Abstract: Nucleic acid detection probes that comprise a pair of complementary, fluorophore/quencher labeled oligonucleotides, one of which is shorter than the other, are able to detect single-stranded and double-stranded targets in hybridization reactions and amplification reactions with real-time detection. Double-stranded probes of equal length are useful in PCR amplification reactions with real-time detection.

Abstract: Double-stranded nucleic acid hybridization probes comprise a longer strand perfectly complementary to a preselected target sequence in an assay and a shorter second strand complementary to the longer strand. The strands are labeled with interactive labels such as a fluorophore and a quencher. The probes may be used in real-time amplification assays to distinguish among alleles.

Abstract: A coding scheme for microcarriers suitable for use in distributed arrays includes labeling the carriers with quenched signaling hairpin molecules with any one of three to eight distinguishable fluorophores wherein the hairpins are of at least two types, most preferably three types, that open and fluoresce differentially as a chemical or physical condition, for example temperature, is changed. Mixtures of microcarriers having immobilized capture probes can be decoded by measuring fluorescence from said fluorophores under conditions under which only one type of hairpin is open, under which two types of hairpin are open, and so on. Mixtures of coded microcarriers with capture probes are used in assays for nucleic acids utilizing microarray methods.

Abstract: The invention provides assays that can detect multiple genetic variants of a gene (e.g., a mycobacterium gene) in a sample using a pool (using 2, 3, 4, or more) of oligonucletide hybridization probes.

Abstract: Kits for highly multiplexed homogeneous in vitro screening assays for numerous possible nucleic acid targets, any of which might be present in a sample, that utilize fluorescent hybridization probes that are combinatorially coded from a panel of fluorophores by subdividing each probe into portions and differently labeling each portion such that, when portions are combined, each probe has a unique code. The kits may include reagents and primers for target amplification and real-time detection.

Abstract: Highly multiplexed homogeneous in vitro screening assays for numerous possible nucleic acid targets, any of which might be present in a sample, utilize fluorescent hybridization probes that are combinatorially coded from a panel of fluorophores by subdividing each probe into portions and differently labeling each portion such that, when portions are combined, each probe has a unique code. The assays may include target amplification and real-time detection. Probe sets and kits containing additional assay reagents may be used to perform the screening assays.

Abstract: Nucleic acid hybridization under steady-state conditions is described by a kinetic model in which the intermediate state is assumed to be locally single stranded. An expression was derived that relates nucleic acid secondary structure to the rate of oligonucleotide-RNA hybridization. The model allows the calculation of a rate factor that is proportional to the rate constant for hybridization between complementary nucleic acids and is generally applicable to any RNA molecule with potential utility for rapid identification of sites for antisense attack of mRNA.

Abstract: Coalescence of cells or other membrane-bound entities is facilitated by anchoring an outwardly projecting first oligonucleotide in one member and an outwardly projecting second oligonucleotide, complementary to the first, in a second member and incubating under hybridizing conditions. Liposomes may be coalesced with cells to deliver hydrophilic agents thereto, such as DNA probes or drugs. Kits containing complementary oligonucleotides containing hydrophobic anchoring moieties may be used.

Abstract: Techniques for the delivery of metered amounts of liquid material include the use of a pin, such as an optical fiber. A sample of the liquid material may be placed on the tip of the pin for delivery to a target area, such as a specific location on a microarray, in a contactless manner. Light transmitted through the pin may be detected to facilitate accurate measuring of the pin's position.

Abstract: The invention features a protein which includes a gp120 V1/V2 domain of an HIV-1 strain and not a gp120 V3 domain of an HIV-1 strain, which protein does not substantially bind CD4. The gp120 V1/V2 domain of the protein displays an epitope which is recognized by an antibody which neutralizes at least one HIV-1 primary isolate with a ND90 of less than 100 &mgr;g/ml.

Abstract: A method of sorting mixtures of nucleic acid strands comprising hybridizing the strands to an array of immobilized oligonucleotides, each of which includes a constant segment adjacent to a variable segment. The constant segment of the immobilized oligonucleotides can be made complementary to the ends of strands obtained by digesting a double-stranded nucleic acid with a restriction enzyme and restoring the restriction sites, thereby permitting the sorting of strands according to their variable sequences adjacent to their constant terminal restored restriction sites.

Abstract: Two genes for proteins of M. tuberculosis have been sequenced. The DNAs and their encoded polypeptides can be used for immunoassays and vaccines. Cocktails of at least three purified recombinant antigens, and cocktails of at least three DNAs encoding them can be used for improved assays and vaccines for bacterial pathogens and parasites.

Abstract: The invention features a protein which includes a gp120 V1/V2 domain of an HIV-1 strain and not a gp120 V3 domain of an HIV-1 strain, which protein does not substantially bind CD4. The gp120 V1/V2 domain of the protein displays an epitope which is recognized by an antibody which neutralizes at least one HIV-1 primary isolate with a ND90 of less than 100 &mgr;g/ml.

Abstract: Non-competitive, quantitative amplification assay methods, including assays employing amplification by the polymerase chain reaction (PCR) process, for accurately measuring levels of target nucleic acid and sequences in samples and for ascertaining the relative amounts of cross-hybridizing alleles and mutants.

Abstract: The invention is based on the discovery that, for many drugs (e.g., antiviral or antimicrobial drugs such as antifungal or antibacterial drugs, including bacteriocidal or bacteriostatic drugs) and many pathogen strains (e.g., viral, fungal, or bacterial pathogens), a concentration of drug can be identified at which drug-resistant mutant pathogen strains are not selected. This concentration is herein referred to as the “mutant prevention concentration” (MPC). Maintaining serum concentrations of the drug above the MPC throughout a course of treatment should severely restrict selection of drug-resistant mutants. Additionally, it is discovered that drug-resistant mutant pathogens are selected exclusively within a drug concentration window, termed the “mutant selection window” (MSW). A quantitative expression of this window, which we call the “window index” (WI), is defined as the ratio of the MPC to the MIC.

Abstract: For nucleic acid amplification including extension of primers by a DNA polymerase, high specificity primers are provided. The primers include a type of hairpin structure in which a single-stranded loop separates complementary 3′ and 5′ arms and in which the loop and the 3′ arm are complementary to the target nucleic acid. Amplification methods, assays and kits including such primers are included in the invention.

Abstract: The invention is based on the discovery that, for many drugs (e.g., antiviral or antimicrobial drugs such as antifungal or antibacterial drugs, including bacteriocidal or bacteriostatic drugs) and many pathogen strains (e.g., viral, fungal, or bacterial pathogens), a concentration of drug can be identified at which drug-resistant mutant pathogen strains are not selected. This concentration is herein referred to as the “mutant prevention concentration” (MPC). Maintaining serum concentrations of the drug above the MPC throughout a course of treatment should severely restrict selection of drug-resistant mutants. Additionally, it is discovered that drug-resistant mutant pathogens are selected exclusively within a drug concentration window, termed the “mutant selection window” (MSW). A quantitative expression of this window, which we call the “window index” (WI), is defined as the ratio of the MPC to the MIC.

Abstract: Ligation methods for manipulating nucleic acid stands and oligonucleotides utilizing hybridization arrays of immobilized oligonucleotides. The oligonucleotide arrays may be plain or sectioned, comprehensive or non-comprehensive. The immobilized oligonucleotides may in some cases be binary oligonucleotides having constant as well as variable segments. Some embodiments include amplification of ligated products.

Abstract: The invention is based on the discovery that, for many drugs (e.g., antiviral or antimicrobial drugs such as antifungal or antibacterial drugs, including bacteriocidal or bacteriostatic drugs) and many pathogen strains (e.g., viral, fungal, or bacterial pathogens), a concentration of drug can be identified at which drug-resistant mutant pathogen strains are not selected. This concentration is herein referred to as the “mutant prevention concentration” (MPC). Maintaining serum concentrations of the drug above the MPC throughout a course of treatment should severely restrict selection of drug-resistant mutants. Additionally, it is discovered that drug-resistant mutant pathogens are selected exclusively within a drug concentration window, termed the “mutant selection window” (MSW). A quantitative expression of this window, which we call the “window index” (WI), is defined as the ratio of the MPC to the MIC.

Abstract: Nucleic acid hybridization probes having a first conformation when not interacting with a target and a second conformation when interacting with a target, and having the ability to bring a label pair into touching contact in one conformation but not the other, are labeled with a non-FRET pair of chromophores and generate a fluorescent or absorbance signal. Kits may include such probes, and assays, including multiplex assays, may utilize such probes.