Abstract: Methods and compositions are disclosed for providing prolonged-release of therapeutic agents by way of in situ stereotaxic implantation in specific loci, including pathways, to treat known disorders. One or more microstructures comprising therapeutic agents and pharmaceutically acceptable carriers are implanted, for example, through a cannula. The microstructures are of a sufficient size and shape to prevent dispersion from the implant site.

Abstract: The invention relates to novel nucleic acids encoding a fibroblast growth factor-23(FGF23) and proteins encoded thereby, mutations in which are associated with autosomal dominant rickets (ADHR). The invention further relates to methods of diagnosing and treating hypophosphatemic and hyperphosphatemic disorders comprising inhibiting or stimulating, respectively, the biological activity of FGF23 in a patient. The invention also relates to methods of treating osteoporosis, dermatomyositis, and coronary artery disease comprising stimulating the biological activity of FGF23 in a patient.

Abstract: The present invention provides a water-soluble luminescent quantum dot, a biomolecular conjugate thereof and a composition comprising such a quantum dot or conjugate. Additionally, the present invention provides a method of obtaining a luminescent quantum dot, a method of making a biomolecular conjugate thereof, and methods of using a biomolecular conjugate for ultrasensitive nonisotopic detection in vitro and in vivo.

Abstract: A wave rotor detonation engine and method are provided. The wave rotor detonation engine includes a rotor rotatably mounted within a housing, an inlet port, an exhaust port, and an igniter for igniting the gases within the rotor. The rotor includes a plurality of circumferentially spaced longitudinally extending combustion chambers in which detonative combustion occurs. The inlet port has a plurality of separate inlet zones for supplying fuel and air mixtures to the inlet end of the rotor. The inlet zones are circumferentially spaced about the perimeter of the rotor so that the combustion chambers interact with these inlet zones sequentially. Each inlet zone is capable of introducing a different combustible mixture sequentially to a given combustion chamber as it rotates past the inlet zones. This results in the stratification of differing concentrations of combustible material within the combustion chambers which is particularly suited to create detonative combustion within the wave rotor.

Abstract: A time-of-flight mass spectra calibration technique uses time-of-flight mass spectrometer instrument operational parameters and known mass and measured time-of-flight data pairs to optimize values of chosen ones of the instrument operational parameters. Electrostatic time-of-flight calculations are conducted in conjunction with an iterative procedure, preferably a simplex optimization procedure, to thereby minimize a residual error between the electrostatic time-of-flight calculations and the measured time-of-flight data values for each of the known mass values. While conventional curve fitting mass calibration techniques are devoid of information that describe ion behavior, the mass calibration technique of the present invention, by contrast, takes into account all of the instrument operational parameters in arriving at a final calibration.

Abstract: Methods of treating a subject having a disorder associated with LHRH activity are disclosed.

Abstract: Disclosed are methods and compositions for identifying, monitoring and treating premalignant and malignant conditions in a human subject. The present invention further discloses methods and compositions for determining cells undergoing apoptosis, and for increasing the efficacy of a cancer therapy. The methods involve the use of apurinic/apyrimidinic endonuclease (APE), independently, as a marker for (pre)malignant conditions and for apoptosis. Also described are polyclonal antibody preparations for use in methods for detecting APE and methods for modulating expression susceptibility of cells to apoptosis.

Abstract: The invention provides methods and compositions for polymerizing a particular nucleotide with a polymerase. In general, the method involves (a) forming a mixture of a polymerase and a nucleoside triphosphate (NTP) comprising &agr;, &bgr; and &ggr; phosphates and a &ggr;-phosphate phosphoester-linked functional group; and incubating the mixture under conditions wherein the polymerase catalyzes cleavage of the NTP between the &agr; and &bgr; phosphates, liberating a pyrophosphate comprising the functional group and polymerizing the resultant nucleoside monophosphate, i.e. incorporates the nucleoside monophosphate in a nascent polynucleotide. A variety of functional groups compatible with the polymerization reaction are provided.

Abstract: A method is provided to determine the ability of a test compound to alter PAK activation of Raf-1 comprising: (a) contacting a polypeptide comprising the catalytic domain of a PAK with the test compound in the presence of Raf-1; and (b) measuring the extent of activation of Raf-1.

Abstract: The present invention includes the receptor protein 4-1BB and the cDNA gene encoding for receptor protein 4-1BB. The nucleotide sequence of the isolated cDNA is disclosed herein along with the deduced amino acid sequence. The 4-1BB protein and fragments and derivatives can be used: 1) as a probe to isolate ligands to receptor protein 4-1BB, 2) to stimulate proliferation of B-cell's expressing 4-1BB, or 3) to block 4-1BB ligand binding. A monoclonal antibody against 4-1BB was developed which specifically recognizes an epitope on the extracellular domain of receptor protein 4-1BB. The monoclonal antibody can be used enhance T-cell proliferation and activation by treating T-cells that have expressed receptor protein 4-1BB with the monoclonal antibody. The effectiveness of the treatment was enhanced when conducted in the presence of protein tyrosinase kinase. A fusion protein for detecting cell membrane ligands to receptor protein 4-1BB was developed.

Abstract: The invention provides a device having two components: a needle advancing apparatus slidable longitudinally along a catheter to advance needles into a tissue membrane, such as a blood vessel wall, around an opening in the membrane; and, a suture retrieval assembly insertable through the catheter beyond a distal side of the tissue membrane The needle advancing apparatus advances suture through the tissue wall. The suture retrieval assembly grabs the suture on the distal side of the tissue membrane for extraction thereof through the opening in the tissue membrane. A method for suturing a membrane beneath the patient's skin is also disclosed.

Abstract: Provided herein are variant alleles of a gene encoding a mu opioid receptor, along with cloning vectors for replicating such variant alleles, expressing vectors for expressing the variant alleles to produce variant mu opioid receptors, and antibodies to such variant receptors. Also disclosed are binding characteristics of such variant receptors regarding binding to opioid ligands, and the using of such binding characteristics to diagnose a subjects susceptibility to pain, susceptibility to an addictive disease, selecting an appropriate pain reliever along with a therapeutically effective amount of the reliever to administer to a subject suffering from pain. In addition, diagnostic methods for diagnosing a disease or disorder such as infertility, constipation, diarrhea, decreased immune response relative to a standard, and decreased ability to withstand stress relative to a standard, along with commercial kits for diagnosing such diseases or disorders.

Abstract: Provided herein are variant alleles of a gene encoding a mu opioid receptor, along with cloning vectors for replicating such variant alleles, expressing vectors for expressing the variant alleles to produce variant mu opioid receptors, and antibodies to such variant receptors. Also disclosed are binding characteristics of such variant receptors regarding binding to opioid ligands, and the using of such binding characteristics to diagnose a subjects susceptibility to pain, susceptibility to an addictive disease, selecting an appropriate pain reliever along with a therapeutically effective amount of the reliever to administer to a subject suffering from pain. In addition, diagnostic methods for diagnosing a disease or disorder such as infertility, constipation, diarrhea, decreased immune response relative to a standard, and decreased ability to withstand stress relative to a standard, along with commercial kits for diagnosing such diseases or disorders.

Abstract: An ion mobility and mass spectrometer instrument includes an ion source region coupled to an ion mobility spectrometer having an ion outlet coupled to a quadrupole mass filter. An output of the filter is coupled to a collision cell which has an ion outlet coupled to an ion acceleration region of a mass spectrometer such as a time of flight mass spectrometer. The instrument is particularly well suited for sequencing analysis wherein a sample is ionized and a resulting three-dimensional ion spectrum (ion intensity vs. ion mobility and ion mass) is observed. If the spectrum reveals that no ions overlap in mobility values, the collision cell is filled with a suitable buffer gas and the instrument is reactivated whereby a complete three-dimensional spectrum of parent and daughter ions results.

Abstract: Described are unique prosthesis systems including superplastically-formed prosthetic elements, and methods and an apparatus for forming such elements. A preferred dental prosthesis system includes at least two osseointegrated fixtures, abutments attached to the fixtures, a bar member interconnecting the abutments, and a prosthesis detachably connected to the bar member, wherein the prosthesis includes a superplastically-formed metal element having a surface conforming to the bar member and abutments, a resin denture base attached to the metal element, and artificial teeth mounted on the resin denture base. The preferred prosthetic components are prepared by superplastic forming under temperature conditions which are repeatedly cycled above and below the transformation temperature of the metal being formed.

Abstract: Methods and compositions are disclosed for providing prolonged release of therapeutic agents by way of in situ stereotaxic implantation in specific loci, including pathways, to treat known disorders. One or more microstructures comprising therapeutic agents and pharmaceutically acceptable carriers are implanted, for example, through a cannula. The microstructures are of a sufficient size and shape to prevent dispersion from the implant site.

Abstract: The inventors have cloned and expressed the chemokine-like genes from MCV type 1 and the closely related MCV type 2 in order to determine a potential role for these proteins in the viral life cycle. These are the first viral chemokines that have been shown to antagonize the chemotactic activity of human chemokines and the first viral chemokines that have been shown to have inhibitory activity on human hematopoietic progenitor cells. Methods and compositions for exploiting these proteins are disclosed herein.

Abstract: An apparatus for treating a body structure with radiation and a method for using the same. The apparatus comprising a concentrator for receiving a solution comprising a radioactive material and for increasing the concentration of the radioactive material in solution; a calibrator operatively associated with the concentrator for measuring a level of radiation associated with the radioactive material; and a delivery unit for transferring the solution directly from the apparatus to a balloon catheter.

Abstract: The present invention relates generally to the fields of chemotherapeutic treatments. More particularly, it concerns the use of ibuprofen, a non-steroid anti-inflammatory drug, in the treatments of disease. More particularly, it has been discovered that the R-enantiomer of ibuprofen, previously thought to be inactive, may be used as an antineoplastic agent and also in the prophylactic and therapeutic treatment of Alzheimer's and Alzheimer's related diseases.

Abstract: Described are DNA-repair fusion proteins of multiple, complementary DNA repair proteins and having the activity of each protein, and related polynucleotides and vectors. The proteins, when expressed in cells, e.g., hematopoietic cells, increase the survival rate of the cells when contacted with chemotherapeutic agents. Also described are transgenic animal models wherein these proteins are expressed in essentially all cells of the animal. Such animal models are useful for instance in testing chemotherapeutic agents.