other end to the label, which spacer comprises a chain having at least four carbon atoms and at least one oxygen atom in the chain. The invention further provides a method for labeling a nucleoside, kits for labeling a nucleoside, and kits for producing a labeled nucleic acid.

Abstract: The present invention relates to oligonucleotides useful for determining the presence of Mycoplasma pneumoniae and/or Mycoplasma genitalium in a test sample. The oligonucleotides of the present invention may be incorporated into hybridization assay probes, capture probes and amplification primers, and used in various combinations thereof.

Abstract: The present invention features novel compositions, linkers, derivatized solid supports, and methods for the efficient solid phase synthesis of oligonucleotides, including RNA, DNA, RNA-DNA chimeras, and analogs thereof.

Abstract: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.

Abstract: Methods and compositions for detecting and localizing light originating from a mammal are disclosed. Also disclosed are methods for targeting light emission to selected regions, as well as for tracking entities within the mammal. In addition, animal models for disease states are disclosed, as are methods for localizing and tracking the progression of disease or a pathogen within the animal, and for screening putative therapeutic compounds effective to inhibit the disease or pathogen.

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: Hydrazino, oxyamino and carbonyl-based monomers and methods for incorporation into oligonucleotides during enzymatic synthesis are provided. Modified oligonucleotides are provided that incorporate the monomers provided herein. Immobilized oligonucleotides and oligonucleotide conjugates that contain covalent hydrazone or oxime linkages are provided. Methods for preparation of surface bound oligonucleotides are provided. Methods for the preparation of oligonucleotide conjugates are also provided.

Abstract: The present invention relates to the use of an inhibitor of CTP synthetase, such as a glutamine analogue, and a substance capable of suppressing toxic effects thereof in vivo, in the manufacture of a medicament for the treatment of a disease caused by a parasitic protozoa. More specifically, said substance capable of suppressing toxic effects may be a nucleobase, such as a purine base or a nucleoside, while the glutamine analogue advantageously is 6-diazo-5-oxo-L-norleucine (DON). The invention also relates to a pharmaceutical composition as such for the treatment and/or prevention of a disease caused by a parasitic protozoa, wherein the disease is selected from the group consisting of malaria, leishmaniasis and trypanosomiasis, e.g. American trypanosomiasis (Chaga's disease), or African trypanosomiasis (African sleeping sickness).

Abstract: A translation template comprising an ORF region coding for a protein, a 5? untranslated region comprising a transcription promoter and a translation enhancer and locating on the 5? side of the ORF region, and a 3? end region comprising a poly-A sequence and locating on the 3? side of the ORF region, is expressed in a translation system in the presence of an agent for modifying a C-terminal of a protein, which comprises an acceptor portion having a group capable of binding to a protein through a transpeptidation reaction in a protein translation system and a modifying portion comprising a nonradioactive modifying substance linked to the acceptor portion via a nucleotide linker, to cause protein synthesis and the synthesized protein is purified. Thus, the yield of modified protein in a method of modifying C-terminal of protein is improved and detection of protein interaction based on various intermolecular interaction detection methods is realized at an improved level.

Abstract: Methods, employing a polycyclic hydrocarbon or a polycyclic heteroaromatic compound as sensitizers, are provided to increase the efficiency of removing, by irradiation, photolabile protecting groups that mask reactive sites on synthesis intermediaries. Preferred groups of photolabile protecting moieties include: ((?-methyl-2-nitropiperonyl)-oxy)carbonyl (MeNPOC), ((Phenacyl)-oxy)carbonyl (PAOC), O-(9-phenylxanthen-9-yl) (PIXYL), and ((2-methylene-9,10-anthraquinone)-oxy)carbonyl (MAQOC). In conjunction with using the sensitizers and protecting groups described above, a method of forming, from component molecules, a plurality of compounds on a support, each compound occupying a separate predefined region of the support is provided. These resulting solid-phase arrays are useful, for example, to assay for the presence of biochemical products in biological samples.

Abstract: Methods for preparing nanoscale reactions using nucleic acids or proteins are presented. Nucleic acids are captured saturably, yet reversibly, on the internal surface of the reaction chamber, typically a capillary. Excess nucleic acid is removed and the reaction is performed directly within the capillary. Proteins are captured specifically and saturably on the modified inner surface of the reaction chamber, typically a capillary. Excess protein is removed and the reaction is performed directly within the capillary. Devices for effecting the methods of the invention and a system designed advantageously to utilize the methods for high throughput reactions involving nucleic acids or proteins are also provided.

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 method of analyzing a target nucleic acid fragment is provided that is capable of being performed simply and promptly, by anyone, using a compact device without requirement of specific technique or complex operation. The method comprises timely detection of a double-stranded nucleic acid fragment formed during the polymerase extension reaction due to a specific base sequence of the target nucleic acid fragment as increase of an electrochemical response under the existence of an electrochemically active intercalator; and the kit utilizes the method.

Abstract: Methods of detecting or measuring the activity of polynucleotide kinase are disclosed as well as methods of detecting an analyte in an assay using polynucleotide kinase as a label on a member of a specific binding pair. The methods rely on the phosphorylation of an oligonucleotide followed by ligation of the oligonucleotide 5?-phosphate onto another template-bound oligonucleotide. The presence of the ligated product signals the presence of polynucleotide kinase. In preferred embodiments, phosphorylation of an oligonucleotide enables the consecutive ligation of a set of oligonucleotides. The oligonucleotides so ligated can be detectably labeled with, for example, other enzymes to provide highly sensitive detection methods.

Abstract: The present method describes the use of thio-phosphate as a feed source for micro-organisms and multi-cellular organisms. This compound enters into nucleotide pools and ultimately into polymers of both RNA and DNA forming stable phosphorothioate internucleotide linkages. The method enables the microbial synthesis of both plasmid and phage DNA substituted with phosphorothioate. Furthermore, methods are described for the preparation of phosphorothioate oligo mixtures from recombinant phage DNA grown in modified media for use in antisense studies.

Abstract: A biological sample containing a target nucleic acid is mixed with a primer, a substrate labeled with fluorescence, and DNA polymerase to prepare a test solution. After a nucleic acid amplification reaction is performed in a predetermined manner, the test solution is attached dropwise on a slide glass, which is mounted on a sample holder of an inverted fluorescence microscope. Data measured by a photomultiplyer are arithmetically operated by applying an autocorrelation function in a data processing apparatus. Based on the arithmetic results, quantification data for the target nucleic acid, are numerically or graphically displayed on a screen of a display apparatus.

Abstract: The present invention relates to novel methods of producing proteins in which one or more domains are full length and correctly folded and which are each tagged at either the N- or C-terminus with one or more marker moieties and arrays containing such proteins, as well as the use of such proteins in arrays for rapid screening.

Abstract: The lifetime probability of a person developing cancer can now be determined based on an allelic variation found in the 3?UTR of the prohibitin gene. The probability is dependent on the sequence of the 3?UTR at position 729, i.e., whether there is a thymine (T) or a cytosine (C) or both at this position. Determining the sequence at the position 729 can be done by any number of standard techniques. Preferably, the sequence is determined by amplifying this region by PCR and subjecting it to an RFLP analysis.

Abstract: Dual nucleic acid probes with resonance energy transfer moieties are provided. In particular, fluorescent or luminescent resonance energy transfer moieties are provided on hairpin stem-loop molecular beacon probes that hybridize sufficiently near each other on a subject nucleic acid, e.g. mRNA, to generate an observable interaction. The invention also provides lanthanide chelate luminescent resonance energy transfer moieties on linear and stem-loop probes that hybridize sufficiently near each other on a subject nucleic acid to generate an observable interaction. The invention thereby provides detectable signals for rapid, specific and sensitive hybridization determination in vivo. The probes are used in methods of detection of nucleic acid target hybridization for the identification and quantification of tissue and cell-specific gene expression levels, including response to external stimuli, such as drug candidates, and genetic variations associated with disease, such as cancer.

Abstract: Nucleotides comprising a reporter moiety and a polymerase enzyme blocking moiety in which the reporter moiety does not also act as a polymerase enzyme blocking moiety are described. Also described are compounds of Formula (I): wherein W is a phosphate group, B is a base, Y is a linker comprising an enzyme-cleavable group, R2 is a reporter moiety, R3 is selected from H or OH, Z and Z? are selected from H, OH, or a group X—R1, wherein X is a linker comprising an enzyme-cleavable group and R1 is a polymerase enzyme blocking group, provided that at least one of Z and Z? is X—R1.

Abstract: Unitary hybridization probes having stem-and-loop structures, wherein the stem portion of the structure comprises a pair of interactive arms that are substantially prevented from interacting with target polynucleotides. One arm of the invented parallel-stem hybridization probe has a backbone polarity opposite that of the target-complementary loop sequence of the probe. Rather than interacting in an antiparallel fashion, the arms of parallel-stem hybridization probes interact in a parallel fashion. The arms of the invented dual inversion probes interact in a conventional antiparallel fashion, but have backbone polarities opposite that of the target-complementary loop portion of the probe. Arm portions of the inversion probes do not substantially contribute to sequence-dependent stabilization of probe:target hybrids. Incorporating inversion linkages into the structures of these probes dramatically simplifies the process of designing stem-and-loop hybridization probes.

Abstract: A method of improving amplification of nucleic acids using a nucleic acid sequence-based amplification (“NASBA”) method is provided wherein target nucleic acids and NASBA primers are electronically addressed to electronically addressable capture sites of a microchip. This improvement uses electronically induced hybridization of the target nucleic acids to the primers. The primers may be solution-based or immobilized on the capture sites of the microchip.

Abstract: Nucleic acids are fixed or immobilized to non-porous solid supports (substrates), and include systems containing such supports and arrays with fixed or immobilized nucleic acids. These compositions are useful for nucleic acid analyses and a host of applications, including, for example, detection, mutational analysis and quantification. The non-porous solid supports can be transparent or translucent, and the surfaces can be treated with agents to fix or immobilize the nucleic acids. Such agents include, for example, amine providing compounds, epoxy compounds and acid solutions. The fixed or immobilized nucleic acids can be unlabeled, or labeled with at least one non-radioactive signaling moiety, such as the case when the nucleic acids are double-stranded.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.

Abstract: The invention provides an apparatus and method for detection of a target molecule. The apparatus includes a probe labeled with a transition metal-ligand complex that hybridizes with the target to form an initial complex, a metal ion for doping the initial complex and forming a final complex, and a potential means for providing a potential to the final complex to produce a detectable signal indicating the presence of the target after redox reaction. The method of the invention teaches the steps of hybridizing a probe with an attached label to the target to produce an initial complex, adding a metal ion to the initial complex to form a final complex and applying a potential to the final complex to produce a measurable signal.

Abstract: The present invention provides methods, compounds, and kits useful in the analysis of reaction products and components of reaction mixtures, and in certain embodiments for the rapid and simultaneous determination of enantiomeric ratios, percent conversions, and absolute configurations.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.

Abstract: A compound which comprises a backbone having a plurality of chiral carbon atoms, the backbone bearing a plurality of ligands each being individually bound to a chiral carbon atom of the plurality of chiral carbon atoms, the ligands including one or more pair(s) of adjacent ligands each containing a moiety selected from the group consisting of a naturally occurring nucleobase and a nucleobase binding group, wherein moieties of the one or more pair(s) are directly linked to one another via a linker chain; building blocks for synthesizing the compound; and rises of the compound, particularly in antisense therapy.

Abstract: VLSIPS™ manufacturing processes are of increasing commercial importance. The present invention provides methods and compositions for monitoring the efficiency and quality of polymer synthesis in VLSIPS™ arrays. Methods for monitoring polymer synthesis in an array on a substrate are provided. Monoisomeric labels for the labeling of synthetic polymer arrays are provided. Methods and compositions for post-synthetically labeling polymers in polymer arrays are also provided.

Abstract: The present invention relates to a labeled deoxyribonucleic acid (DNA) molecule. In one aspect, the labeled DNA molecule is produced by contacting a cell or subject with a detectable amount of a stable isotope label which is incorporated into DNA via the de novo nucleotide synthesis pathway to produce the labeled DNA molecule.

Abstract: Propargylethoxyamino nucleosides are disclosed having the structure wherein R1 and R2 are —H, lower alkyl, or label; B is a 7-deazapurine, purine, or pyrimidine nucleoside base; W1 is —H or —OH; W2 is —OH or a moiety which renders the nucleoside incapable of forming a phosphodiester bond at the 3?-position; and W3 is —PO4, —P2O7, —P3O10, phosphate analog, or —OH. Additionaly, a primer extension method is provided employing the above propargylethoxyamino nucleosides.

Abstract: The present invention provides a method for identifying one or more low abundance sequences differing by one or more single-base changes, insertions, or deletions, from a high abundance sequence in a plurality of target nucleotide sequences. The high abundance wild-type sequence is selectively removed using high fidelity polymerase chain reaction analog conversion, facilitated by optimal buffer conditions, to create a restriction endonuclease site in the high abundance wild-type gene, but not in the low abundance mutant gene. This allows for digestion of the high abundance DNA. Subsequently the low abundant mutant DNA is amplified and detected by the ligase detection reaction assay. The present invention also relates to a kit for carrying out this procedure.

Abstract: A method is described for controllably conducting complex PCR amplifications, wherein at least the following steps are conducted: a) PCR amplification with at least 50 primers of a first type (type 1) of different sequence, which are complementary to one of the strands of a random DNA sample, and also with a primer or a library of primers of a second type (type 2), which is complementary to the other strand of the DNA sample used, wherein the type 2 primers contain a first label (label 1); b) hybridizing of the amplified products to an oligomer array, which comprises oligonucleotides that hybridize to the primers utilized in the PCR reaction or to oligonucleotides that are complementary to these; or hybridizing of the amplified products to an oligomer array, which contains oligomers complementary to the primers utilized in the PCR reaction; c) length determination of the amplified products bound to the array by a second label (label 2) which can be correlated with the length of the respective DNA fragment,

Abstract: Methods are provided for treating arrhythmia in a manner that minimizes undesirable side effects, comprising administration of a therapeutically effective minimal dose of an A1 adenosine receptor agonist with a therapeutically effective minimal dose of a beta blocker, calcium channel blocker, or a cardiac glycoside.

Abstract: Kits for the multiplexed detection of the binding of, or interaction between, one or more ligands and target antiligands 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, a capture agent and optionally a cleaving agent. 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, target antiligands are contacted with a set of e-tag probes and the contacted antiligands are treated with a selected cleaving agent resulting in a mixture of e-tag reporters and uncleaved and/or partially cleaved e-tag probes. The mixture is exposed to a capture agent effective to bind to uncleaved 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 provides a nucleotide having the formula, Sig-PM-SM-BASE wherein PM is a phosphate moiety, SM is a sugar moiety and BASE is a pyrimidine, purine or 7-deazapurine moiety. PM is attached to the 3? or the 5? position of the sugar moiety when the nucleotide is a deoxyribonucleotide and at the 2?, 3? or 5? position when the nucleotide is a ribonucleotide. BASE is attached to the 1? position of SM from the N1 position when BASE is a pyrmidine or the N9 position when BASE is a purine or 7-deazapurine. Sig is covalently attached to PM directly or via a chemical linkage, and represents a detectable moiety covalently attached to SM directly or through a linkage group. Also provided are an oligo- or polynucleotide comprising at least one such phosphate-moiety labeled nucleotide, and other compositions including those wherein a polypeptide is terminally ligated or attached to the oligo- or polynucleotide.

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.