Abstract: Disclosed herein are the methods of using the H4-1BB protein, ligands to this protein, and various mAbs either directed against H4-1BB or other molecules that can be used therapeutically. The nature and importance of the H4-1BB molecule provides the ligands and related co-stimulatory molecules the ability to enhance or suppress T-cell activation and proliferation. By treating T-cells that have expressed receptor protein H4-1BB with one of the four anti-H4-1BB monoclonal antibodies disclosed herein activation or inhibition of the immune response is seen. Also disclosed herein is cDNA for the human receptor H4-1BB. The cDNA of the human receptor H4-1BB is about 65% homologous to the mouse cDNA 4-1BB and was isolated by using probes derived from murine cDNA 4-1BB. A fusion protein for detecting cell membrane ligands to human receptor protein H4-1BB was developed.

Abstract: A method of diagnosing patients suspected of having a neurological disorder is disclosed and includes monitoring movement of a patient in order to obtain movement data that is representative of the movement of the patient. Another step of the method includes processing the movement data in order to obtain an input pattern that is representative of the movement data. The method also includes the step of processing the input pattern with a computational intelligence system that has been trained to classify movement based upon a predetermined group of neurological disorder classifications. Furthermore, the method includes generating with the computational intelligence system an output that is indicative of an appropriate neurological disorder classification for the patient. An analysis system for diagnosing patients suspected of having a neurological disorder is also disclosed.

Abstract: A polymer-micelle complex is disclosed. The polymer-micelle complex includes a micelle having a negative charge. The negatively charged micelle is bound electrostatically to a polymer bearing a positive charge. The complex can be in turn electrostatically bound to a siliceous material so that the complex is immobilized on the siliceous material. In addition, a composition comprising a negatively charged micelle, a positively charged polymer, and an aqueous carrier is disclosed. The aqueous carrier can exhibit salinity. In the composition, the micelle and polymer can electrostatically interact so as to form a polymer-micelle complex (which can either be soluble in the aqueous carrier or in the form of a precipitate or coacervate), or, alternatively, the polymer and micelle can remain separate such that a complex is not formed therebetween.

Abstract: The invention provides novel tetradentate enediyne ligands that are themselves thermally stable, yet react at about room temperature or slightly higher upon addition of metal ions or under photothermal conditions. In another aspect of the invention, a method of treating a disorder in a mammal comprising administering a therapeutically effective amount of a compound or composition is provided. In addition, the free ligand can be delivered to the mammal prior to complexation to metals, such that the ligand is exposed to a metal in the body and forms a metal complex in vivo. Furthermore, a metal complex of the invention can be administered to the mammal such that the complex exchanges the first metal center with another endogenous metal in order to form a second metal complex in vivo. The second metal complex is capable of forming a benzenoid diradical under physiological conditions and/or under photothermal conditions.

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: The invention provides antiviral compounds and compositions comprising a viral specific oligonucleotide. Also provided are methods to inhibit or treat viral infections with the compounds or compositions of the invention.

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 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 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: 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: 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 provides an isolated and purified nucleic acid molecule encoding a Candida albicans sterol methyltransferase (ERG6). Also provided is a C. albicans strain or isolate that has reduced levels of sterol methyltransferase as a result of the disruption of at least one sterol methyltransferase gene. Preferred isolates are more susceptible to a number of sterol synthesis and metabolic inhibitors relative to wild type isolates. Further provided are methods to identify sterol methyltransferase inhibitors and methods to screen for antifungals or metabolic inhibitors which are not normally permeable to the fungal cell.

Abstract: A guide catheter includes a body and a centering mechanism. The body has an elongatable section and a lumen with a stop. The centering mechanism is a plurality of bias elements that forms a self-expanding basket attached to the body so that the elongatable section is within the basket. A straightening catheter engages the stop to stretch the elongatable section and to flatten the basket against the body. The guide catheter can be inserted into a vessel and the centering mechanism can be positioned at a desired treatment site by means of an over-the-wire guidewire system. The straightening catheter can be removed to allow the self-expanding basket to center the guide catheter in the vessel. A dosing device can then be inserted into the guide catheter and located at the centered basket to deliver the brachytherapy to prevent restenosis.

Abstract: Devices and methods are disclosed for the percutaneous administration of a composition to a desired in vivo location. The composition comprises a biologically active substance and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier is preferably non-solid and a polymer, which is preferably capable of being transformed into a gel, thus allowing timed-released delivery of the substance. A preferred use for this invention is to provide local delivery of biologically active substances for the prevention of restenosis following angioplasty or other blood vessel injury.