Abstract: The mechanism of hypertension following acute NO synthase blockage is via endothelin-mediated vasoconstriction. Thus, NO appears to inhibit endothelin activity by blocking its expression and not as a chronic direct acting vasodilator. Administration of an endothelin antagonist to a patient in a ‘normal’ physiological state may result in specific regional vasodilation. This treatment finds utility in the treatment of erectile dysfunction.

Abstract: Methods and compounds, such as &bgr;-heterocyclic-&bgr;-amino acids, useful for the inhibition of epileptogenesis are disclosed. Methods for preparing and using the &bgr;-heterocyclic-&bgr;-amino acids of the invention are also described.

Abstract: Therapeutic compounds and methods for inhibiting amyloid deposition in a subject, whatever its clinical setting, are described. Amyloid deposition is inhibited by the administration to a subject of an effective amount of a therapeutic compound comprising an anionic group and a carrier molecule, or a pharmaceutically acceptable salt thereof, such that an interaction between an amyloidogenic protein and a basement membrane constituent is inhibited. Preferred anionic groups are sulfonates and sulfates. Preferred carrier molecules include carbohydrates, polymers, peptides, peptide derivatives, aliphatic groups, alicyclic groups, heterocyclic groups, aromatic groups and combinations thereof.

Abstract: Methods and compositions which are useful in the treatment of amyloidosis. In particular, methods and compositions are provided for inhibiting, preventing and treating amyloid deposition, e.g., in pancreatic islets, wherein the amyloidotic deposits are islet amyloid polypeptide (IAPP)-associated amyloid deposition or deposits. The methods of the invention involve administering to a subject a therapeutic compound which inhibits IAPP-associated amyloid deposits. Accordingly, the compositions and methods of the invention are useful for inhibiting IAPP-associated amyloidosis in disorders in which such amyloid deposition occurs, such as diabetes.

Abstract: The present invention exploits the discovery that amounts of uracil and thymine metabolites, especially &bgr;-aminoisobutyric acid, in various bodily fluids, especially urine, are correlated with the occurrence of epilepsy when compared to matched control subjects. Analytical and diagnostic protocols, including a novel high performance liquid chromatography system, for use in the invention are disclosed.

Abstract: This invention relates to methods and apparatus for determining the multi-dimensional topology of a substance (system) within a volume (space). A method according to a preferred embodiment of the invention comprises the steps of: acquiring a set of relative values for the density (scalar properties) of the volume, each value for a given location (point) within the volume; interpolating a set of functions to generate a continuous relative density for the volume; identifying critical points of the continuous relative density by using an eigenvector following method; and associating critical points with one another by following a gradient path of the continuous relative density between the critical points. The method is applicable to a wide range of data relating to fields such as crystallography, fluid dynamics, edge detection, and financial markets, to determine the topology of structures contained therein.

Abstract: The present invention provides a method of administration of an agent which acts to remodel neuronal or vascular pathways for the long term management of sexual dysfunction in both males and females. In a preferred embodiment, the invention provides a method of ameliorating or reversing pathogenic vascular degradative modeling in the ilio-hypogastric-pudendal arterial bed and genitalia comprising administering to a human patient in need of such treatment a therapeutically effective amount of an anti-pressor agent. The anti-pressor agent comprises one or more compounds selected from the therapeutic classes of direct vasodilators such as hydralazine and NO donors, ACE inhibitors, angiotensin-II receptor antagonists, &agr;1-adrenergic receptor antagonists, &bgr;-adrenergic receptor antagonists, calcium channel blockers, and phosphodiesterase inhibitors.

Abstract: Heterocyclic organoaluminum and organoboron coordination complexes that are photoluminescent and electroluminescent, emitting intense blue light. Methods of synthesizing such compounds, methods of producing photoluminescence and electroluminescence, methods of applying the compounds in thin films, and uses of the compounds of the invention in luminescent probes, electroluminescent displays and the like.

Abstract: The mechanism of hypertension following acute NO synthase blockade is via endothelin-mediated vasoconstriction. Thus, NO appears to inhibit endothelin activity by blocking its expression and not as a chronic direct acting vasodilator. Administration of an endothelin antagonist to a patient in a ‘normal’ physiological state may result in specific regional vasodilation. This treatment finds utility in the treatment of erectile dysfunction.

Abstract: The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.

Abstract: A method and system for detecting coincidences in a data set of objects, where each object has a number of attributes. Iteratively, equally-sized subsets of the data set of sampled, and coincidences (co-occurrences of a plurality of attribute values in one or more objects in the subset) are recorded. For each coincidence of interest, the expected coincidence count is determined and compared with the observed coincidence count; this comparison is used to determine a measure of correlation for the plurality of attributes for the coincidence. The resulting set of k-tuples of correlated attributes is reported, a k-tuple of correlated attributes being a plurality of attributes for which the measure of correlation is above a predetermined threshold. The method and system (implemented on an array of processing nodes) is suitable for protein structure analysis, e.g. in HIV research.

Abstract: A novel class of thermal hysteresis (antifreeze) proteins (THP) that have up to 100 times the specific activity of fish antifreeze proteins has been isolated and purified from the mealworm beetle, Tenebrio molitor. Internal sequencing of the proteins, leading to cDNA cloning and production of the protein in bacteria has confirmed the identity and activity of the 8.4 to 10.7 kDa THP. They are novel Thr- and Cys-rich proteins composed largely of 12-amino-acid repeats of cys-thr-xaa-ser-xaa-xaa-cys-xaa-xaa-ala-xaa-thr. At a concentration of 55 &mgr;g/mL, the THP depressed the freezing point 1.6° C. below the melting point, and at a concentration of ˜1 mg/mL the THP or its variants can account for the 5.5° C. of thermal hysteresis found in Tenebrio larvae. The THP function by an adsorption-inhibition mechanism and produce oval-shaped ice crystals with curved prism faces.

Abstract: The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.

Abstract: The present invention provides a method of administration of an agent which acts to remodel neuronal or vascular pathways for the long term management of sexual dysfunction in both males and females. In a preferred embodiment, the invention provides a method of ameliorating or reversing pathogenic vascular degradative modeling in the ilio-hypogastric-pudendal arterial bed and genitalia comprising administering to a human patient in need of such treatment a therapeutically effective amount of an anti-pressor agent. The anti-pressor agent comprises one or more compounds selected from the therapeutic classes of direct vasodilators such as hydralazine and NO donors, ACE inhibitors, angiotensin-II receptor antagonists, &agr;1-adrenergic receptor antagonists, &bgr;-adrenergic receptor antagonists, calcium channel blockers, and phosphodiesterase inhibitors.

Abstract: The invention relates to surgical bone cement compositions and more particularly to bone cement compositions having aneasthetic properties, and to methods for producing analgesia.

Abstract: A method of treating a CNS disorder in a subject in need of such treatment, the method comprising administering to the subject an effective amount of an N′N′-dichlorinated amino acid, peptide, peptidomimetic, amine, or a pharmacologically acceptable analogue or derivative thereof, such that a CNS disorder is treated. An N′N′-dichlorinated amino acid, peptide, peptidomimetic, or amine capable of crossing the blood-brain barrier of a subject when administered thereto.

Abstract: Therapeutic compounds and methods for modulating amyloid deposition in a subject, whatever its clinical setting, are described. Amyloid deposition is modulated by the administration to a subject of an effective amount of a therapeutic compound comprising a phosphonate group and a carboxylate group, a congener thereof, or a pharmaceutically acceptable salt or ester thereof. In preferred embodiments, an interaction between an amyloidogenic protein and a basement membrane constituent is modulated.

Abstract: Methods for treating vascular conditions associated with localized imbalance in vascular tone, which are hypothesized to be largely due to elevated endothelin (ET) are provided. The methods involve administration of nitric oxide (NO), agents which are able to provide NO, such as NO donors, agents which activate guanyl cyclase, such as YC-1, or agents which prolong the actions of endogenous NO or cyclic guanosine monophosphate (cGMP; a 2nd messenger molecule), such as phosphodiesterase (PDE) inhibitors. According to the invention, such agents are administered in minimal doses or microdoses by any route known in the art, so as to provide dosages which are about one half to about one twentieth (½ to {fraction (1/20)}) of those known to induce vasodilation in “normal” circulations.

Abstract: Methods for treating vascular conditions associated with localized imbalance in vascular tone, which are hypothesized to be largely due to elevated endothelin (ET) are provided. The methods involve administration of nitric oxide (NO), agents which are able to provide NO, such as NO donors, agents which activate guanyl cyclase, such as YC-1, or agents which prolong the actions of endogenous NO or cyclic guanosine monophosphate (cGMP; a 2nd messenger molecule), such as phosphodiesterase (PDE) inhibitors. According to the invention, such agents are administered in minimal doses or microdoses by any route known in the art, so as to provide dosages which are about one half to about one twentieth (½ to {fraction (1/20)}) of those known to induce vasodilation in “normal” circulations.

Abstract: The present invention provides methods and compositions for enhancing the effect of a neurotrophin on a cell expressing a neurotrophin receptor. The effect is preferably neurotrophin-mediated growth and/or survival, such as neurite growth. The invention employees amphipathic compounds having a hydrophobic membrane-associating face and a hydrophilic face opposed thereto, which preferably mimic the amphipathic domain of the common neurotrophin receptor p75 from amino acid residue 367 to residue 379. Such compounds have charged moieties, polar moieties or combinations that mimic the charged and polar group relationships of p75NTR367-379, and include but are not limited to peptide analogues thereof. The hydrophobic membrane-associating face can interact with a membrane-bound neurotrophin receptor, such as TrkA, and the opposing hydrophillic face can interact with a DNA binding protein, such as nuclear transcription factor NFkB.